Introduction to Clinical Neuropsychology
Chapter 1. The development of neuropsychology
Cerebral localization: the idea (since 1800) that mental functions are localized in specific parts of the
brain
~ Gall and Spurzheim (1810):
o Localisationists
o Mental functions are exactly localized in the brain
o Well-developed mental functions are an effect of better developed cortex
o Cortex volume is reflected by local bulges in the skull (phrenology)
~ Flourens (1821):
o Anti-localisationist
o Removed small pieces of cortex in animals but did not observe specific and
permanent behavioral effects (sometimes functional recovery occurred)
~ Broca (1865) and Wernicke (1874):
o Localisationists
o Physicians observing specific relations between brain damage and language disorders
~ Fritz and Hitzig (1870) and Munk (1881):
o Localisationists
o Found specific relations between cortical areas and motor behavior or sensory
experience in dogs
~ Goltz (1881) and Lashley (1929):
o Anti-localisationists
o Behavioral effects of cortical lesions in experimental animals: the larger the lesion,
the stronger the effect (principle of mass action)
o Effects were often not very specific (principle of equipotentiality) and subject to
recovery (brain’s plasticity)
o Often disturbances of complex behavior (like searching for food) whereas simple
functions (standing, eating, walking) were undisturbed
o In animals, simple functions thus obviously more subcortically localized than in man
o In animals, cortex thus primarily responsible for integration of simple behaviors into
more complex behaviors
~ Penfield and Rasmussen (1950):
o Localisationists
o First to experiment/operate on humans
o During brain surgery they mapped cortical functions by using local electrical cortical
stimulation
o Patients under local anesthesia enabled investigating effects of cortical stimulation in
conscious persons like motor responses, speech, sensory experiences, hallucinations,
memories
Wernicke’s aphasia model (1874): predecessor of modern idea that mental functions are not
localized in specific, single cortical locations but are localized in multiple locations which are mutually
connected.
Neural networks are thus essential, and functional disorders can be an effect of damage of specific
cortical centres (cell bodies, grey matter), but also of damage of tracts connecting these centres
(axons, white matter). Functional disorders may thus occur without clear damage of the cortex.
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,Discrepancy between localisationists and anti-localisationists is reconciled by English neurologist
Hughlings-Jackson (1931) within a hierarchical model of the brain:
~ Brain functions are hierarchically organized: become more complex when ascending from
lower parts of the brain (spinal cord, brainstem, cerebellum) to higher parts (basal ganglia,
cortex)
~ Lower functions are integrated into higher functions, for example simple movements of
separate fingers are assembled into complex movement patterns (e.g. playing the piano)
~ All major parts of the brain are involved in complex behavior
~ Negative effects of the cortical lesions in animals are much smaller than in humans, because
animal behavior is less complex, and thus less dependent on cortical functioning
~ This allows a better functional compensation by subcortical structures after cortical lesions,
and thus a greater chance for recovery (larger plasticity)
Modern ideas about cerebral function localization closely fit with Hughlings-Jackson’s idea:
~ Parallel distributed processing: functions are dependent on different locations in the brain
which are simultaneously active and closely work together (active networks as apparent from
neuroimaging)
~ Good example of distributed processing is language: is based on a number of processes
located in different areas of the brain
~ Complex mental functions are more difficult to localize than simple functions due to their
multiple representation in the brain
~ Function localization is not static but is to a certain extent flexible. Neuronal plasticity
enables adaptation to changing demands of the environment and also enables a better
recovery after brain damage
~ Localization of functions may somewhat differ between individuals, which can partly be
explained by morphologic differences in cortical gyri and sulci between different persons
o Accidental differences in morphology are not of fundamental interest for function
localization. Localization in ‘flattened’ cortex shows good correspondence between
different individuals
Localization of functions in multiple locations (distributed processing) in the healthy brain does not
have negative effects on consciousness and behavior.
Different locations contribute to single, indivisible actions and conscious experiences (the binding
problem).
The same applies to left and right hemisphere: they are partly performing different actions, but they
are responsible for integrated action and subjective experience.
Nevertheless, a great part of our behavior is regulated by the brain at levels which are not attended
with conscious experience (automatic, precognitive, sub cognitive processes).
Chapter 2. Origins of the human brain and behavior
Does a relationship exist between the size of the brain and cognitive functions/intelligence?
~ Higher species have relatively larger brains. In this respect, both encephalization quotient
and absolute number of brain cells are important, not the absolute size of the brain.
~ Larger size is primarily due to relatively larger cortex. Larger cortex is related, among others,
with multiple representations of sensory, motor, and cognitive functions.
o For example, humans have multiple visual projection areas in occipital cortex which
cannot all be found in lower species. Each area has a specific function. The more
areas, the more functional possibilities.
Does in humans an interindividual relationship exist between brain volume and cognitive abilities?
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, ~ Already investigated in the 19th century
~ A clear relationship was not found
~ However, many methodological errors occurred in such studies, such as…
o no control for age effects whereas brain volume on average decreases with age
o No valid intelligence tests available
~ Therefore difficult to draw valid conclusions based on these older studies
Using modern methods, in healthy persons clear interindividual relationships between brain size and
cognitive abilities were neither found. For example, brains on average are smaller in women than in
men but no clear differences in cognitive abilities are found. This is to be expected, as a great part of
the brain consists of other structures than neurons, such as glia cells and blood vessels.
However, within a single person the number of neurons is important for cognitive functioning.
Studies of behavioral and developmental disorders show that such disorders are accompanied with a
reduction of grey matter (cell bodies) or white matter (axons).
Intra-individual relations do exist between brain volume and cognitive/emotional dysfunctions.
Decreasing brain volume in a particular person can have negative effects. Examples:
~ Alzheimer’s disease
~ Huntington’s disease
~ Vascular/HIV dementia
~ Epilepsy
~ Autism
~ ADHD
~ Psychopathic behavior
~ Clinical depression
~ And more…
With recovery of the disorder (as far as possible), brain volume may increase again. Negative effects
can thus be reversible.
Other evidence of intra-individual relationships between brain volume and cognitive functioning:
cognitive training may result in (local) increase in grey and/or white matter.
Chapter 3. Organization of the nervous system
Clinical neuropsychology is primarily directed to cortical functions (i.e., more complex, perceptual,
motoric, and cognitive activities).
Primary role of cortex is memory function: storage of programs suited for performing perceptual,
motoric, and cognitive activities.
According to the computer metaphor we can distinguish between…
~ Memory (storage of programs): cerebral and cerebellar cortex
~ Processors (execution of programs):
o Basal ganglia: processors for motoric and cognitive programs
o Limbic system (amygdala, hippocampus): processors for emotional and memory
programs
Chapter 5. Communication between neurons
Neurotransmitters are important for a better understanding of neuropsychological problems and
therapies.
Major categories of neurotransmitters:
a) Small-molecule transmitters (fast action; fast synthesis from alimentation; quick
replenishment in case of depletion; play a role in many types of behavior)
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, ~ Acetylcholine (active in connection nervous system – muscles)
~ Mono-amines: dopamine, norepinephrine, epinephrine, serotonin
Epinephrine (= adrenaline): only active outside central nervous system (CNS).
Involved in control of organs (heart, blood vessels, etc.) by autonomic
nervous system
~ Amino-acids: glutamate, GABA, glycine, histamine
Most frequently occurring and most active neurotransmitters in CNS
(workhorses of nervous system)
b) Neuropeptides (chains of amino acids; slow action; slow synthesis; not quickly replenished
after depletion; are within CNS involved in many specific behaviors, like pleasure and pain)
~ Are also active outside CNS as hormones (e.g., involved in energy supply, blood
pressure regulation, nociception, stress regulation, attachment behavior)
~ Many different substances, e.g., vasopressin, oxytocin, endorphins, enkephalins,
insulin, cholecystokinin, gastrin, corticosteroids (not primarily relevant in this course)
c) Gaseous transmitters (quick action, e.g., quick vasodilation in the brain and elsewhere in the
body like genitals; activate metabolic processes within nervous cells)
~ NO, CO
Neurotransmitters may activate different types of neuroreceptors, depending on their specific
location within the nervous system. They may therefore have different effects, both excitatory and
inhibitory effects.
In addition, neurotransmitters may have either specific or modulatory effects:
~ Specific excitation or inhibition of postsynaptic neuron
~ Modulation (strengthening or weakening) of effects of other transmitters
Amino acids have relatively many specific effects.
Acetylcholine and mono-amines have relatively many modulatory effects (the term
‘neuromodulators’ is often used).
Amino acids are locally produced at sites where they are active, particularly at cortical sites.
Mono-amines (dopamine, norepinephrine, serotonin) are produced within brainstem nuclei, and are
transported through long ascending axons to locations where they have an activating effect on major
areas of cerebrum and cerebellum (ascending activating systems).
Acetylcholine is produced in nuclei within brainstem and also locally in the frontal lobe (basal
forebrain nuclei) and from there through long axons transported to higher – particularly cortical –
areas. Like mono-amines, acetylcholine has strong activating effects within CNS.
Transmitters with modulating effects (neuromodulators) have important activating functions:
activate larger areas of the brain (particularly cortex) involved in perception, motor behavior,
cognition, and emotion.
Neuromodulators are particularly important for strong and quick actions if such responses are
required by the situation.
They are important for regulating excitability of cortical neurons, and thus for regulating attention
and alertness. They are also important for regulation of sleep and wakefulness.
Neuromodulators are involved in many neurological and neuropsychological disorders.
They are an important point of application of psychopharmacological agents (hypnotics, sedatives,
antipsychotics, antidepressants) and addictive drugs (stimulants, psychedelics, narcotics).
Certain pathological types of behavior (for example ADHD, bipolar disorders, obsessive-compulsive
disorders) probably stimulate production of activating neuromodulators. Such seemingly pathological
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