Weapons in neurophysiologist’s
armory
• Recording
– Individual neurons
– Gross potentials
– Brain scans
• Stimulation
• Le...
Cerebral Cortex
• Every cubic inch of cerebral cortex has
about 10,000 miles of nerve fibers in it
• The number of neurons...
Cerebral Cortex
• Humans are quite good at storing &
processing sensory information
– So we can use it better in making ef...
Cerebral Cortex Silent Areas
• Most areas of the cortex neither respond in
an obvious way to:
– simple sensory +
– nor pro...
The Cerebral Cortex
• Layer I -Molecular Layer
– mostly axons
• Layer II-External Granule Layer
– granule (stellate) cells...
Cerebral Cortex
• Layer IV-Internal Granule Layer
– main granular cell layer
• Layer V- internal pyramidal layer
– dominat...
Cerebral Cortex
• Three major cell types
– Pyramidal cells
• souce of corticospinal projections
• major efferent cell
– Gr...
Cerebral Cortex
• Most output leave cortex via V &VI
– spinal cord tracts originate from layer V
– thalamic connections fr...
Cerebral Cortex
• All areas of the cerebral cortex have
extensive afferent and efferent connections
with deeper structures...
Secret of the Cerebral Cortex
• Resultant network of links between neurons in the
cortex mimics relationships between thin...
Association Areas
• Integrate or associate info. from diverse
sources
• Large % of human cortex
• High level in the hierar...
Prefrontal Association Areas
• prolonged thought processes-elaboration of
thought
– Prefrontal lobotomy
• Executive functi...
Limbic Association Area
• Behavior
• Emotions
• Motivation
Parieto-occipitotemporal AA
• Analysis of Spatial Coordinates of Body
– Neglect syndrome
• Area for Language Comprehension...
Prefrontal Lobotomy
• Surgically disconnect the prefrontal areas
from the rest of the brain (link)
• used to relieve sever...
Prefrontal Lobotomy (cont)
• Loss of ambition
• inappropriate social responses
• loss of morals
• unable to carry through ...
From recognition to emotional
response
• After identification of an object/face
projections from the fusiform gyrus to the...
Dyslexia
• Best known form of specific language
impairment
• Affects 5-17% of U.S. population
• Originally thought to be d...
Story of Phineas Gage
• Tamping iron through face, skull, brain
• regained full consciousness within minutes
• 25 years of...
P. Gage (cont.)
• Personality considerably altered after
accident.
• Prior to accident, he was described as:
– responsible...
P. Gage (cont)
• Damaged area was likely the ventromedial
region of both frontal lobes
– ability to make rational decision...
Ventromedial frontal areas
• Hypothesis that emotion and its underlying
neural machinery participate in decision
making wi...
Ventromedial Frontal Area
• High concentration of serotonin S2
receptors in monkeys whose behavior is
socially adapted
• L...
Executive functions of behavior
• Function of the prefrontal association area
– Judgment
– Planning for the future
– holdi...
Concept of a Dominant Hemisphere
• General interpretative functions of
Wernicke’s & angular gyrus as well as
speech & moto...
Lingustic Dominance &
Handedness
• Dominant Hemisphere
– Left or mixed handed
• Left- 70% Right- 15% Both- 15%
– Right han...
Right brain, left brain
• The two hemispheres are specialized for
different functions
– dominant (usually left)
• language...
Communication between Cortical
Hemispheres
• Corpus Callosum
– Bidirectional communication between most of
the two cortica...
Split brain subjects
• Section of the corpus callosum
– prevents information transfer from one cortex
to the other
– origi...
Allocortex
• Made up of archicortex & paleocortex
• 10% of human cerebral cortex
• Includes the hippocampal formation whic...
Hippocampal formation
• Hippocampus- 3 layers (I, V, VI)
– Connects with septal nuclei, mamillary body &
contralateral hip...
Hippocampal formation
• Plays an important role in declarative
memory
– Declarative- making declarative statements of
memo...
Hippocampal formation
• Role in episodic memory
– Hippocampus through is bidirectional
connections with parahippocampal re...
Learning & Memory
• Memory functions can be localized to
specific regions of the brain
• e.g. hippocampus & hippocampal gy...
Learning & Memory
• Memory traces can occur at all levels of the
nervous system from spinal cord to cortex
• most of memor...
Classification of Memory
• Short term memory
– lasts seconds to minutes
• Intermediate long term memory
– lasts days to we...
NMDA receptor
• Associated with synaptic learning/memory
• Binds glutamate
• Ionic channels associated with the NMDA
recep...
Neural Basis of Memory
• Memory has stages & continually changing
• long term memory- plastic changes
• physical changes c...
Declarative/Explicit Memory
• Conscious memory
– memory of details of an integrated thought
– memory of: surroundings, tim...
Reflexive/Implicit/Skill Memory
• Unconscious- associated with motor
activities
– e.g. hitting a tennis ball which include...
Declarative Memory
• Can be subdivided into Episodic &
Semantic
– Episodic-remembering the episodes of daily life
– Semant...
Role of Hippocampus in Memory
• The hippocampus may store long term
memory for weeks & gradually transfer it to
specific r...
Memory loss
• Bilateral removal of hippocampus produces
profound deficits in memory function.
– loss of capacity to form n...
Memory loss
• The memory capability that is spared
following bilateral lesions of temporal lobe
(hippocampal formation) ty...
• When I was younger, I could remember
anything, whether it had happened or not;
but my faculties are decaying now and soo...
Nonassociative learning
• Habituation
– decrease in response to repeat benign stimulus
• Sensitization (pseudoconditioning...
Associative Learning
• Classical conditioning
– involves learning relationship between 2 stimuli
– pairing of conditioned ...
Learning
• The # of neurons & their connectivities
change significantly during learning
– during the first year of life an...
Learning
• Soon after birth- “use it or lose it”
– in many areas of cerebral cortex may lose 50%
or more of original neuro...
Storage of Memory
• Long term memory is represented in mutiple
regions throughout the nervous system
• associated with str...
Holographic memory model
• Coherent waves
• interference patterns
– constructive & destructive interference
• principal of...
Memory
• Environment alters human behavior by
learning & memory
• Learning
– process by which we acquire knowledge about
t...
Learning
• Many important behaviors are learned
• We are who we are largely by what we
learn & remember
• learned motor sk...
Learning
• Learning can produce dysfunctional
behaviors, and in extreme ⇒ psychological
disorders
• successful psychothera...
Memory
• Implicit-unconscious memory
• Explicit-conscious memory
• Patient H.M. 27 y.o. male
– suffered for over 10 years ...
Patient H.M.
• Surgery involved bilateral removal of the
hippocampal formation, amygdala, and
parts of the temporal cortex...
Food for thought
• Your beliefs become your thoughts
• Your thoughts become your words
• Your words become your actions
• ...
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Weapons in neurophysiologist's armory Recording

  1. 1. Weapons in neurophysiologist’s armory • Recording – Individual neurons – Gross potentials – Brain scans • Stimulation • Lesions – Natural lesions – Experimental lesions
  2. 2. Cerebral Cortex • Every cubic inch of cerebral cortex has about 10,000 miles of nerve fibers in it • The number of neurons in the brain is about 30 X greater than the number of humans on the planet. (180 billion) • A typical neuron is wired to about 1000- 2000 of its neighbors – It is the pattern of these connections that determines what the brain does
  3. 3. Cerebral Cortex • Humans are quite good at storing & processing sensory information – So we can use it better in making effective responses to our environment • Immense degree of convergence and divergence from one neuron to another – Most cortical neurons are a site of converging input from multiple neurons and source of diverging output to multiple neurons
  4. 4. Cerebral Cortex Silent Areas • Most areas of the cortex neither respond in an obvious way to: – simple sensory + – nor produce movements when electrically +
  5. 5. The Cerebral Cortex • Layer I -Molecular Layer – mostly axons • Layer II-External Granule Layer – granule (stellate) cells • Layer III-External Pyramidal layer – primary pyramidal cells
  6. 6. Cerebral Cortex • Layer IV-Internal Granule Layer – main granular cell layer • Layer V- internal pyramidal layer – dominated by giant pyramidal cells • Layer VI- multiform layer – all types of cells-pyramidal, stellate, fusiform
  7. 7. Cerebral Cortex • Three major cell types – Pyramidal cells • souce of corticospinal projections • major efferent cell – Granule cells • short axons- – function as interneurons (intra cortical processing) – excitatory neurons release 1o glutamate – inhibitory neurons release 1o GABA – Fusiform cells • least numerous of the three • gives rise to output fibers from cortex
  8. 8. Cerebral Cortex • Most output leave cortex via V &VI – spinal cord tracts originate from layer V – thalamic connections from layer VI • Most incoming sensory signals terminate in layer IV • Most intracortical association functions - layers I, II, III – large # of neurons in II, III- short horozontal connections with adjacent cortical areas
  9. 9. Cerebral Cortex • All areas of the cerebral cortex have extensive afferent and efferent connections with deeper structures of brain. (eg. Basal ganglia, thalamus etc.) • Thalamic connections (afferent and efferent) are extremely important and extensive • Cortical neurons (esp. in association areas) can change their function as functional demand changes
  10. 10. Secret of the Cerebral Cortex • Resultant network of links between neurons in the cortex mimics relationships between things in the outside world – Probabilistic model of the world in the brain which can predict what is likely to happen next • Mechanism for making the strength of these connections change to reflect observed associations is the secret of the CC – Creating physical connections between neurons that are often active simultaneously “fire together, wire together
  11. 11. Association Areas • Integrate or associate info. from diverse sources • Large % of human cortex • High level in the hierarchy • Lesions here have subtle and unpredictable quality
  12. 12. Prefrontal Association Areas • prolonged thought processes-elaboration of thought – Prefrontal lobotomy • Executive functions of behavior • Broca’s Area • Orbital frontal cortex – Cells hyperactive in OCD – Cells fire strongly when expectation not met • Monkeys with current juice vs. brine experiment – Functions as an error dectector-alerting you that something is amiss
  13. 13. Limbic Association Area • Behavior • Emotions • Motivation
  14. 14. Parieto-occipitotemporal AA • Analysis of Spatial Coordinates of Body – Neglect syndrome • Area for Language Comprehension (Reading) – Wernicke’s-general interpretative area • auditory, visual, somatic all feed into this area – Angular gyrus-just behind Wernicke’s • Higher order visual signal processing • Area for Naming Objects • Area for Recognition-Faces/Complex Form – prosopagnosia-impaired recognition of familiar faces
  15. 15. Prefrontal Lobotomy • Surgically disconnect the prefrontal areas from the rest of the brain (link) • used to relieve severe psychotic depression – lost ability to solve complex problems – unable to string together sequential tasks – unable to learn to do several parallel tasks at the same time – decreased level of aggressiveness
  16. 16. Prefrontal Lobotomy (cont) • Loss of ambition • inappropriate social responses • loss of morals • unable to carry through long trains of thought • usual patterns of motor activity without purpose • Walter Freeman (PBS documentary excerpt)
  17. 17. From recognition to emotional response • After identification of an object/face projections from the fusiform gyrus to the amygdala allow the person to gage the emotional significance of what has been identified – Capgras syndrome • These connections may be damaged/lesioned giving rise to this syndrome
  18. 18. Dyslexia • Best known form of specific language impairment • Affects 5-17% of U.S. population • Originally thought to be due to a defect in visual processing associated with angular gyrus • Problem may also involve the auditory cortex’s inability to process certain speech sounds – Fast ones (phonemes) (30 msec) – Can be re-programed –neuroplasticity • “Fast ForWord” computer program (Science 1/96)
  19. 19. Story of Phineas Gage • Tamping iron through face, skull, brain • regained full consciousness within minutes • 25 years of age at time of accident (9-13- 1848) • survived the accident-died 5-21-1861 of apparent epileptic seizure • damaged area of brain-ventromedial region of both frontal lobes (Science 5-20-94)
  20. 20. P. Gage (cont.) • Personality considerably altered after accident. • Prior to accident, he was described as: – responsible, intelligent, socially well adapted, well liked. • After the accident, he was described as: – irreverent, capricious, no respect for social conventions, use of abundant profanity offended many, irresponsible.
  21. 21. P. Gage (cont) • Damaged area was likely the ventromedial region of both frontal lobes – ability to make rational decisions in personal and social matters is invariably compromised – processing of emotion is compromised – ability to tackle the logic of an abstract problem, perform calculations, and call up appropriate knowledge remains intact
  22. 22. Ventromedial frontal areas • Hypothesis that emotion and its underlying neural machinery participate in decision making within the social domain, and this involves: • ventromedial frontal areas reciprocally connected with: – subcortical nuclei like the amygdala and hypothalamus • involved with basic biologic regulation, emotional processing, social cognition & behavior
  23. 23. Ventromedial Frontal Area • High concentration of serotonin S2 receptors in monkeys whose behavior is socially adapted • Low concentration of serotonin S2 receptors in monkeys whose behavior is aggressive and socially uncooperative – (Science v 264 5-20-94)
  24. 24. Executive functions of behavior • Function of the prefrontal association area – Judgment – Planning for the future – holding & organizing events from memory for prospective action
  25. 25. Concept of a Dominant Hemisphere • General interpretative functions of Wernicke’s & angular gyrus as well as speech & motor control are more well developed in one cerebral hemisphere ∀≅ 95% of population- left hemisphere – If dominate hemisphere sustains damage early in life, non dominate hemisphere can develop those capabilities of speech & language comprehension (Plasticity)
  26. 26. Lingustic Dominance & Handedness • Dominant Hemisphere – Left or mixed handed • Left- 70% Right- 15% Both- 15% – Right handed • Left- 96% Right- 4% Both- 0%
  27. 27. Right brain, left brain • The two hemispheres are specialized for different functions – dominant (usually left) • language based intellectual functions • interpretative functions of symbolism, understanding spoken, written words • analytical functions- math • speech – non dominant (usually right) • music • non verbal visual experiences (e.g. body language) • spatial relations
  28. 28. Communication between Cortical Hemispheres • Corpus Callosum – Bidirectional communication between most of the two cortical hemispheres except for anterior portions of the temporal lobe • Anterior Commissure – Bidirectional communication between anterior portions of the temporal lobe • Amygdala-emotional response transfer
  29. 29. Split brain subjects • Section of the corpus callosum – prevents information transfer from one cortex to the other – originally done to prevent the spread of seizure activity from one hemisphere to the other in severe cases of epilepsy – In matching experiments: • left hemisphere usually matches based on function • right hemisphere usually matches based on appearance
  30. 30. Allocortex • Made up of archicortex & paleocortex • 10% of human cerebral cortex • Includes the hippocampal formation which is folded into temporal lobe & only viewed after dissection – hippocampus – dentate gyrus – subiculum
  31. 31. Hippocampal formation • Hippocampus- 3 layers (I, V, VI) – Connects with septal nuclei, mamillary body & contralateral hippocampus via fornix • Dentate gyrus- 3 layers (I, IV, VI) – projects to hippocampus (Ammon’s horn) • Subiculum (part of parahippocampal gyrus) – merges with entorhinal area • Receives 10 input from the entorhinal cortex of the parahippocampal gyrus through: – perforant & alveolar pathway
  32. 32. Hippocampal formation • Plays an important role in declarative memory – Declarative- making declarative statements of memory • Episodic-daily episodes of life • Semantic-factual information – Functions as a cortical gutter • Sensory information is increasingly analyzed & refined as it passes from neuronal level to level – from sensory projection areas ⇒ complex associational parietal/temporal networks ⇒ draining into hippocampus
  33. 33. Hippocampal formation • Role in episodic memory – Hippocampus through is bidirectional connections with parahippocampal regions • promote more flexible associations among items • differentiating overlapping patterns • encoding of each unique episode – Parahippocampal regions have bidirectional connections with cerebral cortex • encode specific memory cues (semantic)
  34. 34. Learning & Memory • Memory functions can be localized to specific regions of the brain • e.g. hippocampus & hippocampal gyrus • Memories caused by changes in sensitivity of synaptic transmission between neurons as a result of previous mental activity – these changes cause new pathways or facilitated pathways to develop “memory traces”
  35. 35. Learning & Memory • Memory traces can occur at all levels of the nervous system from spinal cord to cortex • most of memory we associate with intellectual processes is based on memory traces in cerebral cortex • positive memory-associated with facilitation • negative memory-associated with habituation (suppression)
  36. 36. Classification of Memory • Short term memory – lasts seconds to minutes • Intermediate long term memory – lasts days to weeks • Long term memory – lasts years to entire lifetime
  37. 37. NMDA receptor • Associated with synaptic learning/memory • Binds glutamate • Ionic channels associated with the NMDA receptor are both ligand and voltage gated – In order to open it needs to be both depolarized and in the presence of glutamate, and Ca++ will influx and cause the cellular machinery to manufacture more AMPA glutamate receptors that require only glutamate to cause depolarization
  38. 38. Neural Basis of Memory • Memory has stages & continually changing • long term memory- plastic changes • physical changes coding memory are localized in multiple regions of the brain • reflexive & declarative memory involve different neuronal circuits • Memories are caused by groups of neurons that fire together in the same pattern each time they are activated. – The links between individual neurons, which bind them into a single memory, are formed through a process called long-term potentiation. (LTP)
  39. 39. Declarative/Explicit Memory • Conscious memory – memory of details of an integrated thought – memory of: surroundings, time relationships, cause & meaning of the experience – acquiring knowledge of people, places & things – involves the hippocampal gyrus • evaluation, comparison, inference
  40. 40. Reflexive/Implicit/Skill Memory • Unconscious- associated with motor activities – e.g. hitting a tennis ball which include complicated motor performance – learn how to do things-acquire motor or perceptual skills that are unavailable to consciousness – certain forms involve amygdala & cerebellum • nonassociative & associative learning
  41. 41. Declarative Memory • Can be subdivided into Episodic & Semantic – Episodic-remembering the episodes of daily life – Semantic-remembering factual information e.g. 2 + 2 = ? • Involves the function of the hippocampus & parahippocampal areas – Hippocampus & related temporal lobe areas thought to process newly learned information & then transfer it to cortical areas
  42. 42. Role of Hippocampus in Memory • The hippocampus may store long term memory for weeks & gradually transfer it to specific regions of cerebral cortex • The hippocampus has 3 major synaptic pathways each capable of long-term potentiation which is thought to play a role in the storage process (Kandel 1995)
  43. 43. Memory loss • Bilateral removal of hippocampus produces profound deficits in memory function. – loss of capacity to form new long term memories (process of consolidation impaired) – retention of memories prior to surgery – short term memory intact – loss of ability to transfer most types of learning from short term to long term memory (exception is reflexive learning; i.e. motor skills) – not well oriented in space & time – forgetting incidents of daily life immediately
  44. 44. Memory loss • The memory capability that is spared following bilateral lesions of temporal lobe (hippocampal formation) typically involves learned tasks that have two things in common – tasks tend to be reflexive, not reflective & involve habits, motor, or perceptual skills – do not require conscious awareness or complex cognitive processes. (e.g. comparison & evaluation
  45. 45. • When I was younger, I could remember anything, whether it had happened or not; but my faculties are decaying now and soon I shall be so I cannot remember any but the things that never happened.- Mark Twain
  46. 46. Nonassociative learning • Habituation – decrease in response to repeat benign stimulus • Sensitization (pseudoconditioning) – strengthening of responses to a wide variety of stimuli following an intense or noxious stimuli – override effects of habituation (dishabituation) – can be demonstrated in the Aplysia (snail) • Imitative learning – important in acquisition of language
  47. 47. Associative Learning • Classical conditioning – involves learning relationship between 2 stimuli – pairing of conditioned & unconditioned stimulus to condition response – importance of correlation between CS & US • Operant conditioning – learning relationship between stimulus & organism behavior – formation of a predictive relationship between a response & a stimulus – animal/person learns to predict the consequences of its own behavior
  48. 48. Learning • The # of neurons & their connectivities change significantly during learning – during the first year of life and perhaps even after this great excess of neurons – neurons looking to connect • if make meaningful connections with other neurons, glands, or muscles, they will flourish • if they don’t they will perish – connections determined by nerve growth factors released retrogradely from + cells
  49. 49. Learning • Soon after birth- “use it or lose it” – in many areas of cerebral cortex may lose 50% or more of original neurons due to nonuse • Even in adults there is modification of the number of neurons & their connections to at least some extent • Concept of neural plasticity
  50. 50. Storage of Memory • Long term memory is represented in mutiple regions throughout the nervous system • associated with structural changes in synapes – increase in # of both transmitter vesicles & release sites for neurotransmitter – increase in # of presynaptic terminals – changes in structures of dendritic spines – increased number of synaptic connections • Neural Plasticity
  51. 51. Holographic memory model • Coherent waves • interference patterns – constructive & destructive interference • principal of reconstruction • redundancy of recording • Some evidence that memory function in the brain works in this manner
  52. 52. Memory • Environment alters human behavior by learning & memory • Learning – process by which we acquire knowledge about the world • Memory – process by which knowledge is encoded, stored & retrieved
  53. 53. Learning • Many important behaviors are learned • We are who we are largely by what we learn & remember • learned motor skills – help us master the environment – learned language enable communication of what we learned • Not all learning is beneficial
  54. 54. Learning • Learning can produce dysfunctional behaviors, and in extreme ⇒ psychological disorders • successful psychotherapy often creates an environment where people can learn to change their behavior.
  55. 55. Memory • Implicit-unconscious memory • Explicit-conscious memory • Patient H.M. 27 y.o. male – suffered for over 10 years from uncontrollable bilateral temporal lobe seizures as a consequence of brain damage sustained at age 9 when he was hit and knocked over by someone riding a bicycle – surgery performed to control epilepsy
  56. 56. Patient H.M. • Surgery involved bilateral removal of the hippocampal formation, amygdala, and parts of the temporal cortex (multimodal association area) • After surgery seizures better controlled but developed a devastating explicit memory deficit • NPR story • Obituary died 12-8-2008 at age 82
  57. 57. Food for thought • Your beliefs become your thoughts • Your thoughts become your words • Your words become your actions • Your actions become your habits • Your habits become your values • Your values become your destiny – Mahatma Gandhi
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