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Brain in Trouble - Hoorcollegeaantekeningen literatuur uitgewerkt
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- Vrije Universiteit Amsterdam (VU)
Brain in Trouble - Hoorcollegeaantekeningen literatuur uitgewerkt
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Brain in Trouble – Literature.Overclocking the brain? The potential and limitations of cognition-enhancing drugs.
Cognitive enhancements (CEs) = interventions designed to improve human form or
functioning beyond what is necessary to sustain or restore good health.
Enhancement of cognition: memory, attention, language, perception, executive functioning.
The most promising CEs nowadays are:
Donepezil (Aricept): acetylcholinesterase inhibitor, used for AD, enhances information
processing, attention, and different kinds of memory.
Methylphenidate + Amphetamine: psychostimulants (dopamine and norepinephrine),
used for ADHD, enhances consolidation of long-term declarative memory.
Modafinil: wake-promoting agent, used for daytime sleepiness (i.e. narcolepsy, sleep
apnea), enhances attention, spatial-working memory, planning, and decision-making.
There are no or benign side effects for donepezil, methylphenidate and amphetamine.
However, because of serious side effects, modafinil would not be approved for CE purposes.
The equivocal findings of studies might be explained by:
1. small effects: insufficient statistical power.
2. insufficient attention to individual differencesL baseline cognitive ability, COMT
genotype.
3. task characteristics:
o ceiling effect: difficulty to improve cognitive performance.
o novelty: impaired effect on previously established performance.
4. single-docs studies: CEs, especially stimulants, follow U-shaped dose response curves.
There are multiple factors that limit the usefulness of cognitive enhancing drugs are:
linear + U-shaped dose-response curves: different effect on cognitive domains.
baseline dependency: ‘leveling of the playing field’.
trade-offs: enhancement of one task + impairment in another task.
overconfidence: impaired self-monitoring
Four potential trade-offs between and within different cognitive domains are:
- long-term memory (hippocampus) vs. working memory (PFC).
- stability vs. flexibility of long-term memory.
- stability vs. flexibility of working memory.
- attentional focus vs. creativity.
Psychiatric aspects of impulsivity.
The high comorbidity of impulsivity and selected psychiatric disorders – including personality
disorders, substance use disorders, and bipolar disorder – is in a large part related to the
association between impulsivity and the biological substrates of these disorders. Before
treatment studies on impulsivity can move forward, measures of impulsivity that capture the
core aspects of this behavior need to be refined and tested based on an ideologically neutral
model of impulsivity.
Purves Chapter 23 – Construction of Neuronal Circuits.
The chemoaffinity hypothesis: each tectal cell caries a chemical “identification tag” and that
the growing terminals of retinal ganglion cells have complementary tags such that the retinal
cell seek out a specific location in the tectum. The behavior of growing axons suggested that
there are gradients of cell surface molecules to which growing axons respond. In the eye and
the tectum, ephrins and Eph receptors are distributed in complementary gradients so that
,similar levels of ligand and receptor are matched. Therefore, the neurons grew back in the
same pattern, after they were removed in the eyes of fish.
Many observations show that many of the same adhesion molecules that participate in axon
guidance (ephrins, CAMs, cadherins) contribute to the identification and stabilization of a
synaptic site on target cells.
Neuregulin1 (Nrg1) is an essential regulator of expression and localization of postsynaptic
receptors and other proteins. Active Neuregulin 1 is cleaved from the presynaptic side, to
trigger postsynaptic neurotransmitter receptor insertion. Neuregulin1 also establishes contact
with many other cells. Neurexin and neuroligin form the link between pre and post. The
expression of neuroligin in non-neuronal cells is enough to from synapses.
Trophic interaction is needed for neurons to remain, without neurotrophic signaling the
contacts are lost and the axons and dendrites regress. There are a few neurotrophins: NGF,
BDNF and neurotrophin 3 and 4.
Purves Chapter 24 – Modification of Brain Circuits as a Result of Experience.
Hebb postulate: coordinated activity of a presynaptic terminal and a postsynaptic neuron
strengthens the synaptic connection between them. This led to understanding of two
phenomena. First, behavior not initially present in newborn emerge and are shaped by
experience throughout early life; and second, the brain continues to grow after birth.
For most animals, the behavioral repertoire for basic survival are innate. Those patterns of
connectivity are made in the embryo. In animals with complex behaviors, like humans, adapt
to the environment. These environmental factors are especially influential in early life during
critical periods, the time when experience and neuronal activity that reflects that experience
have maximal effect on the acquisition or skilled execution of a particular behavior. Imprinting
in birds can only happen in a short period of time. While motor behaviors have more time to
develop. So, critical periods can vary in time. When a specific environmental stimulus is
missing during this period, it is very difficult to develop the right connection in the brain.
Mice lacking genes for several neurotransmitter exhibit changes in experience-dependent
plasticity. Neurotransmitters and other secreted molecules that influence critical periods are
all thought ultimately to modulate levels of intracellular Ca2+, particularly in postsynaptic
cells. Increased Ca2+ can activate several kinases, which leads to modifications of the
cytoskeleton and changes in dendritic and axonal branches.
The critical periods in visual system development is tested in cats and monkeys by Hubel
and Wiesel. The eyes can be shut, and there can be varied with different shades of light.
Also, it is easier to test the sight of an animal compared to smelling or hearing. The afferent
terminals from an alternating series of eye-specific domains in cortical layer 4 called ocular
dominance columns. They can be visualized by injecting a tracer in one eye.
Visual cortical neurons were divided into seven “ocular dominance” groups based on their
degree of response to either the contralateral or ipsilateral eye. Group 1 cells are driven only
by stimulation of the contralateral eye; group 7 cells are driven entirely by the ipsilateral eye,
and neurons driven equally well by either eye were assigned to group 4. Most cells were
activated by both eyes, and about a quarter by only one eye. This normal distribution can be
altered by visual dominance, like keeping one eye shut. When an eye is shut during the
critical period, this eye is blind even when it is opened later, this is called amblyopia. This is
permanent, even if the formally deprived eye remains open, little or no recovery occurs. In
adult cats closing one eye for a year had no effect on ocular dominance.
,The loss of acuity, diminished stereopsis, and problems with fusion that arise from early
deficiencies of visual experience is called amblyopia. In humans, amblyopia is most often the
result of strabismus. Depending on the extraocular muscles affected, the misalignment can
produce convergent strabismus, called esotropia (“crossed eyes”); or divergent strabismus,
called exotropia (“wall eyes”). This results in double-vision and affects about 5% of children.
In these children one eye can be shut for a certain period. Or they can surgical adjust the
muscles of the eye.
There are also critical periods in the auditory, somatic sensory, and olfactory systems as well
as in motor pathways. The development of song in many bird species provides an example
of auditory system critical periods as well as critical periods for motor control of a complex
behavior.
Exposure to language from birth onward is essential for the development of appropriate
capacity to comprehend and produce meaningful communication. Children who have
acquired speech but lose their hearing before puberty suffer a substantial decline in spoken
language, presumably because they are unable to hear themselves or others talk and thus
lose the opportunity to refine their speech by auditory feedback during the final stages of the
critical period for language. Very young infants can perceive and discriminate between
differences in all human speech sounds. Japanese speakers cannot distinguish between the
l and r, because this is not reinforced by experience during the critical period. Children can
usually learn a second language without accent and with fluent grammar until about age 7 or
8.
The number of synapses throughout the cortex increased during prenatal and a limited
period of postnatal life, declined during a protracted period that included much of
adolescence, and reached a steady state in early adulthood. This indicates that critical
periods may first be mediated by local growth in an activity-dependent manner, followed by a
subsequent elimination of some synapses.
, Brain in Trouble HC1 – Introduction.
Learning objectives:
- Explain the contribution of genetic and environmental factors to complex multifactorial
diseases such as mental disorders.
- Elaborate on various treatment options for psychiatric disorders.
- Critically reflect on the boundaries between normal (healthy) and abnormal (ill) behavior
and the implications for society.
Only one class discussion is mandatory. You have to prepare statements.
The computer practicum and the lecture with Sun Mi are also mandatory.
Book: Foundations of Behavioural Neuroscience (8th or 9th edition).
The exam is about the lectures, the book is extra.
Grade:
75% written exam (MC and open questions)
25% 1 class discussion + 3 homework assignments
The goal of this course is to deepen the understanding of the etiology, expression and
treatment of (psychiatric) brain disorders, as well as models used in preclinical science. You
will be encouraged to critically analyze the impact of brain disorders on society.
There are three themes:
- Week 1: addiction and cognitive enhancement.
- Week 2: OCD, eating disorders and impulsivity.
- Week 3: mood disorders and social behaviors.
The trend of substance use among 15- to 16-year old European school student is decreasing
for alcohol and tobacco use. However, the trend for cannabis use is increasing.
In the Netherlands, alcohol and tobacco are used the most and also have the highest
number of related deaths, even though these substances are legal. Drugs have relatively few
(temporary) users and hardly any related deaths.
Drug legalization can be a step towards world peace, because you stop the war on drugs if
they are legal.
The lifetime prevalence of ADHD is 3-5% in adults and 4-8% in children. Since 20 years,
there is an exponential increase in the production of methylphenidate (Ritalin). This can be
explained by more awareness (more diagnoses), misuse of diagnoses (extra time on
exams), etc.
The lifetime prevalence of anorexia nervosa, bulimia nervosa, binge-eating disorders and
other eating disorders varies from less than 0.5% to 2.5%. Almost 50% of the people with
eating disorders meet the criteria for depression. Only 1 in 10 men and women with eating
disorders receive treatment. So, eating disorders have a high mortality rate.
In the US, there is a correlation between states that are the least inactive, the least happy,
and have the highest rates for diabetes and heart disease.
The lifetime prevalence of OCD is 1% in adults and 0.25% in children.
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