Neuropsychology

Brain & Behaviour throughout time

• Aristotle: nonmaterial mind guides behaviour

• Descartes: mind (pineal gland) decides movement of the body

• Darwin: behaviour originates in brain activity

  • Natural selection: environment plays a role

• Today: mind originates from brain function

  • Behaviour depends on both

Donald Hebb

• Considered the ‘father of neuropsychology’

  • Hebbian theory = neural pathways develop based on experiences; as pathways are used more, they become faster and stronger

• Early neuropsychology was closely linked to brain injury and dementia research and diagnosis

  • Relationship between loss of brain function and change in thoughts / behaviors easier to observe

  • Modern neuropsychology includes a variety of disorders

The Hebbian assumption of change

• Environment, culture, customs, family history, lifestyle, and more shape who we are

  • In neuropsychology, we focus a lot on thoughts, behaviours, and their relationship to the brain

  • However, much relevant information is found outside psychology and the brain that influence both

  • For example, cloned mice do not have identical behaviours

• Plasticity, flexibility, and adaptability are fundamental properties of the brain

  • Neuropsychology is founded upon the assumption of change

    • There is no rehabilitation unless the brain can change

    • Therapies would not work unless psychologies can change

Hebbian plasticity is the foundation of neuropsychology

Neurological examination

• Patient’s history

• State of awareness

  • Alert, drowsy, stupor, confused

  • Speech abnormalities, facial asymmetries, body posture

  • Emotions (agitated, anxious, depressed, apathetic, restless)

• Physical examination

  • Blood pressure, brain imaging, reflexes, pain, muscle movement, smell, etc.

• Disorders

  • Strokes, injuries, and lesions may show asymmetry, loss of function

  • Parkinson’s may show loss of smell and motor changes

  • Dementia may show memory loss, disorientation, or agitation

Biopsychosocial model of neuropsychological assessments

• Neuropsychological assessment

  • Combines many tests depending on patients’ symptoms

  • May include IQ, cognitive, and psychometric tests

• Biopsychosocial model

  • Social support networks (friends, family) influence outcomes

  • Patients’ sense of wellbeing influence outcomes

  • Sometimes a mismatch between the patients’ needs and their social network (e.g., patient wanted to stay home, family thinking they should work) or environment (e.g., needing a quiet place to sleep but living somewhere noisy) can add stress that may impair healing

How did the biopsychosocial model change neuropsychology?

Premise: A person is not made of isolated organs, but functions as a whole

• You need good biological, social, and psychological circumstances to have good mental health

  • First conceptualized in 1950 by Roy Grinker - applied "bio" to psychology

  • Proposed as a medical perspective by George L. Engel in 1977 - applied "social" to medicine

Example from Dementia

• Dementia

  • Umbrella term for impaired memory, cognition, and decision-making

    • Common causes: Alzheimer’s pathology, Huntington’s disease, multiple sclerosis (MS)

  • Symptoms include poor mood and perception

    • May include depression, apathy, and hallucinations

• Neuropsychiatric Inventory (NPI)

  • Used to characterize dementia in the clinic

  • Assesses frequency and severity of symptoms

  • Assesses changes in behavior

    • Is it getting worse?

Biopsychosocial perspective in dementia

• Usually applied as part of treatment plan

• External triggers are assessed through history interview

  • For example, one study found that 80% of dementia symptoms had external triggers

• Social support and environmental well-being considered in treatment plan

Biopsychosocial perspective helped lead to other social-clinical models

• Part of our social well-being is our cultural fit

  • Beliefs from our community shape our experience of medicine

• Not all symptoms are symptoms

  • Certain beliefs are cultural

  • Sometimes hallucinations are even considered culturally appropriate

• Cultural Formulation Interview (CFI)

  • Used to determine whether something is pathological

Example from Dementia

• Might assess whether apparent ‘hallucinations’ or ‘delusions’ are considered odd by family members

  • Do the experiences described have a cultural place?

• Might assess relationship to healthcare system

  • Do they believe that Western biomedicine is a valid approach?

  • Do they feel safe?

• Asking these questions can reduce psychosocial distress for some patients

Fissures and Poles

Limbic system

Ventral and Dorsal Streams

Directional terms

Anatomical planes

Lesion studies

• Broca – lesions in a particular region (left front side of the brain), that resulted in not being able to produce words, despite knowing the object / what to communicate (cognition intact)

  • Broca’s aphasia

What the lesions told us

• Clinical cases (like Broca’s aphasia) led to discovery that certain types of damage was consistent with certain types of symptoms

  • Localization: Which area

  • Lateralization: In one hemisphere

  • Distribution of function: Compensation

  • Hierarchical organization: Sophistication of functions very depending on whether a ‘higher’ or ‘lower’ brain area is damaged → Brain processes start with lower levels and are processed through increasingly higher levels

Localisation example

Lateralisation example

Distribution of functions

Hierarchical organisation

• Processing begins with lower (relevant) brain regions then moves to higher brain regions (hindbrain → midbrain → forebrain)

• Loss of function in higher brain regions = dissolution (brain can compensate with lower regions, simplified behaviors) 

• Lower brain areas can sometimes compensate but output issimpler

Brain lesion

Brain lesion = area of brain damage

• Can result from stroke, loss of blood flow, tumor, injury, etc.

• This is what it looks like in an MRI scan

  • (left) White = damage from reduced blood flow caused by a stroke

  • (right) Black = tumor tissue

Genetics – Recessive

Genetics – Dominant

Genetics – X / Y chromosomes

Biopsychosocial model and stress

Stress and genes

Interaction genes – environment (modification)

Stress and Epigenetics

• Epigenetics: changes to the expression of genome.

• Stress has larger biological consequence than originally thought

  • Structural and temporal (functional) changes

• Stress can influence epigenetic changes and mental health

  • Within lifespan

  • Across generations

Epigenetics

Changes to the expression of genome

• Example: specialisation after cel migration – to nerve or muscle cells (same DNA, other function).

• Puberty: body undergoes extensive changes, without DNA changing: hormones regulate gene expression

Applications to neuropsychology

• Behaviour is caused by genetics, epigenetics, and experience-based learning

• Influences on cardiovascular health can also be derived from genetics, epigenetics, or experience (e.g., diet)

• Cardiovascular health directly affects brain function

What is a neuropsychologist?

• A clinician and/or scientist who...

  • Uses neurology, neuroscience, and psychology

  • To understand how behaviours correlate with brain function

  • To assess ‘normal’ and ‘impaired’ cognitive, social, physical, and emotional functioning

• Neuropsychology is usually clinical in nature

  • Neuropsychologists are not medical doctors

  • Clinical tasks are usually diagnostic

  • Referrals to specialists may be given for treatments

  • Research tasks may include investigating causes of a disorder, its brain/behavioral/cognitive processes, its diagnostic approaches, the efficacy of treatments (how well they work), etc.

• Many neuropsychologists are also scientists

  • Use neuroimaging to study relationship between brain and psychology

  • Functional neuroanatomy is crucial

  • Working knowledge of relevant biological and psychological theories

  • May study healthy and patient populations

The Hebbian Assumption of Change in research and practice

• Learning and skill development across the lifespan

• Healing after a brain injury (physical)

• Treating a disorder (psychological)

• Heritable traits passed down across generations

Patients in neuropsychology

• Dementia

• Broca’s aphasia

• Wernicke’s aphasia

• Brain lesions / Stroke

Why start with neurons?

• Neuropsychologists rely primarily on information about larger brain structures and functions

  • Global functions appear trait-based (i.e., fixed, unchanging)

  • Neuropsychology relies on change, which is not always big enough to be observed on this level of organization

• Understanding nerve cells is crucial

  • Principles of change are observed through understanding cellular processes

  • Many disorders have cellular causes

Neuron

• Electrical and chemical signals pass from the axon terminal of one neuron to the dendrites of the next neuron

• Soma → gray matter

• Myelin sheath → white matter

• Both electrical and chemical responses can be measured by brain imaging devices

• Both gray and white matter activations can be measured by brain imaging devices

• There is a correlation between electrical signals and blood flow

Types of neurons

Grey Matter and White Matter

Pyramidal cells

Other types of human multipolar cells

How do neurons function?

• Signal is received from neighboring cell

  • Terminal bouton release neurotransmitters across the synapse to nearby dendrites

• Receiving neuron produces 4 signals (i.e., chemical translations) / stages

  • Input signal = receives messages from other neurons - dendrites

  • Trigger signal = integrates the received message - soma

  • Conducting signal = sends information down axon to terminal boutons

    • This signal goes awry in MS

  • Output signal = chemical neurotransmitters (NTs) are released – terminal boutons

    • This step occurs when neurons fire

Nerve cells: global function neurons

Neuron as a mini-factory

• Nucleus contains genetic information

• Endoplasmic reticulum uses genetic information as though it is a set of instructions for assembling proteins

Chemical signs - proteins

Back propagation

• Hebbian plasticity = brains learn from life experiences

  • Neurons back propagate

  • In artificial neural networks (ANNs), it results in adaptive changes

    • Networks “learn how to learn” through back propagation

  • Theorized to act similarly in neuron

Discovery of the neural transmission

• Discovered by J.Z. Young (1932)

• Alan Hodgkin and Andrew Huxley (1939) began studying squid neurons

• The modern history of ion channels began in 1952 - seminal papers on the theory of the action potential in the squid giant axon

When do neurons fire? 

“All or None” activation

The axon generates an action potential only if the resting potential crosses a threshold (e.g. from -70mV to -60mV)

• The magnitude of the action potential is always the same! (like a light switch) → ALL or NONE

Channels, gates, and pumps

Through the use of pumps and channels, an action potential travels along the axonto the synapse, and is there transmitted to the next neuron

Myelin

• Efficiency of signal transport depends on “insulation” of the axon

• Myelin shaft – thicker is more effective (jumps vs. little steps)

• Damage to myelin common in Multiple Sclerosis (MS)

• More effective = more used

• Every experience has a specific synaptic pattern (see A → B)

• Synaptic growth and myelination:

  • first perception and motor neurons

  • later associative areas

  • last areas for cognition and learning

• Less used pathways are pruned away

NTs are released and received

A neuron transfers its action potential to other neurons through the synapse

Synapse

Mechanisms of neuroplasticity

• Neuroplasticity vs neural flexibility

  • Neural flexibility = adaptive functional changes (temporary)

  • Neuroplasticity = structural (physical) reorganization after learning or injury

• Mechanisms of plasticity

  • homologous area adaptation = opposite hemisphere takes over a sensory/cognitive process

  • cross-modal reassignment = loss of one sensory / cognitive process heightens the remaining senses processes

  • map expansion = some areas involved strengthen to compensate for loss

  • compensatory masquerade = brain uses alternative pathways / strategies for processing (alternative routes)

Homologous area adaptation

opposite hemisphere takes over a sensory/cognitive process

Cross-modal reassignment

loss of one sensory / cognitive process heightens the remaining senses / processes

Map expansion

areas that were involved grow stronger

Compensatory masquerade

brain uses alternative pathways / strategies for processing (taking a different route to get there)

• old areas that were always part of the network may help enough that tasks can still be performed, but the performance isn’t as good

What might prompt brain changes?

• Environment / exposure / experience sampling

  • Learning (changes to neurons / pathways)

  • Therapy (changes to neurons / pathways)

• Biological changes

  • Disease progression / accidents

  • Medical treatments / surgeries

  • Medications

• Psychosocial factors

  • Stress (methylation changes / other epigenetic changes)

  • Emotions (physiological changes / epigenetic changes)

Epigenetic changes

• The epigenome mains, modifies, and regulates genes

  • Determines which genes are expressed (turns genes “on” and “off”)

    • “On” = protein is produced; “Off” = no protein is produced

    • DNA makes RNA makes proteins

  • Genes don’t change, but phenotypes do

    • Phenotype = observable traits that result from a gene x environment (GxE) interaction

    • The same genotype interacting with the environment can producemany different phenotypes

• 3 main mechanisms of change

  • DNA methylation

  • Histone methylation

  • mRNA modification 

DNA methylation

• Methyl groups are added to the DNA molecule

  • Methyl group = 1 carbon and 3 hydrogen atoms

  • Adding a methyl group blocks promoters from expressing the gene

• Can change the activity of a DNA segment without changing the sequence

• Typically acts to repress gene transcription

Histone methylation

• Histone = a type of protein that wraps (“spools”) itself around DNA

• Changes in histone methyl groups can induce or repress gene expression

• Left image “spooled” DNA (not expressed), right image “unspooled” DNA (expressed)

• Methylation increases density (more “spooling”, less expression)

mRNA modification

• mRNA = messenger RNA = dynamic regulators of gene expression

• Primarily refers to 13 different chemical alterations

• Affect translation or stimulate other regulatory processes like mRNA degradation or localisation

• Small changes can large differences in outcome

MULTIPLE SCLEROSIS (MS)

• MS is caused by damaged myelin → Cumulative damage produces brain lesions

  • Immune cells attack the myelin sheath

    • Myelin acts as lubricant

  • Exposed axon is scarred (sclerosis = scars)

  • Information transmitted by that neuron is disrupted

• MS is a heterogeneous disorder = patients have different symptoms & experiences depending on lesion size and location, and how their individual brain is functionally organised

Common symptoms of MS

• Affects brain and spinal cord

• Common early symptoms:

  • Vision problems

  • Numbness/tingling sensations

  • Motor symptoms: clumsiness, weakness of limbs

  • Balance and coordination

  • Fatigue

• Common later symptoms:

  • Mobility problems: muscle spasms, stiffness, weakness, or paralysis

  • Bladder or bowel problems

  • Cognitive problems: difficulties thinking, learning, and/or planning (language preserved)

  • Pain

  • Speech and swallowing difficulties

  • Sexual problems

  • Emotional problems: depression and anxiety

• Most people with MS only have a few of these symptoms

• Average lifespan is 7 years shorter than general population

Types of MS

• Primary progressive (PPMS-green)

  • Symptoms progressively get worse after onset

  • No periods of remission

• Relapsing remitting (RRMS-blue)

  • Relapse = active symptoms / myelin damage

  • Remission = no current symptoms / myelin damage

  • Symptoms disappear and reappear across time

• Progressive relapsing (PRMS-red)

  • Similar to RRMS but symptoms become increasingly disabling with each relapse

  • Very rare, severely disabling

• Secondary progressive (SPMS-orange)

  • Occurs after patient previously had RRMS

  • Remissions stop, symptoms get steadily worse

Overview neurotransmitters

Cholinergic system

• ACh facilitates neuronal communication → Memory formation and learning, attention and arousal

  • Projected to hippocampus and limbic system

• Alzheimer’s disease: substantial loss of cholinergic neurons in the basal forebrain → cognitive decline

• Parkinson’s disease: Higher levels of ACh are suggested to cause dyskinesia, uncontrolled and involuntary movement.

Dopaminergic system

Dopamine and schizophrenia symptoms

Noradrenergic system

• Epinephrine, also known as adrenaline, is both a hormone and neurotransmitter

• Influences mood, motivation, and arousal

  • Low – depression ; High – mania

• Associated with ADHD

Norepinephrine vs. Epinephrine

Serotonergic system

Serotonin and psychopathology

• Serotonin (5-HT, 5-hydroxytryptamine) modulates a broad spectrum of functions, including mood, cognition, anxiety, learning, memory, reward processing, and sleep. 

  • depression, anxiety, tremors, schizophrenia, OCD

Combination of neurotransmitters

Single-cell recording

Intracellular vs. extracellular recordings

• Microelectrode is placed next to a single neuron (almost touching) or inside the cell

• Electrical charge is recorded

• Direct measure of brain activity

• Invasive, cannot be used to study humans

Electroencephalogram (EEG)

• One or more electrodes placed on scalp (and around eye)

• Electrical charges of neurons near scalp are recorded (extracellular)

• Direct measure of brain activity

• Good temporal resolution

  • We know when activation occurs

• Poor spatial resolution

  • Scalp is a bad conductor of electricity

  • Hard to know where the activation occurs

• Non-invasive

• Can also be used to study children, portable

Event Related Potential (ERP)

Magnetoencephalography (MEG)

Magnetic resonance imaging (MRI)

Structural and functional MRI

Diffusion tensor imaging (DTI)

Spatial and temporal resolution

(Hind brain) - Spinal cord

(Hind brain) - Brainstem

(Hindbrain) - Cerebellum

Holds more than half of the neurons in your whole body.

• Grey and white matter

• Subcortical nuclei

• Lobes, fissures etc.

• Balance, coordination, movement, and motor skills

• Integrates them with mental processes

(Hindbrain) - other structures

• Vital functions

• Arousal

• Consciousness

• Bridge to brain

Medulla - Crossing neural circuits

• Visualizations of decussation

  • 90% of motor and somatosensory fibers cross over

• Left brain controls right body, Right brain controls left body

• Remember: many Broca’s infarct have right side body impairments...

Midbrain

• Sensory input from eyes and ears (basic)

• Movement control

• Reflexes, bypass the brain,

  • direct uncontrollable action

Midbrain - Diencephalon

• Thalamus – central hub connecting sensory systems to cortex

• Hypothalamus – motivated behavior

  • Connection pituitary gland

  • Hormones / chemical messages

• Epithalamus

  • Pineal gland – body rhythm

  • Habenula – hunger & thirst

Forebrain – Telencephalon – “the brain”

• Basal ganglia

  • Reward and associative learning

  • Connect sensory to motor systems

  • Regulate (smooth) movement

• Limbic system

  • Amygdala – emotions

  • Hippocampus – personal memory and spatial navigation

  • Cingulate cortex – social interactions, decision making and executive functions

• Cortex

  • Motor cortex

  • Visual cortex

  • Thinking, perceiving, communicate

  • Consciously interact with world

  • Complex high functions

Connecting brain regions

Function of brain regions - hierarchy

The brain’s blood flow

• Blood supply is important for healthy tissue and cellular functioning

  • Blood carries oxygen and glucose

• Some neuroimaging devices measure changes in blood flow to infer which areas of the brain are more active

  • The assumption is that greater neural activity requires greater blood flow

• Asymmetrical blood flow can affect function

• Anterior cerebral circulation - provides blood flow to the eyes and the anterior brain. Blood source include these (among others):

  • Middle cerebral artery (MCA) ↓

  • Anterior cerebral artery (ACA)

• Posterior cerebral circulation - provides blood flow to the the occipital lobes, cerebellum, brainstem and posterior brain. Blood source include these (among others):

  • Vertebral arteries (smaller arteries from the shoulders, lateral chest, and arms)

  • Posterior inferior cerebellar artery (PICA) & Anterior inferior cerebellar artery (AICA)

  • Superior cerebellar artery (SCA) & Posterior cerebral artery (PCA)

  • Basilar artery (blood flow to the midbrain and cerebellum)

  • Pontine branches (includes circle of Willis)

Circle of Willis

• Joins several arteries at the inferior side of the brain

  • Internal carotid arteries branch into smaller arteries

• Supplies oxygenated blood flow to over 80% of the cerebrum

  • Main aqueduct for the brain’s hemodynamic response (what’s measured by fMRI and fNIRS)

Main arteries

• Anterior cerebral artery (ACA): Supplies blood to the medial parts, including the superior frontal and anterior parietal lobes.

• Middle cerebral artery (MCA): Supplies blood to lateral parts, the temporal and lateral-parietal lobes.

• Posterior cerebral artery (PCA): Supplies blood to posterior parts, including the occipital lobe, thalamus and midbrain.

• Carotid arteries are major blood vessels in the neck that deliver blood to the brain (internal carotid artery - ICA), face, and neck

Ventricles 

• Interconnected cavities that produce and circulate cerebrospinal fluid (CSF)

• Lateral: C-shaped in each hemisphere

• Third: between the two halves of the thalamus

• Fourth: between the brainstem and cerebellum

What is laterality?

• Lateralization of brain function = the brain’s two hemispheres have separate functions

  • Cerebral asymmetry

  • Neuronal asymmetry

  • Genetic asymmetry

• Not all brain functions are lateralized

• Brain functions that are going to lateralize usually have by age 6-7

• Asymmetrical functions maybe lateralized = usually appearing on one side (e.g., language is usually processed in the left hemisphere)

What is lateralized?

Cerebral Asymmetry

• Anatomical differences (of most people...)

  • Left hemisphere is larger, heavier, and has more gray matter (cell bodies)

  • Right hemisphere has more cortical surface area*

  • Left hemisphere has a thicker cortex+

  • Language and music are oppositely lateralized, as are corresponding brain regions (Broca’s has more sulci* on the left side)

  • Asymmetry in the temporal lobe corresponds with asymmetry in the thalamus

  • Distribution of neurotransmitters is asymmetrical

  • Cerebral torque = the right side of the brain is slightly forward compared to the left side

*More sulci = bigger surface area → theorized to mean more intelligence/more advanced

+Cortex → theorized to reflect social skills and processes

Neuronal & Genetic Asymmetry

• These asymmetries are difficult to study, and only general principles are known...

  • Neuronal Asymmetry = Neural branches and connections differ across hemispheres

  • Genetic Asymmetry = Gene expression occurs differently in each hemisphere

  • Both are difficult to study because of the sheer numbers of neurons in the brain (and ethics?)

Behavioural asymmetries in the intact brain

 1. Visual asymmetry

• Information presented to only one visual field is processed most efficiently by the hemisphere specialized to receive it

  •   words in left hemisphere (LH)

  •   faces in right hemisphere (RH)

2. Auditory asymmetry

• When different stimuli are presented simultaneously to path wars, as preferreateral access, and the ipsilateral pathway is slower

  • Right ear advantage for words (LH)

  • Left ear advantage for music (RH)

    • Example:

    • "Ga" goes directly to the language processing area in the LH.

    • "Ba" travels first to the RH, then crosses over to the LH. Path takes longer.

    • → Right ear dominance for words

      • Music other way around

3. Somatosensory asymmetry

• Performance = Shape and pattern recognition (cf. Braille)

  • The left hand of a right-handed participant is superior at nearly all tasks of this type

• Identification = See what you feel

  • right-hand advantage for letters (LH)

  •  left-hand advantage for other shapes (RH)

• NB. LH dominance for words / language

4. Motor asymmetry

• Everyone has motor asymmetries

• Easier to study in patient groups

☆ Behaviour does NOT correspond fully with biological/anatomical measures

☆ Laterality might be a question of which information is processed first (timing)

☆ Personal preference for strategies may influence outcomes 

Right vs left ear advantage

Aphasia

• A language disorder caused by damage in a language area of the brain

  • Aphasia leaves a person unable to communicate effectively with others

  • Affects language expression or comprehension via speech or writing

  • Most often caused by a stroke

  • Most recovery (if any) occurs within a few months of onset

Broca’s aphasia

• Broca’s aphasia

  • Difficulty forming words or sentences

  • Loss of grammatical structure (“telegraphical”)

  • Intact understanding of language

• Noticed in the clinic

  • Brain lesion observed in frontal lobe

  • Patients often have right-side weakness or paralysis due to lesion’s impact on motor function

• Hierarchy:

  • Speech is hard to produce but usually not impossible (advanced)

  • Other language functions, like understanding speech as well as simple motor speech routines

  • Production of familiar songs (or automated vocal behaviors) often remain intact (basal)