Brain structure & function


Reading: Chapter 3 - anatomy of the nervous system Chapter 6 - the visual system Chapter 7 - mechanisms of perception - hearing, touch, smell, taste and attention Divisions of the nervous system 5 major structure of the brain 5 divisions are evident in the human brain from embryonic development through to adulthood Myelencephalon - medulla - largely comprises tracts between brain and spinal cord Metencephalon - pons and cerebellum Mesencephalon - tectum and tegmentum Diencephalon - thalamus and hypothalamus Telencephalon - cerebral cortex, limbic system and basal ganglia Cerebral cortex Composed of small unmyelinated neurons Grey matter (other layers are composed of large myelinated axons and are white matter) Convolutions serve to increase surface area Large convolutions = fissures Small convolutions = sulci Ridges between fissures and sulci - gyri Longitudinal fissure separate hemispheres (it remains connected by cerebral commissure, inc corpus callosum) Contains the neocortex and subcortical structures (hippocampus, limbic system, basal ganglia) Neocortex The newest part of the cerebral cortex to evolve Cerebral cortex = largest part of telencephalon, composed of grey matter. Neocortex = largest part of cerebral cortex (90% of cerebral cortex is neocortex in humans). Other part is allocortex (contains hippocampus) Main difference is that neocortex has 6 layers - the most developed in its number of layers and organisation of the cerebral tissue (specific to mammals) Humans have large neocortex ratio, which correlates with complexity of behaviour. For a large neocortex to evolve brain must evolve in size to support it Central lateral fissures divide each hemisphere into 4 lobes (frontal, parietal, temporal and occipital) Lobes are not functional units 4 lobes of the cerebral cortex/neocortex A history of localisation of brain function - from phrenology to histology The rise and fall of phrenology: An enduring question in biopsychology is the extent to which functions of the brain (language, thought movement etc.) can be localised to specific areas of the brain Franz Joseph Gall (1758-1828) – famous proponent of localisation theory – founded Phrenology. Phrenology comes from the ancient Greek “phren” meaning ‘mind’ and “logos” meaning ‘knowledge’ A “pseudo medicine” which attempted to divine individual intellect and personality from examination of skull shape – assumed the surface of the skull faithfully reflects the relative development of various regions of the brain. Borne out of an observation of his schoolmate being able to recite long passages of prose who had bulging eyes – he reasoned the ability for verbal memory lay in the frontal region behind the eyes His lectures on “cranioscopy” offended religious leaders and were condemned in 1802 by Austrian government and banned. Three tears later he was forced to leave the country Gall identified 27 cranial regions in total that corresponded to distinct mental trials He found regions responsible for murder and inclination to steal (by feeling criminals head until he began to 'detect patterns') Localised 'destructiveness' to above the ear - because he has a student who liked torturing animals who had a bump by his ear Gall's positive contributions- Although phrenology was discredited there were some positive contributions to research He believed the brain was the physical organ of the mind which governed mental faculties and feelings He proposed the idea that the cerebral cortex contains areas with localised functions He was proved correct as later specific regions of the cerebral cortex were shown to be specifically involved in language (Broca located a speech centre in 1861) and movement (motor cortex) - many more have been localised since Gall was the first to identify grey matter of the brain with active tissue (neurons) and white matter conducting tissue (ganglia) His views were modern for the time, and they inspired others to explore the brain e.g. Pierre Flourens - 1794-1867 - the first scientist to use lesioning (the removal of tissue from the brain) as a means of experimentally studying the brains different regions Lesion studies - Broca's Aphasia In 1960's Broca was interested in Gall's claims that language functions were located in frontal lobes of the brain Broca was consulted about 51 year old patient with multiple neurological problems who had been without speech for many years Could only say the word 'tan' A test case for question about language localisation in frontal lobes - since no productive language Tan died several days later - autopsy revealed lesion on the surface of left frontal lobe Broca's aphasia A second patient had reduced speech due to stroke 1 year previous 85 year old patient could only say 5 words At autopsy there as a lesion at approximately same region ad Tan This speech deficit is known as Broca's aphasia Inferior frontal gyrus on left cerebral hemisphere Known now as Broca's area Wernicke's aphasia According to Broca - damage restricted to Broca's area should disrupt speech production, but not comprehension The next major even in cerebral localisation of language - Carl Wernicke's 20 clinical cases of language comprehension 1874 ■ Wernicke suggested that selective lesions of Wernicke’s area produce a syndrome that is primarily receptive. Characterised by poor comprehension of written and spoken language and speech that is meaningless, but still retains superficial structure, rhythm and intonation of normal speech ■ Wernicke’s aphasia = word salad ■ Localised by autopsy to the left temporal lobe So work was already being conducted to localise language to specific brain regions ■ Further progress was made by German neurologist Korbinian Brodmann (1868-1918) ■ Began to produce maps of the brain based on cytoarchitectural organisation of neurons in cerebral cortex using the Nissl method of cell staining ■ Identified 52 areas of the cerebral cortex that differ histologically (cells/structures). These are known as Brodmanns functional areas of cerebral cortex Importance of Brodmann areas ■ Brodmann’s areas were defined based solely on their neuronal organisation, but have since been correlated closely to diverse cortical functions. ■ E.g. Broca’s speech and language areas were localised to BA 44 and 45 ■ Thus Brodmann provided a map based on collections of neuron types – which have been examined using lesion studies, experimental ablation, and functional neuroimaging to map onto different brain functions	Functional neuroanatomy With Brodmann’s findings of differing cell types located in clusters – this propelled the idea of functional localisation Since then lesion studies, case studies, experimental ablation in animals and functional neuroimaging have opened up our understanding of how the brain works We move from basic naming of lobes and structures by location to naming areas by function e.g. “motor areas” , “visual cortex” - and that multiple areas contribute to behaviour – these brain regions connect with each other and pass information General classification of three functional areas: sensory, motor, and association We are still figuring out how the brain makes connections and produces behaviour Prefrontal cortex: Very developed in humans Belies complex cognitive behaviour, conscious thought, social behaviour, personality, decision making Executive functions – higher order cognitive functions – inhibitory control, updating memory, switching attention, word fluency Working memory Recall People with head injuries show deficits in these functions Prefrontal cortex damage: Early studies in humans and monkeys report large portions of the PFC can be removed without loss to mental capacity or changes in behaviour (Hebb, 1939) This view contributed to widespread use of psychosurgery (lobotomy or leucotomy) for treatment of psychiatric disorders in first half of 20th century Lobotomy – Severing connections from PFC to other areas of the brain Procedure introduced by Antonio Egas Moniz who won the Nobel prize for physiology and medicine (1949) for the “discovery of the therapeutic value of leucotomy in certain psychosis” Success described as “mixed” with some patients being more docile, able to leave hospital or become more manageable – others committed suicide or were severely brain damaged David Ferrier (1876): experimental ablation of frontal lobes of monkeys – sensory faculties of sight, hearing touch, taste and smell unimpaired, however lost the faculty of attentive and intelligent observation Lesions (due to head injury or cancers) in humans have led to further localisation of functions
		Primary motor cortex: Located in the precentral gyrus of the frontal lobe 1937 Penfield and Boldrey mapped primary motor cortex of conscious human patients during neurosurgery with low intensity electrical stimulations to points on the cortical surface – they noted which body parts moved in response to stimulation Each stimulation activated a contralateral muscle and produced simple movement – they found that the primary motor cortex is organised somatotopically Somatotopic layout referred to as motor Homunculus Primary motor cortex lesions: Extensive damage to human primary motor cortex, does not actually eliminate all voluntary movement Large lesions to primary motor cortex do disrupt ability to move individual body parts (e.g. one finger) independently of others, and reduce speed, accuracy and force of movements Other movements able probably due to association and secondary motor areas Association motor areas: Posterior parietal association cortex – integrates orientation information about body parts, and external objects positions – provides spatial information prior to movement DLPFC received projections from posterior parietal cortex and projects to secondary motor cortex, primary motor cortex and frontal eye field DLPFC responds in anticipation of motor activity Sensory areas (Hearing, touch smell, taste vision): Sensory areas of the cortex consist of primary, secondary and association areas Primary areas receive input from thalamic relay nuclei Secondary sensory cortex receives input from primary sensory cortex of a system or other areas of secondary sensory cortex Association areas integrates info from more than one sensory system Posterior parts of brain behind central sulcus Large parts of the brain dedicated to processing sensory stimuli Postcentral gyrus = location of primary somatosensory cortex Somatosensory system (touch and pain): Sensations from the body = somatosensation Primary somatosensory cortex: Penfield et al (1937) – electrical stimulation to cortical surface – patients who were fully conscious described what they felt Brodmann areas 1-3 (postcentral gyrus) – patients reported sensations in various parts of their body Somatotopic organisation (sensory homunculus) Medial parts = leg, lateral parts = face Distribution biased towards areas where sensory discrimination is high (fingers, mouth) SII – ventral to SI in postcentral gyrus – receives input from S1 (secondary somatosensory cortex) Somatosensory system and association cortex: Damage to primary somatosensory cortex has surprisingly mild effects, due to having multiple pathways Corkin et al. (1970) unilateral lesion of S1 in epileptics – two minor contralateral deficits – ability to detect light touch, and reduced ability to identify objects by touch – deficits were bilateral if lesion went into S2 Somatosensory signals conducted to highest level of sensory hierarchy is association cortex (prefrontal and posterior parietal cortex) Somatosensory agnosia's: Two types: astereognosis and asomatognosia Astereognosis – inability to recognise objects by touch – these are rare in the absence of simple sensory deficits Asomatognosia – failure to recognise parts of one's own body – usually unilateral affecting only left side of the body – associated with extensive damage to the right temporal and posterior parietal lobe (association cortex) (lateralisation I will come to shortly) Case of Aunt Betty Visual cortex: Vision is also represented in the brain in three main regions – Primary visual cortex – located in posterior region of occipital lobes – receives most of input from visual relay of the thalamus Areas of secondary visual cortex (prestriate and inferotemporal corices) receive input from primary visual cortex, and visual association cortex Association cortex (posterior parietal cortex) Damage to primary visual cortex: Damage to an area of the primary visual cortex produces a scotoma (an area of blindness) in the corresponding area of the contralateral visual field Contralateral = relating to the side of the body that is opposite to that on which a structure of the brain occurs Many patients with scotomas are not consciously aware of their deficits – sometimes visual completion can occur “Talking with a friend, I glanced just to the right of his face wherein his head disappeared. His shoulders and necktie were still visible but the vertical stripes on the wallpaper behind him seemed to extend down to the necktie. It was impossible to see this as a blank area when projected on the striped wallpaper of uniformly patterned surface, although any intervening object failed to be seen”. (Lashley, 1941, p. 338) Other areas of the visual system identified from fMRI So far 12 or so functional areas of human visual cortex have been identified There are 30 in monkeys (24 secondary areas, and 7 association areas). The neurons in each area respond to different aspects of vision – colour, movement, shape etc Selective lesions produce different visual losses There are many connection pathways between these Dorsal and ventral stream ■ Information from primary visual cortex project to areas of secondary visual cortex and association cortex via two major streams ■ dorsal stream (projecting up to the posterior parietal cortex) ■ Ventral stream which projects across to inferotemporal cortex ■ Dorsal stream = spatial stimuli (location of objects, and their movement) / where? ■ Ventral stream = characteristics of object (colour, shape) / what? ■ Damage to posterior parietal cortex – can describe objects, but can’t reach out and pick them up ■ Damage to inferotemporal cortex – difficulty describing, but no difficulty reaching to pick them up Damage to secondary visual cortex – Prosopagnosia (face blindness) ■ Term coined in 1947 by German neurologist Joachim Bodamer from the Greek prosipon (side) agnosia (not knowledge) ■ Difficulty recognising people that they have encountered many times ■ Documented cases usually from brain damage to right fusiform gyrus during head trauma, stroke and degenerative disease ■ Dr. P is described by Oliver Sacks in his book “the man who mistook his wife for a hat” ■ An eminent musician with a progressive cognitive failure – he would get confused between objects. At the end of an interview with Dr Sacks – he confused the head of his wife with a hat, and grabbed her in an attempt to put it on his head Other sensory areas Auditory areas – primary auditory cortex: superior temporal lobe, inside lateral sulcus (BA 41). - Auditory association area: posterior to primary auditory cortex (BA22) – evaluates sounds (next to Wernicke's area) Gustatory (taste) cortex (BA43) – roof of lateral succus Olfactory (smell) cortex – medial temporal lobe – connects to limbic system (emotions) Association areas are where primary inputs are processed and comprehended	Monoamine pathways in the brain ■ Neurotransmitter pathways have also been mapped in the brain ■ Dahlstrom and Fuxe (1964) used immunofluorescence staining techniques to visualise the monoamine neurotransmitter pathways of serotonin, noradrenaline and dopamine ■ Monoamine neurotransmitters emanate from brainstem and project to the forebrain and beyond Cerebral lateralisation of function ■ Left and right cerebral hemispheres are separate apart from cerebral commissures connecting them ■ Dax (1836) – noted that he had 40 brain damaged patients with speech problems – all of which had damage in left hemisphere. ■ Both of Broca’s aphasia patients had left hemisphere lesions in frontal cortex – then a further 7 patients all had lesions to Broca’s area – which was localised to left PFC ■ Hugo-Karl Liepmann – apraxia associated with left hemisphere damage – even though symptoms are bilateral ■ Much research then focused on finding out lateralised functions to varying degrees of success ■ fMRI, PET, unilateral lesions, split brain patients have been studied to observe lateralisation of function – language and motor abilities of left hemisphere are readily apparent ■ For many functions there are no substantial differences between hemispheres; and when they do exist it is only slight biases for one hemisphere ■ However lateralisation is statistical rather than absolute – Language is the most lateralised ■ Certain functions display a superiority for one hemisphere above the other ■ Here are some skills that show hemispheric dominance – so it is not what pop psychology would have you believe “creativity is on the right side of the brain etc” ■ We should know by now that many brain regions play a role in any one complex behaviour ■ We are only just starting to unravel how these different areas connect with each other to perform various task Advanced neuroimaging techniques • Our understanding of brain anatomy is advanced – but we are still at a relatively early stage of relating anatomy to behaviour. • Much of our understanding has developed from case studies, lesion studies and experimental ablation studies • Structural and functional MRI can allow us to improve our understanding of structure – functional relationships in the brain in vivo. • “For a long time it has been suggested that the mind is divvied up into distinct components. The effort to discover those components has jumped to warp speed, with the invention of brain imaging technology – especially MRI” Nancy Kanwisher in her TED talk “A neural portrait of the human mind” Functional MRI § With functional MRI we advanced MRI to figure out how to not only show structure of the brain – but also activity § Blood flow and neuronal activation are tightly coupled i.e. blood is pumped to an area of the brain when it becomes “active” § fMRI detects changes in blood flow (i.e an increase) due to bloody being diamagnetic – therefore we can image increases in brain activity fMRI is confirming and expanding our understanding of structure-function relationships ■ e.g. Imaging word generation (dysfunctional in Broca’s aphasia) ■ A meta-analyses of all “word generation” studies (66 papers, 197 experiments, 1552 coordinates), a widely used test of neuropsychological function. ■ The meta-analytic results revealed extensive convergence in large portions of the left inferior frontal gyrus, centering on Brodmann area 44/45 (Broca’s area) fMRI can help us understand plasticity of the brain following injury • Functional imaging can identify brain plasticity changes during recovery from stroke. • These patients recovered language following a debilitating stroke, and their fMRI data shows how structures in the right hemisphere developed to compensate for left hemisphere damage. fMRI can help us understand brain systems: Functional connectivity analysis • Functional connectivity analysis is an fMRI analysis technique that allows to observe which brain regions correlate with one another in terms of their activation during a specific activity • How ‘connected’ are our brain regions of interest? • We can measure the BOLD signal from the entire brain during an interesting task which encompasses the reward system– for example a gambling task. – and compare this in relevant groups, substance abusers vs controls. • We can examine the BOLD signal changes associated with the trials when we expect system level activation (winning trials). • By selecting an appropriate seed area, such as the nucleus accumbens, we can use the BOLD signal from the rest of the brain to see which other regions correlate in activity and whether this differs between groups Frontiers in neuroscience ■ Transcranial stimulation: TMS is a non-invasive method of brain stimulation that relies on electromagnetic induction using an insulated coil placed over the scalp, focused on an area of the brain thought to play a role in mood regulation Brain Computer Interface ■ Researchers e.g. at Stanford university are taking what we have learnt about the study of the brain, and localisation of function, and are developing technologies to help people with paralysis of the body communicate using electrical signals from their brains Summary: ■ From the humble beginnings of phrenology through to Brodmann’s areas we have learnt a great deal about how function is localised in the brain... However we are only just beginning to understand how different areas of the brain cooperate to perform complex tasks ■ Modern imaging techniques are helping us discover more and more about the brain processes that underlie human behaviour. In this way neuroscience is the discipline above any other which can help us to understand ourselves! ■ Our understanding of how the brain functions, in combination with cutting edge technological advances are allowing us to improve the quality of life with people with disability and paralysis. ■ We are constantly learning new things about the brain and developing better treatments for disorders of the brain