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Underlying Neuroscience Principles in Brain Injury Litigation

Larry J. Cohen Arizona Attorney General November 7, 2014 Phoenix, Arizona

Agenda

Neuroanatomy– Neural Circuits and Networks

Regulation Assessment

– Neuropsychology Imaging Assessment

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Method of Presentation

Lecture Questions Materials Follow Up

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Critical Operations to be Carried out by the Nervous System Process Information about the External

Environment Prepare and Execute Actions Encode, Store and Access Information Communicate Select Control and Monitor Complex

Operations

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Fundamentals of Neuroanatomy

Historical View Focused on Areas of the Brain Responsible for Behavior of Interest– Brain Stem: Controls basic functions– Frontal: Management and Expressive Language– Temporal: Processing Information; Receptive

Language; Hearing and Memory– Parietal: Motor and Sensory– Occipital: Vision

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Neural Matter

Gray Matter– Cell bodies and capilaries

White Matter– Sheathing of Axons

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Cortical Structures

Outer layer of neural tissue– Frontal– Temporal– Parietal– Occipital

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Neural Matter

Gray Matter– Cell bodies and capilaries

White Matter– Sheathing of Axons

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Subcortical

Literally, Below the Cortex– Play Central Role in Brain-Behavior

Function

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Subcortical Structures

Hippocampus– Associated with memory function– Encoding

• Memory consolidation• Damage prevents explicit descriptions of

events cannot be learned (episodic memory)• But can still give some meaning and knowledge

to experience (semantic)

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Subcortical Structures

Cerebellum– Learning of Procedural Memory; motor

learning• Coordination• Fine Motor Control• Damage can cause problems with movement

and coordination

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Subcortical Structures

Amygdala– Associated with emotional learning and

memory• Process results in emotional events being more

deeply and accurately encoded into memory• Also important in memory consolidation

– By ascribing value to events

• Damage impairs motivation and processing of emotions

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Subcortical Structures

Basal Ganglia– Associated with learning, memory and

unconscious memory processes• Motor skills and implicit memory

– Damage is associated with dysfunctional learning of motor and perceptual-motor skills

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Subcortical Structures

Thalmus– Implicated in control of sleep and attention– Relay station that receives input from eyes,

ears, spinal cord• Role in relaying information to the cerebral

cortex

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Subcortical Structures

Reticular Activating System– Densely packed cells in thee central core

of the hindbrain– Thought to activate the thalmus and the

cortex– Damage to this system compromises

wakefullness

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Subcortical Structures

Corpus Collosum

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Neural Circuits or Networks

Neural Networks: Interconnected ensembles of cortical and subcortical neurons co-activated to mediate cognitive or behavioral Function

Link structures within the brain– Distributed Cells with Regional specialization– Critical Hubs– Similar Clinical Outcomes from Injury to Different

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Conditions Affecting Networks

Multifocal Insults (TBI, Demyelinating disease)

Focal Insults (stroke, tumor) Developmental Sndromes (ADHD) Normal Age Related Cognitive Changes CNS Infections Neurdegenerative Disease Vascular Cognitive Impairment04/19/23

Neurodevelopment Nervous system is derived from the

outermost tissue layer of the embryo– Subject to damage when exposed to disease,

toxins or trauma After birth development continues through

a process of sprouting and pruning– Believed to continue until early 20’s– Organic basis to account for behavior

through development

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Regulation

Self-Adjustment to Address Distress in the Environment– Use of Energy in Response to Distress

Helps the Individual Return to a Preferred State– Internal– External

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Issues in Neuropsychological Evaluation Estimating Premorbid Baselines

– Individual• History• Hold Functions

– Population• Base Rates

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Issues in Neuropsychological Evaluation Current Brain Behavior Relationships

– Level of Consciousness– Comportment – Interpersonal relationships relative to the

individual– Attention– Executive Function– Orientation– Memory– Language Visuospatial Function– Motor Function– Mood

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Controversy Over Testing Methods Standardized Hypothesis Testing

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Issues in Traumatic Brain Injury TBI Defined

– Force Acting on the Brain• Disturbs levels of consciousness

– Continuum of Injury• Primary

– Direct– Rotational

• Secondary– Interaction with other on-going processes

Distinguish from– Acquired Brain Injury (e.g. stroke)– Developmental Disorders

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Physical Injury from Contact and Inertial Mechanisms Primary Injury

– Occurs Immediately• Contusions• Hemorrhages• Diffuse Axonal Injury

Secondary Injury– Evolves Over Time

• Massive Release of Neurotransmittors• Edema.Ischemia/Hypoxia• Increased intracranial pressure• Triggering of Excitotoxins

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Visualization of Physical Injury

Ability to Detect Depends on Ability to Image– Damage to Tissue– Bleeding

Problematic where Damage at the cellular level– Diffuse Axonal Injury

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Imaging Techniques Static

– X-Ray– CT Scan– MRI

Dynamic– PET– SPECT– EEG/qEEG– FMRI– DTI

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Tertiary Factors That Compromise Assessment Interaction with Other Physical

Conditions Delay in focus on consequences of TBI Potentiation by Environmental Factors Social-Environment Dynamics Secondary Gain Measurement Limitations

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Immediate Consequences Cognitive Deficits Personality Changes

– Social Comportment

– Motivation

– Personal Management (Executive) Psychiatric Disorders

– Due to overlap of TBI and Psychiatric Disorders with respect to the Distribution of Neural Circuitry that Mediates Mood regulation, stress response, impulse control and reward modulation

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Long Term Consequences

Compromises Plasticity– Increases Vulnerability to Developmental

Processes and Disease Reliance on Compensatory Techniques

that May be Compromised Over Time

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Status of Knowledge About TBI

“Emerging science but persistent absence of evidence”

Treatment not Distinctive– Apply Methods Applicable to Other Kinds

of Disorders

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Future Brain Injury Assessment Genetics

– APOE• Provides instructions for making a protein called

apolipoprotein E. • Combines with fats (lipids) in the body to form molecules

called lipoproteins.• Lipoproteins are responsible for packaging cholesterol and

other fats and carrying them through the bloodstream. – Apolipoprotein E is a major component of a specific type of

lipoprotein called very low-density lipoproteins (VLDLs). VLDLs remove excess cholesterol from the blood and carries it to the liver for processing.

– Maintaining normal levels of cholesterol is essential for the prevention of disorders that affect the heart and blood vessel

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Future Brain Injury Assessment

Genetics– APOE

• Amyloid Deposition• Disruption of Cytoskeletal Stability• Cholnergic Dysfunction• Oxydative Stress• Neuroprotection• Central Nervous System Plasticity

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Future Brain Injury

Genetics– Other Genes

• COMT and DRD2 may influence dopamine dependent cognitive processes

– Executive Frontal Lobe Functions

• Interkeukin Genes– Affects inflamatory processes

• ACE Gene– Affects cerebral blood flow

• CACNA1A– Affects calcium channels and so contribute to edema

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