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Neurophysiology for Medicine

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Neurophysiology for Medicine Document Transcript

  • 1. Neurophysiology for Medicine Tutis Vilis Association Areas and Memory http://www.physpharm.fmd.uwo.ca/undergrad/medsweb/ central sulcus The 5 main functional subdivisions of the cerebral Parietal cortex. Frontal 1) Primary sensory. Occipital The primary sensory areas is where the Temporal sensory information first enters the cerebral cortex. ory 2) Higher order (secondary) s ma or en sensory. so mot tos Higher order visual, somatosensory, and Primary vestibular auditory lie near the respective primary sensory taste area. This is where sensory information and motor is further processed. visual 3) Association areas. auditory a) Prefrontal, and b) Parietal-Temporal-Occipital areas. Higher order This is where: i) different modalities Premotor somatosensory combine. ii) attention is shifted iii) Higher planning occurs and iv) memories are order senory Higher order stored. In humans they occupy about and premotor visual 80% of the cortex. 4) Premotor. Premotor areas are higher order motor areas that send commands to the primary motor areas. Higher order 5) Primary motor. auditory The primary motor areas send Association commands to the muscles. In the rat, Prefrontal primary sensory and motor areas association occupy nearly all the cortex. Parietal-temporal-occipital association Reference to Neuroscience Purves et al 4th Edition 1 revised 12-01-2010
  • 2. What is the general pattern of connections between primary, secondary, and association areas? Primary Secondary Higher order Association motor Premotor Prefrontal Long loop reflexes Short loop reflexes working memory P-T-O sensory Sensory attention long term memory Short loop reflexes mediate rapid, but simple, responses eg swatting a mosquito. Long loop reflexes, eg writing down the name of a seen object, require the complex processing power of the association regions. Gray and White Matter Neuron Each neuron’s axons, which form the white Cell Body Gray matter of the cortex, make connections with Matter 1000’s of other neurons in the gray matter. These extensive interconnections predispose White the cortex to epilepsy. A locus of abnormal Matter activity in one area quickly spreads to other Axon regions leading to a seizure. These interconnections are, as we will see later, where our memory is. b) At the cellular level, which are the input and output layers? P668 Information arrives in layer 4, spreads to Columns 200-500um F26.3 more superficial and deeper layers, and is finally integrated by output cells whose primary sensory primary motor bodies are located in layers 3 and 5. I Layer 4 receives input from the thalamus and 2 3 other cortical regions. It is thickest in primary 4 sensory regions. The striate cortex (primary 5 visual) is so called because of its thick layer 4. 6 Layers 3 and 5 send output to other cortical and sub cortical regions. These layers are output to other thickest in primary motor cortex. Such cortical regions input and sub-cortical anatomical differences allow Brodman to structures such as divide the cortex into more than 50 areas. the thalamus and spinal cord Only now are we confirming that Beach has a unique function. All have columns. 2
  • 3. Higher order auditory Association Prefrontal association Parietal-temporal-occipital association c) List the main functions of each association area and the experimental supporting evidence. Prefrontal: P680 Planning and working memory The prefrontal cortex has become larger, as a percentage of total brain size, over the course of evolution. Close your eyes, wait, and then point to a particular object that you remember being in the room. Your ability to remember the location of an object is an example of spatial working memory, a form of short term memory. Lesions in the prefrontal association cortex produce deficits in motor tasks that are spatial and delayed. Children prior to the age of 1 yr have not developed this working memory. If a toy is covered by one of two covers, the child cannot find it. Out of sight is out of mind. Decision making These are large areas located on the underside of the cortex. There are two parts. 1) Orbito frontal: involved in emotion. After lesions, no anger is displayed when the patient makes mistakes. Because this has a calming effect, frontal lobotomies used to be a popular cure for aggression. Unfortunately it also destroyed initiative. Neurologist António Egas Moniz won the Nobel Prize for medicine in 1949 for inventing this technique. Dr. Walter Freeman used an ice pick hammered through the back of the eye socket into the brain. He performed thousands of lobotomies in minutes from his office. His patients included Rosemary Kennedy, the sister of John F. Kennedy. Parietal- Occipital-Temporal (PTO): Functions: Box 26B 1) Poli-modal convergence of senses. Primary sensory areas are activated by a single sensory modality. In the PTO we find areas activated by more than one modality The right PTO specializes in the spatial representation of objects by touch, sight, or sound. The left PTO specializes in language: the sound of words, written words (sight), or Braille (touch) 2) Attention. The PTO allows us to focus in on specific objects and neglect others. An analogy that is simple and useful in beginning to understanding attention is that of a flash light that selectively casts light on particular objects. One's capacity to attend to more than one object is limited. The limit is 3 to 5. 3) Inferior Temporal lobe: involved in long term memory. We will look at memory in detail later in this session. P676 3
  • 4. Neglect P668 The converse of attention is neglect. A lesion of the right PTO causes neglect of the left half of objects. The patient is unaware that one half is gone. When a patient is asked to copy a flower, the patient will draw only the right side. This is independent of where the patient is looking. This is different from the deficit seen after a right V1 lesion. Here the patient is blind to everything to the left of where the eyes look. The neglect patient also neglects the left Normal Right PTO side of his body. Lesion You might suppose the a lesion of the left PTO would result in neglect of things on the right. Strangely it does not. Functional imaging shows this is because the right PTO contains a bilateral representation (of things on the left and right) while the left contains only a representation of things on the right. Thus after a lesion on the left, the right side still attends to things on the right (as well as left). After a lesion on the right, the representation of things on the left is lost. Front Front Front R L R normal left lesion right lesion F26.6&7 4
  • 5. How and why do the two sides of the cortex differ in function? a) In what tasks does each hemisphere excel? F27.3 Dominant (usually left) - sequential or serial tasks eg: language (reading writing speaking signing), analytic (math A=B, B=C, therefore A=C) Non-dominant (usually right)- tasks requiring parallel processing eg: spatial tasks, intuitive (C resembles O as I resembles L), geometry, music . b) Patients with section of the corpus callosum. P697 A patient with a lesion of the corpus callosum is shown an apple on the left. The patient cannot name the apple because it is not seen by the language center on the left. The patient can visually recognize an apple and pick it out from a group of other Front objects with his left arm (the one controlled by the right side of the brain). to left arm Two independent brains function in one person (e.g. patient would hug his wife with one arm and push her away with the other). motor area left arm 5
  • 6. Learning & Memory P792 Definitions: Memory: information that is stored. (The basis of memory is the strength of synapses) Learning: the storage process. (Learning occurs when the synaptic strength is changed.) Remembering: the retrieval of stored information. Types of Memory Short term / Working memory Characteristics: l scratch pad which allows for temporary a sort of storage of information Long term l 1: storing numbers when adding. Example l 2: spatial location of objects (eg when Example you close your eyes and point to remembered objects). l tonic activity of neurons in the frontal involves lobe. l limited capacity (limited to about a 9 Has a very digit new #) Declarative (knowing that) Characteristics: Reflexive / Procedural (knowing l representations of objects and events e.g. the face how) of a friend or the friend’s telephone # Characteristics: l associations e.g. name with face involves l skills such as skiing or how to includes l often established in one trial dial a telephone l of memory conscious l slowly by practice established l after the age of 2 yrs starts only l conscious of remembering one is not l by amnesia affected the skill l formation (learning) requires the memory l develop at birth starts to hippocampus in medial temporal lobe l is not affected in amnesia l storage of places and faces occurs in memory l much of the CNS, for occurs in inferior temporal areas. example, the tuning of binocular V1 cells during the critical period for stereopsis & the cerebellum for motor skills. 6
  • 7. Declarative memory is divided into two parts. Declarative memory Episodic Semantic Characteristics: Characteristics: l Remembering particular objects and l Remembering faces and places. places in one’s personal past. l Remembering facts and Episodic memories are composed of concepts, eg that Paris is in several semantic memories. France. l Associating who and what with l places are recognized Familiar where and when. in the parahippocampal place l 1: In episodic memory one Example area (PPA) in the medial parts of not only recognizes the person in the the inferior temporal lobe. picture but also when the picture l faces are recognized in Familiar was taken."My wife and I visited the fusiform face area (FFA) in Paris when the kids were young". more lateral areas of the inferior l 2: The sequence of places Example temporal lobe. one passes while walking across a city. The synthesis of such representations provides us with a map of the spatial layout of the city. 7
  • 8. The amygdala is also involved face recognition. When we encounter someone we know two things happen: A) the conscious identification of who that person is. B) an automatic concurrent ‘glow’ of familiarity. This ‘glow’ can occur without the conscious recognition of the person. This ‘glow’ is accompanied by autonomic responses such as sweating. These responses can be entirely unconscious. These autonomic responses are the basis of lie ventral what detector tests which measure changes in skin stream conductance caused by sweating. A B These two aspects of recognition are mediated by two parallel pathways fusiform face limbic A) the inferior temporal cortex (fusiform face area amygdala area). B) the amygdala unconscious A lesion of A but not B produces sense of conscious autonomic familiarity without being able to identify who identification resposes that person is (prosopagnosia). A lesion of B but not A produces the converse. The patient can identify who the person is but has no sense of familiarity. One young man, after a car accident which affected the path through the amygdala, 1) could recognize his parents 2) but felt that they had been replaced by aliens (ie no sense of familiarity) 8
  • 9. Mechanisms of Learning Procedural Memories. You can be trained to produce blinks in response to a sound by classical conditioning. One begins with a naive subject; one that does not blink in response to a flash of light or a sound. The next thing needed is a good teacher: a stimulus that will always produce a blink. A puff of air is a good teacher. A puff of air, through strong synapses, almost always produces a blink. This is called classical conditioning: the puff depolarises the blink cell. This strengthens the synapses from the paired sound's synapse. That is, the puff of air teaches sound to produce a blink. A similar strengthening and pruning of synapses is the basis of all forms of long term memories. After conditioning, the synapse from the sound is strong and can produce a blink on its own. That is, the blink becomes associated to sound but not to some other stimulus such as a light. This conditioning also involves pruning of connections. While connections from sounds are strengthened, those from light are weakened. This procedural type of memory involves the cerebellum.A lesion of the deep cerebellar n. eliminates the learnt blink to a sound. Billions of such connections are changed in a similar way throughout one's life in other parts of the brain. 9
  • 10. Encoding Long Term Declarative Memories The ventral stream 1) extracts the visual features, 2) encodes them as objects, and 3) stores them temporally in working memory. Consolidation of short term working memory into long term declarative memory involves the hippocampus. Unlike procedural long term memory which requires repetitive practice, declarative memory often require only a single exposure. This is because the hippocampus is an excellent teacher. The hippocampus is located in the medial part of the inferior temporal lobe. It is a unique part of the cortex. Unlike other cortical areas, it continuously generates new neurons. The hippocampus is well connected: an important attribute of a good teacher. It receives input from all the association areas and sends signals back to them as well as others thus creating new associations. The hippocampus associates the current features of the perceived object with other older memories related to the same object. The activation somehow binds together/associates various feature combinations into a rich multi modal memory. The memory of your grandmother's face is associated with the sound of her voice and a multitude of related memories. This long term memory requires the changes in the structure of synapses. These Voice structural changes involve the expression of genes and the synthesis of proteins. Face Patients like HM suggest that once this long term memory is formed, seeing the same object, e.g grandmother’s face, will activated the same associations directly, without the need of activating the hippocampus. Remembering involves transferring these long term memories in temporal lobe association areas back to working memory in the frontal Voice lobe by as yet a poorly understood process. Face F31.11 10
  • 11. Brenda Milner's famous patient H.M. P801 Much of what we know about the consolidation of long term stems from Brenda Milner's work at McGill U. with patient H.M. To relieve severe epilepsy,perhaps caused by a bicycle accident at the age of nine, H.M.’s medial part of the temporal lobe and hippocampus medial temporal lobe Short term Reflexive OK (how) remembers names Declarative OK for as long (what) e.g. language as not distracted old memories new memories OK Lost recognizes cannot remember his mother new acquaintances Retrograde old new Anterograde forgets facts and events forgets facts and that occurred prior to events that occurred lesion (as in retrograde anterograde after the lesion. Prosopagnosia or damage Alzheimer's disease). patient H.M. H.M. died in 2008 at the age of 82. Remarkably, late in life, he had trouble recognising himself in a mirror. His memory of himself was as he was at the time of surgery when he was 27. He was also unable to remember the contribution he made to our understanding of memory. 11
  • 12. For practice problems see http://www.physpharm.fmd.uwo.ca/undergrad/medsweb/L3AssMem/AssMemProb.swf 12