Cognitive neuropsychology (540033-B-6-2018)
Summary of the slides and notes of the lectures
Lecture 1 introduction
Cognitive neuropsychology = the research about the relation between structure and function of
the brain and specific cognitive functions (language, memory, attention etc.). We do this by
investigating these cognitive processes in normally healthy people. Also, we can do this by
investigating brain-damaged people. What is it that they can’t do as a result of the brain-damage?
During ancient Egypt people thought that the brain was the heart of the soul and memory, instead
of the head. To reach this “soul” they used a method called trephination. This is a surgery in which
a hole is drilled into the skull to expose the brain. They performed this surgery when people were
suffering epileptic seizures, migraines and mental disorders or to prevent the forming of blood
clots.
During ancient Rome and Greece, there were three people who had certain beliefs about the
brain.
Hippocrates: the brain is very important because it’s an organ of intellect, it controls the senses
and movement. Hippocrates also introduced the term “contralateral”. Lesions produced a
contralateral effect.
Aristotle: the brain is not very important, it’s just a radiator to cool the body. The heart is important!
This is the center of intellect.
Galen: tried to deduce function from structure of the cerebrum, cerebellum, ventricles and nerves.
He believed that the cerebrum is for sensations, the cerebellum is for muscles, the ventricles are
for communication and the nerves are for humors (in Dutch: humeur). Galen based this conclusion
mainly on animal research.
During the Renaissance, there were three people who said something about the brain.
Vesalius: first person to write an anatomical text based on research of the human body.
Descartes: mind and body are separated but they do interact. The pineal gland is the place where
mind and body come together.
Willis: linked specific brain damage to specific behavioral deficits. He made some very accurate
brain representations.
At the end of the 18th century people believed that (1) injury in the brain can disrupt sensations,
movement and thoughts and can cause death. (2) the brain communicates with the body through
nerves. (3) the brain has different identifiable parts, which probably perform different functions.
And (4) the brain operates like a machine and follows the laws of nature.
During the 19th century people gained a lot of knowledge about the brain. They learned about:
nerves, function localization, the nervous system and neurons.
What did they learn about nerves? Galvani discovered that electrical stimulation of a nerve caused
a muscle to contract. Bell and Magendie discovered that nerve fibers carry sensory or motor
information. The information-flow in a nerve fiber is unidirectional; it only flows in one direction.
,What did they learn about localization of specific functions to different parts of the brain? Gall is a
pioneer in ascribing (in Dutch: toeschrijven aan) cerebral functions to various areas of the brain.
This is called phrenology = science of correlating head structure to personality traits. Broca made
the first model of neuropsychology of language. He said that language is located in a particular
part of the cortex.
What did they learn about the nervous system? Darwin suggested that human and animal nerves
systems share a common underlying mechanism. Therefore, he said we could use animal models
for studying the brain. Darwin also discovered the phenomena “natural selection”. Natural
selection says that traits which are an advantage for survival are more likely to be passed on by
generations than traits which are not-advantageous. So, some traits are heritable.
What did they learn about neurons? Golgi said: there is no space between neurons, they are all
connected with each other. Cajal said: No, neurons are separated by synaptic space. Each neuron
is an independent unit. So, Golgi and Cajal disagree.
What’s the story of Phineas Gage? An iron bar passed through the left side of his skull, which
damaged the orbitofrontal regions. During this, Phineas remained conscious and alert. Long term
consequences were that he was no longer able to pay attention and concentrate. Also, his
personality drastically changed.
What’s the story of Henry Molaison? He had severe epilepsy. To cure this, doctors performed
surgery in which they removed a big part of the hippocampus and a little bit of the amygdala and
surrounding cortex. This led to severe anterograde amnesia, little or no retrograde amnesia and
little to no problems with implicit memory. Here they concluded that the hippocampus is an
important mechanism for storing new and explicit memories.
Angelo Mosso discovered the first
neuroscientific method. He believed that
you could measure brain activity by
putting a person on a balance. He said:
the brain needs more blood when it works
harder, so when you perform a task which
takes much mental effort, the balance will
flip because there’s more blood in the
brain then in other parts of the body. This
was a non-invasive measure of blood redistribution.
What is pneumoencephalography? In this procedure, they drain cerebrospinal fluid out of the brain
and replace it with oxygen. This is a very painful procedure. But why do they perform this when it
hurts so bad? Walter Dandy said that this led to an increased structural resolution of the brain on
an X-ray because there’s greater contrast between brain and air. On this X-ray doctors were able
to localize brain lesions.
What is cerebral angiography? Moniz said that you can see where blood vessels are by injecting
a certain fluid in these vessels. A contrast agent (fluid) is introduced within a large artery and
dispersed throughout the brain. This is a very precise method.
,Hans Berger invented the Electro Encephalogram (EEG). He recorded neuroelectrical impulses
within the brain across the scalp. He used EEG as a diagnostic tool to determine whether a patient
had epilepsy or sleep disturbances. On an EEG you can see abnormalities.
How are peripheral measures executed? You can do this in different manners: skin conductance,
heart rate, muscle activity, eye movement and pupil dilation.
Lecture 2 animal research
With help of animal research people have discovered a lot about the brain. Research can be done
in several ways: anatomically, lesions and pharmacological manipulations, recording neuronal
activity and neuroimaging.
Anatomically:
In the image above you can see an example of anatomical research. In this case, a tracer is
injected into a localized area and the transport along axons is studied. There are two tracers:
Anterograde tracer = from cell body to termination site of axons
Retrograde tracer = from termination site of axons to the cell body
Polysynaptic means that the tracer can project to synapses which are further away. Monosynaptic
means that the tracer can only project to the synapse which is next to the synapse where the
tracer is injected.
Viruses are polysynaptic, they can form chains of connections.
Why do we use animals instead of humans in anatomically research? An animal brain provides
much more detailed information than a human brain. In animals you can get information about
which of the six layers receives or sends the information (based on the method above). This level
of detail is not possible in humans. We are able to localize to which area the tracer is transported
in the human brain, but it is unethical to inject tracers in human subjects.
Lesions and pharmacological manipulations:
With help of lesions we can conclude something about the function of a region or neurotransmitter
system. Some lesion-methods only damage grey matter and some only damage white matter.
There are different lesion-methods, which differ in the kind of damage they cause: permanent
techniques and reversible techniques. Permanent techniques damage something forever, when
it’s gone, it doesn’t come back. Reversible techniques can be changed back to how it was before.
, Permanent lesions:
Aspiration = removing tissue by sucking it out through a pipette. It can only remove surface areas,
but damages more than just the specific area.
Electrolytic = pass an electric current through an electrode and destroying adjacent ( in Dutch:
nabijgelegen) tissue.
Excitotoxic/neurotoxic = selectively destroying cells and spare fibers by infusing a chemical
through a cannula (= thin tube). A benefit of this technique is that you can also reach deep
subcortical structures.
Reversible lesions:
Pharmacological injections = inducing agonists and antagonists to change neurotransmitter re-
uptake, synthesis and break-down. For example: GABA agonist muscimol increases local
inhibition.
Optogenetics = combination of genetic and optical methods to achieve gain or loss of function in
specific cells. In simple words: turning neurons on and off by using light for example. This has a
better spatial and temporal resolution than pharmacological interventions.
Chemogenetics = instead of light (above) we use drugs. Certain receptors only react on certain
drugs. Therefore, it’s a specific method. DREADDS: Designer Receptors Exclusively Activated by
Designer Drugs.
Cryogenic inactivation = cooling leads to inactivation/inhibition of a certain synapse. A
disadvantage is that this technique requires direct access to the tissue, so it’s not well-suited for
deep and subcortical structures.
An important difference between permanent and reversible lesions is that as a result of permanent
removal, the brain will compensate for this “loss”, but with reversable lesions this doesn’t happen.
After you compared the effect of a permanent and a reversible lesion, you can say something
about compensation.
Why do we use animals instead of humans in lesion and pharmacological research? First, it’s
possible to remove grey matter without damaging white matter in animals. In human, you always
damage both. Second, it’s possible to target a very specific area. Third, you can place the exact
same lesion in animals and thereby compare them what makes results more reliable. In humans,
this would be unethical. Last, you can monitor cognitive function before and after the lesion, where
in humans you mostly only monitor afterwards. Therefore, there will be no baseline.
