Brain & Cognition 2 Lecture 1 - Introduction PDF

Brain & Cognition 2 Lecture 1 – Introduction What is (clinical) neuropsychology? = scientific area that studies the relationship between brain and behavior (attention mostly towards behavior) Clinical applicability of assessment, treatment and care of individuals with (presumed) cognitive (dys)func...

Brain & Cognition 2 Lecture 1 – Introduction What is (clinical) neuropsychology? = scientific area that studies the relationship between brain and behavior (attention mostly towards behavior) Clinical applicability of assessment, treatment and care of individuals with (presumed) cognitive (dys)function as a result of disorders (developmental, neurological or psychiatric) Behavior must be sensed in a broad sense in this definition Behavioral symptoms = latent variables that objectively can be assessed through tests that subjectively can be observed by the patient or significant others Clinical neuropsychology = comparable to the function of the population Clinical psychology is more related to treatment, clinical neuropsychology is more related to assessment Historical development There are ways of viewing brain regions as local aspects (activation resulting in specific behaviors), but the holistic view sees it as a whole, where the “brain does everything” Before neuroimaging Conclusion based on dents and bumps, patient description, theories were developed based on relationships between brain and behavior (picture of ray → the way in which people try to remember was a way to tell whether or not someone had brain damage; deficient validity) Based on the performance in the test (like the picture of ray) you could determine whether there was brain damage (organicity; is there a hole in the brain) Now it is the other way around; we know something is wrong and do psychological tests after Luria: language can not be located in only one part of the brain There was no more need for assessing the “hole” in the brain, but for assessing the healthy part of the brain because that part is useful for treatment = re-orientation Clinical neuropsychology is highly relevant in modern-day health care because there is higher interest in quality of life Increase in people with brain damage or dysfunction; decrease in mortality rates (improvements in medical rate) Conclusion A clinical neuropsychologist is a scientist practitioner whose focus lies on behavior and cognition A clinical neuropsychologist is not a brain researcher ICF = related to function Nowadays you test hypothesis in the following way: Multi-informed o Patient o Significant others Multi-method o Tests o Questionnaires o Clinical interview o Observation Multi-conceptual o Neuropsychological o Personality o Contextual environment Step-wise way of diagnosis: referral question → analysis of complaints → analysis of problems → analysis of cause → analysis of indication → treatment Testing is just a tool; assessment is much more than test administration Theoretical background; methods a)What does it mean to say that a neuropsychologist must be a scientist-practitioner? How does this relate to the diagnostic cycle of neuropsychological diagnostics? b) Formulate the difference between a referral and a diagnostic question. c) What is the difference between a neuropsychologist, a health-care psychologist and a clinical neuropsychologist? d) Why has interest in clinical neuropsychology sharply increased? What are the advantages and disadvantages of this? g) Master the concepts of NVN, INS, NIP, AST, Cotan. h) Master the concepts of reliability and validity, and all their facets. i) What are confounding factors? j) What is under-performance? Lecture 2 – Korsakoff’s and alcohol related cognitive disorders Terminology Problematic alcohol use: drinking pattern resulting in physical complains and or psychological or social problems. The amount of alcohol units consumed is not leading for the diagnosis Alcohol Use Disorder (AUD): problematic alcohol use meeting the DSM-5-TR criteria for this classification Binge drinking: consumption of large amount of alcohol (men; 5 or more, women; 4 or more) in a short time period, with periods of full abstinence Alcohol intoxication: result of excessive alcohol use in a short period of time, with dose related symptoms (disorientation, sexual/aggressive disinhibition, inability  to make judgements) and a (risk of) severe complications like loss of consciousness, shock or breathing problems o = acute effect o Can be life threathening Alcohol withdrawal syndrome: result of sudden withdrawal after long-term excessive alcohol use o Seizures o Refeeding syndrome Alcohol-related cognitive disorders Broad concept, describing (long-term) cognitive impairment associated with problematic alcohol use In DSM-5-TR terminology: o Mild or major alcohol-induced neurocognitive disorder (formally incorrect terminology!) ▪ Alcohol consumption itself may not necessarily be the cause of an alcohol-related cognitive disorder o Amnestic-confabulatory subtype (or nonamnestic subtype) But ranges from short-term, reversible effects on cognition to chronic and irreversible deficits Wernicke’s encephalopathy and Korsakoff’s syndrome Korsakoff’s syndrome Victor et al. (1989): “an abnormal mental state in which memory and learning are affected out of all proportion to other cognitive functions in an otherwise alert and responsive patient” Addition by Kopelman et al. (2009): “resulting from nutritional depletion, ie, thiamine deficiency” o sudden onset after Wernicke encephalopathy o frontal and diencephalic damage (mammillary bodies and thalamus) as a result of chronic thiamine deficiency (vitamin B1) o often caused by chronic alcohol abuse in combination with poor nutrition  o But vitamin deficiency can result from other causes, such as anorexia, pregnancy, severe illness with vomiting (eg covid-19) Excessive alcohol use is the cause of the vitamin deficiency; not eating well because of the excessive alcohol use. Vitamin deficiency is the cause for Korsakoff’s syndrome Wernicke’s encephalopathy ▪ The acute neurological disorder that precedes Korsakoff’s syndrome ▪ Timely thiamine suppletion is essential (B1) But diagnosis is often missed in clinical practice ▪ Korsakoff’s syndrome may be the result in case of treatment delay When Wernicke’s encephalopathy is not treated in time, Korsakoff’s develops Wernicke’s encephalopathy can develop overnight when the vitamin level goes below the “threshold” Cognitive profile - Korsakoff’s syndrome: diencephalic amnesia Characteristics: Personality changes with irritability or apathy Confabulations (=incorrect memories) and lack of insight → no idea what happened Amnestic syndrome characterised by: o Anterograde amnesia = difficulty with forming new memories o Retrograde amnesia with temporal gradient in autobiographical memory = memory loss before the disease; older memories are relatively preserved and recent memories are more affected o Retrieval problems (executive as well) o Contextual memory: problems with placing memories in time o Increased sensitivity to interference (proactive and retroactive Executive dysfunction (and sometimes other cognitive deficits associated with AUD) Confabulations Provoked: incorrect response to a question or situation in which a person feels compelled to say something (What did you do yesterday? – Yesterday I visited my cousin; but patient lives in clinic so it’s not true) Spontaneous: occur without a trigger, patient acts accordingly (e.g., suitcase packed to go to a meeting with the boss of Shell)  Not just “filling in memory gaps” due to amnesia, but result of o temporal confusion o strategic retrieval deficit, and o impaired reality monitoring (“executive-memory dysfunction”) Spontaneous confabulations may diminish over time, provoked confabulations still present in chronic phase Anterograde amnesia Inability to store and retrieve new information Specifically in episodic memory (‘everyday memory’; ‘what, where and when’) Contextual confusion (target information related to wrong time and/or place Increased (proactive) interference Can be established with any episodic memory test that includes o Delayed recall o Free recall vs recognition o Verbal and nonverbal stimuli Proactive and retroactive interference Temporal gradient in memory Memories from the more distant past are remembered better than the memories from the recent past Intact memory functions Korsakoff is characterized by severe impairments in long-term episodic memory (anterograde and retrograde amnesia) But: Working memory is unimpaired – phone numbers Long-term memory is intact – procedural memory  Priming is intact – presented information had effect on later performance Emotional memory is intact Flashbulb memories: KS patients remembered 9/11 (emotional tagging) as well as contextual details (flashbulb memories) Non-memory domains that are affected Executive functioning – especially shiting and updated Social cognition o Theory of mind = ability to infer thought and feelings of others o Emotion perception o = relevant for successful social interaction Apathy – neuropsychiatric symptom = a lack of motivation that is not attributable to intellectual impairment, emotional distress, or diminished level of consciousness Three dimensions of apathy – often not present in KS patients Behavioral activation o Immediately doing something after having planned this Social motivation o Starting a conversation with others Emotional sensitivity o Feeling bad when someone close to you is informed to be seriously ill Agitation is also sometimes seen in KS patients The effects of alcohol on the brain Estimate: 50% of people with alcohol-use disorder (AUD) have cognitive impairments 10% have severe cognitive impairments (incl. Korsakoff’s syndrome) Mechanisms: Direct neurotoxic effect: alcohol damages neurons and axons (but possibly even reversible) Indirect neurotoxic effect: high calcium concentrations damage the neurons after sudden withdrawal/abstinence Indirect effect of vitamin deficiency (B1/thiamine) – Korsakoff Indirect effect of comorbidities (hepatitis, multiple drug use, traumatic brain injury, cerebrovascularrisk factors Brain abnormalities Impaired cognitive functions Executive functions o Response inhibition o Risk taking o Decision making o Abstract reasoning o Mental flexibility Memory o Learning & retrieval efficiency o Not an amnestic syndrome Visuospatial functions o Often with an executive component (e.g., Rey complex figure) Social cognition o Affective prosody o Perception of facial expressions o Interpersonal interaction Ethanol neurotoxicity The continuity hypothesis Quantity of alcohol intake and duration predict the severity of the cognitive disorders Continuity hypothesis also mentioned as explanation of the memory disruptions with temporal gradient in Korsakoff’s: old memories are better preserved than recent ones, with a gradient No recent support for this hypothesis Current view = a combination of factors explains the brain dysfunction that is seen in alcohol-related cognitive disorders Lecture 3 – Vascular cognitive impairment – h. What is vascular cognitive impairment Cognitive disorders with a cerebrovascular aetiology All disorders that affect blood supply to the brain Vascular Cognitive Impairment (VCI) Covers the entire spectrum from mild cognitive disorders to vascular dementia All forms of cognitive disorder associated with cerebrovascular disease Aetiology - Large vessel disease - Small vessel disease Normal and abnormal blood supply of the brain From artery to vein Arteries: carry oxygenated blood from the heart Veins: carry deoxygenated blood to the heart The blood vessels in our brain Two major blood vessels that supply blood to the brain – carotid arteries and vertebral arteries = incoming arteries Major branches are crucial for blood supply to the brain From the circle of Wills the arteries perfuse blood to different regions of the brain The circle of Wills is sort of a safety mechanism because other arteries can supply blood to some parts when arteries are blocked Large versus small vessel disease Infarct = oxygen deprived area due to obscured artery Large – affects bigger parts of the brain → e.g. major stroke → lots of damage Small – may affect deeper brain structures → micro bleeds → smaller signs of damage Silent infarct = infarct that goes unnoticed – no noticeable cognitive impairment Vascular risk factors and SVD: aging Causes: prevalence of vascular risk factors Arteric sclerosis is part of aging – arteries become harder and stiffen, and plaques impair blood flow Vascular risk relates to accelerated cognitive decline Lots of risk factors – cognitive performance is similar to the cognitive impairment of someone that is 10-20 years older Causes: vascular risk factors and dementia Global increases in unhealthy lifestyles Obesity - Sedentary behavior A 78-year-old man with history of hypertension and type 2 diabetes awoke with inability to move his right side. On examination, his blood pressure was 180/98, his pulse was regular, and he had no carotid bruits. He had a dense right hemiparesis with no other associated neurological deficits. Initial CT of scan of the head did not reveal any acute intracranial abnormalities. Brain MRI (Figure 7- 2) showed an acute small subcortical stroke in the posterior limb of the left internal capsule. Carotid ultrasound and cardiac workup were unremarkable. The patient was discharged on antiplatelet therapy, antihypertensives, an adjusted regimen for his diabetes, and a statin. He evolved favorably over the subsequent few months Modifiable risk factors of dementia Cardiovascular risk factors make aging related changes more pronounced E.g. hypertension, alcohol usage, obesity, smoking, physical inactivity, diabetes Modifying these might prevent or delay up to nearly half of all dementia cases And generally improve healthy aging Aging, cerebral blood flow and grey matter loss From 30 years old you can already see decline in perfusion of the brain – relatively small effect at this age Prevalence of SVD (small vascular disease) in aging Cognitive profile of aging Executive functioning and (psycho)motor speed are most prominently affected by SVD Around the age of 85 there is a big decline in cognitive functioning Time to start moving! A lot of damage can be prevented by a healthy lifestyle – decreases risk on dementia Cerebral perfusion – healthy lifestyle also positively affects cerebral perfusion Higher activity over the life span → higher cerebral perfusion The effect of physical activity 9 years later Those who were more physically active at base line Exercise as an intervention Those who exercised performed better on a working memory test and on the stroop test – they only exercised around 3 times a week Executive functioning and psychomotor functioning improved due to the activity 16 older adults (age 72.1) 4 weeks exercise, minimum 2 to 3x a week + additional activities at home 16 older control adults (no exercise, age 73.6) Cerebrovascular accident (CVA) Stroke CVA = stroke 40 00 people per year – 15% between 18 and 50 yrs Ischemic stroke – obstruction of vessel – most common Penumbra = area located around the ischaemic core o Embolic stroke = clotted material that breaks off from elsewhere in the body  o Atherothrombosis = formation of blood clot (thrombotic stroke) in brain artery o Lacunar = clotted material in smaller blood vessel in the brain Haemorrhagic stroke – bleeding rupture of vessel o Intracerebral haemorrhage (within brain) – more common ▪ Lobar: located in one of the cerebral lobes ▪ Non-lobar: located in basal ganglia, thalamus, cerebellum or brain stem o Subarachnoid haemorrhage (not within brain) – severe headache, cognitive problems, aneurysms ▪ Bleeding in the subarachnoid space Perfusion areas of the major arteries What happens after a stroke depends on the affected artery Middle cerebral artery is affected in almost 80% of strokes Supratentorial – in the cerebrum Infratentorial – in the brainstem of cerebellum Type of motor or cognitive dysfunction depends on location of stroke: Supply area of anterior cerebral artery  Supplies blood to the dorsal and medial parts of the frontal and parietal lobes. Impairments are found in: o Language o Executive function o Social cognition o Behavior and emotion Supply area of middle cerebral artery Supplies blood to the frontal, temporal and parietal lobes, and deep brain structures (eg thalamus). Accounts for approximately 80% of all stroke cases. Common consequences: o Memory disorders o Aphasia o Apraxia o Hemispatial neglect – more common after right sided damage o Extinction Supply area of posterior cerebral artery Supplies blood to the occipital and temporal lobes. Common consequences: o Hemianopsia or quandrantanopsia o Visual agnosia (e.g., object agnosia, proposagnosia) Transient Ischaemic Attack (TIA) Recovery < 24 hours. TIA: Brief ischaemic event Focal symptoms: Problem is specific to a certain area of the brain Abnormalities often also appear on acute brain scan Increased risk of having a stroke Many people still report cognitive problems three months after a TIA Impairments on neuropsychological assessment = temporary – shows that there is something wrong with the vessels because there is a (temporary) obstruction → higher risk at major stroke Cognitive recovery 49% cognitive impairments in acute phase → 31% at follow-up  ‘Unimpaired’ patients still unimpaired after six months Other group generally shows progress o Dynamic recovery and not ‘demented’ o Dependent on affected domain – ischemic stroke o May be linked to location of recovery o For haemorrhagic strokes the size is an important factor to determine whether there is lasting damage – strategic strokes like basal ganglia has a big effect Determinants o Schooling/age → ‘cognitive reserve’? (Stern et al., 2003; Robertson & Murre, 1999) o Lesion volume less important than location → small strategic infarcts sometimes accompanied by dementia (see Auchus et al., 2002) Mood disorders post-stroke Depressive symptoms occur in one third of stroke survivors Frequency is highest within the first year after stroke event Associated with poor recovery and long-term outcomes Suggested underlying mechanisms: o Biological hypothesis – direct brain damage ▪ Due to neurological changes caused by the stroke o Reactive hypothesis – psychological consequences ▪ Confrontation with the fact that they have been through a life threatening event – emotional reaction to stroke o Vascular depression hypothesis – cerebrovascular changes ▪ Cerebrovascular disease/vascular changes in the brain Vascular dementia Dementia subtypes Alzheimer’s -50-75% Vascular dementia – 20-30% o Cortical vs. subcortical profile o No specific neuropsychological pattern o Course often fluctuates o Strategic infarct or multi-infarct may contribute Lewy body – 10-25% Frontotemperal – 10-15% Most important cognitive deficits Executive deficits (thought, behavior, emotion) Additional defecits o Mental processing speed o Memory o Visuoconstruction o Language Lecture 4 – Mild cognitive impairment and Alzheimer’s dementia – h. What is dementia You can have dementia without Alzheimer’s – and the other way around Dementia in the DSM-5 Cognitive decline with regard to previous performance level o In one or more cognitive domains Presence of interference in daily activities o Support needed to perform complex (or instrumental) activities of daily living (iADL), such as internet banking, using a smartphone, administration, medication intake, cooking, etc. No delirium present – toestand van geestelijke verwardheid No other psychiatric disorder present that could explain the cognitive disorders o Such as depression, schizophrenia Epidemiology - 12.000 people in the Netherlands with dementia 65, but younger people can also get Parkinson’s – young onset Parkinson’s = 10-15% of all cases Parkinsonism – resting tremor (50% of the cases), bradykinsesia, rigidity and postural instability Neurodegenerative process o Idiopathic Parkinson’s disease o Parkinson Plus Drug-induced A-typical parkinsonisms – lewy body dementia (cognitive problems and hallucinations) Balance and cognitive problems early in the course → parkinsonism Good responding to medication of Parkinson’s→ most likely Parkinson’s You can only be sure if you can look in the brain after death Even automatic movement is less or absent Parkinson’s spectrum Parkinson’s disease symptoms core symptoms – yellow Parkinson’s is more than a tremor Motor and non-motor symptoms Motor problems are the first visible problems (and usually lead to a diagnosis); but they do not develop first Prodromal phase of Parkinson’s disease = Before the diagnosis; when the disease starts developing – no motor symptoms yet Detecting Parkinson’s in this phase may lead to the ability to slow down the process Pathophysiology Braak’s stadia Parkinson’s is starting much earlier than when it shows When people start showing symptoms they are already in phase 4 Prodromal phase – phase 2 Non-motor symptoms Non-motor symptoms are the first to develop. Lively dreaming is very common; people with Parkinson’s can move in their REM sleep Hallucinations are a late symptom Reactive depression can be a consequence of Parkinson’s as well because of low dopamine – can be solved by medication Flexibility is difficult for people with Parkinson’s, it gives stress and therefore worsens the tremors - Trying to reduce tremors also stresses people with Parkinson’s and this makes the tremor even worse Memory problems can release in later stages Treatment of PD Medication can reduce motor symptoms L-dopa – adds dopamine to the brain – reaction? → Parkinson’s Longer usage → fluctuating effect Eventually adverse effects can arise Dopamine agonists – stimulating dopamine that is already in the brain Finding a good balance with medication is very important because too much can have adverse effects, but when using too little it won’t work well Slowing down & prevention: exercise Moving and exercising is effective to slow down the disease Motivation is a big thing because the reward of lifetime interventions is late and not direct Multidisciplinary & network care Important development because people with Parkinson’s do not have to come to the hospital all the time which is better for them Advanced PD; response fluctuations Deep brain stimulation After the stimulation you can take half the dose of the medication that was taken before the stimulation; it also lessens fluctuations of effects The electrodes are put into the brain surgically Slow reduction of medication after the surgery is very important because otherwise there may be too little dopamine The surgery won’t stop de disease from progressing Cortico-basal ganglia-thalamocortical circuits Dopamine is more needed in the dorsal pathway, but since you can’t direct the medication there will be too much dopamine in the ventral pathway Stimulation can have different effects than medication Hypodopaminergic vs. hyperdopaminergic Hypodopaminergic Motor loop o Bradykinesia o Apathy (motor component) Associate loop o Bradyphrenia o Empty brain (absence of ideas) o Apathy (cognitive component) Limbic loop o Depression o Apathy (emotional component) o Anhedonia o Anxiety, harm avoidance Hyperdopaminergic Motor loop o Dyskinesia o Motor impulsibity Associate loop o Cognitive impulsivity o Flight of ideas o Novelty seeking Limbic loop o Euphoria, mania o Behavioral addictions o Hedonism, creativity, risk-taking behavior Dopaminergic desensitization Apathy and PD It may look like people are depressed, but people with Parkinson’s do not feel depressed they just don’t have the initiative to do something (difficult to get started) They need external control to do things ICD in PD Finding balance Cognitive domains Social cognition Social cognitive problem may arise, because some patients do not feel or have the insight that their behavior is not in line with the rules. This can be paired with a impulsivity problem; hard to be fixed because of the lack of motivation (TOM) Social mild cognitive impairment Slowness is usually the first problem in Parkinson’s They need external cues to do/know things Cognitive spectrum Memory problems can occur early as well, but usually they start later  = multi domain mild cognitive impairment Criteria MCI and PPD MCI Cognitive impairment, single and multiple domain, with difficulties in daily function Significant impact and dependency absent PDD Cognitive impairment, single and multiple domain, with significant impact on daily functioning Often presence of apathy, depression, hallucinations and axial symptoms Exclude delirium PDD – LBD (lewy body) – AD (Alzheimer) Fluctuations in LBD > PDD > AD Hallucinations (early) in LBD > PDD > AD Motor impariment in PDD > LBD > AD Memory impairment in AD > PDD and LBD Visuospatial impairment in PDD and LBD > AD Noradrenergic+cholinergic deficits in LBD > PDD Dopamine deficits in PDD > LBD and AD MDS criteria for assessment Level I = global assessment (cognitive screening test) o MoCa o MDRS – mattis dementia rating scale Level II = comprehensive assessment (min. 2 tests o Two impaired tests in a single cognitive domain  o One impaired test in two different cognitive domains ▪ Impairment ▪ Significant decline on serial cognitive testing ▪ Significant decline from estimated premorbid levels o Course Cl uncertain with sometimes rapid progression to dementia Diagnostic certainty level II > I Assessment of cognition Treatment = very personalized – training, exercising ICF model Lecture 6 – epilepsy Epilepsy can cause cognitive problems There are no typical seizures Non convulsive epileptic seizure – freezing Whole brain is involved Takes a while to be diagnosed – not very obvious Non convulsive because there are no contractions Epilepsy = having seizures – differences are the common characteristics Conceptual definition - ILAE Seizure = transient signs (it stops) and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain Focal epilepsy is not synchronous – only in certain parts of the brain Epilepsy = disorder of the brain characterized by an enduring predisposition to generate epileptic seizures, and by the neurologic, cognitive, psychological and social consequences Course of the seizure Ictal = seizure Preictal and postictal – neurologists Interictal – psychologists Basic mechanisms epileptogenesis Sequence of events that converts normal brain to epileptic brain 2 essential epileptogenic processes o Seizure: as a clinical manifestation of abnormal and excessive excitation and synchronization of a population neurons ▪ Changes of the normal balance between inhibition and excitation ▪ But also change this balance ▪ Epilepsy as the tendency of recurrent unprovoked seizures o Neuronal network defect: sequence of changes that converts normal neuronal network to a hyperexcited network ▪ Changes in the functioning of one or more neuronal cells can have significant changes in normal functioning neurons nearby Declining threshold → seizure – repeated? → developing epilepsy Operational definition 1. At least two unprovoked seizures > 24h apart 2. One unprovoked seizure and a probability of another unprovoked seizure (next 10 years) 3. Diagnosis of an epilepsy syndrome Epidemiology Most frequent chronical neurological disease Prevalence 0.7-1% No difference in gender Incidence: 20 to 70 / 100000 o Varies strongly with age – developing brain is more reluctant to epilepsy o Excluding febrile seizures – can cause epilepsy after a few years but they do not account for epilepsy; look very much alike Course Children: 15 years follow up → 71% remission at least 5 years; 12% refractory  Adults: 20 years follow up → 70% seizure free; refractory 20-30%; average of 20 years Refractory patients can not be helped with the current drugs More risk for psychosocial problems when having refractory epilepsy Cognitive School performances Behavioral and emotional problems Social difficulties Diagnostic steps Seizure → first aid or general practitioner Neurologist general hospital o Clinical interview, clinical description of seizures o Diagnostic investigations ▪ EEG (standard, after sleep deprivation, video-monitoring, MEG, etc.) ▪ Neuroimaging techniques (MRI, PET, SPECT, CT, etc.) Treatment o Neurologist, general practitioner o Specialized epilepsy centers ▪ Medical treatment is insufficient ▪ Psychosocial problems Status epilepticus is the only kind of epilepsy where you should do something when a seizure happens, because the next seizure will start right after so they need medicine Classification systems Classification of seizure types – seizure as clinical phenomenon Classification of epilepsies – type of epilepsy as syndrome Not anymore; it’s more like a flow chart now Seizure type = a useful grouping of seizure characteristics for communication in clinical practice; purely observational Involuntary movements Global behavior changes  Changes in consciousness Perceptual or autonomous changes Dependent on localization so high variation between patients and low variation within patients Epilepsy types = the diagnoses made on clinical, supported by EEG findings Epilepsy syndromes = cluster of features incorporating seizure types, EEG, and imaging features that tend to occur together Often dependent on age, etiology, prognosis, treatment Seizure symptoms – semiology Involuntary movements Global behaviour changes Changes in consciousness Perceptual or autonomous changes ➔ Dependent on localisation ➔ Variations between patients high ➔ Variations within patients low → Classification Revised classification of seizures Every generalized seizure comes from brain stem activity Simple partial seizure – focal seizure with intact awareness Complex partial seizure – focal seizure with impaired awareness o Temporal lobe seizures – unpleasant feeling in stomach ▪ Touching the nose is very common in temporal lobe epilepsy ▪ Semantic memory comes back (know their age, name etc) ▪ Episodic memory still dysfunctions (don’t know which day it is) ▪ Memory is dysfunctional when the hippocampus is involved in the seizure Seizure types Focal seizures with impaired awareness Temporal localisation Epileptic abnormalities in specific cortical structures o Focal or secondary generalized Clinical manifestations directly related to function, focus and spreading  Mostly temporal structures → sensation of fear, epigastric sensation, automatisms of mouth and lips, loss of consciousness increases slowly, postictal confusion Duration of a few minutes Perceptual phenomena – sound, visualizations, odors, smells Cognitive features (cortical): aphasia Affective phenomena (involvement amygdala): (un)pleasant feelings, depersonalization, derealization, déjà vu 75% postictal amnesia, 30% never remembers seizures Parietal localization Can’t read the time – intelligence question; you need parietal lobe for this Talking is intact Tonic-clonic seizure Tonic phase – whole body is tensed o You can’t prevent them from biting their tongue, because all their muscles are tense Clonic phase – “typical epileptic” jerks Non-epileptic seizures Usually caused by emotions Prevented herself from falling in the video – not possible for epileptic seizures Develop in adolescence in most women; sexual harassment in the youth is the most common cause No epileptic activity in the EEG during the seizure Swoon = very typical characteristic → falling down like a ballet dancer Non-epileptic seizures take much longer than epileptic seizures Treatment factors Treatment with AED o Type of AED o Mono vs. poly therapy o Subjective complaints o Serum levels o Do patients take AED, medication regime Aims: seizure freedom (resective) Neurosurgery – most chance to be effective Deep brain stimulation Vagal nerve stimulation Ketogenic diet Antiepileptic drugs First choice in focal seizures: lamotrigine, levetiracetam  Focal seizures - first choice in case of side effects: carbamazepine, lacosamide, oxcarbazepine, valproate - In case first choice is not effective or causes side effects: → second choice monotherapy → add on polytherapy - Only 30% of the patients receive the same regime after 3 years Focal seizures – second choice: brivaracetam, clobazam, gabapentin, perampanel, pregabaline, topiramate, zonisamide First choice – generalized seizures: levetiracetam, valproate Side-effects Significant side effects: First generation AED (before World war-II) - Phenobarbital - Phenitoin Some side effects: Second generation AED (from 1960) - Carbamazepin - Valproic acid Some / specific side effects + unknown: Third generation AED (new AED) - Lamotrigin - Topiramate - Levetiracetam - Vigabatrin - Stiripentol, remacemide, zonisamide,.... (resective) Neurosurgery, Deep Brain Stimulation, Vagal Nerve Stimulation, Ketogenic diet VNS: Epileptogenic zone Aims: determinate epileptogenic zone the cortical area that is essential for generating seizures and if removed will lead to complete control of seizures Wada test Determine language dominance Risk of language and memory problems post-surgery Lecture 7 – Rare genetic disorders Genetics 101 Quiz People have 46 chromosomes, 20.000 genes (2% of the genome; = coding DNA) A change in your DNA does not mean you have a genetic disorder – every human has them (genetic mutations/variations); they usually have no effect but they can even have a positive effect Genetic disorders are not always inherited Autosomal dominant inheritance – only one affected gene is needed for the disorder; autosomal recessive inheritance – two infected genes are needed for the disorder X-linked dominant inheritance – daughters of affected father are affected, when the mother is affected boys and girls can be affected; X-linked recessive inheritance – affected father → daughter that is a carrier, when the mother is a carrier, boys can be affected and daughthers cannot be. De novo variation = People with the same genetic mutation don’t have to be very similar, but they do probably have some of the same characteristics People with genetic disorders do not always have an intellectual disability Types of disorders Chromosomal disorders = partial or complete absence or duplication of a chromosome – Down/Turner syndrome Monogenic disorders = variation in a single gene – noonan syndrome Polygenic or multifactorial disorders = combination of different genetic variants at the same time and gene-environment interactions – cardiovascular disease Mitochondrial disorders = variation in DNA located outside the cell nucleus in the mitochondria Clinical neuropsychology and genetic disorders Clinical neuropsychology: why?  Clarity for client Clear plan to improve Clinical neuropsychology: how? Comprehensive neuropsychological assessment – to have a complete picture of strengths and weaknesses – provides options for personalized treatment (repeat) at key moment in development – problems can through different life phases Careful interpretations o Medical, psychological, and contextual factors o Level of intellectual functioning should be controlled Indications for treatment o Neuropsychological interventions, psychoeducation, pharmacological interventions Three genetic disorders Three ‘rare’ genetic disorders Common for rare disorders With and without intellectual disability Chromosomal and monogenic disorders Limitations of scientific studies in rare genetic disorders o Small samples o Not controlled for intelligence o Cross-sectional Individual variation Noonan syndrome 40 year old man with Noonan syndrome Facial features are more pronounced in childhood SENS: Social-Emotional training for adults with Noonan syndrome Online group training docused on social cognition and alexithymia 10 group & 9 individual sessions Psychoeducation, strategies, (homework) exercises, training partner Turner syndrome 26 year old with Turner syndrome Prader Willi syndrome 18 year old man with PWS Conclusions Imporance of KNP in rare genetic disorders Think of genetic aetiology when you meet a patient with a combination of cognitive, behavioral, somatic, and physical problems Mind the large degree of heteregenity Be aware of the complex interaction between somatic, neurocognitive, psychological and environmental factors over the course of development Provide personalized treatment based on neuropsychological assessment Too normal to be special, too special to be normal Lecture 8 – neuropsychological rehabilitation Non-progressive brain injury Traumatic brain injury Stroke Encephalitis Anoxia Epilepsy Progressive conditions – get worse over time Dementia Multiple Sclerosis Parkinson’s disease Huntington’s disease Brian tumours Spontaneous recovery After the occurrence of a brain injury, a period of recover follows, even if no treatment is offered Neuroplasticity This spontaneous recovery (injury induced change) usually happens in the first 12-14 weeks Diffuse and redundant connectivity Structural and functional networks formed through remapping (cortical reorganization) Recovery in: Motor skills Language (aphasia) Neglect = a failure to report, respons, or orient to stimuli in the contralesional (opposite to the lesion) space after brain injury that is not explained by primary sensory or motor deficits o Especially after right hemisphere stroke – left hemisphere cannot take over the role of the right hemisphere considering sight o Acute phase – 30% of stroke survivors o Chronic phase – 3% Experience-dependent recovery = under the influence of stimulation and treatment Neuronal repair without training or treatment – only to a limited extent Another way to achieve functioning new connections between neurons is by promoting plasticity through learning But, knowledge about recovery after BI has not yet led to forms of treatment that lead to recovery of cognitive functions Cognitive rehabilitation Interventions are applicable at all stages of post injury recovery Stage 1 – acute (+/- 0-1 month): hospital, lifesaving measures Stage 2 – sub-acute (up to 6 months): recovery phase, clinical rehabilitation, often emphasis on sensorimotor rehabilitation Stage 3 – chronic (after 6 months): outpatient rehabilitation, emphasis on cognitive, psychosocial and emotional problems = process whereby brain injured people work together with health professionals to remediate or alleviate cognitive deficits arising from neurological insult Framework of Fasotti Cognitive training Function training Restorative model Repeated practice approach Evidence? Brain training? Lumosity Researchers – make sure games maintain core mechanics of the original task designed to challenge a cognitive skill Game designers and developers – add game features and themes to make sure the games are accessible, engaging and challenging Skill training (re)training a skill/activity Repeated practice Task specific? Methods? Errorless learning = preventing errors during learning Feedforward instructions Cues Modeling Gradually reducing assistance Preventing errors and practicing step-by-step Trial-and-error = five-letter word that starts with QU, guess Errorless = five-letter word that starts with AP, and the word is apple Mechanisms of errorless learning Implicit memory  Residual explicit memory Executive memory (see next page) Skill training: long term YES – transfer NO Strategy training Compensatory model Learning an algorithm Set of general steps / questions that have to be carried out o Time pressure management – information processing o Goal management training – executive functioning o Problem solving therapy – executive functioning Strategy training: long term YES – transfer YES So, errorless learning can be applies in people with executive disorders for (re)learning everyday activities as well – not only in patients with memory impairments Cognitive rehabilitation Education and information Psychoeducation Environmental modification/control ‘making the environment predictable’ Low learning ability Everything on a fixed place ‘lay out’ clothes the night before – cue to get dressed Clear signs to toilets in a rehabilitation center Etc…. Training Skill training Function training Strategy training Neuropsychological rehabilitation = amelioration of cognitive, emotional, psychosocial and behavioral deficits caused by an insult to the brain Framework of Fasotti Psychosocial o Work o Study o Home environment o Social contacts Behavioral & emotional o Neuropsychotherapy = interventions for people suffering from emotional, behavioral or personality problems after BI ▪ CBT ▪ ACT ▪ EMDR Cognitive (rehabilitation)