Psychology 393 Cognitive Neurology. Introductions. Logistics. Spring, Lecture # 1

Transcription

1 Psychology 393 Cognitive Neurology Spring, 2006 Lecture # 1 Introductions Instructor: Gary Turner PhD Candidate, University of Toronto (Graduation this Spring hopefully!) Research Interests Frontal Lobe Functions and executive control of behaviour Neural correlates of higher cognitive processes following brain trauma (working memory capacity and goal directed behaviour) Neurorehabilitation ( Applied cognitive neuroscience ) How about you? Neuroexperience? Current projects / future plans to study in this area? 2 Logistics 9 a.m. is pretty early for a 3 hour lecture a few strategies to help get us through the term I ll start most classes with a case to get you thinking and engaged The case-based approach is meant to be interactive so discussion is very much encouraged We ll break for caffeine etc. at around 10:15 and wrap around 11:50ish whenever possible to allow for after class discussion and questions. 3 1

2 Quick Course Facts Text: Banich (2004) at the bookstore ($120ish) Website: How to reach me: Office hours after every class or by appointment is faster and more reliable than phone messages. Questions to me: lectures or course content; Vedran: exams/grading and specific term paper?s 4 Important course info Grading scheme: Midterm, February 13 th (40%): Based on lectures, videos, readings (sample on website) Term-paper, Due March 20 th at beginning of class (20%). More on this next week. Final exam, TBA (40%) Lectures:.pdfs posted on the website 24 hours before class. Readings: responsible for all readings in the syllabus: Banich: all materials whether or not discussed in class Other readings: I will emphasize key aspects in class. NO MAKE UPS 5 Course Overview Lecture Format: Case-based approach. Cases will be presented at the beginning of class and you will identify presenting signs and reported symptoms Most lectures will emphasize a particular domain of cognitive deficit. I will lecture on the key aspects of the topic, relate it back to the case(s) and present patient data and/or videos to give you a sense of how these cognitive dysfunctions manifest in brain damaged humans. 6 2

3 Course Overview: Objectives At the end of the course you should: Be able to review a neurological case relating to cognitive dysfunction and identify relevant presenting signs and symptoms; Understand the nature of the cognitive domain(s), and the particular aspects of that domain, that appear to be principally impacted; Be able to relate these signs and symptoms to a brain region or network of regions; Know how to conduct a comprehensive differential diagnosis analyses and present your diagnoses with respect to the likely etiology and neuropathology involved in the case. 7 Course Overview: Topics January 09: History, Approaches and Methods.pdf January 16: Brain Structure and Function Term paper Tutorial January 23: Agnosias (Disorders of Perception) January 30: Apraxias (Disorders of Motor Control) February 06: Amnesia (Memory Disorders) February 13: Mid-Term Test (40%) February 20: Reading Week February 27: Aphasias (Language Disorders) March 06: Neglect (Attention Disorders) March 13: Executive Dysfunction (Frontal Lobe Disorders I) March 20: Executive Dysfunction (Frontal Lobe Disorders II) [TERM PAPERS DUE AT BEGINNING OF CLASSS] March 27: Neuropsychiatric Syndromes (Affective Disorders) April 02: Neuropathology & Neuroplasticity April 09: Syndrome "Quiz" (Uncommon Neurological Syndromes) Course Review 8 History and Methods: Outline Brain-behaviour relationship Historical perspective (four major eras) The great debates Relationship to other disciplines in the cognitive neurosciences (neuropsychology, cognitive neuroscience) Pieces of the puzzle Animal models Human neuropsychology (lesion and deficit approach) Brain imaging methods Putting the pieces together (cognitive neurology) Signs, Symptoms and Syndromes Case # 1 (M.C.) Differential diagnoses and etiology 9 3

4 Historical Perspective Linking Brain and Behaviour: Four eras of investigation and progress Egyptians Cardiocentrism Ancient Greece Cerebrocentrism The Renaissance Mind/body issue - pineal gland and animal spirits 19 th century Localism/holism debate 10 The Egyptians Cardiocentrism heart and diaphragm considered the seat of mental life. Brain considered to be marrow of the skull. Early head trauma triage. a man having a wound penetrating his temple bone..if thou put thy fingers on the mouth of that wound and he shutters exceedingly and he speak not to thee while copious tears fall from both eyes this is an ailment not to be treated. 11 Ancient Greece Earliest considerations of the brain as the organ responsible for mental life. Hippocrates (4 th century B.C.) brain is responsible for intellect, senses, knowledge, emotions, mental illness. Aristotle return to cardiocentrism ( brain designed to cool heat and seething of the heart ) Galen (1 st -2 nd century A.D.) Brain as the seat of the psyche Ventricles and vital spirits central to action and senses Ascribed role for brain tissue in highest cognition. 12 4

5 Perception Reason Memory The ventricular system: Albertus Magnus, The ventricular system (21 st century) Jacob L. Driesen 14 The Renaissance 4 th -5 th centuries, brain substance took back seat to ventricular cavities. Descartes (17 th century) man unique in possessing a rational mind that can over-ride reflexes. So how do the immaterial mind and the material body interact? (the mind-body problem) Central operational control center was necessary pineal gland. Soul modulated the reflexive loop through pineal gland. 15 5

6 Early 1800s - localism emerges Ventricles fall out of favor. Cerebrum considered seat of volition, memory, cognition, imagination as a single, indivisible mass. Gall ( ) Distinguished early career: gray/white matter distinction; Aphasia linked to frontal lobes then Cranioscopy: study of faculties through skull structure (phrenology) beginnings of localism (with Spurzheim) Mid 1800s - The Great Debates Jean-Baptiste Bouillaud Localized speech ability to anterior cerebrum Library of 700 clinical cases Speech = anterior center, overlooked hemispheric asymmetry. Société d Anthropologie (1861) Pierre Gratiolet: holism (equipotentiality) Ernest Auburtin: localism Paul Broca: presentation of patient Tan (1861); cerebral dominance (1865) (Marc Dax publish or perish) 18 6

7 Late 1800s: Connectionism Small number of critical centers underlying higher cognitive functions. Carl Wernicke ( ) Sensory aphasia Associationism Hitzig, Fritsch and Ferrier Functional mapping of sensory and motor cortex Other connectionist models emerged for apraxia, alexia without agraphia etc. 19 Turn of the century John Hughlings Jackson ( ) to locate the damage which destroys speech and to locate speech are two different things (1874). Hierarchical organization/interactionism the aphasic will be lame in his thinking since speech is a part of thought. Influence of Gestalt psychology Mid 20 th century localism triumphs Luria, Geschwind 20 Historical Review Linking brain and behaviour Four eras: Egyptians: cardiocentrism Ancient Greece: cerebrocentrism Renaissance: Animal spirits, ventricles, pineal gland. 19 th / 20 th century: final ascendancy of cerebrocentrism (1990s = decade of the brain) Three debates: Heart versus the brain as seat of the soul Ventricles versus the cerebrum as center of cognition Localization of function versus equipotentiality 21 7

8 Emergence of a new discipline Early Neurology/Neuropsychology: Study of individual cases or small groups of similar cases. Naturalistic observation, no planned experimental protocol or quantification. Experimental Neuropsychology (1960s/70s) Merging of neuropsychology with methods from experimental psychology treatments = naturally occurring brain lesions Focus on localization and functional organization. 22 Cognitive Neuroscience Integration of research from neuroscience, experimental neuropsychology and cognitive psychology (1980s) Non-human animal models will only take you so far in understanding human cognition Cognitive psychology couldn t overcome the problem of the black-box (identifiability) Experimental neuropsychology concerned with cognitive abilities (speech, memory etc.) and not the component cognitive processes which are more likely represented in neural circuitry. Investigations of all mental functions that are linked to neural processes. Includes both animal and human experimentation. 23 Cognitive Neurology: solving the puzzle of cognitive dysfunction Key Sources of Information: Healthy human subjects Atypical neural organization (without cognitive dysfunction any lefties in the room?) Control subjects in neuropsychology research (setting the normal baseline) Brain imaging controls Non-human animal research Single-cell recordings Lesion methods Experimental neuropsychology Finding brain-behaviour associations and dissociations in braindamaged humans Brain imaging Structural Functional 24 8

9 Non-human animal investigations Two general approaches: Single cell recordings Fuster & Alexander (1972) recorded continuous firing of neurons in the prefrontal cortex during delay interval of short term memory task. Lesions Goldman-Rakic (1987) lesioned same region of prefrontal cortex and observed delayed response deficits in monkeys. Stimulus Delay Probe 25 Non-human animal investigations Advantages: Organization of cerebrum in non-human primates very similar to humans. Can be trained to do complex tasks Control for environmental and lesion characteristics Disadvantages: Cerebral organization is not exactly homologous. Impact of verbal mediation on cross-species comparisons. Ethics? 26 Neuropsychological Investigations (humans with brain damage) Early experimental neuropsychology (e.g. Broca, Wernicke, Luria) Inferences largely based on associations: Identify a group of patients with fairly homogeneous functional impairment homogeneous brain damage Identify a syndrome (fluent / non-fluent aphasias, dysexecutive syndrome) 27 9

10 Neuropsychology (lesion and deficit approach) Modern neuropsychology = Study single cases or groups with homogeneous brain damage (e.g. Milner & hippocampal resections) Focus on dissociations 28 Lesion and Deficit Approach (Dissociations) Single dissociation Patient with lesion in brain region A Performs well on task A Performs poorly on task B Inference: brain region A mediates performance on task B but not task A e.g. Patients with frontal lobe damage have no problem with recall of verbally presented digits but perform much poorer when those digits have to be recalled while doing another task. Frontal lobes involved in multitasking? 29 Lesion and Deficit Approach (Dissociations) Problems with single dissociation Does not rule out other interpretations Patient may suffer some global deficit (e.g., general cognitive resource) that Task A does not require (e.g., because it is easier) Thus, performance differences between Tasks A and B may reflect task difficulty, not the function of Brain Region A 30 10

11 Lesion and Deficit Approach (Dissociations) Double dissociation Patient with lesion in brain region A performs well on Task A and poorly on Task B Patient with lesion in brain region B performs well on Task B but poorly on Task A Inference: Brain region A mediates Task B; Brain Region B mediates Task A Since subjects are equated for damage, global deficit argument circumvented Cognitive processes underlying two tasks may be assumed to be modular (i.e. independent), mediated by separate neural processes or resources 31 Lesion and Deficit Approach (Qualifiers) Lesions need to be Stable Demarcated Referable to a neuroanatomical unit Ascribing structure-function relationships may be compromised by: Degeneracy: different structures = same function Diaschisis: deficit may be result of disconnection in a neural network not directly related to lesion site. 32 Brain Imaging Structural CT MRI Functional fmri PET ERP TMS 33 11

12 Structural Brain Imaging CT MRI 34 Structural Brain Imaging Localization of lesions 35 Structural Brain Imaging Computerized Axial Tomography: X-ray technology Information on tissue densities (CSF, brain tissue, bone) Advantages Inexpensive Disadvantages Poor spatial resolution Ionizing radiation 36 12

13 Structural Brain Imaging Magnetic Resonance Imaging: Static magnetic field: lines up hydrogen atoms Pulse sequence: disrupts hydrogen atoms Relaxation time: time it takes to return to original position; differs according to tissue type Advantages Good spatial resolution Disadvantages Can t be used with people who have metal in their bodies or pacemakers 37 Functional Brain Imaging Functional MRI (fmri) Positron Emission Tomography (PET) Event-Related Potentials (ERP) Transcranial Magnetic Stimulation (TMS) 38 Functional Brain Imaging: fmri Functional MRI: As neuronal activity blood flow blood oxygenation fmri relies on the BOLD effect Blood Oxygen Level Dependent Oxygenated blood magnetic De-oxygenated blood paramagnetic neural activity blood flow oxyhemoglobin MR signal 39 13

14 Functional Brain Imaging: fmri neural activity blood flow oxyhemoglobin MR signal Compare MR signal in different conditions 40 Functional Brain Imaging: fmri Functional images 2. Subtraction Condition 1 Condition 2 Difference Condition 1 3. Superimpose on structural MRI Time Condition

15 Functional images fmri Signal (% change) ROI Time Course Time Condition 1 Time Condition 2 Condition Region of interest (ROI) 43 Functional Brain Imaging: fmri Advantages: Good spatial resolution Disadvantages: Indirect measure of brain activity (i.e., doesn t measure active neurons but increased blood flow) Regions of signal dropout : junctions between air and tissue sinuses ear canals 44 Functional Brain Imaging Functional MRI (fmri) Positron Emission Tomography (PET) Event-Related Potentials (ERP) Transcranial Magnetic Stimulation (TMS) 45 15

16 Functional Brain Imaging: PET Positron Emission Tomography: As neuronal activity Supply of glucose and oxygen to region PET uses radioactive forms of glucose and oxygen to trace regional cerebral blood flow (rcbf) How it works: Inject / inhale tracer Tracer reverts to its stable form by emitting a proton This collides with electron annihilation Two gamma photons are emitted in opposite directions detected by scanner 46 Functional Brain Imaging: PET Advantages: Good spatial resolution Metabolic studies Receptor mapping (e.g. dopamine receptors) Disadvantages: Invasive (injecting radioactive substances) Poor temporal resolution Indirect measure 47 Functional Brain Imaging Functional MRI (fmri) Positron Emission Tomography (PET) Event-Related Potentials (ERP) Transcranial Magnetic Stimulation (TMS) 48 16

17 Functional Brain Imaging: ERP Event-Related Potentials: Neurons generate electromagnetic fields when active If a large number of neurons are simultaneously active they can generate fields detectable on the scalp EEG: Recording the brain s ongoing activity ERP: Recording the brain s electrical activity in relation to an event (e.g., onset of a stimulus) 49 Functional Brain Imaging: ERP 50 Functional Brain Imaging: ERP Advantages: Good temporal resolution: millisecond by millisecond Non-invasive Comparatively inexpensive Disadvantages: Limited spatial resolution Difficulty in imaging cells parallel to surface 51 17

18 Functional Brain Imaging Functional MRI (fmri) Positron Emission Tomography (PET) Event-Related Potentials (ERP) Transcranial Magnetic Stimulation (TMS) 52 Functional Brain Imaging: TMS Transcranial Magnetic Stimulation: Doesn t image neural activity Modulates or disrupts neural activity creates a reversible lesion or scrambles neural activity How does it do this? Coils placed on scalp create a magnetic field that induces an electrical field This alters membrane potential of neurons, causing them to fire randomly 53 Functional Brain Imaging: TMS Advantages: Creates temporary lesion: can investigate if a region is necessary for a function (causal not correlational) Disadvantages: Adverse effects (e.g., seizures) Only useful for brain regions close to the surface 54 18

19 Cognitive Neurology: solving the puzzle of cognitive dysfunction Quick review Non-human animal research Single-cell recordings Lesion methods Experimental neuropsychology Finding brain-behaviour associations and dissociations in brain-damaged humans Brain imaging Structural Functional 55 Patient Data: Signs, Symptoms, Syndromes Signs: objective abnormalities abnormal eye movements tremor Symptoms: subjective sensations Headache Blurred vision Syndrome: constellations of signs / symptoms 56 Patient Data: Neuropsychological Assessments: Standardized assessment batteries (see Banich, Table 3.4 for an example) Domain specific test batteries (e.g. Wescheler memory scale memory; Behavioural assessment of the dysexecutive syndrome executive function) Compare patient s performance to normative data

20 Our first Case: M.C. Hx: M.C. is a 45-year-old female. She works as a data entry clerk at a large pharmaceutical company. Her job requires her to keep track of long sequences of numbers, often performing complex on-line manipulations of these data. Recently, she has had trouble completing these manipulations. Her excellent interpersonal skills have her in line for a promotion, but recently her boss has questioned some serious errors in the data she has submitted. The problem has become serious enough that human resources at M.C. s company has referred her for a neuropsychological assessment. At interview, M.C. reported that she seemed to be more forgetful around the house, especially if she has a lot to remember or it has been a busy day. But she reports no trouble remembering people, places or events. She also reports having some difficulty concentrating for longer periods and doing more than one thing at a time. She had been having mild headaches over the past 6 months. Family medical history was significant for hypertension. 58 Cognitive Neurology: solving the puzzle of cognitive dysfunction What cognitive domain do you think is affected? Ideas on where the brain damage might be? Etiology (i.e. what caused the damage)? What do we know? Patient s data? Non-human animal research? Experimental neuropsychology? Brain imaging? What else would you like to know? 59 See you next week Neuroanatomy Term paper tutorial Chapter 1, Mesulam paper (will be on the website on Wednesday) 60 20