Language Lateralization & Aphasia: A Summary of Neurological Conditions PDF

18-LANGUAGE Lateralization: speech comprehension = left side of brain Prosody: rhythm, emphasis, tone of speech Location: in right hemisphere indicates emotional state regular rhythm of speech emphasis on certain words change of pitch shows phrasing (statement vs question) if left brai...

18-LANGUAGE Lateralization: speech comprehension = left side of brain Prosody: rhythm, emphasis, tone of speech Location: in right hemisphere indicates emotional state regular rhythm of speech emphasis on certain words change of pitch shows phrasing (statement vs question) if left brain damage: still know emotional state, phrasing of speech Recognition of voices recognition independent of word comprehension if left brain damage: recognize but don’t understand voices Phonagnosia: hard to recognize voices bc of damage to right temporal lobe Metaphor left hemisphere = literal meaning right hemisphere = metaphorical meaning Aphasia Defn: difficulty understanding, repeating, producing meaningful speech Not caused by: sensory/ motor deficit lack of motivation Must be: isolated: can recognize when others trying to communicate aware of what is happening around them Damage to: Middle cerebral artery = aphasia symptoms vary based on location of cell death Sensory association cortex = can’t understand language Frontal lobe = can’t speak or write Posterior language area Function: language comprehension Location: at junction of temporal, occipital and parietal lobes neurons of PLA activate neurons throughout sensory association corticies -> find meaning of words Transcortical sensory aphasia damage to posterior language area can’t understand meaning of words can’t express thought through speech word perception + speaking =ok: can repeat words can read + write without understanding Byron after stroke After 5 years: understands half words he hears understand what he reads cannot repeat/spell words can read numbers, do math, … Conduction aphasia: inability to repeat exact words damage to arcuate fasciculus (axons that connect Wernicke’s and Broca’s) language comprehension and expression = good Wernicke’s area Function: speech recognition Location: auditory association cortex in left temporal lobe not for word comprehension (posterior language area) not for ability to hear (primary auditory cortex) Wernicke’s aphasia damage to Wernicke’s area and posterior language area combination of transcortical sensory aphasia and pure word deafness poor language comprehension fluent, meaningless speech, many function words (a,the,in,about) type of receptive aphasia/fluent aphasia Difference btwn TSA and Wernicke’s aphasia = Wernicke’s cannot repeat what is saids to them spoken word recognition and word comprehension cannot be differentiated in brain scan Pure Word Deafness cannot recognize auditory words: comprehending and repeating caused by damage to small part of Wernicke’s ppl can still: hear interpret non-speech sounds read,write read lips speak without recognizing words Pure Alexia damage to visual word-form area (VWFA) in visual association cortex in fusiform gyrus in left hemisphere disrupts ability to perceive written words cannot read bc cannot recognize words can write properly Reading When damage to V1 in left cerebral hemisphere, VWFA still intact: can read out of left peripheral vision if corpus callosum damaged also, cannot read Reading: 2 processes Sight reading: recognition of whole word (whole-word reading) uses VWFA Sound reading: recognition by sounding out strings of letters (phonetic reading) most important cues for object recognition = constant when viewed from different angles: lines that meet at vertices, junctions with shapes like L, T, X Dyslexia difficulty reading, hereditary Surface dyslexia: inability to recognize whole words, while able to do phonetic reading, hard to read irregularly spelled words Phonological dyslexia: can read familiar words but cannot read unfamiliar or non-words developmental dyslexia = type of phonological dyslexia: difficulty learning to read, trouble with grammar, spelling, order of sounds Direct dyslexia: inability to extract meaning from written words, even though they can read them out loud seen in transcortical sensory aphasia Broca’s area Function: speech production Location: left inferior temporal lobe Damage= hard to express self verbally Broca’s aphasia: slow, laborious, nonfluent speech -> have something to say, have trouble saying it 3 issues: 1. Articulation issue Articulation = mouvement of speech organs to make speech sound, difficulties can cause sequencing issues 2. Agrammatism difficulty with grammatical devices and word order don’t find meaning in sequence of words/ grammar of sentences only use content words (nouns, adjectives, verbs) without function words (preposition, article…) 3. Anomia difficulty finding appropriate word to describe object, action,… symptom of all aphasia Anomic aphasia: mild aphasia where ppl have hard time thinking of words they want to say understand and speak well but describe things in alternative ways (circumlocution) 19- EMOTIONS abstract: thinking and expressing emotions on face happen in neocortex raw, reflexive feelings processed in limbic system 2 pathways of sensory inputs: 1. Stream of thought: processed in cerebral cortex 2. Stream of feeling: processed in limbic system Wheel of emotion 4 opposite dimensions of emotion that create emotional blends many emotions without clear bounds Variable 1: Arousal -> how far off center point Variable 2: Valence -> in which direction Expression of emotion Facial expressions = innate, unlearned complex muscle response displayed in young babies reduced when ppl are alone automatic, rapid, accurate recognition of emotions through facial expression 6 categories of facial expressions that we can discriminate: fear, anger, sadness, disgust, happiness, surprise Ability vs Motivation identifying emotion = learned skill inability to recognize emotions = frustration inability to recognize emotions can be mistaken for lack of interest in a person no difference in display of emotions across cultures, language, btwn blind and non-blind genuine, involuntary facial expressions = different muscles than artificial expressions Volitional facial paresis: cannot voluntarily control facial muscles, can express genuine emotions with same muscles Emotional facial paresis: cannot show automatic facial expressions, can make voluntary facial expressions seen in Parkinson’s disease Reading emotions emotional expressions not very specific: same expression for ++ emotions or different expression for same emotion inferring emotions = not reliable generalizability of emotion is not well studied -> there are 25 blends and no prototypical facial expressions Identifying emotions in others having amygdala removed to stop seizures still able to generate artificial expression of emotion could not identify or feel fear diminished ability to detect disgust, sadness, happiness Animals Fear: emotional feelings occur with behavioural and physiological responses 1. Behavioural responses: muscle mouvements 2. Autonomic responses: facilitate fight-or-flight 3. Hormonal responses: reinforce automatic responses animals seem to feel core emotions, no way to be sure lack language and culture:. don’t know if emotion experienced same way Anthropomorphize: give human characteristics to non-human Anthropectomy: denying that animals have human-like characteristics Intracranial self-stimulation: animals like pressing lever bc increases dopamine in ganglia poor correlation btwn dopamine and pleasure dopamine related to reinforcement learning: craving, not pleasure Sexual behaviour circuitry glutamate and GABA neurons on medial amygdala light activates specific cell types GABA stimulation: low frequency stimulation: normal sexual response medium frequency stimulation: high sexual response high frequency stimulation: high aggressive behaviour Glutamate stimulation: stimulation = grooming + complete social disengagement Theories of emotion Common sense view: stimulus -> feeling of emotions -> behavioural/physiological responses emotion precedes and causes physiological response in early research, ppl with spinal cord damage felt emotions less intensely James-Lange theory stimulus -> behvaioural/physiological responses -> emotional response from PNS feedback interfering with muscular mouvements associated with emotion decreases experience similar effect to botox Critiques of James-Lange: internal organs insensitive: don’t respond quickly enough to cause emotional response cutting sensory nerve btwn internal organs and CNS doesn’t eliminate emotional feeling artificially activating nervous system doesn’t produce specific emotions Limbic system Cingulate cortex: interconnects limbic areas Hippocampus: explicit memory formation Amygdala: recognition of fear both amygdala and hippocampus have their own nuclei Central nucleus of amygdala Stimulation = fear, anxiety, agitation Consistent stimulation = stress induced illness Lesion = no more innate or learned response to fear, can only be scared through suffocation seeing threatening stimulus activates amygdala damage to visual cortices: still activity in amygdala when viewing faces and can mimic facial reaction Beyond the amygdala somatosensory cortex, insular cortex, premotor cortex, cingulate cortex activated when we see emotional face Right hemisphere = recognition of emotion Damage in these areas = hard to identify emotional facial expression in others Eye mouvements and fixation in recognition of emotions ppl automatically look at eyes to identify emotional state SM had bilateral amygdala damage: didn’t naturally look at eyes got better at recognizing emotion in photos after she was taught to look at eyes Ventromedial prefrontal cortex (vmPFC) inhibitory influence in regulation of emotional expression connection btwn amygdala and vmPFC strengthened with learned response to fear lesion of pathway = disrupts extinction, restores original fear Damage = hard to control emotions, more childlike attitude/ outbursts weakened decision making and behavioural control bc of emotional dysregulation Phineas Gage rod through skull Before injury: kind, good-natured, responsible After injury, childlike, irresponsible, outbursts, inability to plan Risky behaviour correlation btwn risky behaviour, impulsive agression and low serotonin levels = small monkey with lowest 5-HIAA (serotonin) = risk-takers died from attack by stronger monkey Humans: low cerebrospinal 5-HIAA = aggression + antisocial behaviour drugs that increase serotonin decrease agression + antisocial behaviour Strokes Ischemic stroke Hemorrhagic stroke Cause: blocked cerebral blood vessel Cause: ruptured cerebral blood vessel Treatment: drug that dissolves blood clots for ischemic strokes Thrombolytics: “clot-busting” drugs tPA (tissue plasminogen activator) devices that thread through vascular system: coil, aspiration device, stents After stroke: anti-inflammatory drugs physical, speech and occupational therapy exercise and sensory stimulation Other details: Atherosclerosis: internal carotid artery lining develops plaque made of cholesterol/fats/calcium/ waste Thrombus: blood clot in blood vessel Embolus: piece of tissue that detached from original and lodged somewhere else Tumours Cause: uncontrolled cell growth -> rogue cell division Other details: Metastasis: cells break off the tumour, transported by blood vessels and grow elsewhere in body Malignant Non-malignant cancerous not cancerous, but can damage NOT encapsulated encapsulated grows by infiltrating surrounding tissue can be removed by surgery Glioma: rapidly proliferating tumour Meningioma: tumour between both hemispheres that originates from neural stem cell made of cells of meninges that make glia still causes brain damage bc it takes up space very resistant to chemotherapy and compression: destroys brain tissue directly or radiation indirectly (blocks cerebrospinal fluid) infiltration  Encephalitis: inflammation of brain caused by infection Meningitis: inflammation of the meninges cause by virus or bacteria Well-known viruses Polio: viral disease that destroys motor neuron of brain and spinal cord Rabies: viral disease cause by brain damage and death transmitted through bite of infected animal Herpes simplex virus: virus that normally causes cold sores near lip or genitals rare cases: enters brain, causes encephalitis and brain damage Traumatic brain injury Closed-head injury Open-head injury Cause: blow to the head with blunt object Causes: penetrating brain injuries Other details: Other details: Coup: brain violently hits inside of skull exacerbated by damaged blood Contrecoup: brain recoils and hits vessels, increased pressure in brain opposite side of skull caused by blood loss and inflammation many people affected and die from it scarring in brain increases risk of seizures mild, undiagnosed TBI increase risk of brain problems (ex. Alzheimer’s) Seizure disorder Causes: scarring related to injury, stroke, tumour, abnormal brain development, high fever (children) and withdrawal from GABA agonists many are idiopathic (have unknown causes) some gene mutations that affect amount/function of ion channels in brain, reciprocal wiring of excitatory/inhibitory neurons, ruling of synaptic plasticity Treatments: anticonvulsant drugs (benzodiazepines) that make inhibitory synapses more effective sometimes requires brain surgery Other details: most don’t involve convulsions Convulsion: violent sequence of uncontrollable muscle mouvement caused by seizure Partial seizure: focalized in one brain region Simple partial seizure: no loss of consciousness Complex partial seizure: loss of consciousness Generalized seizure: involves most of the brain (tonic-clonic, atonic and absence seizures) seizure can spread across brain areas within and across different episodes Grand mal seizures Aura: sensation that precedes seizure, cause depends on location of seizure’s focus Tonic phase: skeletal muscles contract Clonic phase: rhythmic jerking mouvements Absence seizures (petit mal seizure) brief common in kids stop what they are doing, stare into distance, blink repeatedly Development disorder (ex. Zika, rubella virus) Causes: exposure to toxins, drugs, viruses, heavy metals during pregnancy alcohol Fetal alcohol syndrome: alcohol consumption between 3rd and 4th week of pregnancy that cause facial anomalies and intellectual disabilities Inherited metabolic disorders Causes: “errors of metabolism” -> genetic abnormalities in both genes when instructions for a protein have an error:. not synthesized Other details: Phenylketonuria: hereditary disorder caused by absence of enzyme that converts phenylalanine into tyrosine accumulation of phenylalanine = brain damage unless special diet Tay-Sachs disease: hereditary, fatal disorder where lack of enzyme in lysosomes causes accumulation of waste -> swelling in brain cells Down syndrome Cause: extra twenty-first chromosome Other details: congenital (from birth), but not always hereditary moderate to severe intellectual disability and physical abnormalities brain degeneration after age 30 Multiple sclerosis Causes: sporadic (not obviously caused by an inherited gene mutation or infectious agent) Symptoms: go through cycles (flare ups) remitting-relapsing MS followed by progressive MS Consequences: demyelinates axons:. action potentials don’t propagate well myelin sheaths attacked by own immune system variety of neurological disorders Other details: autoimmune disease starts in late 20s Sclerotic plaque: hard patches of debris left behind by attack on myelin sheath damage in white matter of brain and spinal cord Progressive MS: slow continuous increase in symptoms growing up far from equator = increased risk of MS Treatment: none Interferon: protein that modulates immune system activity Glatiramer acetate: peptides that mimic myelin sheath -> decoy approach Prion disease (Transmissible spongiform encephalopathy) Cause: accumulation of misfolded prion protein Symptoms/ consequences: widespread degeneration (brain looks like sponge) Other details: contagious: spreads within body and across animals Prion: misfolded protein that causes other copies of same protein to misfold and so one only infectious agent that is a protein all others contain nucleic acids Huntington’s disease Cause: mutation in huntington gene :. misfolding of huntington protein, degeneration of basal ganglia Symptoms/consequences: lack of coordination jerky limb mouvements dementia -> death Treatment: none, but Antisense therapy = promising - Antisense therapy: injection of DNA that directly compliments mRNA into spinal cord DNA + mRNA = no translation :. no protein Other details: rare genetic huntington gene expression in basal ganglia Parkinson’s disease Cause: degeneration of dopamine neurons in midbrain (substantia nigra)-> misfolding and clumping of alpha-synuclein protein also caused by mutated parkin age Symptoms/ consequences: reduced dopamine signalling causes: muscle rigidity slowed mouvement shaking dementia cognitive, emotional and sleep disturbances Other details: Ubiquitin: protein added to misfolded/ old proteins to cause degeneration -> like a “tag” Parkin: carries ubiquitin -> when defective, makes misfolded proteins accumulate, aggregate and kill the cell Proteasome: organelle that breaks down ubiquitinated protein for recycling Alpha-synuclein: abundant protein in midbrain dopamine neurons Lewy body: clump of misfolded apha-synuclein protein in cytoplasm of midbrain dopamine neurons Toxic gain of function: dominant gene mutation produces a protein with toxic effects Loss of function: recessive gene mutation on both chromosomes = absence of necessary protein Treatments: none, but ways to decrease motor issues increase dopamine levels in brain dopamine receptor agonists, but many side effects daily administration of L-Dopa, converted to dopamine in brain brain lesions and deep brain stimulation to part of basal ganglia that is overactive damaging globus pallidus, disrupting subthalamic nucleus activity remove one of the brakes on motor behaviour Alzheimer’s disease Cause: clumping of misfolded beta-amyloid protein and severe degeneration in and around hippocampus and neocortex ( looks like brain shrivels up) age, traumatic brain injury, obesity, diabetes, high cholesterol, hypertension= risks Symptoms/ consequences progressive memory loss motor deficits death Treatments: none, some meds reduce symptoms a bit - Immunotherapy: injection antibodies that bind to ApopE or Tau protein so they are tagged to be destroyed - Other details: Dementia: progressive impairement of memory, thinking, behaviour bc of neurological disorder less prevalent in well-educated ppl Amyloid plaques: clump of beta-amyloid protein around glial cells and degenerating neurons Tau protein: microtubule protein that is hyper-phosphorylated in Alzheimer’s, disrupts intracellular transport Neurofibrillary tangle: intracellular accumulation of twisted Tau protein in dying neurons Beta-amyloid precursor protein (APP): name explains it, on chromosome 21 Secretase: class of enzymes that cut APP into smaller pieces like Beta-amyloid Presenilin: protein that forms part of secretase mutations cause abnormally long beta-amyloid:. early onset of Alzheimer’s Apolipoprotein E (ApopE): glycoprotein that transports blood cholesterol role in cellular repair E4 allele of apoE increases risk of late-onset Alzheimer’s ALS-FTD Cause: mostly unknown starts at age 50 Symptoms/ consequences: ALS attacks motor neurons in spinal cord and cranial nerves spasticity: increased muscle tension progressive weakness, muscular atrophy paralysis -> death Treatment: none Other details: ALS and frontotemporal dementia are part of same disease spectrum bc of genetic, clinical and pathological similarities  Parkinson's Prior Huntington's Alzheimer's cluster of degeneration of · clumping of misfolded misfolding · mutation + misfolded prion of huntington gene dopamine neurons beta-amyloid protein protein misfolding clumping+ · of alpha-synuclein protein basal ganglia degeneration · muscle rigidity severe degeneration of - brain degeneration · lack of jerky coordination limb mouvements · slowed mouvement hippocampus/ neocortex (brain shrivels up) (sponge-like) · shaking · dementia dementia progressive memory loss · motor deficits Antisense decrease motor issues Immunotherapy F therapy increase dopamine levels injecting antibodies that bind to inject DNA · e complementary in brain ApopE or Tan protein to fag ! to mRNA administration of L-Dopa them to be destroyed brain lesions + deep brain stimulation Reproductive success not everyone reproduces physical + mental health impact likelihood of having kids in pop. with severe mental illness, not as fertile :. reduces reproductive success theory of evolution and natural selections says: gene variants that increase risk of developing severe health issue should get eliminated across generation not the case for these diseases Genetic variation new gene mutations with each generation different versions of gene -> multiple alleles for that gene most are common if more than 1% of pop. has specific allele: unlikely that it is uniformly bad unlikely that it is uniformly good Bad genes natural selection eliminates bad genes over time the more harmful, the quicker they get eliminated less harmful gene mutations common in humans, but won’t persist forever if they slightly reduce reproductive success, only persists from ~1000 years Good genes Gene goes to fixation: beneficial alleles increase until everyone has them ex. gene mutations that caused different skin colour, hair types, body shapes… depending on region you live in went to fixation most of human genome has gone to fixation bc promoted survival and reproduction compromise species-typical human genome Genetic basis of disease variety of alleles = common most diseases and disorders have genetic basis some alleles increase risk of disease, other are protective strong evolutionary pressure on gene variants harmful gene variants common bc of rapid lifestyle and environments change Clear gene-environment interaction: strong genetic component, but prevalence varies across world some variants that are problematic today were neutral or beneficial in the past bc of environment risk factors that didn’t used to exist Gene-environment interaction in stable environment, only beneficial and neutral alleles are maintained Gene-environment interaction: when an allele is neutral in one environment but not another prevalence of diseases vary across cultures often straightforward environmental explanations Environmental risk factors: obesity/ diabetes: abundance of cheap, unnatural food asthma: changes in air quality drug addiction: highly purified synthetic drugs heart disease, strokes, cancer late onset neurodegenerative disease depression, anxiety Mental illness some don’t show gene-environment interactions ex. Scizophrenia and autism = heritable, large genetic basis, but prevalence rates don’t vary Severe mental disorders: reduce reproductive success are heritable are very common are genetic, but alleles are widespread and were not eliminated through natural selection  SCHIZOPHRENIA Schizophrenia susceptibility genes hundreds of common gene variants that individually create small increase in susceptibility to scizophrenia combination of gene variants = likely mental illness if one twin has schizophrenia, 50% chance the other twin will also regardless of raised together or apart Cause: genetic predisposition and bad luck Why are these genes so common? some combinations of schizophrenia susceptibility genes can improve reproductive success -> not true wrong combo = schizophrenia BUT no difference in fertility rates or cognitive abilities :. no know advantage of schizo. genes Diagnostic categories mental illnesses are very variable, ppl present very differently:. can’t group ppl to a disease based on symptoms There is too much - heterogeneity with diagnostic categories - comorbidity across categories - continuity with normality: no natural way of classifying ppl, arbitrary diagnostic categories = result of historical conventions diagnostic categories = hard to change very similar symptoms can mean completely different things in the brain Mental disorder susceptibility genes gene variants that increase risk of schizophrenia also increase risk of autism, bipolar disorder, depression, OCD, ADHD risks by gene variants have no diagnostic boundaries (i.e no schizophrenia genes, autism genes…) gene variants tell vulnerability to developing a mental illness in general (not any specific one) gene variants that increase risk of mental illness also regulate brain development and neural plasticity :. variants don’t directly cause mental illness often natural variabilities in ppl’s brain structure, but mentally ill have more peculiarities same mental illness rarely same gene variants Brain development unavoidable randomness that impact brain, but genome evolved to buffer them gene mutation = stress for developing brain Neurodevelopment robustness both sides of body develop independently using same genomic instructions symmetrical body = clear genetic instructions = robustness of genetic instructions = a bit of intelligence, physical attractiveness, health indicates clear genetic instruction that can withstand environmental variation Mutation-selection balance mental illnesses = result of unfortunate combo of gene mutations that disrupt neural network Gene mutation selection balance: harmful genes are naturally selected out, but new gene mutations arise with each generation To maintain healthy brain, must have healthy body: stay active eat well reduce stress, lower blood pressure good sleep habits limit alcohol intake, avoid tobacco, hard drugs Future of mental disorders identification of gene variants and neural circuit disruptions associated with mental illness to create new treatments idea to use gene editing techniques or to target intracellular signalling cascades (as opposed to neurotransmitter signalling) deep brain stimulation? -> closed loop stimulation strategies using implanted metal wire in brain Schizophrenia Causes: Consequences: social withdrawal disorganized thinking abnormal speech inability to understand reality Symptoms (in order of appearance): Negative: absence of behaviour -> withdrawal, reduced emotion, poor speech Cognitive: disorganized irrational thinking, learning deficit, poor memory, problem solving Positive: presence of delusions and hallucinations also neurological symptoms and subtle differences in brain structure Heritability: measures fraction of phenotype variability attributed to genetic variation 50% chance if identical twin or both parents have it, 13% if one has it, 8% if one of siblings has it Highly penetrant gene mutations = rare gene copy number variations Environmental factors mother’s nutrition and stress during pregnancy infections birth month Seasonality effect: most born in Feb., March, April, May raised in city childhood trauma social isolation brain damage prenatal environment monochorionic twins have more concordance than dichorionic (2 umb. cords) Evidence for abnormal brain development behavioural + anatomical evidence shows that prenatal development = associated with schizophrenia Behavioural in children: less social, bad psychomotor skill Anatomical in kid: minor physical abnormalities (ex. slightly webbed feet, highly-steepled palate) Treatment: none medication + psychological/social support Antipsychotics/neuroleptics: block dopamine D2 receptors drugs to relieve positive symptoms Meth/cocaine = dopamine receptor agonist :. elicit positive symptoms in ppl Dopamine hypothesis excessive dopamine D2 receptor activity in nucleus accumbens (striatum) = positive symptoms dopamine D2 antagonists reduce positive symptoms, not negative symptoms negative symptoms largely responsible for long-term disability, poor functional outcomes result of abnormal activity in prefrontal cortex - negative symptoms similar to those of damage to prefrontal cortex - Hypofrontality: decrease in activity of frontal lobes related to hypoactivity of local dopamine D1 receptors -> causes negative symptoms Excess dopamine signalling in striatum = positive symptoms Reduced dopamine signalling in prefrontal cortex = negative symptoms Schizophrenia associated with too little dopamine somewhere, and too much somewhere else Atypical antipsychotic clozapine: in monkeys, decrease dopamine levels in striatum and simultaneously increase them in prefrontal cortex Atypical antipsychotic drugs Atypical antipsychotic drugs: second generation antipsychotics that reduce positive and negative symptoms influence activity of multiple neurotransmitter receptors Clozapine: first atypical antipsychotic medication that blocks dopamine D2 and serotonin 2A receptors Aripiprazole: atypical antipsychotic that is partial agonist at dopamine D2 and D3 receptors and serotonin 1A reduce dopamine receptor activity in striatum and boost dopamine receptor activity in PFC Autism, ADHD, Depression Neurodevelopment disorders vs mental illness Mental illness: occur at any age, episodic or temporary (used to have a healthy state) Neurodevelopment disorders: evident in children, lifelong Sex differences similar for Schizophrenia and bipolar disorder i More common in females (mental illness) anxiety disorder major depression obsessive-compulsive disorder PTSD Anorexia Bulemia More common in men (neurodevelopmental) autism ADHD Intellectual disability Tourette’s syndrome Theories behind sex differences: they aren’t real all has to do with culture and socialization, not biology under-diagnose anxiety and depressive disorder in males/neurodevelopment in female real differences of how we present symptoms, but they only reflect differences btwn how men and women are perceived in society perceptual biases: normal and abnormal behaviour for men and women Obviously, culture and society do contribute too Autism diagnoses: MALES when look at genome of family, diagnosed men have fewer harmful gene variants than diagnosed females Rare gene copy number variations (CNV): section of genome is duplicated or missing CNVs cause more autism in males CNVs are inherited by mothers perceptual biases don’t explain higher frequency of neurodevelopment disorders in men Sex chromosomes mammals and most insects: females have 2 of same chromosome Homogametic sex: 2 of same chromosome (XX) Heterogametic sex: 2 different chromosomes (XY) within species, heterogametic = more variability at young age in many traits In humans, having one X chromosome = developmental instability XX promotes developmental robustness Mental illness differences: FEMALES social/ cultural stressors Hormone fluctuation: anxiety and depression fluctuate during puberty, childbirth and menopause hormone signalling affects neural networks -> female brain has to constantly adapt to changes in hormone signalling ex. hot flashes at menopause: hypothalamus mistakenly believes body temp. is too high bc of change in hormone signalling Autism spectrum = wide range of disorders, wide range of causes Causes: genetic and environmental factors that affect early brain development Symptoms/ consequences: Category 1: trouble with social interaction and communication Category 2: restricted (deep interest in one subject), repetitive behaviour (can extend to ritualistic behaviour) Other details: first signs during 2nd to 3rd year of life first symptom = social impairment hereditary Trouble with social interactions/communication many ppl with autism = abnormal, no language 1/3 don’t develop enough speech to meet daily needs repeat what is said to them refer to themselves in 2nd or 3rd person Restricted, repetitive behaviour atypical interest/ behaviour more stereotyped mouvements some exhibit compulsive/ ritualistic behaviour Autistic disorder not everyone has clear cognitive impairments mild forms (Asperger’s syndrome): deficient/absent social interactions, repetitive stereotyped behaviour, obsessional interests not always delay in language development or cognitive deficits many ppl with autism have comorbid psych. diagnosis: intellectual disability, seizure disorder, ADHD, depression, anxiety Heritability of autism 70%-90% heritable 10% linked to rare chromosomal abnormalities/ multigene interactions of common and uncommon variants/ maternal viral infection bc of pregnancy Brain development in autism at birth, not usually difference btwn brain of autistic/ non autistic kids But, abnormally quick brain growth Hypotheses of quick brain growth: - Altered neuronal migration during early gestation - Abnormal formation of synapses/ dendritic spines - Over connectivity in brain regions - Unbalanced excitatory-inhibitory neural networks some abnormalities in brain activity in fMRI (less activity in fusiform gyrus when looking at face) Treatments: lessen impact of deficits and family distress -> increase quality of life intensive special education programs behaviour therapy in early life (self-care, communication, life skills) -> improve functioning, decrease symptom severity meds don’t address core symptoms, reduce irritability, inattention, repetitive behaviours: - Anticonvulsants (increase GABA receptor activity) - Antidepressants (increase serotonin receptor activity) - Antipsychotics (decrease dopamine receptor activity) - Stimulants (increase dopamine receptor activity) ADD/ADHD Symptoms: problems paying attention difficulty controlling behaviour in age-appropriate manner hyperactivity act without reflecting bored/ distracted easily Other details: more than 5% children diagnosed with ADHD symptoms appear before age 12 (when kids start school -> must quietly pay attention) diagnosis/ symptoms not well defined kids with ADHD have good attention span for things they are interested in comorbid with learning disabilities, depression, anxiety, low self-esteem, aggression, conduct disorder mostly genetic, but rates vary drugs, alcohol, smoking during pregnancy = increased chance bc of low birth weight Treatment: counselling medication (stimulants that increase dopamine levels, block dopamine reuptake transporter) antidepressants Mood disorders Affect: feelings, emotions affective disorder = disordered feelings Mood (affective disorder): serious mood disorder, bipolar disorder and major depressive disorder Bipolar disorder: cyclical periods of mania and depression Major depressive disorder (MDD): unremitting depression and periods of depression that do not alternate with periods of mania traumatic/ abusive childhood = environmental factor affective disorders = dangerous and prevalent ppl with mood disorders have high risk of self-harm/ suicide feel unworthy, hopeless, strong guilt Bipolar disorder Symptoms/ consequences Mania: state of unjustified euphoria nonstop speech and motor activity, risky behaviour Mania followed by depression Treatments Lithium chemical element rapid effect unknown mechanism treats manic phase once mania is eliminated, depression does not follow Anticonvulsant drugs that block VG sodium channels -> mood stabilizers Antipsychotics/antidepressants combined with mood stabilizer Major depressive disorder Treatments: drugs that increase serotonin/norepinephrine signalling inhibit enzymatic breakdown or block their reuptake *ECT -> most effective Ketamine (NMDA glutamate receptor blocker) Deep brain stimulation Transcranial magnetic stimulation vagus nerve stimulation Bright light therapy Sleep deprivation  Tricyclic antidepressants: inhibit reuptake of serotonin and norepinephrine Serotonin specific reuptake inhibitor (SSRI): class of drugs that specifically inhibit reptake of serotonin doesn’t affect reuptake of other neurotransmitters most common = Prozac Serotonin and norepinephrine reuptake inhibitor (SNRI): antidepressant that specifically inhibits reuptake of norepinephrine and serotonin Monoamine hypothesis of depression depression may relate to insufficient monoamine receptor activity monoamines = serotonin, norepinephrine, dopamine based on success of tricyclic and SSRI treatments focus on norepinephrine and serotonin bc dopamine receptor agonists don’t relieve depression symptoms Serotonin made from a.a tryptophan low-tryptophan diet + tryptophan-free cocktail lowers tryptophan levels, decrease serotonin synthesis > can cause depressive episodes SSRI and SNRI increases serotonin and norepinephrine levels symptoms relieved after weeks of use Role of frontal cortex subgenual ACC less active when depression is gone deep brain stimulation targeting it = unsuccessful Electroconvulsion therapy (ECT) most effective treats severe depression and bipolar disorder short term memory loss, no brain damage SSRI is only treatment that is not quick Sleep and depression disordered sleep = prominent in depression shallow, fragmented sleep more time in stage 1, less time in stage 3, 4 enter REM soon after falling asleep (earlier in the night) most effective antidepressant treatment is sleep deprivation immediate antidepressant effect returns after a normal night’s sleep REM sleep deprivation also works over several weeks Stress, anxiety, OCD, Addiction Stress general physiological reaction to threatening situations, mobilizes body for action triggers autonomic and endocrine systems adaptive in short term, long term = illness can lead to anxiety Anxiety persistent feeling of worry, uneasy without an actual threat no obvious trigger anxiety = more intense than stress Physiology of stress 1. Sympathetic NS: adrenal gland releases epinephrine and norepinephrine into blood 2. HPA axis: signalling cascade that increases glucocorticoids in blood Hypothalamus: CRH/CRF -> Pituitary gland: ACTH -> Adrenal gland: cortisol increase heart rate, bp, blood flow Glucocorticoids group of hormones essential to survival act on almost all organs: maintains homeostasis make glucose and fat available for use prep. body for immediate action, deprioritize non-survival functions persistent glucocorticoid signalling = weak immune system (slower healing) PTSD Causes: traumatic events like abuse, death, warfare,…. Symptoms: vivid, intrusive memories, dreams of event (flashbacks) avoidance of stimuli associated with trauma symptoms interfere with social hyperarousal/hypervigilance interactions -> increased risk negative mood, hopelessness of suicide Treatments: cognitive behavioural therapy, group therapy SSRIs = first line of medication (not very effective) Other details: NOT an anxiety disorder bc includes feelings of guilt, shame, anger more common in women (30% variance related to genetics) abnormalities in HPA axis Severe symptoms = smaller hippocampus and PFC -> unclear if cause or effect kids more susceptible than adults Anxiety disorders variety of psychological disorders characterized by unrealistic fear and anxiety Symptoms: expectation of impending disaster overactive auntonomic nervous system continuous vigilance Generalized anxiety disorder excessive anxiety and worry that cause disturbance of daily life Anxiety disorders Social anxiety disorder: excessive fear of being judged by others Panic disorder: episodic periods of severe, unrelenting terror Anticipatory anxiety: fear of having panic attack Agoraphobia: fear of being away from home or protected place  very common more common in females Causes: genetic and environmental often comorbidity with major depressive disorder, personality disorders, substance use disorder no obvious brain circuit disorder Treatment: lifestyle changes Cognitive behavioural therapy SSRIs: first line of treatment Benzodiazepines: rapid onset, emergency use Obsessive-compulsive disorder (OCD) Causes: genetic and environmental factors Symptoms: repeated thoughts (obsessions) ritualistic behaviour to control obsession (compulsions) Cleaning: germs, bodily fluid, contamination Hoarding Symmetry Forbidden thoughts: violent, religious or sexual intrusive thoughts Treatments: therapy Exposure and response prevention: increase exposure to what us causing problem, without allowing repetitive behaviour to occur form of CBT antidepressants like SSRIs no treatment = longlasting condition Deep brain stimulation in basal ganglia is being researched Other details most ppl with OCD notice that their behaviours don’t make sense difficult to control obsessions and compulsions more common in females onset of symptoms later in females (but before age 25 in men and women) increased activity of frontal lobes, striatum Substance abuse disorder some genetic predisposition addictive =drugs positively reinforce behaviour speed of reinforcement perceived by brain may explain addictive potential all reinforcers cause dopamine release in striatum more addictive = more rapid increase of dopamine partially maintained by negative reinforcement (removal to reinforce behaviour) drug cravings outlast withdrawal symptoms :. negative reinforcement does not maintain drug addictions  Tolerance: drug effect gets smaller with repeated exposure compensatory mechanisms that oppose effect of drug Withdrawal: symptoms opposite to those produced by drug when drug is taken away compensatory mechanisms Physical dependence: physical symptoms of tolerance and withdrawal tolerance and withdrawal can occur without addiction and vice versa Comorbidity of drug addiction, schizophrenia, and ADHD most schizophrenics smoke cigarettes abnormalities in PFC and interactions btwn striatum and dopamine neurons deficits in tasks that involve PFC Treatments: 1. Block the receptor approach: Nalterexone: high affinity, slow onset, long-acting opioid receptor blocker - prescribed to alcoholics and opiate addicts - reduces high produced by opiates - reduces cravings Naloxone: rapid, short lived opioid receptor antagonist - reverse effects of opiate overdose - reverse loss of consciousness, loss of breathing and create temporary withdrawal symptoms 2. Maintenance approach: Methadone: strong opiate that has slower onset/ offset than heroin - substitute for heroin - methadone maintenance programs: ppl have to come to clinics, drink it in front of clinician Buprenorphine: high affinity, partial opioid receptor agonist - treats weak opiate addiction - binds strongly but weak psychological effect - mixed with naloxone to decrease ability to abuse it Varenicline: partial agonist at acetylcholine receptors - prescribed to treat nicotine addiction 3. Brain stimulation approach: Deep brain stimulation Transcranial magnetic stimulation (TMS): use of magnetic pulses to stimulate cerebral cortex - noninvasive - approved for major depressive disorder, OCD, smoking, migraines - not much know ab optimal frequency, intensity Similarities : More common in women OCD MS Autism N anxiety disorder N 3 > - & > - major depression ↓ - OCD mental illness 30 > - PTSD 20 48 Parkinson's > - Anorexia + Dulemia A zheimer's ALS More common in men 3 - ADHD > - autism neurodevelopmental - Tourette's - Intellectual disabilities Influenced by genes+ environment (ASSOA) genes (HPIDD) > - autism - Huntington's > - Schizophrenia - Parkinson's ( + age) > - seizures > - inherited metabolic disorder > - OCD -down syndrome - ADHD (mostly genetic > - dyslexia (hereditary) environment (DTP) none of above/unknown (MATS) MS developmental disorder > - > - ALS injury > - - traumatic brain > - PTSD > - tumours > - strokes