Introduction to Neuropsychology Lecture Notes PDF

Introduction to Neuropsychology Ahmad Abu-Akel Semester II, 2024 Lecture outline n Housekeeping: Class administration n Historical perspective n Neuroanatomy of the cortex: An overview n What is neuropsychology? n Inferring normal processes from lesions q Neurological disorders as...

Introduction to Neuropsychology Ahmad Abu-Akel Semester II, 2024 Lecture outline n Housekeeping: Class administration n Historical perspective n Neuroanatomy of the cortex: An overview n What is neuropsychology? n Inferring normal processes from lesions q Neurological disorders associated with cognitive impairment q Associations and dissociations  (202.3216) Semester II, 2024 Introduction to Neuropsychology Thursday 09:15-11:45 Professor: Ahmad Abu-Akel (Email: [email protected]) Teaching assistants (TAs): Moran Knafo (Email: [email protected]) Hagai Barshad (Email: [email protected]) Tamar Radai (Email: [email protected]) Prerequisites: Introduction to cognitive psychology Office hours: By appointment Textbook: Banich, M.T. and Compton, R.J. 2018. Cognitive Neuroscience. 5th Edition, Cambridge: Cambridge University Press. An eBook is available from the library (System #: 9920006497602791) - Chapters 1 and 3 are required reading Course administration Weekly lectures: Attendance mandatory Bi-weekly practicum: Attendance mandatory The class will be divided into groups. Each group will typically attend the practicum once every two-weeks. Student list for each group and associated practicum material are posted on the course site. Each unjustified absence during the semester will result in a deduction of one point from the final mark. You are required to submit 4 reports of 4 articles. Reports must be 3submitted to your TA via Moodle, the day before the practicum no later than 20:00. See instructions and schedule Textbook: Banich, M.T. and Compton, R.J. 2018. Cognitive Neuroscience. 5th Edition, Cambridge: Cambridge University Press. An eBook is available from the library (System #: 9920006497602791) Introduction to Neuropsychology - Chapters 1 and 3 are required reading Course administration Weekly lectures: Attendance mandatory Bi-weekly practicum: Attendance mandatory The class will be divided into groups. Each group will typically attend the practicum once every two-weeks. Student list for each group and associated practicum material are posted on the course site. Each unjustified absence during the semester will result in a deduction of one point from the final mark. You are required to submit 4 reports of 4 articles. Reports must be submitted to your TA via Moodle, the day before the practicum no later than 20:00. See instructions and schedule below. For each of the reports you are required to read the 4 assigned articles indicated in the syllabus (see schedule below). For each of the articles, write a 1 to 2-page report, double- spaced that covers the following points: § What is the research question? § What are the main findings? § Strengths of the study § Limitations of the study § Future research Final Grade: Final grade consists of 4 reports (60%), 15% each, and a final in-class short multiple-choice exam (40%). 4 Bonus mark: On first-come, first-served bases, and in coordination with the TAs, students  § What are the main findings? § Strengths of the study Introduction to Neuropsychology § § Limitations of the study Future research Final Grade: Final grade consists of 4 reports (60%), 15% each, and a final in-class short multiple-choice exam (40%). Bonus mark: On first-come, first-served bases, and in coordination with the TAs, students can, as of the 3rd practicum, present an article. Presenters will receive 3 points bonus to the final grade. Number of presenters is limited, but up to 4 students can present during a practicum. The article must be empirical and relate to neuropsychology from the last 5 years. Presentation should not exceed 5 minutes. In case your TA does not approve the article, you will have the opportunity to propose another within a week from receipt of the TA’s answer. 5  ‫הפקולטה למדעי החברה ע"ש שמואל והרטה עמיר‬ The Herta and Paul Amir Faculty of Social Sciences Introduction to Neuropsychology Dates and lecture topics: Week Date Lecture topic Chapter 1 May 2 Introduction 1, 2 2 May 9 Research Methods 3 3 May 16 Brain development and plasticity 15 4 May 23 Hemispheric specialization and Sex Differences 2 5 May 30 Spoken and Written Language 8 6 Jun 6 Learning and Memory 9 7 Jun 13 Visual perception 5,6 8 Jun 20 Spatial cognition 7 June 27 Student Day 9 Jul 4 Attention and executive functions 10,11 10 Jul 11 Emotions and social cognition 12,13 11 Jul 18 Psychopathology: Neurodevelopmental and 4, 14, 16 neurodegenerative diseases + Exam 6 Questions A Historical perspective: Trepanation Our understanding of the brain has developed, as technology, culture and science has evolved 6500 BCE The Extraction of the Stone of Madness, by Hieronymus Bosch depicting trepanation (c. 1488–1516).  A Historical perspective: Our understanding of the brain has developed, as technology, culture and science has evolved Gage, Wernicke, Aristotle Vesalius Broca Sherrington & Adrian Lauterbur & Mansfield 335 16th 19th 1932 2003 BC Cent. Cent. AD Electricity Frontiers in Brain Research: Charting the fire the Neurons, Communication Connectomics; Brainbow; nervous nerves & units of the in the brain: BMI; Optogenetics; system phrenology brain Action Potential Modeling (Blue Brain Project) The brain as Charting the The brain Communication Imaging the a radiator nervous has regions in the brain: brain: system Synapses MRI & fMRI 1037 1790s 1900s 1963 21st AD AD AD AD Cent. Avicenna Galvani & Gall Cajal & Golgi Hodgkin Huxley Eccles  interventricular septum. The existence of these so-called pores was a puzzle for anatomists for over a thousand years, but they What does werethe brain do? a necessary A of feature Historical perspective the Galen scheme because it was not appreciated that a large amount of blood flowed from the Cardiocentrism vs. Cephalocentrism Ancient Egyptians Herophilus Pythagoras Magnus ca. 2655-2600 BCE 550 Historical Perspective 1878 IBN AL-NAFIS many Islamic and European universities up to the early 19th century. He was particularly interested in clinical pharmacol- ogy, experimental physiology, infectious diseases, and clinical trials, but also made contributions to physics. His most famous textbooks were The Canon of Medicine and The Book of Healing. Because of political problems, he was forced to move Figur Fig. 1. Approximate time line showing the period of the Islamic Golden Age frequently as an adult but spent most of his life in what is now modern Iran. Avicenna was perhaps the most eminent scholar from of the Islamic Golden Age (Fig. 1). Albert The brain as a IBN AL-NAFIS and the long influence of the teachings of the Galen School. His full name was Ala al-Din Abu al-Hassan Ali Ibn Abi- (I) com Hazm al-Qarshi al-Dimashqi, and so not surprisingly he is imagin commonly referred to as Ibn al-Nafis (13–15). He was born in phanta radiator Damascus (or very nearby) in 1213 and had his medical evaluat education there at the Medical College Hospital (Bimaristan al- reminis Noori). At the age of 23, he moved to Cairo where he first worked at the Al-Nassri Hospital and subsequently at the Al-Mansouri Hospital, where he became physician-in-chief. When he was only 29, he published his most important work, the Commentary on Anatomy in J Appl Physiol VOL Avicenna’s Canon, which included his ground-breaking views on the pulmonary circulation and heart that are referred to below (1–6, 8). He also worked on an enormous textbook, The Comprehensive Book of Medicine. This was never completed but was the largest medical 105 DE encyclopedia to be attempted at the time and is still consulted by scholars. Ibn al-Nafis was an orthodox Sunni Muslim and, as men- The ventricular doctrine, mainly b Downloaded from journals.physiology.org/journal/jappl at Bib tioned above, wrote extensively in areas outside of medicine, This "Cell Doctrine" localized the mind to including law, theology, philosophy, sociology, and astron- omy. He also authored one of the first Arabic novels translated of Albertus, maintained its influence d as Theologus Autodidactus. This is a science-fiction story ing Middle Ages, until the Renaissanc about a child brought up on an isolated desert island who eventually comes in contact with the outside world. An alternative understanding to PULMONARY CIRCULATION At the time of Ibn al-Nafis, the teachings of Galen and his the ventricular system of the brain known on the theme was proposed b (1596-1650), a French philosopher, ph school had held sway for a thousand years. Avicenna studied Galen’s writings extensively and embellished them to some Fig. 2. Scheme of the circulation of the blood according to the school of ematician. He regarded the ventricles extent. In Galen’s scheme (Fig. 2), food in the gut underwent Galen. From Ref. 19, with permission. and the width [solid part] of the cereb “concoction” and was transported to the liver where the blood was formed and imbued with “natural spirit.” The blood then lum fashioned by an internal net with lungs to the heart. In the left ventricle, the blood was mixed flowed to the right ventricle where some entered the lungs via with “pneuma” from the air that was inhaled, and the result was tubes, and an external part composed the pulmonary artery to nourish them, but the remainder of the the formation of “vital spirit,” which was distributed through- blood reached the left ventricle through “invisible pores” in the filaments, with intervals (pores) betw Adapted from: J Appl Physiol 105: 1877–1880, 2008. out the body by the arterial blood. Some reached the brain interventricular septum. The existence of these so-called pores was a puzzle for anatomists for over a thousand years, but they where it received “animal spirit,” which was then distributed ter could allow the passage of the anim via the nerves, which were thought to be hollow. The formation were a necessary feature of the Galen scheme because it was of “vital spirit” in the left ventricle led to the generation of in the ventricles and derived from not appreciated that a large amount of blood flowed from the fuliginous (sooty) waste products that traveled back to the lung through the pulmonary vein and then were exhaled with the the flow being regulated by movem breath. (Figure 2). The filaments could chang In his Commentary on Anatomy in Avicenna’s Canon, Ibn al-Nafis made three important advances with respect to Galen’s the pores could be variably enlarged or scheme. ing to the force of the inflowing [anima First, he stated categorically that the interventricular septum between the right and left ventricles was not porous, and could nism that constituted the functional b  Historical perspective: Dualism vs. Monism n Descartes (17th century) q Dualism: mind and body are separate things n The “soul” is nonmaterial q Soul modulated the reflexive loop through pineal gland q Cortex is a protecting shield Historical perspective Dualism vs. Monism Monism: mind & body are the same § All is matter § Mind is the sum of all brain functions What difficulties does this materialistic approach face? § Reductionism § Free will § Legal responsibility Neuroscience News Update Mind-Body-Brain Article Cardiogenic control of affective behavioural state https://doi.org/10.1038/s41586-023-05748-8 Brian Hsueh1,6, Ritchie Chen1,6, YoungJu Jo1, Daniel Tang1, Misha Raffiee1, Yoon Seok Kim1, Masatoshi Inoue1, Sawyer Randles1, Charu Ramakrishnan1, Sneha Patel1, Doo Kyung Kim1, Received: 31 December 2021 Tony X. Liu1, Soo Hyun Kim1, Longzhi Tan1, Leili Mortazavi1, Arjay Cordero1, Jenny Shi1, Accepted: 20 January 2023 Mingming Zhao2, Theodore T. Ho1, Ailey Crow1, Ai-Chi Wang Yoo1, Cephra Raja1, Kathryn Evans1, Daniel Bernstein2, Michael Zeineh3, Maged Goubran3 & Karl Deisseroth1,4,5 ✉ Published online: 1 March 2023 Open access Emotional states influence bodily physiology, as exemplified in the top-down process Check for updates by which anxiety causes faster beating of the heart1–3. However, whether an increased heart rate might itself induce anxiety or fear responses is unclear3–8. Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain9. Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour. Nature 615: 292–299 (2023) Interoceptive processing of visceral physiological signals, such as has—although widely debated—remained largely experimentally intrac- cardiac palpitations or stomach fullness, is crucial for maintaining table11. Available nonspecific interventions that might disrupt cardiac homeostasis1–3. Diverse psychiatric conditions, such as anxiety dis- signals (such as electrical vagus nerve stimulation) are well known to orders, panic disorder, body dysmorphic disorders and addiction, also induce numerous physiological changes that would be unwanted Localization vs. Holism: Flourens n Localization: a “center” responsible for a function. n Holism: functions are not localized to a specific brain areas (Pierre Flourens 1794-1867): n Loss of function is correlated with size of damage, regardless of location (animal experiments). n Functions recover by taking over undamaged cortex. n The famous myth: “Most people never use more than 10% of their brain” (Flourens). Localization vs. Holism: Phrenology n Gall (1758-1828) n Spurzheim (1776-1832) Phrenology A practitioner of phrenology measuring the bumps on a boy's head to assess his future, painting by Frank Dadd, 1886. Phrenology n Problems: q Outer skull doesn’t mirror inner skull or brain structure q Traits are subjectively defined q No support from brain lesions q Not Experimental Phrenology Revolutionary ideas for the time: § The cortex is the functioning part of the brain; not just a covering for the pineal gland/ ventricles. § The brain produces behavior through control of other parts (e.g. the corticospinal tract) Spurzheim, G. The Anatomy of the Brain, 1826 § Localization of brain function Localization vs. Holism: Broca n Paul Broca (1824-1880) – “Localizationist” q First to describe patients with inability to speak n “Tan” and 8 more. n In autopsy, all showed a lesion in the Left frontal lobe. q Marked a historical change in the analysis of brain function à experimental Localization & Holism: Connectionism n Broca’s strict localization: q Language is controlled by a specific brain area n However, Wernicke found: q similar deficits with different damaged areas q deficits result from lesion to connecting fibers between brain regions (Disconnection syndromes) n The critical role of the connecting pathways. q Functions are distributed in networks q Not localized nor equipotential Localization & Holism: 20th century pendulum n Karl Lashley 1950’s: mass action, equipotentiality n Sperry 1960’s: hemispheric specialization n 1980’s: Connectionist computational models q Networks n 1990’s: imaging à specialization n 2000’s: Specialization, overlap & integration q Brain regions are involved in various functions Cognitive Psychology n Originated in 1960s (Miller, Neisser) in a break away from behaviorism (Watson, Skinner) n Took the study of mind away from biology q Theories were developed and tested without relevance to the brain q Topics, such as consciousness, attention, personality, were THEN irrelevant for biology Cognitive Psychology n A shift from serial models n To parallel connectionist models (Mclleland and Rumelhart, 1970s-1980s); q Interactivity Parallel Distributed Processing Models q Top-down processes q Distributed Neural networks q Neural plausibility (i.e., analog to how the neurons might be wired)? Questions? Anatomy of the cortex Anatomy of the cortex Brain § What is the brain’s main function? Anatomy of the cortex Brain § 2% of body weight § 86 billion neurons § Cortex (1233g) = 16x109 § Cerebellum (154g) = 69x109 § 1015 neuronal connections § 25% O2 § 20% Calories § Extremely energy efficient Anatomy of the cortex Brain § 2% body weight: § The average brain weight of the adult male was 1336 g § For the adult female 1198 g § With increasing age, brain weight decreases by § 2.7 g in males per year, § 2.2 g in females per year § Per centimeter body height, brain weight increases independent of sex by an average of about 3.7 g. Anatomy of the cortex Azevedo et al. 2009 Anatomy of the cortex v. horn d. horn Anatomy of the cortex Anatomy of the cortex Enteric division (gastrointestinal system) Anatomy of the cortex Anatomy of the cortex (motor) (sensory) Brain stem 34 Anatomy of the cortex Rolandic Fissure 35 Anatomy of the cortex Cerebellum Brain Stem Cranial nerves 36 Anatomy of the cortex 37 Anatomy of the cortex 38 Anatomy of the cortex um pellucid Septum  Anatomy of the cortex Choroid Plexus pellucid um Septum Pineal Pineal Gland Gland Brain stem Reticulospinal tracts ascending reticular activating system (ARAS) 40  Anatomy of the cortex Ventricles: production, transport and removal of cerebrospinal fluid (CSF = 125–150 mL x ~4/day) v protection v Buoyancy: net weight of the brain is reduced to ~25g v Chemical stability: low extracellular K+ for synaptic transmission 41 Anatomy of the cortex 42 Anatomy of the cortex: basal ganglia structures  Anatomy of the cortex: basal ganglia structures Dorsal Striatum Ventral Striatum  Anatomy of the cortex: basal ganglia structures Medium Spiny Neurons = MSNs Anatomy of the cortex: basal ganglia structures Dorsal Anatomy of the cortex: basal ganglia and other structures Tectum  Brodmann Brain evolution Cytoarchitectonic map n based on cell structure 10 3b 17 from 100 µm thick Nissl-stained sections showing some cytoarchitectonic , and 17, respectively) and severalfrom Photomicrographs mammals. 100 μmScale bar: 250 thick µm. Adapted Nissl-stained sections showing some cytoarchitectonic differences between frontal, parietal, and occipital cortical areas of the human (areas 10, 3b, and 17, cal respectively) feature and they [DeFelipe, 2011]in non-cortical structures can be found kland, 2010). In turn, the neocortex of all species contains a f elements similar to that of any other part of the brain (i.e., Anatomy of the cortex Frontiers in Brain Research What is neuropsychology? n Neuropsychology studies the relations between behavior, cognition, emotion and underlying brain mechanisms and functioning n It uses diverse basic and applied methodological approaches including animal and lesion studies, neuroimaging and stimulation n It seeks to develop reliable diagnostic tools and effective treatments of individuals with brain injuries, neurological and psychiatric disorders Studies in patients with brain lesions Acquired brain pathologies causing cognitive impairment Vary in onset (gradual vs. sudden) and locality n Vascular disorders, e.g., CerebroVascular Accident (CVA) n Traumatic brain injury (TBI) n Tumors n Infectious, metabolic disorders n Degenerative diseases (Dementia) n Epilepsy n Hypoxia (cf. anoxia) 54 Vascular disorders n Damage to blood-vessel reduces oxygen flow to brain cells and can result in cell death. n Stroke / Cerebrovascular Accident - ‫שבץ‬ q Sudden appearance of neurological symptoms resulting from interruption of blood flow. n Infarct (necrosis) q An area of dead tissue resulting from stroke. Cerebral arterial circle n Symptoms depend on location & (Circle of Willis) available compensation from other blood vessels. 55 Vascular disorders Correlation Between the Integrity of the Circle of Willis and the Severity of Initial Noncardiac Cerebral Infarction and Clinical Prognosis (Zhou et al. 2016, Medicine) Cerebral arterial circle (Circle of Willis) 56 Vascular disorders n Ischemia – stroke caused by vessel blockage q Thrombosis (‫ )קריש דם‬- a clot that remains in place (e.g., blood coagulation) q Emboly (‫ –)תסחיף‬a clot brought through the blood from another vessel q Arteriosclerosis (‫ –)הסתיידות עורקים‬thickening and hardening of arteries n Hemorrhage – stroke caused by massive bleeding into the brain q Caused mainly by high blood pressure q Abrupt onset q May be fatal 57 Vascular disorders 58 Vascular disorders n Aneurysm: vascular dilation (balloon like) due to local defect in elasticity of vessel. q Weak and may rupture q Congenital or acquired from hypertension q Severe headache may result from pressure on dura 59 Neuroscience News Update The subarachnoid lympha5c- like membrane (SLYM). Møllgård et al., Science 379, 84–88 (2023) 60 Vascular disorders n Cerebral Angioma (also known as Cavernous Angioma): Vascular malformation consisting of dilated, thin-walled capillaries q They are of irregular structure q Because they are weak may leak, lead to stroke q Can be congenital 61 Questions?  19 trauma centres, of which 2494 patients were diagnosed with TBI. Among those suffering from TBI 1655 (66.4%) Statistical analysis were males and 839 (33.6%) were females. Children (aged 0– Traumatic Brain Injuries (TBI) The incidence of hospitalized injured patients diagnosed with 17) comprised 22.9% of TBI patients, adults (aged 18–64) TBI per 100 000 person years was calculated on the basis of 35.5% and seniors (aged 65+) 41.7%. The overall incidence the following information: (a) The number of hospitalized rate of TBI in 2011 was estimated at 31.8/100 000 residents. injured patients with TBI reported in Israel was used as the The annual incidence of TBI by age and gender is presented numerator and (b) Demographic data detailing the Israeli in Figure 1. The annual incidence was 42.7/100 000 for male population in each year (based on the Israel Central Bureau of residents and 21.2/100 000 for female residents. The age- Statistics data) was used as the denominator. specific incidence rate was highest for seniors (!65 years) in TBI demographic and injury characteristics are expressed addition to a dramatic increase during the last decade (from as percentages and were examined for the three age groups 68.2/100 000 in 2002 to 115.8/100 000 residents in 2011) Most common form of brain damage under age 40 using the Chi-Squared-test. Continuous variables were (Figure 2). TBI incidence among Jews was 31.7/100 000 q compared by ANOVA test or Median test. Multivariable logistic regressions were performed among TBI patients to residents per year compared to 37.1/100 000 among Arabs residents. calculate the odds ratio of in hospital mortality adjusted for Children and elderly – falls age, gender, ethnicity, ISS (as categorical) and mechanism of TBI patterns q injury. Analyses were performed using SAS software, version Table I presents a comparison of the demographic and injury 9.2 (SAS Institute, Cary, NC). A value of p50.05 was characteristics for TBI patients in three different age groups considered to be statistically significant. Males between 15-30 – car & motorcycle accidents for the year 2011 (n ¼ 2494). Among children and adults the Study population q majority of TBI patients were males, whereas among the elderly there were no gender differences in the frequency of In 2011, the population in Israel was 7 836 600. The median TBI. Similar to the distribution in the general population, age of the population was 28.3, while 10% of the population is Arabs hospitalized with TBI were younger in comparison to over 65 years of age. Children and adolescents (0–17 year old) Jews, 58.1% of Arabs were under the age of 25 compared to Incidence of TBI in Israel (2011) comprise "30% of the population, which is relatively high in 22.4% of Jewish TBI patients. comparison to other Western countries. The Israeli External causes of injury varied with age (Table I, Figure 3). population has two main ethnic populations; the majority Falls were the leading cause of severe TBI, 86 especially among M. Siman-Tov et al. Brain Inj, 2016; 30(1): 83–89 Figure 1. Incidence of hospitalized patients with traumatic brain injury, by age group and gender, 2011. Figure 2. Annual incidence of hospitalized patients with traumatic brain injury, by age group during the years 2002–2011. Siman-Tov et al. 2016, BrainTableInjury, 30:1, 83-89 lia] at 06:22 30 January 2016 I. Demographic and injury characteristics of hospitalized patients with traumatic brain injury: A comparison of three age groups, 2011. Totala Children 0–17 Adults 18–64 Seniors 65+ (n ¼ 2494) (n ¼ 570) (n ¼ 884) (n ¼ 1040) n (%) n (%) n (%) n (%) p Valueb Gender Male 1655 (66) 399 (70) 720 (82) 536 (52) 50.001 Female 839 (34) 171 (30) 164 (18) 504 (48) 63 Ethnicity Jews 1873 (75) 306 (54) 607 (69) 960 (92) 50.001 Traumatic Brain Injuries (TBI) n Open (bone fracture; gunshot) n Closed 64 TraumaJc Brain Injuries (TBI) n Can be classified into 5 major types: q Concussions n Second impact syndrome (SIS) q Contusions (bruising) q Penetrating q Anoxic or Hypoxic (severe oxygen deprivation) q Diffuse axonal injury 65 Traumatic Brain Injuries (TBI) n A TBI’s severity can be: q Mild n No loss of consciousness (or only for few seconds – minutes) n Confusion, disorientation n Headache, Nausea q Moderate n Loss of consciousness (up to hours) n Confusion lasting up to weeks n Long term (months) and even permanent physical, cognitive and behavioral complications q Severe n Life-threatening, fatal 66 Traumatic Brain Injuries (TBI) n Terms you might come across q Hematoma: blood (clotted) caught within the skull q Edema: brain swelling due accumulation of fluids q Acceleration and deceleration: coup contrecoup injury 67 Questions? Brain Tumors n Even benign tumor can have serious consequences due to inaccessibility to surgery n Encapsulated tumors can cause pressure on brain n Infiltrahng tumors can destroy normal cells or interfere with their funchon. 69 Meningiomas § Attached to meninges (= dura mater, arachnoid, SLYM, pia mater) outside the brain § Encapsulated § Mostly benign 70 Gliomas § Originate from glia (support cells) including microglial (red), astrocytes (green), oligodendrocytes (blue) and ependymal (pink) cells. § Range from benign (low grade 1 and 2) to malignant (Grade 4: Glioblastoma) § Constitute 33% of all brain tumors and can occur in various locations of the nervous system including the brain stem and spinal column § Symptoms include headache, seizures, irritability, vomiting, visual difficulties, weakness or numbness of the extremities 71 Degenerative diseases: Dementia n 1-6% of people over 65 years of age n Acquired & persistent intellectual impairment q Memory and other cognitive deficits q Social and occupational impairments n Gradual degeneration Examples Examples Alzheimer Multi infarct Parkinson AIDS Huntington Multiple Sclerosis Creutzfeld-Jakob B12 deficiency Picks Korsakoff syndrome 72 Brain atrophy in Alzheimer’s Disease Brain injuries/ pathologies Focal Diffuse Stroke (CVA): sudden Open or closed TBI onset Acceleration - Penetrating wound: deceleration: coup and sudden onset countercoup trauma Tumor, abscesses: gradual Hypoxia / ischemic stroke onset Infectious / metabolic Degenerative diseases: disorders Local then generalized; Compressing tumors gradual onset Degenerative Diseases – Neurosurgery late stages Questions? Association vs. dissociation for establishing brain- behaviour relations § Associahons n What funchons are disrupted by damage to region X? § Dissociahons n Can a parhcular funchon be impaired independent of another funchon? Associations: based on single case studies The brain is the Loss of speech Living day-by-day seat of our soul Phineas Gage Louis Victor Leborgne Henry Gustave Molaison 1848 “Tan” 1861 Patient H.M. 1953 Ces trois accidents qui ont révolutionné les neurosciences Limitations of association studies n Anatomical proximity ≠ common mechanism q Hemiparesis (= hemiplegia) and aphasia q Gerstmann’s syndrome: left angular/ supramarginal gyrus v Arithmetic deficit (acalculia) v Deficit in right-left awareness v Agraphia / dysgraphia v Finger agnosia n Functions are not localized Associations: Associations based on group studies q A group of patients q ~ homogeneous functional impairment q ~ homogeneous brain lesion (in autopsy) q Identify a “syndrome” Limitations of group studies Face Object Place Task recognition recognition recognition Patient 70 75 70 1 80 70 25 2 75 80 30 3 75 25 75 4 70 30 80 5 80 20 70 6 25 80 75 7 30 75 70 8 20 70 80 9 58.3 58.3 58.3 Average: Patients 83 80 78 Average: Controls The pattern of the group may not reflect individual patients or subgroups Dissociations: Single Dissociation Patient with lesion in a specific brain region performs poorly on task A, and well on task B (e.g., vowels and consonants) q CF is a paQent with selecQve dysgraphia for vowels (Cubelli, Nature 1991) q PaQent G.D. with selecQvely more spelling errors with consonants (Kay &Hanley 1994). Record Recorg Double Dissociation n Patient with lesion in brain region A: q Performs poorly on Task A and well on Task B n Patient with lesion in brain region B: q Performs poorly on Task B but well on Task A Double Dissociations n What can we Infer? q Tasks A and B are represented by separate mechanisms in the brain. q Brain region A mediates Task A and not B Brain Region B mediates Task B and not A n Another example: q Prosopagnosia and visual agnosia (face and non-face object recognition) Single vs. group studies: Advantages n Single case studies q Identify dissociations that implicate building blocks of normal cognition v Even if they do not necessarily generalize to other patients. q Given individual variability among patients, it is more accurate than averaging over a group of patients. n Group studies q Identifying syndromes q Prognosis and intervention in diseases q Inferring that region X is critical for function F q Enable replication & generalizations to other patients. Limitations in inferring normal processes from brain lesioned patients n Non-specific changes to behavior q Cerebral Edema: Swelling of the brain q Diaschisis: Dysfunction at sites remote from, but connected to, the site of injury or insult q Scarcity of control groups with lesions n Damage to nearby pathway/cortical area [Natural lesions (strokes, tumors, trauma) don’t respect functional anatomical boundaries] q Causes the symptoms n Symptoms caused by damage to a related function q e.g., attention for memory n Compensation and partial recovery q Reorganization may alter normal correspondence.  s ? ion s t u e Q Thank you for you attention & See you next Lecture!