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Brain Development and Plasticity

Neuropsychology

Brain development outline
• Phases of neurodevelopment
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• Brain plasticity
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• The ageing brain
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• Behavioural development
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Growth and development of neurons
• Cell origins – from stem to specialised and neurogenesis in the aging brain
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• Migration – radial and tangential, somal translocation and gila-mediated migration
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• Differentiation – blueprint, timing, chemical signals: complete at birth
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• Development of dendrites – dendritic arborisation and growth of dendritic spines
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• Synaptic pruning – apoptosis (programmed cell death), neural Darwinism (functional neural network
and up to 42% are eliminated
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• Experience and the brain – “intelligence can be influenced by experience” (Hebb, 1947), experience
can change neuronal structure and prenatal effects (e
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maternal voice)
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• Sensitive – stronger effect during time window
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• Human language – initially perceive all phonetic contrasts, ability is honed in first year of life and also
true for second language
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Imprisoned alone in a darkened room for 20 months
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Restrained at night in a sleeping bag
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Beaten if she made a sound
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Family members forbidden to speak to her
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Escaped at age 13
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• “If language is not acquired at the right time, the cortical tissue normally committed for language and
related abilities may atrophy” (Curtiss, 1977)
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Aspects of regeneration
• Regional processes
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Neurodevelopmental disorders - Autism
• Prevalence: one in 4 out of 10,000, 4 times more likely in bots and number is increasing (may be due
to mercury in childhood vaccines)
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Impaired ability to interpret emotions/intentions
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Impaired capacity for social interaction
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Preoccupation with single subject/activity
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• Neuropathology – smaller cerebellum and immature organisation of frontal lobes
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• Treatment – no cure but behavioural therapy may help
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• Diagnosis – use of DSM-IV, ICD-10, TOVA, QEEG and questionnaires, three subtypes:
1
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2
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3
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• Symptoms for 6 months that are maladaptive and evident prior to age 7
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• Aetiology:
1
...

2
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3
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• Treatment – medication (methylphenidate – Ritalin) and EEG biofeedback
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• Memory – decline in delayed recall (ageing-related not age-related)
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• Theories of cognitive change – general decline across all abilities: reduction in mental resources and
slowing of processing, however deficits are specific e
...
inhibitory responses
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Aerobic exercise – proliferation of blood vessels to the brain, resulting in enhanced oxygen
supply
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Keeping mentally challenged – new hobby, language or engaging in new learning experience
is beneficial
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Super-agers – a subgroup whose brains appear relatively immune to the physical effects of
ageing (exceptional mental performance and no thinning of the cortex)
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CAT, PET, fMRI and TMS
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Use of EEG in diagnosis
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Patient data
• Naturally occurring lesions
...
g
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• Double dissociation, e
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both short-term and long-term memory are affected
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• Computer constructs a 3D map
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• Poor temporal resolution
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• Difference in activity represents region involved
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• Scanner detects location of tracer – changes in rCBF
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• Temporal still slow – 40 seconds
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• Ratio of oxygenated/deoxygenated
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• Better temporal – down to a few seconds
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• Test the integrity of motor pathways
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• Brief and limited to cortical surface
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• Bipolar (sequential) – two active electrodes
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Spectral components of the EEG
• Delta (0
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• Theta (4 – 7Hz) – mental calculation and word recognition
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• Beta (12 – 30Hz) – relaxed yet focused
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Extraction of the ERP
• Averaging epochs of the EEG
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• Exogenous – external events
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Some ERP components
• Event preceding negatives – contingent negative variation (CNV)
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•
•
•

Attention related effects
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Language related effects
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• ADHD – EEG abnormalities
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• ADHD – improved behaviour and IQ
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• Drugs, experience and context – tolerance and sensitisation
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Types of drug
• Medical drugs – a natural or artificial substance given to treat or prevent disease or to lessen pain
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Route of administration
• Injecting a drug directly into the brain allows it to act quickly in low doses because there are no
barriers
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• Drugs administered into the muscle encounter more barriers than do drugs that are inhaled
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• Drugs injected into the bloodstream enough the fewest barriers to the brain but must be hydrophilic
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• Drugs that are weak bases pass from the intestines to the bloodstream
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• Capillaries in the brain are not leaky, have tight barriers and are covered with astrocyte feet
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• Capillaries in the body are leaky and have few tight junctions
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• Small, uncharged molecules are able to pass through the endothelial membrane and reach the brain
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• Large and electrically charged molecules are unable to pass out of the capillary
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Drug effectiveness
• Dose response curve – when the curve plateaus, the drug ceases to produce any stronger effect
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Placebo effects
• From the Latin placere (to please) – an inert substance that produce no specific effect
...

• Brain activation – fMRI studies show placebos and opioids activate the same brain region (Petrovic et
al, 2002), placebos activate endorphins (Zubieta et al, 2005)
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Synthesis
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Storage
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Release
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Receptor interaction
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Inactivation
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Reuptake
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Degradation
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• Antagonists – decrease effectiveness of process
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• Receptors: agonist – nicotine stimulates ACh receptors, antagonist – curare blocks ACh receptors
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Classification of psychoactive drugs
• Sedatives, hypnotics and antianxiety agents – barbiturates, alcohol and benzodiazepines
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• Antidepressants – monoamine oxydase inhibitors, tricyclic antidepressants and atypical
antidepressants
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• Narcotic analgesics – morphine, codeine and heroin
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• Psychedelics and hallucinogens – anticholinergics, noradrenergics, serotonergics and
tetrahydrocannabinol
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• Tolerance can be built up, which may lead to accidental overdose
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• Block D2 dopamine receptors – dopamine hypothesis
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• Improve chemical transmission of serotonin
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Narcotic analgesics and stimulants
• Narcotic (sleep inducing) analgesics (pain relief) – often derived from opium, morphine is the most
effective analgesic, acts on endorphin sites
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Behavioural stimulants – cocaine and amphetamines (dopamine agonists, increase motor
behaviour, elevate mood)
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General stimulants – caffeine (general increase in metabolic activity)
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Psychedelic stimulants – mescaline, marijuana and LSD (alter sensory perception and
cognition)
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• Tolerance:
1
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2
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3
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• Sensitisation – increased response with subsequent dose
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• Three stages of dependency – activation of pleasure, associative learning and incentive salience
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• Psychomotor activation – may act on dopamine neurons
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• Pineal gland – reproductive maturation and body rhythms
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• Thyroid – growth, development and metabolic rate
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• Pancreas – sugar metabolism
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• Three main groups:
1
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2
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3
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Homeostatic hormones
• Negative feedback system – deviation from appropriate balance triggers compensatory action
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g
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Reproductive hormones
• Gender – injections of testosterone led to more “male like” behaviours (Phoenix et al, 1959), lack of
exposure to testosterone led to increase in “female behaviours” (Grady et al, 1965)
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Stress hormones
• Ending a stress response – hippocampus and cortisol
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Summary
• Principles of drug action – enter CNS, removed, effectiveness, placebo effects and site of drug action
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• Response to drugs – tolerance, sensitisation, addiction and brain damage
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Motivation and Emotion
Outline
• Motivation and behaviour
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• Emotion
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• Emotion and the brain
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What is motivation?
• What motivates people?
• Process or thing? – more of a process
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• Internal or external? – both, internal = own personal wants or needs, external = social peer pressure,
need for a good grade etc
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• Drive – internal, used to maintain homeostasis (Hull, 1951)
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, e
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if something Is not assessed, why turn up?
• Arousal – striving to maintain preferred level of arousal (Fiske & Maddi, 1961)
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– not controlled by homeostatic
mechanisms
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Neural circuitry
• Hypothalamus – three regions:
1
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2
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3
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• Pituitary gland
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• Hypothalamus to anterior pituitary circuit – hormone prolactin
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Hormones are synthesized and sent to axon terminals in the posterior pituitary
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Hormones released by axon terminals in the posterior pituitary are picked up by capillaries
and carried into the bloodstream
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Releasing hormones are synthesized and secreted into capillaries that carry them to the
anterior pituitary
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Releasing hormones then leave the capillaries and act on hormone-secreting anterior
pituitary cells
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• Liver stores glucose as glycogen – sensitive to shifts in levels of glucose
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• Damage to the lateral hypothalamus results in aphagia (undereating)
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Body weight exceeds average for a given height and sex by 20%
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Associated with health/social problems (Kolata, 1985)
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In 2000, the World Health Organisation identify obesity as a worldwide epidemic
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Environmental stressors – obese individuals increase consumption when stressed
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Three times more fat cells
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Heredity or environment?
Anorexia nervosa:
1
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5-1% of the population
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Characterised by severe decrease in eating but not due to loss of appetite
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Distorted body perception
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Loss of control of food intake
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Gorging followed by purging
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Needs to occur at least twice a week for three months for diagnosis
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Preoccupied with body shape
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• Social factors – type of food
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Emotion
• What is emotion? – “everyone know what emotion is, until they are asked to define it” (LeDoux,
1996)
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• Distinct from mood and affect:
1
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2
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• Three core components:
1
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2
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3
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Classification of emotions
• Positive and negative (Izard, 1971)
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• Emotional intensity (Buss, 1966)
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Theories of emotion
• James-Lange theory: three stages to an emotional response –
1
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2
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3
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• Two major assumptions:
1
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2
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• Cannon-Bard theory: changes in physiology from adrenaline did not produce fear –
1
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2
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3
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• Schacter-Singer theory: no unique physiological reaction is associated with each emotion; two factors
contribute to emotional arousal –
1
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2
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Emotion and the brain
• Limbic system: border between cortex and brainstem
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The amygdala
• Kluver-Bucy Syndrome: flattening of affect, hypersexuality and ingesting
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– suffered from epilepsy, seizures originated in amygdala, produced aggressive
behaviour
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Frontal lobe
• Left frontal damage = catastrophic reaction (emotionally volatile and prone to sad moods)
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• EEG research - more activity over left prefrontal cortex for happy film, reverse pattern for sad weepy
film
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bipolar
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endogenous
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6% unipolar and 1& bipolar, prevalence in females is twice that of males, approx
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• Cause:
1
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2
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3
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4
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• Anxiety – five major classifications:
1
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2
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3
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4
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5
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• Cause:
1
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2
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Movement and the Brain
Outline
• Principles of motor function
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• Motor cortex and movement
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Principles of motor function
• Hierarchical organisation – top down, principle of dissolution
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, 1982)
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Example: process of grasping a cup
1
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2
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3
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4
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5
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7
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Sensory receptors on the fingers send message to sensory cortex saying that the cup has been
grasped
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Basal ganglia judge grasp forces, and cerebellum corrects movement errors
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Motor cortex
• Primary motor cortex – controls movement, sends information to the spinal cord, damage can
produce muscle weakness, not paralysis (Leonard, 1998)
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, 2001)
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• Stimulation of human brain during neurosurgery (Penfield & Boldrey, 1937)
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Brain-computer interface
• BCI enabled paralysed patient to control robotic arm (Kennedy & Bakay, 1998)
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• Forms neural circuit with cortex (Groenewegen, 2003)
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Cerebellum
• Up to 10% of mass with 50% of neurons
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• Accuracy of movement (Thach et al
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Brainstem
• Stores complex patterns of reflexes, many species have typical behaviours
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• Stimulation interacts with presence of objects (von Hoist, 1973)
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• If cut higher up = quadriplegia, lower down = paraplegia
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Muscles
• Muscle types – skeletal (flexors/extensors), smooth and cardiac
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• Monitored – golgi tendon organs and muscle spindles
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• Force and direction – force hypothesis (Evarts, 1968), direction hypothesis (Georgopolous et al
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, 2004)
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• Somatosensory pathways – dorsal spinothalamic tract and ventral spinothalamic tract
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Damage to the somatosensory cortex
• Somatosensory thresholds (Semmes & Turner, 1977)
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• Somatoperceptual disorders (Teuber, 1968)
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Summary
• Principles of motor function
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• Motor cortex and movement
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Memory, Learning and the Brain
Overview
• What is memory?
• How do we learn new information?
• Where are memories stored?
• Amnesia
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• Theoretical interpretations
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• Hebbian synapse – reverberation (Hebb, 1949)
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, 1972), dendritic spines (Turner &
Greenough, 1985) and neurogenesis (Gould et al
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Long-term potentiation
• LTP can last for a long time
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• Processes:
1
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2
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3
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• Glial cell effects – astrocytes (Ge et al
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, 2005)
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• Susceptible to disruption (Bourtchouladze et al
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Where are memories stored?
• Inferotemporal cortex (Naya et al
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• Amygdala (Canli et al
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• Prefrontal cortex (Smith, 2000)
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, 2003)
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• Caveat – storage or processing
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•

Compelling evidence that a form of memory could be passed between generations (Pembrey et al
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Types of amnesia
• Amnesia – any partial or complete loss of memory
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• Anterograde amnesia – memory loss of events after onset
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• Amnesia of Korsakoff’s syndrome – thiamine deficiency: confabulation, meagre conversation content
and apathy
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• Concussive amnesia – a blow to the head produces coma; when victim regains consciousness, there is
a period of confusion; when the period of confusion ends, the victim has retrograde amnesia for
events that occurred during the period just before the blow and anterograde amnesia for events that
occurred during the period of confusion
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• Lateralisation of function
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• Factors that influence asymmetry/lateralisation
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Cerebral asymmetry – anatomical asymmetry
• Temporal lobe of left hemisphere larger, more grey matter in left hemisphere – Geschwind &
Levitsky, 1968
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• Broca’s area larger in the left hemisphere – Geschwind & Galaburda, 1985
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, 1985
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• Rodent right hemisphere cortex larger – Stewart & Kolb, 1994
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, 1984
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, 2005
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, 1983
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• Repeated testing doesn’t always produce the same results, practice effects (Effron, 1990) and task
difficulty (Weissman & Banich, 2000)
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• Local-global approach – LH functions as a collection of focal regions whereas the RH functions more
diffusely, LH is logical and analytical, RH is a synthesiser and more concerned with overall
configuration
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• Hemispheric encoding and retrieval asymmetry (HERA) – PET research shows lateralisation of memory
processes (Nyberg et al
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, 1994), true for both verbal and non-verbal material (Habib et al
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•

Interaction models – to better perform a function, one hemisphere inhibits the other (Kinsbourne and
Hiscock, 1977)
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• Structural asymmetry – corpus callosum; 11% larger in left handers (Witelson and Goldsmith, 1991),
not clear if more fibres, thicker axons or more myelin
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• Theories of hand preference:
1
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, 1977)
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Genetic – left handedness occurs following cerebral deficit (Bakan et al
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3
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4
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• Gender – caution (a lot of “pop” psychology)
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, 1992), posterior section of corpus callosum larger in
females (de Lacaste-Utamsing et al
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• Language vs
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• May be over simplification – females excel at both perceptual speed and visual memory
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Differential brain organisation – for males, LH lesions depress verbal skills and RH lesions
depress performance IQ; for females, LH lesions depress both (Inglis and Lawson, 1982)
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Maturational differences – girls mature earlier; regardless of gender, early maturers perform
better on verbal tasks (Waber, 1976)
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, 1983)
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, 2005)
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• Having your picture taken – put your left-side forward, posers’ left cheeks exhibit greater emotion,
left side of faces rated as more pleasing (Blackburn and Schirillo, 2012)
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, 2013)
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, 2010)
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• Impact of deficit/lesions on the hemispheres
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• Factors that influence hemispheric specialisation
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• Neurodegenerative disorder
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Brain injury
• Classification – acute (quick onset e
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stroke) or chronic (slower onset)
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) and specific vs
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Recovery of function
• Prospects of recovery (Levin et al
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• Variables affecting recovery:
1
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, 1976)
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Age (Martin, 2006) – hemispherectomy (Vanslancker-Sidtis, 2004)
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Handedness and gender
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Intelligence (Darley, 1972)
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Personality (Kolb & Whishaw, 1996)
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• Non-degenerative – Korsakoff’s
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Increases in lifespan – from 4% to 20% over 65yo (Kolb and Whishaw, 2011)
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Risk of dementia – double by 2030 and triple by 2050 (WAR, 2010) and costs
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• Costs – social and economic, cost of care is between £5 and £15 billion a year
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• Clinical features:
1
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2
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3
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• Neuropathological observations – cortical shrinkage of the amygdala, entorhinal cortex and
hippocampus, loss of pyramidal neurons from the frontal, temporal and parietal lobes, dendritic
arborisation, senile/neuritic plaques and neurofibrillary tangles
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• Aetiology of the cholinergic theory – pros = accounts for neurotransmitter loss, agonists can be used
to treat Alzheimer’s, relates to severity and blocking acetylcholine produces similar amnesia to
Alzheimer’s; cons = widespread neural degeneration
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Medication – redress loss of acetylcholine, limited improvement
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Vaccination – early trials with mice show a relief in symptoms
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Neural transplants – limited evidence, fail to halt the degenerative process
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• Physical exercise – reduced mental decline
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• Almost 50% of people with a psychiatric disorder experience behavioural problems
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Schizophrenia
• Prevalence – annual incidence of 0
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5 per 1000, approximately 2
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• Diagnosis – progressive deterioration with dismal outcome, heterogeneity suggests a syndrome,
presence of two or more symptom for 6 months (DSM-IV):
1
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2
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3
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4
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• Symptoms – positive or negative, acute or chronic
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Catatonic – posture, mute, echolalia
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Paranoid – delusions and hallucinations
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Disordered thought and behaviour
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Undifferentiated – doesn’t meet criteria for previous subtypes
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• Neurochemical observations – dopamine hypothesis; amphetamines = schizophrenic symptoms,
antipsychotics = reduce symptoms
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• Classification – two distinct sub-types:
1
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2
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• Aetiology:
1
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2
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, 2000)
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Developmental – consistent with age of onset (Woods, 1998), neuropathological data (Jones
and Murray, 1991)
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MPETD – “a threshold of influences is reached and schizophrenia results
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• Treatment:
1
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2
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, 1989)
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Control of emotional climate (Parker and Kadzi-Pavlovic, 1990)
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EEG biofeedback (Gruzelier et al
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5
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• Prognosis:
1
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2
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, 1989)
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Level of social stimulation is an important factor

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