The Brain Story

Cognitive Neuroscience ‘The Brain Story’ by Vaia Lestou

A brief History of Cognitive Neuroscience • Ancient humans although they wondered extensively about the nature of human feelings, memories, attention, communication, motion and many other ‘cognitive functions’, they had one big problem. Problem: • They did not have the ability to systematically explore the mind through experimentation.

A brief History of Cognitive Neuroscience

• But if you can observe, manipulate & measure then you can start to determine how the brain gets its job done Debrück (1986) ‘Mind From Matter?’

• If you want to understand how a biological system works then a laboratory is needed and experiments are essential.

A brief History of Cognitive Neuroscience • Enigma of whether the brain works in concert or parts of the brain work independently is still the focus of contemporary research – face area – specialised only for faces? – or objects as well?

A brief History of Cognitive Neuroscience • Franz Joseph Gall & J.G. Spurzheim claimed that the brain was organised into 35 specific functions – founders of phrenology in the early 19th century

• Functions ranged from language and colour perception to hope and self-esteem • If a person used one of the faculties more than the others the brain representation area grew (bump in the skull idea!)

A brief History of Cognitive Neuroscience • Gall and colleagues believed that by studying carefully the skull of a person you could go a long way in describing the personality of the person inside the skull • Anatomical Personology

A brief History of Cognitive Neuroscience • P.J.M. Flourens (1794-1867) challenged Gall’s localisation views – bird experiments

• According to Flourens(1824) :‘All sensations, all perceptions and all volitions occupy the same seat in these (cerebral) organs. The faculty of sensation, percept and volition is then essentially one faculty.’

A brief History of Cognitive Neuroscience • In France Paul Broca treated a man who had suffered from stroke • the patient could understand language but could not speak • the patient’s left frontal lobe was damaged • Broca’s area

3D MRI of human brain with Broca's area highlighted in red

A brief History of Cognitive Neuroscience • The German Neuroloist Carl Wernicke in 1876 reported a stroke victim who could talk freely but what he said made little sense • Patient could not understand spoken or written language • Wernicke’s area

3D MRI of human brain with Wernicke's area highlighted in blue

A brief History of Cognitive Neuroscience • The most famous of all physiologists was Brodmann who analysed the cellular organisation of the cortex and characterised fifty two distinct regions • It was soon discovered that the cytoarchitectonically described brain areas represent distinct brain regions

A brief History of Cognitive Neuroscience • The revolution in our understanding of the nervous system was brought by Camillo Golgi (Italy) and Ramon y Cajal (Spain) • Golgi developed a stain that impregnated individual neurons • Cajal found that neurons are discrete entities • He was also the first to suggest that neurons transmit electrical information in only one directions from the dendrites to the axonal tip

A brief History of Cognitive Neuroscience A brief History of Cognitive Neuroscience

A brief History of Cognitive Neuroscience • The term Cognitive Neuroscience was first coined in a taxi in the 70s and by that time a new mission was clearly required • neuroscientists were discovering how the cerebral cortex was organised and functioned in response to simple stimuli • specific mechanisms were described, such as those relating to visual perception by Hubel & Wiesel • models were build to describe how single cells interact to produce percepts • and psychologists started to abandon the ideas of learning and associationism and believed that the behaviours they were interested in had biological origin and instantiation.

Mission Statement of Cognitive Neuroscience:

‘How the brain actually does enable the mind’

Anatomy of the Brain • Brain = Cerebral Cortex • Has two symmetrical Hemispheres • Each hemisphere consists of large sheets of layered neurons • The human cortex is highly folded to pack more cortical surface into the skull. • The surface area of the average human cerebral cortex is about 2200 to 2400cm2 • The infolding of the cortical sheets are the sulci and the crowns of the folded tissue are called the gyri

Anatomy of the Brain • The cortex has a high density of cell bodies, the ‘grey matter’ • The underlying region is composed primarily by axons of neurons and is known as the ‘white matter’, they connect the neurons of the cerebral cortex to other locations in the brain

Anatomy of the Brain • Cerebral Hemispheres have four main subdivisions – – – –

Frontal Parietal Temporal Occipital

The methods of Cognitive Neuroscience 1. Neuroanatomy 2. Neurophysiology 3. Neurology 4. Functional Neurosurgery 5. Cognitive Psychology 6. Computer Modelling 7. Converging Methods

1. Neuroanatomy • • • •

Studies the nervous system’s structure Describes how the parts are connected Descriptions can be made at many levels For the neuroanatomist investigations occur at two levels: – gross neuroanatomy: general structures and connections – fine neuroanatomy: main task is to desribe componenents of individual neurons

• Histology is the study of tissue structure through dissection, and is essential for neuroanatomists to know

1. Neuroanatomy • Primary concern of neuroanatomy is the pattern of connectivity in the nervous system that allows information to get from one site to another – problem made difficult by: • fact that neurons are not wired together in a simple fashion • often innervated with many neurons

• Solution: Refinement of New Stains • stains for cell bodies • stains for axons • have the characteristic that they are absorbed from specific chemicals and therefore ‘colour’ specific targets

1. Neuroanatomy • Interested in describing the structure of different neurons • Neurons are heterogeneous, varying in shape and size

2. Neurophysiology • Structure is closely tied to function • We cannot understand brain function from neuroanatomy alone • Neural function depends on electrochemical processes and numerous techniques exist to measure and manipulate neuron activity • Some record cell activity in passive or active conditions and other manipulate activity by electrical stimulation or chemical induction a. Electrical Stimulation b. Single Cell Recording c. Lesions

A. Electrical Stimulation • Early insights to cortical organisation were made by directly stimulating the cortex of awake humans undergoing neurosurgery • Pioneers, Penfield & jaspers (1954) explored the effect of small electrical currents applied to the cortical surface Stimulation of the motor cortex: movement

Stimulation of the somatosensory area: somatic sensation

B. Single-Cell Recording • The most important technological advance in neurophysiology has been the development of methods to record directly the activity of single neurons in laboratory animals. • An thin electrode is inserted into an animal’s brain (brain does not hurt!) • The primary goal of single cell recording experiments is to determine experimental manipulations that produce a consistent change in the response rate of a single neuron

C. Lesions • Neurophysiologists have studied how behaviour is altered by selectively removing one or more of brain components. • Logic: if a brain structure contributes to a task then removing that structure should impair performance in that task. • Human cannot be subjected to such procedures, so human neuropsychology requires patients with naturally occuring lesions.

MRI scan of a normal and lesioned brain

3. Neurology • • • •

Human pathology has provided key insights to the relation between the brain and behaviour Postmortem studies by early neurologists such as Broca and Wernicke were instrumental in linking the left hemisphere with language functions By selecting patients with a single neurological impairment, we can best link brain structures to specific cognitive functions. Sometimes patients have diffused damage and then conclusions are harder to draw. – Structural imaging of neurological damage (CT) helps define the damage (advanced method of x-ray studies)

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Causes of Neurological Disorders – vascular disorders (ie strokes) – tumours – degenerative and infectious diseases (MS, Huntington’s Disease)

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– trauma Functional Neurosurgery (lobectomy)

Phineas Gage Case • Most famous patient who survived severe brain damage • He was a railway construction worker who got injured by an accidental explosion • Severe personality change after the accident

4. Cognitive Psychology • Cognitive Psychology assumes that our perceptions, thoughts and actions depend on internal transformations or computations – Mental Representation and Transformations • information processing depends on internal representation » ball rolls down a hill -pictorial representation better than one that encompasses the laws of physics

• mental representations undergo transformations » imagine two letters presented in a screen one vertical the other one rotated in order to decide if they are the same or different you transform them to be into the same position

– Constrains on Information Processing • exploring the limitation in task performance » Stroop task

5. Computer Modelling • Models are explicit – they can be analysed in detail, the way the computer represents the process must be completely specified

• Representation in Computer Models – models differ greatly in their representations (ie. symbolic of object recognition would have units that represent visual features such as corners)

• Models lead to Testable Predictions • Limitations with computer models – radically simplified and limited in their scope – some of their requirements come in contrast with what we know about living organisms – restricted to narrow problems – modelling often also occurs in isolation to current theories

7. Converging Methods • • • •

Cognitive Deficits Following Brain Damage Single and Double Dissociations Groups versus individuals Imaging the Healthy Brain

Single and Double Dissociations • Single dissociation • Two groups differ on one critical behavioral task • One group has a particular brain lesion, the other doesn't (the other group is usually a control group who is considered healthy and without any known brain abnormality) • We then tentatively conclude that the difference on the behavioral task is due to the brain lesion • This, in turn, suggests that the brain region that is lesioned probably was responsible for some aspect of the behavior being studied • However, this connection is not guaranteed to be the case

Single and Double Dissociations • Problems with interpreting a single dissociation: • The task measuring the behaviour may not be sensitive to the true underlying behaviour that is disrupted • The task may reflect something similar to, or a derivative of, or part of the real behaviour that brain region is involved in, but it may not be a completely accurate measure

• The behavioural change, though apparently narrow in scope, may be part of a broader behavioural change that we haven't yet identified • The lesioned brain area may also affect other brain areas responsible for producing this and related behaviours

Single and Double Dissociations • Double dissociation • Two groups differ, in different ways, on two different behavioral tasks • Usually, the two groups each have different types of brain lesions • For example, one patient with Broca's area damaged and another patient with Wernicke's area damaged • The first patient shows difficulty producing speech, while speech comprehension is apparently normal • The second patient shows difficulty comprehending speech, while speech production is apparently normal • We conclude, fairly confidently, that Broca's area is responsible for speech production while Wernicke's area is responsible for speech comprehension

Single and Double Dissociations • Double dissociations are more powerful than single dissociations because we can isolate fairly specific behaviours that change with one type of lesion but don't change with a different type of lesion • The problems with the task (how sensitive it is to the actual behavioural change) are still a concern, but we are more confident with conclusions about brain localization when there are double dissociations

Groups versus individuals •

Individual case studies • Study one individual carefully with a known brain deficit • If there is a specific behavioural deficit (after careful testing), it can be correlated with the known brain deficit • And if two case studies are compared, each with different lesions, and double dissociations are found, we have strong confirmation for the link between behavior and brain region • We are, of course, concerned that one individual case study may not reflect a larger population • If you are familiar with statistical analysis, you should know that one research subject (N=1) is not very useful in statistical analyses • We cannot know for sure that the behavioural deviations from normality are due to the brain deficit and not just because this person was different (with or without the brain deficit)

Groups versus individuals • Group studies • In this approach, we compare groups of people with similar brain deficits and determine if they show a consistent pattern of behavioural deficits • This minimizes the chance that individual differences are masking the results of brain damage • The bottom row shows the proportion of overlap for a given brain region • So we would be fairly confident that the areas of highest overlap were most likely involved in producing the behavioral deficit

• Comparing across brains is not trivial, however, because of individual variation • To accomplish this, individual brains are matched to a "standard" brain • The common technique is to use the Talairach brain--the brain of a French woman • After matching certain landmark features, the image of a brain is distorted until it matches the Talairach brain • Then all the brains are compared from this common, standard brain image

Imaging the Healthy Brain • Transcranial magnetic stimulation (TMS) • The goal of this technique is to intentionally induce a temporary "lesion" • As far as we know, the brain is not damaged in any way, but a region is temporarily deactivated • A strong electrical signal is sent to a region of the scalp • We don't exactly know how this works, but it seems to disrupt neural function • So for a very brief period of time, the behaviours associated with the focus of the TMS should be impaired

• There is some control over the location of the "lesion," but the precision is limited • The device that administers the electrical pulse is fairly large • It is usually held in place manually, lacking much precision

Imaging the Healthy Brain Scalp recordings • Electroencephalogram (EEG) • Passively measure electrical activity from neurons that reaches the scalp • Place electrodes on the scalp to record electrical activity • Hook the electrodes to an amplifier to boost the signal (very little neurally generated electricity will reach the scalp) • Have a representation of global neural activity • Very useful for determining sleep patterns

Imaging the Healthy Brain • Event-related potential (ERP) • The development of ERPs is when the EEG became useful as an experimental tool • The procedure involves time-locking an EEG recording to the onset of a particular stimulus or behaviour • One EEG reading is very noisy; i.e. the electrical signal is very chaotic and variable • But if we measure EEG multiple events of the same type, all timelocked to the onset of the event, and average them together, a smooth pattern arises

Imaging the Healthy Brain • Magnetoencephalogram (MEG) • The methodology of MEG is very similar to the methodology for ERP • The sensors for MEG are actually measuring magnetic fields produced by neurons, not electrical signals • The inverse problem still exists for MEG, but because there is less distortion of the magnetic signal than there is for the electrical signal, the solutions end up being more accurate, on the whole • However, this technique is extremely expensive ($1 million for a reasonably good set-up)

Imaging the Healthy Brain • Positron-emission tomography (PET) • Methodology: • Water labelled with radioactive oxygen, is injected into a subject • Brain cells require oxygen (and glucose) for energy • The radioactive oxygen is unstable enough that protons break off and collide with electrons in the brain • These collisions are measured by a PET scanner

• With this technique, we do not directly measure neural activity • It is assumed that the higher concentration of radioactive isotopes reflects higher neural activity • The more active a neuron is, the more energy it should need to replenish and the more likely the radioactive oxygen will enter into that brain region

Imaging the Healthy Brain •

We use the subtraction method to determine relative levels of neural activity • PET scans are taken separately for two experimental conditions • The two conditions are identical except for one feature--the behavior being studied • Then one PET images are subtracted from the other, so the resulting difference should reflect the defining feature • So if Task 1 required Processes A, B and C, and Task 2 required Processes A, B, C and D, the difference between the PET images for Tasks 1 and 2 should reflect the activity unique to Process D

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One consideration when using PET as an experimental technique is that it takes 20-45 minutes for the radioactive isotope to get flushed out of the brain

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So each experimental condition takes that long, meaning it is impossible to compare too many conditions in one PET experiment

Imaging the Healthy Brain • Functional magnetic resonance imaging (fMRI) • The BOLD response • BOLD stands for Blood Oxygen Level Dependent • What is measured is dependent on the levels of oxygen in the blood for any local region of the brain • When oxygen is used by cells, the result is the blood becomes more deoxygenated • Deoxygenated hemoglobin is more ferromagnetic (the iron in the blood is more prominent), which is what the MRI scanner can measure • Basically, fMRI measures the ratio of deoxygenated to oxygenated hemoglobin

Imaging the Healthy Brain • Subtraction method is one technique also used with fMRI • Present variations of a task that each differ in one respect • These differences may be different levels of a single cognitive dimension (e.g., different amounts of visual information presented) or they could be completely different cognitive functions • Contrast the fMRI signal from these conditions with each other and with the signal from a control condition, when the extra cognitive function was not present (but everything else was) • These subtractive differences are reported as correlating with changes in behavior • Many different variations are possible with fMRI, unlike PET, because it is not necessary to wait minutes between conditions • We can use alternating epochs of a fixed length of time doing each variation of the task

Concluding Remarks • Advances in science are often fueled by technological developments • The maturation of cognitive neuroscience as a scientific field provides a tremendous impetus for the development of new methods • The questions we ask are constrained by the methods available but new research tools are promoted by the questions we ask.