Kevin S. LaBar, Ph.D. Associate Professor. Duke University.

Transcription

1 Neuroanatomy, Methods, and Current Controversies Kevin S. LaBar, Ph.D. Associate Professor Center for Cognitive Ne euroscience Duke University

2 Overview Brief tour of brain anatomy Cognitive neuroscience methods Current issues and co ontroversies of relevance to law Resource: Purves, D., Brannon, E. M., Cabeza, R., Huettel, S. A., LaBar, K. S., Platt, M. L., & Woldorff, M. G. (2008). Principles i of Cognitive i Neuroscience. Sunderland, d MA: Sinauer Press.

3 Par rt 1: The Human Nervous System

4 Major Divisions Sk keletomuscular

5 Information flow through the nervous system

6 Major divisions of the CNS

7 Gross Brainstem & Diencephalon Anatomy Hindbrain

8 The Cerebrum What structure separates the two cerebral hemispheres? What are the major lobes of the What are the major lobes of the cerebral hemispheres? corpus callosum

9 Gray matter vs. white matter Structural features of CNS organization

10 Gray matter: sulci vs. gyri separates frontal and parietal lobes separates parietal and occipital lobes separates frontal and temporal lobes separates temporal and occipital lobes

11 Cell types What are the two major cell types contained within the CNS? Neurons and glia What are the three major components of neurons? Dendrites Soma (cell llbd) body) Axon

12 Laminar arrangement of neurons in cortex Brodmann areas (nomenclature based on cell types)

13 Input-output arrangement of neocortical circuitry

14 Anatomical planes of section What are the 3 primary anatomical planes of section? Coronal (frontal) Sagittal Horizontal (axial, transverse) Other terminology for Other terminology for anatomical divisions

15 Overview of Fun nctional Anatomy Sensory Systems Motor Systems Attention Memory Emotion Language and Social Executive Function Communication

16 Par rt II: Cognitive Neuroscience Methods

17 Part II: Overview Perturbing Function (manipulation n) Measuring Function (correlation) Multimethodological Convergence

18 Human lesion studies Fields of neuropsychology/behavior h ral neurology have yielded d seminal insights into most cognitive neuroscience domains Some famous patients: Phineas Gage Harlow, 1850 s Personality, motivation, executive function Tan Broca, 1860 s Language H.M. Milner/Corkin, Memory

19 Advantages of lesion method Determines essential (necessary) functions of brain areas Determines what rest of brain can do in absence of it (recovery) Can corroborate some functions in non-human animals

20 Disadvantages of brain lesion method What are some difficulties with this method? Organic lesions do not follow functi ional or anatomic boundaries

21 Neuropsychological studies: Lesion location and extent variability S.P. CB C.B. Bechara et al., Science, 1995 R L Phelps et al., Neurocase, 1998 Graham et al., Neuropsychologia, 2006 Healthy human amyg gdala Rat lesions Amunts et al., Anat Embryol, 2005 Amorapanth et al., Learn Mem, 2001

22 3-D MRI reconstruction and co-registration methods to extract anatomic locus overlap Solution to the overlap problem

23 Other disadvantages Small sample size Lack of pre-morbid assessments (IQ, personality) Co-morbidities (depression) Recovery of function (cancer, stroke)/developmental compensation and plasticity Functional heterogeneity Agnosognosia Diaschisis language mapping

24 Interpretational difficulties with neuropsychological assessment Consider delayed verbal recall: Name the 3 case studies, their doctors, their year of discovery/research, their cognitive function, and brain area involved What are problems in interpreting result? Complex cognitive processes are multi-componential (i.e., attention, language, memory) and require comprehensive assessment

25 Single vs. Double Dissociation: Evidence needed for functional localization

26 Other perturbation methods Pharmacological l interventioni n (agonists/antagonists) i problem: localization Propranolol l (β-adrenergic blocker) as case in point can gain traction by multimethodological li l i l convergence

27 Perturbation by brain stimulation Intracranial electrophysiology advantages: highly localized, direct measure of electrical activity of neurons, best temporal resolution of all methods, converging evidence with non-human anim mal electrical l recordings disadvantages: invasive, only used in clinical populations (epilepsy), p small sample size, lack of control over location

28 Perturbation by brain stimulation Transcranial magnetic stimulation (TMS) 1990 s repetitive/single now FDA-approved as treatment for depression Advantages: virtual lesion in healthy adults Disadvantages: spatial localization of magnetic field is broad and superficial; safety issues discomfort in overlying muscle/scalp

29 Alternative approaches: Measuring brain function Overall benefits can use healthy adult populatiop ons good spatial/temporal resolution simultaneous visualization of multiple areas permits assessment of functional connectivity i of brain Disadvantages: techniques relatively new (especially fmri 1990 s) brain-behavior b i relationships are correlative; cannot determine essential functions readily (networks of activity) generally need many trials for signal averaging g requirements complex data analysis strategies

30 Electrophysiological recording Intracranial single units/mul li ltielectrode l arrays mostly in non-human animals excellent spatial and temporal but also in epileptic patients resolution but can miss big picture

31 Electrophysiological recording Scalp electroencephalogram (EEG G) 1920 s Commonly used to study sleep/epilepsy but can be used to study some cognitive processes Electrophysiological basis: synchronous firing of synaptic input to local dendritic fields results in voltage gradient oriented perpendicular to cortical surface and volume-conducted to scalp Unlike many single-unit recordings, not measuring action potentials

32 Scalp EEG Ongoing EEG reflects oscillat tions of synchronous firing of many cells that are summed and amplified Different frequency bands of delta < 4 Hz; theta 4-8 Hz; alpha 8-12 Hz; beta Hz; gamma Hz high gamma Hz (intracranial only) Relative power in each band is related to stages of sleep/arousal/alertness and cognitive functions oscillation

33 Derivation of Event-Related Potentials For cognitive i neuroscience applica ations, need to time-lock the ongoing EEG to repetitions of specific stimuli (time-locked averaging) Component waveform potentials named according to latency and polarity (negative/positive)

34 Advantages and Disadvantages of ERPs Advantages Direct electrical signal Excellent temporal resolution (on order of 10 s of millisecs) Some spatial resolution (by measuring scalp topography) Disadvantages Signal averaging requirements Deep structures t do not volume conduct to scalp Best for cortical activity with strong laminar organization Misses neurons oriented parall lel with scalp (some sulci) Inverse problem: don t know unique solution to electrcial change at scalp vis-à-vis internal generator(s), so poor confidence in spatial localization Requires discrete signal for time-locked averaging

35 Spatiotemporal mapping with ERPs

36 Hemodynamically-based functional brain imaging positron emission tomography (PET) functional magnetic resonancee imaging (fmri) dvantages: better spatial resolution (especially fmri 3 mm 3 ; high-res fmri -- 1 mm 3 ) isadvantages: cost, subject part ticipation i limitations, it ti temporal resolution (secs), indirect measure of neuronal activity (dependent measure is statistical difference map) asic concept: active neurons need oxygen (and other molecules) to function, so greater blood flow/blood oxygenation utilization and extraction in task-relevant brain areas

37 PET Developed in 1980 s but not used currently for cognitive i neuroscience questions due to: cost ($1,000 per subject), need for cyclotron (to develop radioactive isotopes of molecules injected into bloodstream with short half-lives) participant p exposure to small doses of radiation lack of repeated measures (due to radiation exposure) long temporal window for measuring radioactive decay Still used for mapping of receptor molecule pathways in psychopathology h (shizophren h nia) and degenerative diseases (AD)

38 PET

39 functional MRI (fmri) Structural MRI volumetry Functional MRI -- measured cognitive task Basic idea: while participants perform deoxygenated and oxygenated hemoglobin are differentially magnetic neurons actively recruited during a task require oxygen local oxygen depletion results in greater blood flow to area to replace deoxygenated hemoglo obin in local capillary bed this change is detected by high-field magnets around head need to administer pulses to align magnetic fields first (noises) blood-oxygenation-level-dependent (BOLD) signal

40 fmri

41 Methodological issues with fmri Use same time-locked averaging as with ERPs for event-related designs Noisy, potentially-claustrophic en nvironment No magnetic materials can be present (pacemakers, anurysm clips, electrical recording equipment, amplifiers, etc.) Signal is integrated over about a second, so not as good temporal resolution as with ERPs and time-delayed Magnetic susceptibility artifact t precludes imaging i brain areas at the border of sinus cavities (due to differences in magnetic sensitivity at air/tissue interface) Need to co-register data with high-res structural MRI Images are statistical differences between activity levels for different portions of task (not direct image of blood flow!)

42 MEG Optical brain imaging Other methods

43 Multimethodological convergence Gold standard = to derive brain-behavior correlations is to combine information across different methods which each have their own relative strengths/weaknesses th and spatiotemporal/neurobiological t l i l sensitivities

44 Part III: Current Controversies

45 Part III: Some Controversial Topics Reverse inference problem with fmri - Case in point: neuroimaging specific emotions, such as guilt Fallability of emotional memories - Implications for eyewitness testimony Assessing implicit attitudes towards social groups -Implications for hate crimes Development of behavioral regulation in adolescence - Implications for assessing respo onsibility and agency Other issues: brain fingerprinting, lie detection