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Biological Psychology Lecture Notes 1222014 Lecture Chapter 15 Mental Disorders Mental Illness 13 of US population reports symptoms at some time in their life that match features of major psychiatric disorders Rates between men and women are similar although depression is more prevalent in women and drugalcohol dependence is prevalent in men Historical Origins Through the ages mentally ill patients have been treated with various methods limited only by the human imagination Some approaches were inspired by the idea that af icted individuals were possessed by demonic forces Trephination ie drilling a hole through the head has been practiced by disparate cultures throughout the world it was thought that the unhealthy spirit could escape from the brain of the af icted Origins of a biological perspective on treating mental illness began in the early 20th century At the time 14 of all patients in mental hospitals suffered from a psychosis called paralytic dementia sudden onset of delusions grandiosity poor judgment impulsivity Patients pupils were noted to not constrict in response to light but did when focusing close in on objects Origins were thought to be due to stresses of life and quotweak characterquot Nouchi 1911 discovered that these patients sustained brain damage from a bacterial infection syphilis Disorder was renamed syphilitic psychosis and was virtually eradicated years later by antibiotic treatment This success inspired researchers to study other forms of mental disorders in hopes of nding a treatment 1930 s experiments on frontal lobe lesions performed in chimps inspired Egas Moniz to attempt similar operations in humans Moniz was intrigued by the calming in uence that such lesions were reported to produce Thus began the era of psychosurgery the use of surgical manipulation to treat severe mental illness 1940 s Labotomy frontal lobe lesions During its heyday 1050K patients in US were estimated to have had this surgery Surgery was supposed to induce relaxation and calmness in individuals with severe or intractable mental disorders Side effects were not so good among many mood swings change in personality lnitialy there was much enthusiasm for this procedure although as side effects became more noteworthy and controlled assessments were made the procedure was eradicated Walter Freeman American psychiatrist that performed and aggressively advocated the perfrontal lobotomy he probably deserves much of the blame of its overuse as opposed to Moniz Procedures involving much more restricted lesions are still used to this day although these are very rare 1970s Cingulotomy lesion pathways to cingulate cortex used to treat depressionanxiety 13 of severely OCD patients bene tted from this procedure ZOOOs Capsulotomy discrete lesions in anterior part of internal capsule white matter projections underlying cortex ong lasting bene ts in some cases of severe anxiety Patients with frequent occurring seizures can remove part of the brain where the electrical discharge occurs Cures the epilepsy however side effects of lesion remain eg Henry Molaison Deep Brain Stimulation DBS approved by the FDA 5 years ago for treatment of severe depression involves stimulating ventral portion of medial prefrontal cortex with a surgically implanted electrode DBS has also been used to treat Tourette s syndrome ie heightened sensitivity to sensory stimuli that l accompanied by the urge to emit verbal tics via stimulation of caudate nucleus In summary Neurosurgeries to treat psychiatric disorders are risky and have not been reliable except maybe DBS although the jury is still out on thisgt therefore they are rare and only used on the most severe cases as a last resort Their use also highlights the degree of desperation on the part of patients and caregivers and willingness to employ untested and even unsound ideas for treating mental illness Depression and stressrelated mental illnesses Stressrelated mental illnesses Exampes major depressive iness usu reactive depression anxiety disorders posttraumatic stress disorder PTSD There is a substantial degree of comorbidity ie overlap between the occurrence of these disorders Stressreated mental illnesses follow the classic model of interaction between genes and environment eg understanding how individual differences esp genetics may increase vulnerability to these disorders Depression 3 types of depression 1 Colloquial eg quotI m depressed because the Hawkeyes ost yet another heartbreaker last weekendquot 2 Reactive Depression due to an adverse life event contrasted from normal grieving usually resolves within 6 months with therapymeds 3 Major Depressive Disorder Severe prolonged depression may be precipitated by trauma but not necessarily MDD Major Depressive Disorder MDD extreme feelings of sadness and helplessness every day for weeks on end ncudes although does not require all of the following characteristics DSMIV Lack of energy Feeings of worthlessness Suicida thoughts Feeings of hopelessness Difficulty Sleeping Difficulty concentrating Litte pleasure decreased role in the mesolimbic pathway Postpartum depression Postpartum depression is depression after giving birth Affects about 20 of women and most recover quickly More common among women who have suffered depression at other times May be associated with a drop in estradiol and progesterone levels DepressionContinued Depressive symptoms may also result from hormonal problems head injuries brain tumors substance abuse or other illnesses Absence of happiness is more reliable symptom than increased sadness Occurs at any age but uncommon in children Twice as common in women esp over the age of 40 15 lifetime prevalence Severe MDD can lead to suicide 80 of suicide victims show depression High concordance rate from twin studies 60 for monozygotic 20 for dizygotic Regardless of whether twins reared apart or together prevalence is more relative to biological rather than foster parents Despite the advances in drug therapy treatments in recent decades this has had little impact on public health burden and suicide rates in western society Depression Treatment data Antidepressants 50 of people taking antidepressants get better 50 of people undergoing therapy get better 30 of people taking placebos get better Combining treatments produces little to no increased effect Litte difference regarding the various types of antidepressants lnterpersona and cognitive behavioral work as well as medications Antidepressant drugs and their biological mechanisms MAOls Monoamine Oxidase Inhibitors Tricycics SSRs Selective serotonin reuptake inhibitors Atypica antidepressants H MAWE block the en2yme MAD prevent it from breaking transmitters into inactive metabolites willEiluiili lglt Tricyclic drugs and Reupt h E El ls block reuptake Release I 21399 Can gage Learnih g Monoamine Oxidase Inhibitors MAOls MAO monoamine oxidase is an presynaptic enzyme that degrades neurotransmitters into metabolites MAO inhibitors blocks MAO activity and thus prevents the breakdown of monamine NTs DA NE 5HT Net effect is increased terminal release dea for MAOls came from observation in the 19505 that the hypertension drug reserpine makes monoamine vesicles leaky caused depressive symptoms Observation of reserpine and MAOls also fostered the monoamine hypothesis of depression Causes of Depression Monoamine hypothesis of depression Schildkraut and Kety 1967 depression is caused by low 5HT and NE neurotransmitter activity Based upon the observation that the earliest known antidepressant meds were MAO inhibitors and depressive effect produced by reserpine Tricyclics Blocks transporter proteins that reabsorb 5HT NE and DA back into presynaptic terminal Effect is lingering increases in NT levels in synaptic cleft Results in increased stimulation of postsynaptic neurons Side effects Blocks histamine receptors drowsiness Bocks acetylcholine receptors dry mouth dif culty urinating muscle problems decreased sex drive Blocks peripheral sodium channels heart irregularities Block transporter proteins that reabsorb serotonin and NE and DA Effect is lingering increase of NT in synaptic cleft Results in increased stimulation of postsynaptic neurons Selective Serotonin Reuptake Inhibitors SSRls As the name suggests SSRls block serotonin 5HT reuptake back into presynaptic neurons The term selective derives from the fact that these drugs are more preferential to 5HT than other monoamine transporters although not entirely exclusive Hence one gets the bene ts from the tricyclic drugs minus a number of their side effects However milder side effects remain Blocks serotonin reuptake in the presynaptic neurons Atypical antidepressants Describes drugs with different pharmacologu that also acts as antidepressants Bupropion inhibits reuptake of DA and NE but not 5HT EXpect to see more of these marketed by drug companies in coming years ef cacy will be trialanderror more error without a better understanding of the basic neurobiology bupropion inhibits the reuptake of DA and NE but not serotonin Effects of antidepressants Alteration of synaptic activity is rather rapid within hours However signs of recovery from depression does not happen until weeks later Some depressed patients show normal or even increased levels of serotonin turnover in blood samples although assay of NTs in the blood or CSF is not a reliable predictor of brain levels of NTs aternation of synaptic activity is rather rapid but signs of recovery from depression takes weeks Electroconvulsive Therapy ECT ECT involves electrically producing seizures for a therapeutic bene t ECT was rst used to treat schizophrenia similar to lobotomies it made patients temporarily more docile and calm Nowadays ECT is only used to relieve depression however only done on severe cases where patient is suicidal ECT is an effective treatment for these conditions used to treat mental disorders lnvolves producing seizures for bene t was used to treat schizophrenia made them more calm used to treat severe depression when patients are suicidal it takes drugs weeks to work ECT produces rapid effects in suicidal individuals Other Treatments ECT has adverse sideeffects mostly by impairing shortterm memory and mildly increasing the risk of heart attack ECT likely increases NTs levels in the brain esp monoamines May also stimulate growth factors such as BDNF and hippocampal neurogenesis How ECT works is not well understood if ECT produces rapid antidepressant effects the biological changes in the brain might tell us something novel that is happening in the brain in a depressed individual Transcrania Magnetic Stimulation is a much less invasive means for treating depression with fewer sideeffects which has recently received FDA approval Deep brain stimulation DBS involves implanting an electrode in the prefrontal cortex and giving mild stimulation DBS is only used in patients with intractable depression has been shown to work very well but in very small patient samples Causes of Depression The causes of depression are still poorly understood although a pervasive idea is that depression results from dysfunction of the brain serotonergic system genetic component 5HT stress Low BDNF Hippocampal neurogenesis Genetic basis for depression et al Predisposition for MDD depends on a variety of genes no single locus One gene that has received a lot of attention is the 5HT TLPR serotonin transporterlinked polymorphic region lndividuas with the short from of this gene have an increased likelihood of MDD anxiety disorders or PTSD remember comorbidity of these disorders 53 I sis is f A sfl E FM 2 3 m Frebebili ty elf msj er depressmn eplsude 39 l Number ef stressful life events 23quot 9 CEWWQE Wartime Patients that have different alleles for serotonin transporter S shorter form of gene people that are homozygous for the short gene have high levels of depression versus people that are homozygous for the long gene Stress is a predisposing factor People with high levels of circulating cortisol are prone to depression Suicide victims show very high levels of cortisol Roy 1992 as do hospitalized patients with depression Remember that HPA axis feedback negatively regulates subsequent cortisol release Many individuals of people with depression have high levels of cortisol that are off the charts ink between dysregulation of the stress response system and depression HPA system can regulate itself 1 Stress W Serum cortisol pgdL 8 Negative feedback 51 1 Gamma 25m mama eat ta eel ema Lemma OI NUJlPmti mm Adrenal Glucocorticoids gland including cortisol Primary Psycatric Normal depress controls controls ives Kidney Biological Psychology Be Figure 1614 Part 1 ZD1 ISInauarAssoclalasi m Stress and Depression Dexamethasone Suppression Test is one test for depression in patients hospitalized for this disorder Dexamethasone is an agonist for cortisol receptors Cortiso ebbs and rises in a circadian manner in the AM period it rises f DEX is given to a healthy person it will suppress the AM rise in cortisol via negative feedback on HPA axis at the level of the pituitary C Normal controls 30 20 10 Serum cortisol ug dL Biological Psychology e Figure 1614 Part 2 momsmuemswmsi Inc n depressed patients DEX treatment does not shut off the HPA axis 01 Patients with depression 20 Day 1 preDEX 7 16 Day 2 postDEX to g 12 o 93 t 8 8 E 5 Ed on 4 0 I I I I I I I 12 AM 4 AM 8 AM 12 PM 4 PM 8 PM 12 AM Biological Psychology 6e Figure 1614 Part 3 2U1DSInauerAssociales Inc have impaired negative feedback happening in these individuals ndividuas that have high levels of cortisol are not only succectpful to more psychiatric disorders but also more health disorders Mechanisms of DepressionBDNF ncreased release of NTs due to antidepressant treatment has also been shown to prompt axons to release brainderived neurotrophic factor BDNF BDNF aids in neuron growth guidance and synapse formation BDNF is highly important during cortical development but also for plasticity and learning during adulthood BDNF may therefore promote synaptic growth andor maintenance in limbic and cortical structures dea originated from Ron Duman Yale quotneurotrophic hypothesis of depressionquot Levels of BDNF are decreased in animal models of depression antidepressant treatment has also shown to increase the release of BDNF BDNF aids in neuron growth guidance and synapse formation highly important during cortical development but also for plasticity and learning during adu hood Mechanisms of Depression Hippocampal Neurogenesis Some have argued that low levels of hippocampal neurogenesis may underlie depression BarryJacobs Ron Duman Animal studies provide some support for this idea Antidepressants increase levels of neurogenesis Hippocampa volume is reduced in patients with MDD may be related to low levels of neurogenesis low levels of hippocampal neurogenesis may underlie depression hippocampal volume may be reduced due to low levels of hippocampal neurogenesis in depressed individuals Summary The neurobiology of depression likely involves all of these processes Finaly a new development quotFastactingquot antidepressants NMDA R antagonists like ketamine and PCP have very rapid antidepressant effects These drugs stimulate signaling pathways in neurons that may increase plasticity and circuit function akin to BDNF and neurogenesis hypotheses The search is on to understand their mechanism and to develop treatment with fewer adverse sideeffects PTS D Posttraumatic stress disorder PTSD occurs in some people after certain crises or terrifying experiences Symptoms Frequent distressing recollections Nightmares Avoidance of reminders of the event Exaggerated arousal in response to noises and other stimuli PTSD victims have been shown to have smaller hippocampal and prefrontal cortical volumes and larger amygdala PTSD victims show lower cortisol levels after the trauma in contrast with MDD and may show HPA hyperreactivity during certain stressors One idea is that impaired HPA axis functioning may render an individual more prone to the damaging effects of stress 12414 Lecture Bipolar Disorder Unipoar Cycling between being feeling normal and depressed Bipolar cycles between two extremes generally mania and depression Mania Restless activity Bipolar l disorder full blown episodes of mania wbouts of depression Bipolar ll disordermilder episodes of mania also wbouts of depression Bipolar disorder used to be called manic depressive illness Bipolar disorder treatments Lithium salts ithium has been most common treatment and works relatively well was discovered by accident decades ago as a control treatment from a drug different trial works quite well with mania and treating the depression probem is its toxic very easy to cause harm if give too much of a dose quotMood Stabilizersquot valproate carbamazepine vaproate enhances GABAergic transmission both decrease activity in Vgated Na channels thereby altering prob Slowing conduction of action potentials in the brain All bipolar drugs decrease number of AMPA type glutamate receptors in cortex Excessive glutamate activity linked to mania Antipsychotics are sometimes prescribed vaproate enhances GABA transmistion both affect voltage gated Na channels decreaseing the conduction of action potentials Peope report feeling more balanced not having mood swings Decrease AMPA type glutamate receptors in cortex glutamate receptors related to mania Schizophrenia John Nash mathematician with schizophrenia suffered from auditory hallucinations not visual hallucinations very rare for schizophrenics to suffer from visual hallucinations Charasterstics Deteriorating ability to function in everyday life due to hallucinations delusions thought or movement disorders and inappropriate emotional expressions Acutesudden onset and likely to recover Chronicgradual onset and long term Behavioral Symptoms Positive symptoms new behaviors Psychotic deusions halucinations Disorganized inappropriate emotional display bizarre behavior incoherent speech thought disorder Negative symptoms absent behaviors more dif cult to treatgtnot alleviated through antipsychotic drugs Limited Social Interactions Weak emotional expression poor working memory Early Development and later Psychopathology Neuroogica precursors can be diagnosed early but psychological symptoms develop around 20 years of age Childhood psychological symptoms are different but present Attention Memory lmpuse Control Prefrontal cortex which seems to be linked to schizophrenia matures slowly so emergence of symptoms correlates with nal steps in development of this cortical region Neurodevelopmental hypothesis Suggests that subtle abnormalities in prenatal and neonatal development of nervous system leads to major behavioral abnormalities later in life Probem environmental effects aggravate the symptoms but are not the ultimate cause Hypothesis of schizophrenia subtle differences in early development abnormal problem no solid evidence this is the ultimate cause of the disorder Prenatal and neonatal environment Risk factors increasing likelihood poor nutrition of mother during pregnancy premature birth ow birth weight compications during delivery increased stress in mother early in pregnancy Season of birth effect People born in winter are 58 greater at riskwhy is this environmental factors play a role but they are not the determince genetic factors are the main role or cause of the disorder Viral infections Vira infection of mother during pregnancy Viiurs does not cross placenta but cytokines do Excessive cytokines can impair brain development lnfections also induce fevers Fever of 385C slows division of fetal neurons Pregnant mice with in uenza have litters of pups with developmental defects Neonatal environment Probem can also arise in neonatal environment eg parasite toxoplasma gondiigt induce speci c changes in amygdala circuitry leads to memory problems and mania and hallucinations can infect infants eads to memory disorder hallucinations and delusions Genech Like depression there is a genetic basis but it is complicated monozygotic twins the strongest evidence for a hereditary Twin Studies High prevalence in M2 twins MZ twins who didn t know they were MZ still have high prevalence Therefore being monozygotic is more critical than being treated as monozygotic Genes in schizobhrenia attempts to nd genes underlying schizophrenia began in the early 80s studies failed to reach any consensus on common genetic mechanisms within the past several years improved methods and larger databases have afforded more comprehensive analyses these have yielded attempts have been made to nd the genes but these studies have failed to reach common genetic mechanisms major histocompatibility complex MHC family of proteins MHC proteins are cell surface receptors known for their role in immune function Other genes DSC1 stands for Disrupted in Schizophrenia 1 What is this gene Not sure and no one is the search continues ldenti ed from individuals who had schizophrenia Brain Abnormalities Some schizophrenics show mild abnormalities in brain anatomy disorganized hippocampal cell layers Probably not a single gene it s probably a variety of genes not genetic differences per se its epigeneticsgt manner that the expression of genes can be altered changes in gene expression are heritable can be passed down nll Iris 139 lilrrr smrn u fi scal1quot 5w r 1 ram My H 39l 7 1 k quot39 H V l Hr 39l 39 r39 u u a 3 quotLJE EHEL39Ei w Hypofrontality in schizophrenia Strongest de cits in left temporal and frontal cortex Orangeyeow indicates decrease in gray matter hypofrontaity reduced reactivity Ventricular enlargement in Schizophrenia Enarged ventricles Difficult to make interfences in how the sizes of the ventricles translate to behavioral features of this disorder Larger ventricles implies smaller brain volume and fewer neurons subventricular zone SVZ is also different than in normal individuals Hemispheric lateralization abnormal in schizophrenic patient ie hypofrontality Unike other diseases Parkinson s Huntington s Alzheimer s brain damage seems inconsistent with age unike other neurological diseases these affects are inconsistent with age when looking at imaging data might represne ta more reliable effect Prefrontal cortex lesion studies in monkeys Prefronta cortex lesioned in infant monkeys Monkeys act normal around 1 year of age Monkey s behavior deteriorating by 2 years of age Therefore prefrontal cortex is most likely not used as much during early age In later ages when the area begins to be used more often the damage begins to affect behavior Antibsvchotic drugs and dooamine Effective drugs for treating schizophrenia block dopamine receptors Dopamine hypothesis of schizophrenia Schizophrenia occurs from excessive dopamine activity in certain areas Concentration of dopamine is not larger turnover is faster rate of release and synthesizing Dopamine receptor antagonist any kind of medication can relieve a mental illness Schizophrenia was the rst disorder to nd a treatment forthe drugs that block the dopamine receptors result in excessive levels of dopamine faster rate of release of dopamine is fasternot mechanism or cause of schizophrenia Larger doses of amphetamines methamphetamines and cocaine induce substance induced psychotic disorder hallucinations and delusions Above mentioned drugs increase dopamine activity at synapse LSD also affects dopamine activity mainly serotonin though and does not worsen severity of schizophrenia arge dose of amphetamines can induceexcessive dopamine signaling is playing a role in showing these symptoms of this disorder these drugs fail Limitation of dopamine hypothesis Biological effects of dopamine antipsychootic drugs happens in minutes But Behavioral change only occurs 23 weeks later similar to SSRls in depression Role of glutamate Glutamate hypothesis of schizophrenia de cient activity at glutamate synapses mostly in frontal cortex Dopamine inhibits glutamate release Therefore antipsychotic drugs ts both hypotheses Phencycidine PCP inhibits NMDA glutamate receptors At high doses symptoms look almost like schizophrenia hallucinations delusions thought disorder loss of emotions memory loss Can t just administer glutamate because overstimulation of glutamate synapses kills neurons However some drugs that stimulate glutamate metabotropic receptors show promise Glycine increases effects of glutamate Drugs aimed at increasing glycine increase effectiveness of antipsychotic drugs Learning and Memory 1 Biological Perspectives What makes learning and memory special It is a fundamental property of our nervous system and makes us who we are De nition An experientially induced change in the nervous system that may be expressed in future behaviors Pasticity quotchangeabilityquot of neurons not just functional but structural modi cations underlie learning and memory Learningmemory has never been observed only inferred Cant observe learning based on this Localization a reprise Compelling arguments against strict localization did emerge and found a home in the eld of learning This began with observations that Broca s areas were not as strictly localized as originally endorsed also some instances of contralateral hemispheric localization for Broca s area we know now that it depends on handedness The other main idea is that localization of symptoms following brain damage are not necessarily equal to localization of function JH Jackson c 1890 Numerous observations of patients regaining recovery of function after brain damage also challenged strict localizationism Localization vs Holism Concept of quotreleasequot ie that focal brain damage decreased some function but in some instances actually enhanced others Jackson c 1890 This observation comes up time and again in the learning eld Hoism the idea that the whole is more important than individual parts very similar in theme to the Gestalt movement Franz 1907 showed that cats and monkeys with various types of frontal lobe lesions despite dif culties in remembering previously learned tasks they could still relearn also if sustained a reasonable criterion of mastery prior to damage then they showed no impairment Localization vs Holism Finaly an argument along the lines of evolution was adopted by Franz asserting that a quotsafety factorquot must exist in the nervous system if an individual can live with one kidney then perhaps the same could be true with half a brain Enter Lashley Kar Lashley collaborated with Franz in some experiments that are considered to be classical in shaping the eld of learning and memory lnitialy they showed that rats previously trained on a brightness discrimination task performed with no appreciable de cit following transection of large parts of the frontal lobe 1917 A followup study also showed that simple maze learning remains intact following damage to any limited part of the cortex Therefore Lashley agreed with Franz that lesion size not locus was more important for impacting intellectual function Lashley s quotlawsquot Lashey proposed two quotlawsquot in a landmark monograph Brain Mechanisms and Intelligence 1929 1 Equipotentially all parts of the cortex contribute equally to complex behaviors such as learning and part of the cortex can substitute for any other 2 Mass Action the cortex functions as a whole such that lesion effects on function require suf ciently large portions ie larger lesions greater de cits arguing there is no real locus for a particular function any part of the cortex can work it just depends on how much is damaged End of Lashley Engram physical representation of what has been learned Lashey argued against the idea of any localization or engram or memory storage 2 problems with Lashley 1 his learning tasks were compex multidimensionalmultisensory 2 Cerebral cortex is not an ideal brain region for nding evidence of an engram 3 not all types of memory are physiologically the same different types of memories serve different functions and are controlled by distinct regions or systems within the brain Engram physical representation of what has been learned attempts to localize memory storage to a certain region based on localization principle where memories are stored in a particular place probems envoking number of brain systems the cerebral cortex isn t an ideal place for looking for evidence of an engram not many regions comprised of distinct portions learning tasks requires multiple areas are not meaningful to nd evidence not all types of memories are physiological the same different types of memories serve different functions and are controlled by distinct regions or systems within the brain Memorv Stages from our own thinking we can probably come to some conclusions about memories Memory is not instantly formed yet we have the capacity to remember what happened just the moment before Therefore there are probably separate processes underlying memory DEPENDING on the time point after the learning event Sensesgt sensory buffergtworking memoryshortterm memorygtlong term memory Consolidation putting memories into longerterm storage form more resistant to disruption or forgetting 1 Why isn t all information stored 2 Why do we have multiple stages of memory 3 Why isn t information immediately put into longterm storage 1 There is too much information to store most of which would probably be irrelevant and uncessary 2 We can sift information for value and therefore store only importantrelevant information 3 Achieving longtermpermanent storage requires processes in the brain that take a long time This of course explains the necessity of shorter forms of memory we need to have information for recent events before LTM kicks in 1 Sensory systems designed to distract the meaningful info 2 Allows us to sit through things that have differential value that are either more necessary to hold on to 3 Encoding info for long term memory is more labor intensive limited amount of time that we have available to learn How are memories selected for longterm storage Rehearsalsimply going over information multiple times massed vs spaced training Connecting with old information Emotiona arousal Persistence of memorv Memory is NOT like a video recorder Most information gained through senses is lost most information in STM is lost MOREOVER memories can become distorted older or newer information can interfere change alter them Eizabeth Loftus showed that memories can be arti cially repressed and recovered Recent evidence suggests that memories also become unstable or prone to alteration each time they are retrieved Earlv Localization studies medial temporal lobe Patient HM Henry Molaison died in 2008 Bilateral medial temporal lobectomy included hippocampus amygdala and cortices around hippocampus This resulted in anterograde amnesia could not form new memories whereas old memories form before surgery remained intact Distinction between old and new memories tells us about consolidation vs storage HM could still learn other types of tasks HM had no ability to store new memories his memories before the surgery were still there but new memories he was not able to know he could still learn new tasks at rst he has a lot of mistakes but as time goes on he gets better example of procedural learning task HM also gave evidence for distinct memory systems Longterm memory Declarative Things you know that you can tell others Nondeclarative procedural Things you know that you Can show by domg Declarative memory can be tested readily in humans because they can talk Henry Molaisorl was unable to form new declarative memorieei NondecllaratiVe memory can be tested readily in other animate as well as in hum39ms Henry was capable of this form of memory exempli ed by the skill of mirror tracing Biological Psychology Go Figure 1123 no 2010 Smauer Associam Inc 9 a i d e n C e for distinct memory systems declarative domain of medial temporal lobe and nondeclarative other parts of the braingt removal of the hippocampus and nearby cortex left patient HM unable to form declarative memories that lasted more than a few minutes He could however learn new skills such as mirror tracing showing his nondeclarative or procedural memory for perceptual and motor behaviors was intact Temporal effects of memory formation HM provided the rst insight the relevance of the hippocampal formation in declarative memory HM and other patients with hippocampal damage also reveal distinct mechanisms for temporal effects of memory 100 a Recency effect A r 80 Primacy effect 50 1 Percentage of correct responses I Normal adults 40 20 39 Patients with amnesia 0 l m I i l 7 l l I I ll 2 3 4 5 6 7 8 9 1i lltern number Biohgical Psychology See Figure 175 meiosinawerrsmtesm May have an individual remember 10 items Serial positon effect you remember the things in the beginning and the end but you don t remember the middle Primacy effect rst things memorized Recency effect later items memorized Patients with amnesia did nd the recency effect but not the primacy effect his ability to store or process memory was lost Primacy vs recency effect provides support for different TEMPORAL stages of memory in this model hippocampal damage results in impairment of earliest remembered items from the list no primacy effect in normal subjects if one lengthens the time between studying and testing recall recency is lost becomes a long term memory task These studies suggest that distinct neural structures mediate primacy vs recency effects Learning and Memorv Patient NA damage to left dorsal thalamus and bilateral damage to mammillary bodies NA also has robust anterograde amnesia very similar to HM cant form new memories The similarity of damage in these patients suggests that a larger circuit is important in declarative memory than just hippocampus and adjacent cortical elds Korsakoff s syndrome involves damage to mammiary bodies and to basal frontal cortex Results from a chronic thiamine de ciency typically from alcoholism Symptoms failure to recall past events and recognize familiar objects patients deny that anything is wrong Korsakoff s syndrome patients confabulate which means that they often provide a narrative of events that never happened or when trying to recall information will ll in details of a story with ctitious information again these observations support the role of mammiary bodies and thalamus as part of extended system for declarative memory Patient KC brain damage to frontoparietal areas has impaired episodic memory cannot retrieve personal memories from past but has good general knowledge of facts Led to distinction between episodic vs semantic memories all under the umbrella of declarative memory Longterrn memory Declarative Nondeclarative procedural Things you know that Things you know that you you can tell others can show by doing Episodic Semantic Skill learning Priming Conditioning Remembering Knowing Knowing how Being more Salivating your first day the capital to ride a bicycle likely to use a when you in school of France word you heard see a recently favorite food 1 75 201DSinauerAesm ates Inc Animal studies highlight different memory systems Hippocampus also plays an important role in spatial memory Spatial memory is not declarative per se but can be contrasted from procedural memory functions Learning and Memorv Brain svstems Many studies have investigated the role of the hippocampus in learning in rats These studies have shown that this region is critically important for spatial learning aka place learning There is some debate whether the hippocampus is necessary involved in spatial processing or if it involves processing more fundamental features that are important for spatial memory Tmaze learning and radial arm maze learning tasks highlight differences between place learning and quotrulequot learning there are cells in the dorsal hippocampus that have ring properties re only when animal is in a particular location in space important for spatial learning debate of whether the hippocampus is involved in spatial processing or if it involves processing more fundamental features that are important for spatial memory Radial 8 arm maze Simple T maze Regardless of where you start the animal you want it to end up in a certain space place learning Regardless of where you start you want them to turn 90 degress rule learninghabit learning Pace learning vs habit learning pace learning is mediated by the hippocampus Habit aka response learning is mediated by the striatum Habit learning becomes more robust over repeated trials Evidence supports a dissociation between these systems if lesion hippocampus will inhibit animal to learn place learning but its response learning is intact if lesion dorsal striatum response learning impaired but place learning is enhanced Hippocampus contains quotplace cellsquot these are cells that can be recorded from while the animal is running around a maze and will become active selectively during a certain place on the maze Other cells in the hippocampus show different spatial selectivity a quotcognitive mapquot can be constructed ln monkeys there and place cells AND quotspatial viewquot cells hippocampal cells that respond when the monkey looks a particular direction Grid cells interlinal hippocampus they will re in multiple locations in space locations are points in a triangle showing electrical ring in a grid says something different of how spatial info is processed Place cells process further encoding about our environment it Sign all home range an i I Mali Female 2m i H range Sim Emil ill Meadow mm F39iim will bl Wiring in spatial learning i Mali 3 Female 1le Spatial ability rank n Mimide Emile malig It Relative ihipipmz aimpiail aim illit i mm Female iil ti HJLHE Relative himmmm pal slam il l39reazlnw trolls Pine wile the larger area that they cover in their environment the larger there hippocampal size anatiomical cortex of spatial learing in animals that explosre larger areas of space So where are memories STORED Is there an engram Many believe that portions of the association cortex upstream from sensory processing areas are involved in memory storage although this gets philosophical very quickly Learning and Memory ll Cellular Mechanisms Donald 0 Hebb and the quotHebbianquot synapse model ceuar and molecular models of learning is the study of models cells that re together are wired together if have networks sementicaly then you know that Neuron A shows ring patterns and Neuron B shows ring patterns that activity is consident and a association is developed is shown between them Hypothesized that learning would be associated with synapse strengthening nonassociative types of learning being mediated this way motor learning associative learning two stimuli are paired to produce motor output Long term potentiation LTP the rst important piece of evidence for synaptic changes in the mammalian brain came from studies of neurons in the rat hippocampus Biss and Lomo 1973 discovered the phenomenon of longterm potentiation LTP LTP a stable and enduring increase in the effectiveness of synapses that results from a speci c type of stimulation if one electrically stimulates axons in a circuit at a slow rate eg 1 Hz the size of the response in the postsynaptic neurons is quite stable HOWEVER if one stimulates the axons at a high frequencyie tetanus for a brief period 12 s the size of the EPSP responses increases markedly and remains so for a prolonged duration minuteshours thereafter Hippocampa trisynaptic loop 121114 Lecture Learning and Memory ll Cellular Mechanisms Learning and Memory Mechaniss Aplysia aka sea hare has been used as a very simple invertebrate model for understanding the cellular mechanisms of learning It is possible to label speci c neurons in the nervous system and study them in different animals whereas the mammalian brain has too many to do this Eric Kandel is one of the pioneers in the study of learning and memory using Aplysia Kande won the Nobel Prize in Medicine 2000 for identifying cellular mechanisms of memory Aplysia show very simple kinds of learning and memroy Habituation decrease in response to a stimulus that is presented repeatedly Sensitization increase in response to mild stimuli as a result of previous exposure to more intense stimuli These types of learning can be studied in the context of siphon or gillwithdrawal re ex Sensitizationaplvsia Sensitization is mediated by a facilitating interneuron pink that release 5HT onto the presynaptic terminals of sensory neurons 5HT release does 2 things 1 blocks K channels in these membranes such that these cells take longer to repolarize 2 Increases Ca2 release at presynaptic terminal both serve to stimulate more NT release onto motor neuron Sensory neuron Sensory neuron Long term potentiation LTP The rst important piece of evidence for synaptic changes in the mammalian brain came from studies of neurons in the rat hippocampus Bliss and Lomo 1973 discovered the phenomenon of longterm potentiation LTP LTP a stable and enduring increase in the effectiveness of synapses that results from a speci c type of stimulation If one electrically stimulates axons in a circuit at a slow rate eg 1H2 the size of the response in the postsynaptic neurons is quite stable HOWEVER if one stimulates the axons at a high frequency for a brief period 12 s the size of the EPSP responses increases markedly and remains so for a prolonged duration minuteshours thereafter LTP was rst identi ed in the hippocampus but has since been observed throughout the brain and is fundamental property of neurons The rst study of LTP involved delivery of tetanic pulses via the performant pathway axons and recording from granule neurons in the dentate gyrus of hippocampus LTP has been subsequently described in other parts of the hippocampus ie in mossy berCA3 and Schaffer collateralCA1 pathways Subsequent work has focused on LTP in Schaffer coatera axons to CA1 pyramidal neurons Cellular features of LTP Celular mechanisms of LTP AMPA and NMDA receptors both are inotropic Glu receptors mediate fast excitatory neurotransmission NMDA receptors exhibit a unique voltagegated property Under conditions of normal synaptic activity NMDA receptor activity is normally prevented by Mg2 which blocks the receptor channel pore thereby preventing Na entry a Normal synaptic transmission if Axon If terminal iii fgi Resting conditions lDendritic spine 63 1722 Part m 20105inauernssociaiiesdna A strong enough stimulation can depolarize the postsynaptic membrane such that Mg2 becomes dislodged from the channel pore thereby activating NMDA receptors NMDA receptors are permeable to Na AND CA2 It is Ca2 in ux that can initiate signal transduction cascades induce changes in gene expression and protein synthesis related to functionalstructural changes A recently uncovered mechanism that is central to understanding synaptic strengthening is AMPA receptor insertion during LTP Depolarization during LTP induction opening of NMDARs and Ca influx Retrograde messengersz NO arac hidonic acid and others a 201i Sinausr Assamclams inc 6 Enhanced synapse after induction of LTP Maintenance phase of LT P AMPAR insertion into synapse Biological Psychology 5e Figure 122 Part 339 aECmSmauar Asso 11111 c Mechamisms for quotlongterm changes in neuron function may occur in activated synapses following LTP Ca2 activates protein kinases these are a class of enzymes that phosphorylate ie addition of a phosphate group other proteins protein phosphorylation is a way of storing energy tearing off the phosphate group from the protein at a later time releases energy that can be coupled to drive other activities in the neuron Examples of protein kinases activated by LTP PKA PKC CaMKll These proteins phosphorylate CREB cAMP response element binding protein in the nucleus which binds DNA promoter regions thereby turning on gene expression Endoplasmic reticulum Biological Psychafogy Be Figure 1123 emanaummmm Strong Stimulation of the neuron leads to rapid increase in the intracellular concentration of Ca2 ions 2 Increased Ca2 ion concentration activates protein kinasesincluding CaMKll PKA and PKC which activate proteins 3 CREB protein binds to cyclic AMP response elements in the promoter regions of many genes CREB binding regulates the transcription of many different genes 4 Changes in gene transcription leads to changes in proteins including enzymes and structural proteins Some of these proteins are necessary to maintain LTP Like memory the potentiated response in LTP has stages Eary stages 1 hour characterized by changes in receptor channel properties eg increased permeability to Na increase in receptor number Eary stages do NOT depend on protein synthesis Protein synthesis required for later and longerlasting ie gt24h stages of LTP For example if CREB is blocked then memory consolidation can be disrupted LTP is widely implicated as a learning mechanism and a lot of animal learning studies have linked changes in LTP and signaling pathways with the learning event and memory storage 1 Correlates well with the time course for memory 2 Manipulations that block LTP also block memory formation 3 Behavioral training has been shown to be accompanied by enhanced LTP Long term potentiation LTP is a powerful physiological model for learning LTP is mediated via NMDA Glu receptors which seem to match the criteria of Hebb s quotconincidence detectionquot Chapter 14 Cognitive Functions Cerebral Hemispheric Lateralization An Overall View Probaby one of the most important things that I hope you will take away from this class are some quotbig picturequot concepts One idea concerns how neuroscientists think about the brain particularly with regard to its organization and how functions are carried out We can discard most views from antiquity outright and most views leading up and even into the 19th century as quaint The phrenologists starting with E Gall initiated the idea of localization theory albeit if misguided and pseudoscienti c However Broca s initial report of the patient quotTanquot in 1861 provided scienti c weight to the idea that functions could be localized in this case language to the left hemisphere Broca s work also is important because it directed attention to the idea that the two cerebral hemispheres are not identical Other evidence came forth particularly with regard to discovery of the primary motor cortex Hitzig and Fritsch just caudal to the central sulcus Opponents of localization were also against the idea of the neuron doctrine they believed that the quotnervenet theoryquot where neurons were all fused together in a single functioning entity was incompatible with localization of function to any one region in the brain However strict localization would be challenged by the holistic school Broca s language production center was not always in the same place nor even in the same hemisphere RememberJackson s 1890 key point about brain function localization of symptoms following brain damage are not necessarily equal to localization of function The Holists amassed evidence against strict localization of function at least for more complex behaviors Franz and later Lashley Lashey s main conclusions were wrong but his ideas helped for the subsistence of antilocalization thinking Research dealing with the neural circuitry of emotion seemed consistent with the idea of a system that had multiple cell groups that were interconnected at least those upstream from the hypothalamus a la Bard s work Later on the concept of the limbic system Papez and later popularized by MacLean pointed to the idea of interconnected cell groups contributing to an overall function The nal Answer How do we get out of this quandary The whole course quotsimpequot functions are subserved by single brain regionsloci complex functions require multiple loci In later instance each locus performs part of the function which are assembled as neural systems into a coherent behavior or function Now on to Lateralization Questions concerning cerebral dominance are central to our changing conceptions of brain function over the past 150 years Since Broca numerous examples of lateralization of function has been shown to be evidenct in cerebral cortex Popuar notions of cerebral dominance or being left or quotrightquot brained are overstated and inaccurate here we are in the 21st century thinking like dogmatic localizationists Hemispheric Asymmetry Lateraization of function refers to the idea that each hemisphere of the brain is specialized for different functions Each hemisphere is connected to the contralateral opposite side of the body Examples Skin receptors and muscles on the right side of the body are connected to the left hemisphere Each hemisphere processes visual information from the opposite side of the world The left hemisphere is dominant for speech in 95 of righthanded people Language dominance for lefthanders is a bit different 19 have right hemispheric dominance 18 have bilateral language functions YET there are differences even within language functions in terms of aspects of language processing eg semantics syntax prosody lnterestingy the rst localizationists of note ie the phrenologists thought that the cerebral hemispheres were largely symmetrical and that a lack of symmetry say following brain damage could be detrimental Bichat although not a phrenologist stated 1824 quotIf both hemispheres of the brain however be affected equally the judgement though weaker will be more exact Perhaps it is thus that we should explain those observations so frequently repeated of an accidental stroke upon one side having restored intellectual functions which had long remained dormant in consequence of a blow received upon the other sidequot Wigan 1844 was the rst to argue that the cerebral hemispheres were two separate wholes each associated with a distinct and entire mind He based these ideas on several observations of individuals that had damage to part or all of one hemisphere and showed normal function Even in cases of asymmetries Wigan argued that functioning should be n ie no clobbering to the other side of the head is necessary to balance things out Broca hypothesized that language was localized in the left hemisphere in right handers and viceversa for left handers Car Wernicke 1874 strengthened this position by documenting a verbal aphasia mostly in comprehension in a region caudal to Broca s area ie production of speech in the left parietal lobe Arcuate fasiculus axon ber pathway that connects Broca s speech production and Wernicke s Speech comprehension areas John Hughlings Jackson 1874 was the rst to establish ideas about right hemispheric specialization Jackson acknowledged Broca s discoveries although he noted that patients with Broca s aphasia could still blurt out utterances under emotionally charged situations Jackson hypothesized that these functions were at least partially bilateral although the left hemisphere was important for being conscious in wordsquot Patients with damage to the left hemisphere showed intact perceptual functions Patients with damage to the right hemisphere showed various quotimperceptionsquot ie loss of memory for people objects places Many more observations were made in the coming decades since Broca s and Jackson s ideas for hemispheric specialization These observations have generally served more as re nements to Jackson initial insights RGHT HEMISPHERE numerical computation approximations estimation anguageintonationaccentuation context spatial information LEFT HEMISPHERE numerical computation exact calculations Language grammarvocabulary literal meaning factbased episodic information Several gross anatomical differnces may be readily observed by looking at human brains eg the lateral sulcus is often longer on the left than right side of the cerebral cortex in humans however this has not been shown to correlate with differneces in any speci c trait or function Yet there are signi cant differences in lamination patterns as a function of rightleft hemisphere The planum temporale is an area of the temporal cortex that is larger in the left hemisphere in 65 of people MRI studies indicate that the a big difference in the ratio of left to right planum temporal is related to increased language performance Damage to left hemisphere often results in language de ciencies Left side seems to be specialized for language from the very beginning in most people Functiona imaging studies have revealed more extensive differences in activational patterns and networks in a lateralized manner lmaging evidence supports the early ideas about RL hemispheric specialization The left and right hemisphere exchange information primarily through axonal bers coursing through the corpus caosum Other areas that exchange information include the anterior commissure the hippocampal commissure A few other small commissures nformation crosses the other hemisphere with only a brief delay Evidence from quotsplitbrain patients Damage to the corpus caosum interferes with the exchange of information between hemispheres Long ago physicians cut the corpus caosum to prevent seizures from spreading to the opposite side of the body in patients with severe epilepsy people who have undergone surgery to the corpus caosum are referred to as quotsplitbrain patients Spit brain people maintain normal intellect and motivation but they tend to Uses hands independently in a way others cannot Respond differently to stimuli presented to only one side of the body Each hemisphere of the brain gets input from the opposite half of the visual world Light from the right half of the visual eld shines into the left half of both retinas Light from the left visual eld shines onto the right half of both retinas The left half of each retina connects to the left hemisphere The right half of each retina connects to the right hemisphere Half of the axons from each eye cross to the opposite side of the brain at the optic chiasm The auditory system is arranged differently in that each ear sends the information to both sides of the brain Sperry 1974 revealed subtle behavioral differneces in splitbrain patinets Because the left side of the brain is dominant for language in most people most split brain people have dif cult naming objects brie y viewed in the left visual eld Key Concepts Anatomy main control center of the circadian rhythms for sleep and temperature ocated dorsal to the optic chiasm damage to the SCN results in less consistent body rhythms that are no longer synchronized to environmental patterns of light and dark light resets the SCN via a small branch of the optic nerve traves directly from the retina to the SCN comes from a special population of ganglion cells that have their own photopigment called melanopsin these cells respond directly to light and do not require any input from the rods or cones regulated by the SCN an endocrine gland located posterior to the thalamus secreates melatonin a hormone that increases sleepiness Activating system in the midbrain actively drove wakefulness 1 Forebrain System SW5 2 Brainstem System activates forebrain into wakefulness Reticular Formation collection of cells throughout brain stem many of which are cholingergic Ach project to variety of structures in brain to promote wakefulness Locus Coeruleus major source of NE for entire forebrain has stimulatory effects on alertness 3 Pointine system triggers REM sleep 4 Hypothalamic system affects other 3 brain systems to determine sleepwake Gene called Tau Review Cranial nerves Autonomic Nervous System Figure 1326 slides 2130 Strange terms in slides not highlighted Evoution Natural Selection Adaptation JamesLange theory Slide 42 Lecture 2 103014 Lecture Chapter 9 Part 1 Biological Rhythms Many kinds of rhythms that govern our bodies and behavior Ultradian Rhythms Frequency greater than onceday eg restactivity cycle in humans is 90 minutes Infradian rhythms Frequency less than once a day eg menstrual cyceprimates or estrous cyceother mammals Some animals generate endogenous circannual rhythms internaI mechanisms that operate on an annual or yearly cycle eg bird migratory patterns animals storing food for the winter hibernation All animals and plants and fungi and cyanobacteria produce endogenous circadian rhythms internal mechanisms that operate on an approximately 1day cycle This rhythm also regulates the frequency of eating and drinking body temperature secretion of hormones urination even things like sensitive to drugs Lightdark cycle can in uence circadian rhythm BUT a true circadian rhythm is independent Why do we need a circadian rhythm The purpose of the circadian rhythm is to keep our internal workings in phase with the outside world Human circadian clock generates a rhythm slightly longer than 24 hours when it has no external cue to set it Resetting our circadian rhythms is sometimes necessary ALL LIFE ON EARTH HAS A BIOLOGICAL MECHANISM FOR TIME KE E P N G FreeRunning Rhythm is a rhythm that occurs when no stimulus resets it it is still rhythmic but not phaselocked with day length Phase Shift shift of activity due to a shift in a synchronizing stimulus Entrainmentprocess of this shift Zeitgeberterm used to describe any stimulus that resets the circadian rhythm Iight is the primary one Exercise noise meals and temperature are other zeitgebers Suprachiasmatic Nucleus SCN If we have a natural endogenous circadian rhythm SOMETHING must be producing this Suprachiasmatic Nucleus SCN part of the hypothalamus and the main control center of the circadian rhythms for sleep and temperature ocated dorsal to the optic chiasm Damage to the SCN results in less consistent body rhythms that are no longer synchronized to environmental patterns of light and dark The SCN is activated by light C oripius calllosum Thalamus CE39FLFEBI ZIHCDH IIEX Cerebral cortex Suprachiasmatic nucleus Optic clhiasm EC mgcwagetwrning The pineal gland important for the circadian rhythmunder control by SCN releases hormones Evidence for SCN as rhythmmaker Lesions of SCN destroy rhythmicity Hamsters with a selective mutationin a gene caed tau have an unusually short circadian rhythm Transpantation of SCN cells following lesions or from SCN or mutant to non mutant or viceversa effects rhythmicity Dhl I I m ini II39QIIII I39C Example of experiments 2 Alf P L39III I39L39IMII II I39IIIII r50 39 hTransplamtt 431 so g be I r U 39 2quot I 100 I 120 Rhythm is now 19 39v h I II 1 I 160 l 20 Time h Biological Psychology Be Figure 1454 mamasmgmm m Entrainment of rhythms How are circadian rhythms entrained to the lightdark cycle Many invertebrates have photoreceptors outside of the eye eg pineal gland ln mammalsa subtype of retinal ganglion cells transduces light information to SCN Resetting the SCN Light resets the SCN via a small branch of the optic nerve known as the retinohypothalamic tract Travels directly from the retina to the SCN The retinohypothalmic tract comes from a special population of ganglion cells that have their own photopigment called melanopsin These cells respond directly to light and do not require any input from the rods or cones mammamwemmmm Lesions of the visual cortex and accessory pathways do not alter entrainment to the lightdark cycle although animals with such lesions appear blind and show no indication of visually guided orientation or discrimination behavior SCN has intrinsic activity The SCN genereate circadian rhythms in a genetically controlled unlearned manner Singe cells extracted from the SCN and raised in tissue culture continue to produce action potentials in a rhythmic circadian pattern How does a cell Know how to generate such a rhythm Eary work with drosophila pointed to a gene called per for quotperiodquot From that the mechanisms underlying SCN circadian rhythms in mammals were eventually discovered Molecular steps in circadian regulation in SCN 1 Proteins go into nucleus and bind to the DNA 2 Activate expression of 2 genes Period and cryptochromme 3 Per and Cry will go into cytoplasm and bind to another protein which is TAU 4 This protein complex then travels back to the nucleus and blocks the transcripton of itself Proteins degrade Light can reset this process to the phase dark cycle 99 39 Nucleus Glutamat Biological Psycholbgy 6e Figure 14 2o1osmaumsseclates Cellular origins of circadian rhythms Mutations in any of these genes can affect circadian rhythms eg clock mutants show dysregulation of rhythm except only when light cues are removed recall that light activates expression of Per and Cry to restart the rhythm Which rhythm are you In humans night owls vs morning people could be explained by different alleles for some of these genes There may also be individual differences in patterns of wakefulness and alertness Change as a function of age How about jet lag et lag refers to the disruption of the circadian rhythms due to crossing time zones stems from a mismatch of the internal circadian clock and external time Characterized by sleepiness during the day sleeplessness at night and impaired concentration Traveing west quotphasedelays our circadian rhythms Traveing east quotphaseadvances our circadian rhythms lf circadian rhythm is longer than a day which direction would it be better to travel west bc if the phasedelaymaking a longer rhythm Disruptions of rhythms circadian rhythms remain consistent despite lack of environmental cues indicating the time of day Most people can quickly adjust to 23or 25 hour day but not to a 22or 2 8 hour day gt it takes a lot longer to adjust to bigger time changes eg people who engage in shift work often fail to adjust completely There are a number of quothome remediesquot for jet lag but no scienti cally proven treatments as of yet Melatonin and the pineal gland The SCN regulates waking and sleeping by controlling activity levels in other areas of the brain The SCN regulates the pineal gland and endocrine gland located posterior to the thalamus The pineal gland secretes melatonin a hormone that increases sleepiness Melatonin secretion usually begins 2 to 3 hours before bedtime Melatonin feeds back to reset the biological clock through its effects on receptors in the SCN Melatonin taken in the afternoon can phaseadvance the internal clock and can is sometimes used as a sleep aid gt it slightly phaseadvances the rhythm but doesn t induce sleepiness per se Part 2 Sleep and Brain mechanisms Stages of sleep and brain mechanisms Seep is a state that the brain actively produces Characterized by a moderate decrease in brain activity and decreased response to stimuli Seep differs from the following states Coma Vegetative state Minimally conscious state Brain death Coma extended period of unconsciousness caused by head trauma stroke or disease characterized by low brain activity that remains fairly steady person shows little response to stimuli Vegetative state person alternates between periods of sleep and moderate arousal but no awareness of one s surrounding some autonomic arousal to painful stimuli No purposeful activityresponse to speech Minimally Conscious state one stage higher than a vegetative state marked by occasional brief periods of purposeful action and limited speech comprehension Brain Death no sign of brain activity and no response to any stimulus The Electroencephalograph EEG allowed researcher to discover that there are various stages of sleep EEG measures brain activity from noninvasive electrodes placed on the scalp 11414 Lecture Sleep Architecture Alpha waves are present when one begins a state of relaxation Stage 1 sleep is when sleep has just begun The EEG is dominated by irregular jagged low voltage waves brain activity begins to decline Stage 2 Sleep is characterized by the presence of Sleep spindles 12 to 14Hz waves during a burst that lasts at least half a second Kcomplex a sharp highamplitude negative wave followed by a smaller slower positive wave Stage 3 and stage 4 together constitute Slow Wave SleepSWS and are characterized by EEG recording of slow large amplitude wave Sowing of heart rate breathing rate and brain activity Highy synchronized neuronal activity initial stages are called slow wave sleep large amplitude synchronized waves where all of our perpherial signals are slower After slow wave sleep other stage of sleep where suddenly the EEG looks like someone is active but the individuals are sound asleep called paradoxical bc it didn t make sense Rapid Eye Movement sleep REM also known as paradoxical sleep EEG waves are irregular lowvoltage and fast Postura muscles of the body are more relaxed than other stages REM sleepmore common term called bc our eyes move back and forth EEG looks like an EEG of someone awake Stages other than REM are referred to as NonREM sleepNREM when one falls asleep they progress through stages 1 2 3 and 4 in sequential order After about an hour the person begins to cycle back through the stages from stage 4 to stages 3 and 2 and than REM The sequence repeats with each cycle lasting approximately 90 minutes Stage 3 and 4 sleep predominate early in the night The length of stages 3 and 4 decrease as the night progresses REM sleep is predominant later in the night Length of the REM stages increases as the night progresses REM is strongly associated with dreaming but people also report dreaming in other stages of sleep First REM Brief Final REM 91315ng ff awakening s 5 episode REM 1 U Elm E 2 U m 4 I I ll ll 1 2 4 5 6 7 Hours of sleep Biological Psychology 69 Figure 1412 2010 Sinauernssociaies Inc Re m p e ri 0 d S 9 et longer Slow wave sleep cycles become more shallow and shorter By the end of sleeping its mostly REM sleep Most of dreaming occurs in REM sleep if wake ppl up they report the same dream in REM sleep and very little in other stages of sleep Sleep Neural Systems Classic studies gave insight early on into neural mechanism of sleepBremer 1935 1 Cerveau isole animal with transection at level of medulla shows normal responsiveness and sleep wake patterns lsoating the entire brain transected at the medulla animals show normal responsiveness and sleep cycles transection of the lower brainstem produces an isolated brain which exhibits signs of alternating between wakefulness SWS and REM sleep showing that systems controlling sleep are found in the brain 2 Encephale isole transection through the midbrain shows constant unresponsiveness and SWS lsoating the midbrain animal can t be aroused looks like a coma Transection of the brainstem at the midbrain produces an isolated forebrain which exhibits signs of constant SW showing that a forebrain system promotes SWS and that brainstem system promote wakefulness and REM sleep Bremer wrongly interpreted these observations to mean that the cortex must receive sensory afferent information for wakefulness to occur or to be maintained Morruzi and Magou1952 later showed that this was wrong and that an quotactivating systemquot in the midbrain actively drove wakefulness this became known as the ascending reticular activating systemARAS We no longer think of the ARAS as one systemour modern conception is of 4 major systems that interact to mediate sleep 1 Forebrain system can display SWS by itsel 2 Brainstem system activates forebrain into wakefulness 3 Pontine system triggers REM sleep 4 Hypothalamic system affects other three brain systems to determine sleepwake 1 Forebrain system remember that this alone is suf cient for producing SWS Basal forebrain stimulation produces sleepiness whereas lesions produce insomnia Basal forebrain neurons become active at onset of sleep and inhibit hypothalamic regions important for alertnessarousal A region called the basal forebrain promotes SWS by releasing GABA into the tuberomammillary nucleus in the hypothalamus Electrical stimulation of the basal forebrain makes animals sleepy while lesions of this region induce insomnia Transections that create an isolated forebrain result in constant SW5 2 Brain stem activates forebrain into wakefulness Reticular formation collection of cells throughout brain stem many of which are cholinergicAch project to variety of structures in brain to promote wakefulness Locus Coeruleus major source of NE for entire forebrain has stimulatory effects on alertness The brainstem contains a system called the reticular formation which projects axons to the brain that activate it Electrical stimulation here promotes wakefulness and alertness Lesions can produce constant sleep states 3 Pontine system triggers REM sleep Small group of cells in pons just ventral to locus coeruleus triggers REM sleep Some cells project to motorneurons and strongly inhibit them makes muscles accidnot just relaxed unresponsive Near the locus coeruleus is a region that sends widespread projections to promote REM sleep Axons projecting to the spinal cord profoundly inhibit motorneurons so they cannot re causing profound muscle atonia Other axons project to the brain to activate other regions 4 Hypothalamic system controls other three brain regions this discovery was made from studying dogs with narcolepsy Narcolepsy personor animal has sudden intense bouts of sleep during day SeepLast 530 minutes often narcoleptics suffer cataplexy as well sudden loss of muscle tone without loss of consciousness As with the dogs cataplexy can be caused by strong emotionspositive or negative in narcoleptics Condition where someone has sudden and intense bouts of seep go into REM sleep Catapexy sudden loss of muscle tone but no loss of consciousness awake but cant control any muscles in the body descending inhibition that occurs in the pointene system during REM sleep out of body experenience is related to cataplexy if in REM sleep this experience being disconnected from the body is cataplexy Narcoeptics have onsest of sleep and cataplexy from experinceing a strong emotion Narcoepsyperson typically enters REM immediately upon falling asleep rather than SWS at night Narcoeptic dogs also show immediate entry into REM sleep in Narcoleptic dogs mutant gene was isolated encoding for a receptor of Hypocretinaka orexin Mice with the Hypocretin gene knocked outgt narcolepsy Humans with narcolepsy have also been shown to have profound loss of hypocretin neuronsocated in hypothalamus When go to sleep go right into REM sleep If look at EEG state is going into REM sleep very quickly when they fall asleep Narcopetic dogs have a single gene that is mutated gene coding a receptor or what is a novel neural peptide called hypocretinorexin investigators generetaed transgenic animals mice now have narcolepsy Humans that have narcolepsy also have defects in hypocretin gene Stages of Sleep and Brain Mechanisms HypocretinOrexin is a peptide neurotransmitter released in a pathway from the ateraLH and tuberomammillary nucleiTMN in a hypothalamus HypocretinOrexin system has a stimulatory effect on arousal Stimulates Ach neurons in the basal forebrain for wakefulness and arousal TMN also has histaminecontaining neurons that have projections to forebrain and are arousalpromotingthis is why classis antihistamines make one drowsy Expressed in the lateral and tuberonammillary nuclei cell groups in the hypothalamus ce groups play critical role in awkaeing arousaldon t control arousalcan knock out these cells and still see awakeing and arousal hypoeretin and orexin play a modulatory effect on arousal TMN in hypothalamus has a group of histamineNT function in the brain similar to orexin and are arousal promoting Antihistamines make one drowsy antihistamines are antagonists produces in ammation but gets pass Blood brain barrier and shuts down histamines receptors and causes drowsiness Whv do we Sleep Seep deprivation studies pp do not go crazy with lack of sleep Few people have occasional hallucinationsproonged deprivation of gt 8 days Most common changes increase in irritability dif culty concentrating and disorientation Even with moderate sleep deprivationie still getting 4 or 6 hours of sleep per night for 2 weeksgt de cits in attention and reaction times Why do we sleep no simple answer Four functions frequently ascribed to sleep 1 Energy Conservation 2 Niche Adaptation 3 Body restoration 4 Memory Consolidation 1 Energy Conservation Reduced body temp slower respiration slower heart rategt reduced metabolic activity Do this at a time of day when an animal would not be good at getting food esp for herbivores in slow wave sleep decrease in body temp metabolism slows down we use less energy might be helpful when we can t nd food Pant eaters engage in is inversely related to their size Small animals sleep more but on average as increase size amount of sleep is less the animal has to spend more time eating Meat eaters don t show that same trend shows that here is no relationship bw body mass and metabolism between sleeping 2 Niche Adaptation Seep enforces this adaptaion to a particular ecological niche might be useful to sleep in secluded place during the night if live in a place where there are predators be sleeping when they are out and about 3 Body restoration seep helps rebuildrestore body materials and functions proonged deprivationgt weakened immune system work at night vs daygt increased risk of cancer Does not refer to simple wear and teargt eg exercise does not cause people to sleep longer have chronic disruption in sleep work at night vs daygt increased risk of cancer 4 Memory consolidation Considerable evidence indicates that sleep PROMOTES memory consolidation Strong evidence for procedural memories and SWS More recent evidence for declarative memories and sleep Stil debating REM sleep and memory Decarative memories in REM sleep Procedura memories are consolidated in SW5 Sleep Disorders Narcolepsy Different medications can treat this including new one called moda nilMs effects are not wellunderstood Common symptom of narcolepsy quotsleep paralysisquot May occur due to continued activity in pontine system Two common ones in young children Night terrors and sleep enuresisbedwetting Both occur during SWS can be treated with drugs to decrease stage 34 SWS sleep or with an antidiuretic SomnambulismSleepwalkingmore common among children but can persist into adu hood Aso occurs during SWS patients are NOT acting out a dream Aduts that have sleep walking have some neurological problem occurs during slow wave sleep Rem Behavior disorder Patients appear to be acting out a dream of somewhat organizedseeming behavior Begins around age 50 and more common among men onset often followed by Parkinson s or dementia Patients appear to be acting out a dream movement during a dream indicates that the person due to inhibitor signals if not complete desceding disinhibiton see small motor activity occurs in later in life and predicts the onset of parkinsons disease lnsomnia 2 categories 1 SleepOnset often caused by situational factorsdif culty to fall asleep 2 SIeepmainteneance insomnia variety of reasonsno problem falling asleep just can t stay asleep A common cause of the latter is sleep apnea respiration becomes unreliable and person may stop breathing for a minute seep apnea may kill neurons and may lead to a variety of cardiovascular problems reated to obesisitybreathing becomes unreliable snoringinterference in throat they stop breathing Sudden infant death syndromeSlDS may be due to abnormalities in serotonin system in brainstem that regulate respiration pretty rareoccurs in rst months of life prevented when putting baby on their back for sleep Treatments for insomnia Various drugsbarbituratesaddictive Recent drugsbensodiasepines Benzo mimicsAmbien Sonata Lunesta Problem with all drugs Loose effectiveness over timetolerance Do not produce normal sleep Drowsiness during day Drugs that treat sleep disorders either wake people up or they have side effects that will help you sleep but you feel drowsy during the day For Sleep problems the best approach is to develop a regular routine to exploit the body s circadian clock Webb 1992 Use an alarm clock to wake up at the same time of the day including weekends go to bed in the evening when you feel seepy have a bedtime routineeg dark quiet environment ignore preconceived notions about how much sleep you need Otherwise for persistent insomnia a sleep clinicwork with sleep disorder expert would be advised 11614 Lecture Internal State Regulation Homeostasis regulation of biological processes that keep certain body variables within a xed range Keeps certain body parameters in a particular range Autonomic NS important for homeostasis Set Point refers to a single value that the body works to maintain Exampes levels of H20 Oxygen glucose sodium chloride protein fat and acidity in the body Processes that reduce discrepancies from the set point are known as Negative Feedback Homeostasis is not an equilibrium A steady state maintain energy balance for a particular function Ex Body Temp Equilibrium of body temp would be room temp Term we used to describe the parameter that we regulate Set Point Works through negative feedback any change to system will change Heat from furnace pm des negative feedback inl39dbiting the thermostat from calling for more heat swayicawsvcmmer swe A temperature drop below the set point activates the thermostat which turns on the heating system Heat from the furnace provides negative feedback inhibiting the thermostat from calling for more heat as the temperature returns to the set point There is a degree of tolerance in the feedback system equivalent to a small range between the quotturn onquot and quotturn offquot signals Without this tolerance the system would be going on and off too frequently So for most systems there is really a set zone rather than a set point Temperature regulation is achieved by neural systems that re recruited to maintain a set pointeg 986 F Thrist neurocircuitry helps to maintain 2 parameters uid volume and sodium ion concentration The mechanisms for these are pretty straight forward and are described by Kalat Regulation of food intake is signi cantly more complicated than with temperature and uids This is largely due to the fact that eating serves the dual role of supplying nutrients and energy eg essential amino acids9 15 vitamins variety of minerals a few fatty acids there is a signi cant public health relevance for understanding more about this topic Food and Energy Regulation All of the energy we need to move think breathe and maintain body temperature is through breaking of chemical bonds in complex molecules down to smaller ones 33 of energy in food is lost to digestion 55 of energy is consumed by basal metabolism basic day to day of cells in quiet awakening 12 is used for active behavioral processes Basic relation of basal metabolism Kleiber 1947 CalDay 70 X weightquot075 Eating take in energy and use it to drive basic reactions in body the process of eating food and ingesting food is a complex series about results in reduction of molecular form that can be used at cellular level Basal metabolic rate kcal h 10 l2 10 9 102 1 10Ci 100 103 1o5 lug lmg 1g lkglmet39ric Body Weight 5 ton mammmmmma As you increase the size of the animal you increase the basal metabolic rate However Kleiber s equation describes population better than individual differences within a species eg food restriction affects metabolic rate more than body weight 3500 450 kcal clay lkcal day JL A r f l 100 l w 90 8f 20 10 0 4 3 12 16 2o 24 28 32 Days masiwimmme risumm When decrease calories body weight declines but it is compensated by the decline in basal metabolism Digestive system provides for energy intake Every step along the way plays an important role in breaking down food major organs that are important for digestion each of these steps play an important role in breaking down food Digestive system breaks donw food for energy utilizationstorage and nutrient absorption 2 pancreatic hormones lnsulin Promotes glucose uptake into cells promotes conversion of glucose to glycogen a more storagefriendly carbohydrate Glucagon increases blood levels of glucose mediates breakdown of glycogen back to glucose No insulin required Insulin 7 required Fat energy store 1 N0 insulin 1 f required Fattfacids ready energy Biological Psychology e Figure 1320 mml iWeIA wm W In people with diabetes insulin levels remain constantly low but blood glucose levels are high people eat more food than normal but excrete the glucose unused and lose weight People with diabetes have low levels of insulin stem cell therapy to develop cells that can harvest cells and put them back in the body a possible treatment T Eating mod glucese increases but insulin 4 levell is ew 39Gflzucese tines net enter cells leaves in urine and feces irretead Hunger remains high Bleed gulucese levels stay high but celis are starving 2999 CEWEIEQIELEEFWW What happens when someone has low insulin levels Cassic lesion studies rst implicated the hypothalamus in control of appetite Bilateral lesions of the ventromedial hypothalamus VMH could cause obesity in ratsie hyperphagia Bilatera lesions in the lateral hypothalamusLH had the opposite effectie aphagia YET neither of these regions are the sole regulators of satiety and hunger respectively Lesion of VMH ED 400 l E SUD Static Recovery Recovery 3 200 plhase of quot quot391 Preoperative 39 obes y g 100 phase fTilTlE 24 Forced lFood Dynamic feeding deprivation phase of weight gain Emma pmmm 69 Fig 339 S h ows a n exa m pl e w h e re its weight is moderated The lesion to the vmh see increase in weight it eventyally stablisez its regulating at a set point If force feed the animal maybe it will regulate at a higher weight it doesn t 300 23900 Normal rat Recovered 100 LHsleS ioned rat Body weight g Time rr 39 Food Feeding deprivation on very rich food Biological PSychology 5e Figure 1324 mmemmgmmm More recent research has shown that peripheral peptide hormones drive appetite controlling mechanisms in the hypothalamus Arcuate Nucleusof the hypothalamus appetite control center that is governed by a variety of circulating hormones in the peripheryeg insulin leptin ghrelin cholecystokinin CholecystokininCCK this is the classic peripheral signal that when discovered was thought would solve all the world s problems about regulation of eating CCK is released by the gut after ingestion of food high in protein or fat Activates receptors in the vagus nerve that send ascending projections to hypothalamus and other brain regionsvia the nucleus of the solitary tract to signal satiety obese individuals appear to be CCK insensitive Leptinproduced by the body s fat cells when amount of fat stored reaches a certain level also signals to the Arcuate N to increase energy use You can think of leptin as inhibiting appetite although this is not quite accurate Discovered from transgenic mice with defect in gene encoding leptin Low levels increase hunger although high levels do not necessarily decrease hunger Obese individuals show some evidence of reduced leptin sensitivity Ghrelin is released into the bloodstream by endocrine cells in the stomach Circuating levels of ghrelin rise during fasting and immediately drop upon eating treating ratshumans with ghrelin produces a rapid increase in appetite PYY336 release into bloodstream from the gut it affects are opposite of ghrelin levels are low during fasting and rises right after eaUng PYY336 is associated with feelings of satietygt effects of PYY are somewhat like CCK and leptinie satietyrelated hunger inhibiting lnformation from all parts of the body regarding hunger impinge into 2 kinds of cells in the Arcuate Nucleus 1 Neurons sensitive to hunger signasie appetiteenhancingNPYAgRP neurons 2 Neurons sensitive to satiety signasie appetitesupressing POMCCART neurons 2 Groups of cell in Arcuate Nucleus control of eating NPYAgRP neurons have appetite stimulating effects 1 lnhibit POMCCART cells 2 Activate paraventricular hypothalamus 3 Activate LH POMCCART neuronshave appetite suppressing effects 1 lnhibit NPYAgRP neurons 2 Inhibit LH Downstream effectorNTS Appetite stimulating effects of PVH and LH are relayed to and integrated in the nucleus of the solitary tractNTS NTS receives information from the periphery via incoming Vagus Nervegt eg stomach distention change in glucose levels in the lever etc to also regulate eaUng Other effector for eating Paraventricular HypothalamusPVH Activating PVH on its own stimulates appetite gtPVH sends outputs to NTS gtPVH is also a control center of hormones by projecting to pituitary gland and activating hormonal systems to alter metabolism Role of Peripheral Signals in Arcuate Leptinlnsuinactivate POMCCART neurons and inhibit NPYAgRP neurons reguation is on a longer time scale Ghrelin activates NPYAgRP neurons reguation is on a much shorter time scale POMCCART neurons inhibit eating by inhibiting the LH Peripheral signals a Lateral hypothalamus decrease food intake 39 Nucleus of 39 the solitary tract Paraventricudar nucleus increaslz39 Affermts f 7 h J L 00d mtake from GI tract Leptin A rcuate nucleus 1 I gt quot NP39YAgR P newou Gmelm 39 forquot 39 I Li tin Ghrelin rings a Insuljm 39 Y Hormones Biological PsychoJOQy 6e F igu 13367 a 2mm slnaumgeaates inc An appetite controller located in the arcuate nucleus of the hypothalamus responds to levels of several peptide gut hormones Leptin providing a chronic signal about fat levels stimulates arcuate POMCCART neurons to release g MSH in the lateral hypothalamus to activate MC4R receptors to decrease appetite Leptin inhibits arcuate NPYAgRP neurons decreasing their release of NPY and AgRP to suppress appetite further Ghrelin and PYY335provide moreacute signals from the gut Ghrelin stimulates and PYY336 inhibits the arcuate appetite control system Correspondence with Classic Studies Lesioning the VMH led to hyperphagiaover eating probably because the arcuate was functionally disconnected from the rest of the hypothalamus and no appetite expressing signals could be transmitted from the periphery Effects of LH lesions damage appetitestimulating effects of arcuate on this region and also likely has some effects on DA mesolimbic pathway which passes through this region Chapter 12Emotional Behaviors What are emotions Emotions have 4 different aspects 1 FeelingsSubjective Experience 2 Actionseg laughing attacking in response to threat 3 Physiologicalautonomic endocrine responses 4 Motivationapproach or avoidance behaviors Charles Darwin sets another eld into play pubished the quotexpression of emtions in man and animalsquot in 1872 argued that basic emotions characterize a species just as much as bones or teeth A key idea in Darwin s studies of emotion is that expressive acts such as disappointed look of a chimpanzee must be the result of adaptive actions that have had value for the survival of a particular species emotions have survival value for the animal More Examples Starting with wide eyes in surprise may have come about because dilating the pupils allowed the organism to see more clearly snaring and showing ones teeth during rage could have emerged from the act of biting and could serve to scare or disarm opponents in a ght sneering could have come from movements of the nose when smelling something irritable emotions have natural selection effects different behavioral characteristics that are adaptive will be gradually selected over time William James and the JamesLange Theory Wrote short essay quotWhat is Emotionquot1884 Latched on to Darwin s ideas and placed them in the context of nervous system involvement James argued that the nervous system is predisposed to respond in certain ways to particular features of the environment Sensation triggers bodily changes which in turn lead to subsequent conscious experiences of these responses James theory turned conventional wisdom on its head as it was traditionally thought that emotional awareness triggered the physiological changesand not the other way around Car Lange the Danish physician proposed a similar theory in 1885 L1 Folk psychology St 1 Perception Particular emotion Specific pattern of interpretation T experienced autonomic arousal ang39 danger fear heart races etc b JamesLange theory St 1 Perception Specific pattern of Particular emotion interpretation autonomic arousal experienced ang danger heart races etc fear JamesLange theory leads to two predictions 1 People with a weak autonomic or skeletal response should feel less emotion 2 Increasing one s response should enhance an emotion There is some evidence for each of these ideas but numerous notable exceptions Critics ofJamesLange Theory The physician Charles Dana1921 reported a patient that feel off a horse and broke her neck at C3C4 of spinal cord and lost all cutaneous and deep sensation form the neck down yet still showed all the ranges of emotion People with quotpure autonomic failurequot still report feeling emotion This suggests that other factors are involved in the perception of emotion Final Theories ofJamesLange James had a high level of status and his theory of emotion gained a lot of support even despite the controversy it generated Ultimatey the attacks on JamesLange came not from psychologists but from the eld of physiology James s lasting contribution is the idea that the experience of emotions may involve the reading of the state of one s own body Enter Walter Cannon Cannon recognized that cutting the nervous system projections form the viscera to the brain in cats still resulted in many emotional responses indicative of anger disgust fear etc Aso appreciated that visceral responses were slower to appear than conscious emotional states that they were supposed to trigger Viscera responses were nonspeci c regardless of emotional statea similar set of responses were initiated Autonomic SystemsReprise Cannonc1911 became interested in this after he noticed that movements of the digestive organs decreased when animals were aroused Emotiona excitement was associated with increased diffuse activity of the sympathetic nervous system increase of adrenalin release into the bloodstream redirection of blood ow from the viscera to skeletal muscles and brain increases in blood pressure and glucose levels quotThese were vigorous responses directed toward mobilizing bodily resources and preserving life under challenge conditionsquot 51 Folk psychology st 1 Perception Particular emotion Specific pattern of interpretation experienced autonomic arousal mg39 danger fear heart races etc b IamesLange theory st 1 Perception Specific pattern of Particular emotion interpretation d autonomic arousal experienced mg danger heart races etc fear C Cannon Bard theory Perception 1mg danger General autonomic arousal heart races etc Particular emotion experienced fear BiologicawsvcholowseFigure151Part1 Emotions are feelings actions physiological arousal and motivational programs ThelamesLange theory considered emotions to be the perceptions of stimulusinduced autonomic activity while the CannonBard theory emphasized simultaneous emotional experience and bodily response CannonBard Theory Also emphasized the role of the brain in emotional processes which was also a departure from JamesLange This provoked many studies of the effects of brain lesions and electrical stimulation on emotion Early lesion studies on emotion Animals that have their cerebral cortices removedie decorticated show undirected rage reactionsGoltz 1892 Cannon showed that stimulation of the diencephalon could result in vocalizations changes in respiration and circulation piloerectionhair standing up on back and coordinated movements this phenomenon was known as quotshamerage sham rage resulted in a 5fold increase in blood glucose levels and increased secretions of the adrenal gland Philip Bard1930 performed a series of experiments rst he docorticated cats to produce sham rage then he performed a series of cuts through the brainstem he discovered that once he cut the posterior hypothalamus animals ceased to show sham rage other investigators veri ed that the posterior hypothalamus played an important role in the expression of emotions It Nit tilmm ringer Crrt39h39lrul curler Hlk39Pliltl39i k nuei I TUE1 LlllEi I mhill ha i n Hui quotShari n1 remains levels will mariaH a 75m He39d Ll 1 Mirthmiquot Once if hypo is intact have sham rage Hl i Pli Itl 1iL39l muss if hypothalamus is disconnected show no sham rage ldenti ed the hypothalamus important for producing the expression of emotional behaviors identi ed from the decorticateremova of entire cerebral hemispheres shows inherit strong aversive emotional responses reacting to a threat of a predator showed that the posterior hypothalamus is critical for mediating these responses made knife cuts in the hindbrain and midbrain When disconnected the hypothalamus blocked sham rage completely Walter Hess1920 was the rst to ever electrically stimulate the brain in feely moving awake animals Hess found that stimulating the posterior hypothalamus in cats produced hissing and spitting piloerection pupillary dilation ears moving backgt they all ceased when the stimulation ended he developed the rst methods where you can take an electrode and record and stimulate neurons in the posterior hypothalamus behaviors induced by stimulating the hypothalamus and stopped when removed the stimulus Summary of early work on emotions These studies explained anger and rage but nothing about other types of emotions Cinica evidence from patients with cerebral cortical damage particularly in the frontal lobesshowed disinhibition of certain types of emotional behaviors These observations were compatible with the sham rage observations in decorticate animals and also highlighted the role of the hypothalamus in expression of emotions didn t inform any other types of emotions with emotional regulation in generally patients with cerebral cortical damage in the frontal lobes show disinhibition of certain behaviors Today we understand emotion as a multidimensional concept that can be described in terms of subjective experiences actionsboth behaviorally and physiologically and motivational states As Darwin rst predicted emotions have adaptive value for the individual and show conservation across evolution emotions are more a neurocircuit based Levels of intensity Hi gh lEcstam39 Vigilance Adoration Terror Boredom 7 iPe iir nesa Biological Psychology 6e Figure 152 23105inauer swci31e5zInc Brain systems controlling emotion Work that followed expanded on the work of Cannon and Bard James Papez1937 outlined a new circuit to account for emotion This involved new regions not previously considered as being important for emotion Hippocampus cingulate gyrus anterior thalamic nuclei Limbic system system in the brain that governs all of our basic emotional responses comes from lineage work and predictions that are based on little evidence result of work from cannon and bard James Papezoutlined circuit that accounted for emotion anatomica connections or pathways took series of subcortical structures and linked them together More predominatly linked the cortex to emotional process more than cannon and bard did A key idea is that Papez distinguished between emotional expressionhypothaamus and subjective emotional experiencecerebrum This concept was further expanded upon and described as the quotLimbicquot systemMacLean 1949 The concept of the limbic system has pervaded even to this day Limbic system Parahippocampal gyrus hippocampus mammillary bodies formix cingulate gyrus anterior thalamic nuclei septal nuclei frontal lobe olfactory buld amygdala Nonetheess there are considerable problems with the quotlimbic systemquot in terms of it being an emotional relay system Now we refer to it mostly out of convenience In humans at least evidence from MRI and PET studies shows that the cerebral cortex plays a key role in the subjective experiences of emotions What is emotion Emotions tend not to be localized in speci c parts of the cortex A single type of emotion increases activity in various parts of the braingt but not in one single region 11 Sadness III II Ii TAnterior ll osterior finsula Dorsal poms cingula te cingulate cottex cortex b Happiness 2 139 Right posterior Left insula l Left anterior cingulate cortex cingulate cortex 5 Fear 1 Left anterior cingulate cortex TP Psychology BE 396 20105i3nauermsociates inc Major players in emotion 1 Prefrontal regionsie orbitofrontal cingulate gyrus 2 Amygdala fear 3 Insular cortex disgust Red and yellow increase in functional activity Purpledecrease in activity In humans cortical localization seems to be evident for at least one emotion disgust The insular cortex is strongly activated during exposure to stimuli perceived as disgusting aso the part of cortex responsible for processing taste information part of the cortex responsible for processing taste info olfactory or strong sensory stimulation that elicits and emotional response on the border of temporal lobe and frontal lobe Brain systems of approach behaviors While a common set of brain structures seem to provide for multiple types of emotions we can highlight individual pathways Olds and Milner1954 had a landmark nding brain selfstimulation idea of activating mesolimbic pathway is the brain self stimulation medial forebrain pathway rats will bar press to receive electrical stimulation when electrodes were implanted in the septal region other subcortical sites were later discovered Dorsal brainstem Cerebellar nuclei forebrain Nucleus accumbens Locus Ventral coer uleus Medial forebrain Ventral t t 1 S b t t e men a u s an 1a bundle mldbram g area mgra PSFChO39OQ39y Be 20105i nauerAssociales Inc SelfStimulation sites in the Rodent Brain Mesolimbic pathway VTA nucleus accumbensgt stimulating the brain in a variety of different regions increases self reinforcement stimulating the brain in different regions increased this selfreinforcement Animals can be trained to engage in any behavior that you want them to perform quotapproach behaviorsquot mediates reinforcing behaviors to promote survival eating and sex The common feature to all of these manipulations is that the ascending pathway the medial forebrain bundle is activated This pathway contains dopamine neurons that innervate the nucleus accumbens Peasurabe experiences or emotions pertaining to joy happiness are thought to involve activation of the dopaminenucleus accumbens pathway Brain systems of Avoidance behaviors The neural circuitry for fear learning has also been well described For these studies a model of Pavlovianassociative learning is usedcassica conditioning In this model a previously neutral stimulussuch as a tone or conditioned stimulus CS is paired with a noxious stimulusunconditioned stimulus US such as an electric shock and will result in fear responses when only presenting CS alone Fear conditioning requires the amygdala primary mediator for classical conditioning One of the key features of this workLeDoux 2000 is that the hypothalamus is no longer critically important for expression of emotions lnformation relevant to the behavior ie freezing response leaves the amygdala and may bypass the hypothalamus projecting directly to the brainstem for motor and visceral responses C Sensory cortex Hippocampus Thalamus is Sensor 6 Y organ Central Lateral Bed nucleus of gray hypo stria terminalis Stimuli thiamine Emotional Autonomic Hormonal behavim responses responses Biological Psychology is Figure 1512 Part 5 mm inc Evidence from fear learning studies allows us to think about the neural mechanisms involved in the emotional expression under a speci c context and frames how future studies may clarify the mechanisms of different types of emotions Stress in Health and Disease Stress not same thing as emotion but t in with internal regulatory systems internal systems that help us adapt to a variety of changes What is Stress Stress is familiar to our every day experience We refer to being under stress the body s response to stress certain life events as stressful Stress is a mulitdemnsional concept with no easy de nition Hans SIeye19071982 was the rst to popularize the use of this term Seye1956 de ned stress as quotthe rate of all wear and tear caused by lifequot negative emotions were hypothesized to be one source of quotwear and tearquot The connected between stress and disease is highlight by the general adaptation syndrome General Adaptation Syndrome has 3 phases 1 Alarm Reactioninitial response to stress 2 Adaptation stageincludes activation of appropriate responses systems and reestablishment of homeostatic balance 3 Exhaustion stage occurs when stress is prolonged or severe characterized by increased susceptibility to disease A better de nition of stress Stress is the body s multisystem response to any challenge that overwhelms or is judged to overwhelm selective homeostatic response mechanisms Stress and Health Stress activates two physiological systems in the body 1 The sympathetic nervous system quot ght or ightquot response that prepares the body for brief emergency responses 2 HPA axis the hypothalamus pituitary gland and adrenal cortex HPA axis activation predominates during prolonged stressors so we will focus on this system Common Components of the Stress Response hypothlamo pituitary Hypotnaamus adrenal H PA axis Pi Utaj ACTH Adrena Gland sympathoadrenal system Gluoooorticoids Catecholamines Metabolic mobilization increased heart rate blood pressure respiration Redistribution of blood flow Suppression of immune digestive systems Restores resting homeostasis negative feedback loop HPA axis activation is initiated when afferent information enters into the brain and is ultimately conveyed to the paraventricular nucleus of the hypothalamusPVH HPA considered to be the primary mediator of stress responses Paraventricular Hypothalamic Nucleus PVH is the Final Common Pathway in the Brain for HPA Regulation BLOOD BQHNE VISUAL PAIN IGL CG r 5 LIMBIC 1 SF0 PVT 7899 CERAL MePO 0L FA C TOR Y Adrenal Gland Glucocorticoids Cellular and Functional Organization of the PVH Taret Signature Function P39tu39tary Lactation Parturition I Activate sympathetic Autonomlc nervous system Neurosecretory subdivision of the PVH This is the region that expresses CRF and whose secretion stimulates ACTH release in the pituitary into the blood stream and ultimately GC release from the adrenal gland sometimes called CRH is synthesized and secreted by neurons in the PVH A subpopulation of neurons in PVH project to the median eminence where they release CRF into the anterior pituitary portal system Cells in the anterior pituitary synthesize and secrete into the bloodstream ACTH stimulates the release of from the adrenal cortex PVHreleases CRFgtPitutary Glandreleases ACTHgt Adrenal Gland gtcortisol Hyp ophyseal x artery Direction of blood ow 4 4 q H Prmrtary A i Cells rhat produce 6 anterior pituitary Pituitary hormones I Median P J g emmence 3 I J a 54 HYPOPhYSEal k portal veins Posterior 4 4 4 4 h TIOPIC hormones Biological Psychology 6e Figure 514 Prolac n Gonadotropic hormones FSH and LH Thyroid stimulatmg hormone ACTH Growth hormone I 201 E21 Sinauer Associates Inc Categorization of Stress Paradigms Physiological Targeted perturbations in homeostatic parameters Transduced by peripheral andor central receptors Effective stimuli processed subcortically Examples hemorrhage saltloading immune challenge Emotional Effective stimuli often not readily specified Initial transduction via one or more exteroceptive modalities Significant cognitiveaffective component Examples Footsnock restraint open field loud noise etc Different types of stress PhysiologicalBody temp dropping bc its cold outside get bad cold or virus that gives you a fever Emotionalpublic speaking taking a big exam They all impinge on the PVH and have the same effect which is release of cortisol Pathways to PVH are category speci c Physiological Ventra lateral MedulaVLMgtPVH Emotionalphysioogica stress LimbicAmygdaIagt PVH Cortisol does 3 major things 1 Increases blood sugar by activating glucose metabolismie via gluconeogenesis 2 Catabolizes fat and proteinsaso for energy use 3 Inhibits immune function 4 speculative may enhance cognition via a different mechanism Finally once the stresseor subsidescortisol feeds back onto the brain to shut off HPA axis response negative feedback loop Glucocorticoid Receptor Mechanism Finaly once the stressor subsides cortisol feeds back onto the brain to shut off HPA axis response heps prevent the system from overriding a V l v I D 4 l 4 a b I E 9 39 1 F pmep rme ACTH M I n A I v Adrenal FaNorepmeplhrme 393 nquot l glam I Adrenal 39 y a steroids iluaiiw i a I 1 u n air 39 D Iquot I Target Organs ii l I it 739 Target organs 2010Sinauer ssocia lesInc Ursin1978 studied recruits in the Norweigan military both before and during the early phase of parachute training Subjects were propelled won a long sloping wire suspended 40 ft high Blood samples were taken to measure physiological responses before the day jump see an increase in cortisol levels 2nOI day levels are elevatedbut not as much As days go on they become adaptive to the avtivity see a restoration of cortisol activities Less lifethreatening stiuations activated stress response systems Riding in a commuter train was found to provoke release of epinephrine longer rides and more crowded trains increase levels Pasma catechholamines also incresein days before a major graduate exam Sapolsky studied baboons living in a natural reserve in Kenya This troupe has an abundance of food and no predators yet animals show a considerable amount of stress Vigorous competition surrounds courtship and establishment of dominance hierarchies Stress physiologyie cortisol and epinephrine levels is largely in uenced by status in hierarcy lnvestigators have shown that two factors are important for determination of whether a experience or event is psychologically stressful 1 Predictability 1 Controlability things that we can both predict and control are not stress Acute and Chronic Effects of Stress Short Term Adaptation Mobilization of energy reserves ncreased cardiovascular output Suppression of digestion Supression of growth Supression of reproduction Altered immune function Heightened awareness cognition Long Term Patholoqv Myopathy fatigue type 2 diabetes Hypertension Ulcers irritable bowel disorder psychosocia dwari sm amennorrhea impotency loss of libido immunosuppression risk of infection nerve cell ossie hippocampus mention Glucocorticoids as mediators of this effect Psychosocia dwari sm Growth failure that results from psychological and social factors mediated through CNS and its control over endocrine functions When such children are removed from stressful circumstances many begin to grow rapidly Proonged cortisol from HPA hyperactivity secretion may inhibit growth hormoneGH release Somatomedins a group of proteins made in the liver released in response to GH aid body growth and maintenance Organizing effects of cortisol HPA axis may have organizing effects during development that tie together differences in stress reactivity in adulthood Levine 1967 found that rats brie y handled 15 mindaily by experimenters as pups had reduced HPA axis responses to stress during adulthood he called this stress immunization Folow up work found that this brief maternal deprivation resulted in increased grooming of pups when returned to their cage however prolonged deprivation3hdaily led to greater stress reactivity More recent research showed that these early maternal experiences produce epigenetic eventsie alterations in gene expression that mediate alterations in stress reactivity during adulthood Stress and health Proonged elevations in corticosterone in rats have been shown to produce dendritic atrophy synapse loss in hippocampal and prefrontal cortical pyramidal neurons In extreme cases hippocampal neurons may die if exposed to prolonged increases in circulating corticosterone Cushing s disease endocrine syndrome where cortisol levels are chronically elevated these patients show massive hippocampal shrinkage and cell loss Key to why stress is bad HPA axis feedback may becomes disrupted from prolonged elevations in circulating cortisol Add to this the fact that brain regions like hippocampus and prefrontal cortex play an important role in dampening the HPA axis response to stress If these brain regions are compromised by the stress itself over time there ability to regulate this system fails Remember acute stress hormone release is adaptive chronic cortisol is maladaptive Stress hormones are damaging because they have catabolic effects on the body they break down proteins for energy utilization Over time their toll on neurons is signi cant enough to compromise their function The question of when stress becomes quotbadquot is a topic of great interest in psychology medical and research elds Health Psychology is concerned with understanding how biological psychological environmental and cultural factors are involved in physical health and the prevention of illness aka behavioral medicine It has also been appreciated that stress andor negative emotions can effect immune function Psychoneuroimmunology deals with the way in which experiences alter the immune system also how the immune system in uences the central nervous system Neuroimmune interactions Fever somnoence lethargy Loss of appetite Metabolic endocrine effects Activation of HPA axis Adrenal 7 7 l a amp O 3 Glam 6 Metabolic mobilization Increased heart rate blood pressure respiration Redistribution of blood flow Suppression of immune digestive systems Cytokines proteins made by immune cells and glia that lead to in ammation and organize system s responses to foreign invaders Cytokines activate the HPA axis during an infection HPA activation in turn has a counterregulatory effect on immune activationwhy 1 Remember that acute bene ts of stress involve dealing with immediate dangers 2 Over reactivity of immune system can produce harmful effects by damaging host tissuesorgans or lead to autoimmune diseases
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