diff --git a/language.md b/language.md new file mode 100644 index 0000000..58d23fb --- /dev/null +++ b/language.md @@ -0,0 +1,215 @@ +## Paul Broca (1861) + +* Believed that functions could be localized in the brain +* Studied patients with aphasia– language disorders found in patients who have had a stroke +* Had a patient that could understand language but could not speak, problems with the organizational aspects of language. Found lesion in posterior frontal lobe (Brodmann areas 44/45) +* This kind of aphasia is called a motor or expressive aphasia +* Eight patients with similar problems all had similar lesions, always on the left side +* "Nous parlons avec l’hemisphere gauche!" "We speak with the left hemisphere!" + +Note: + +We also define regions of the brain based on studies of brain lesions in patients. Recall the guy with the railroad spike from last lecture. Well the French physician Paul Broca in the 19th c. + +-- + +## Broca and a patient’s brain + +
+ +Note: + + +--- + +## Carl Wernicke (1874) + +* Had a patient that could speak but not understand language. Called receptive aphasia +* Damage was to a different area– left side, posterior part of the left temporal lobe (Brodmann areas 22/39/40) +* Argued that simple perceptual and motor activities were localized to a specific area and that most functions result from interconnections between areas. Idea of "distributive processing" + +Note: + + +--- + +## Major brain areas involved in the comprehension and production of language + +
Neuroscience 5e Fig. 27.1
+ + + +Note: + +*Arcuate fasciculus: major association fiber tract in CNS that connects Broca’s and Wernicke’s areas* + + +--- + +## Characteristics of Broca's and Wernicke's aphasias + +
Neuroscience 5e Table 27.1
+ + +Note: + +*Broca's aphasia patients have limited writing. Loss of the ability to produce language (spoken or written)* + +Apraxia +: verbal apraxia is difficulty starting and making voluntary movements (motor plans) needed for speech (with no paralysis or weakness of speech muscles) + +dysarthria +: inability to move the muscles of the tongue and mouth to produce speech + +agraphia +: inability to write + +Agnosia +: inability to process sensory information +: affects a single modality + + +syntax +:the arrangement of words and phrases to create well-formed sentences in a language + +Grammar +:in linguistics it is set of structural rules governing the composition of clauses, phrases, and words in any given natural language. The term refers also to the study of such rules, and this field includes morphology, syntax, and phonology, often complemented by phonetics, semantics, and pragmatics + + + +--- + +## Other evidence of brain regionalization + +* Fritsch and Hitzig (1870)– discrete limb movements in dogs can be produced by electrical stimulation of the contra-lateral motor cortex. Thus the right hand is controlled by the left hemisphere. 'Dominant' hemisphere +* Wilder Penfield (1950)– neurosurgeon, localized motor functions by stimulating specific areas of the brain +* Roger Sperry (1960s)– split brain patient studies + +Note: + +And there is lots of other evidence for localization of brain function, especially for sensory and motor information for limbs and body. In fact Fritsch… + +And the Canadian physician Wilder Penfield performed classical mapping of motor function in the cerebral cortex by localized electrical stimulation. + +And then there is the fascinating split brain studies of Sperry and Gazzaniga in the 1960s + + +--- + +## Penfield stimulation studies + +
Stimululation based brain mapping
+ +Note: + +Epileptic patient. mapping the cortical tissue before resecting the site of tissue where the seizures are being generated. + +*Start about minute 3* + +--- + +## Split brain studies: Nobel prize 1981 + +
+
+ +* The corpus callosum and anterior commissure are the two axon tracts that connect the two sides of the brain. They are sometimes cut to prevent the spread of severe epilepsies +* Each side of the brain works independently from the other +* Roger Sperry showed that the left hemisphere dominates speech, writing, right hand stereognosis, analysis of right visual field +* Right hemisphere dominates, emotional coloring of language, spatial abilities, left hand stereognosis, analysis of left visual field + +
+ +
R. Sperry
+ +
+
+ +>"for his discoveries concerning the functional specialization of the cerebral hemispheres" + +
+ + + + + +Note: + +The classic split brain studies which Roger Sperry got the Nobel for in 1981 showed the lateralized localization of language that Broca and Wernicke anticipated as well as several other higher functions. They took advance of the fact that in patients with severe epilepsies, sometimes the commissures connecting the two hemispheres are cut to prevent the spread of seizures. + +And since each side of the brain to some degree can work independently of the other + +* Humans are 90% right handed as a population and the degree of lateralization among individuals is strong, regardless of left or right-handedness +* 96% of right handers having left hemisphere speech, compared with 70% of left handers +* Twin studies have demonstrated some genetic influence on handedness, but 75% of the variance is nongenetic and individually specific, with only 25% explained by genes [#Bishop:2013]. Even the segregation of of handedness and language laterality suggests a complex polygenic set of factors, with 96% of right handers having left hemisphere speech, compared with 70% of left handers [#Bishop:2013]. + +--- + +## Confirmation of hemispheric specialization for language + +
Neuroscience 5e Fig. 27.3
+ + +Note: + +Here is an illustration of the experiment performed by by Sperry and his colleagues for these split brain studies. + +After the corpus callosum connecting the two hemisphere was cut to alleviate epileptic seizures, the patients were asked to fixate on a point and name objects presented in each visual field. + +Now you haven’t learned about the visual system yet, but just as sensory information from your left hand goes to your right hemisphere, visual information from the lateral part of your left visual field goes to your right visual cortex. + +Split brain patients could not correctly name objects presented in their left visual field, presumably because that info could not reach the left hemispheres because the callosal connections were severed. But split brain patients could correctly name an object when presented in their right visual field, because that information was received by the left visual cortex and could be passed onto the language centers. + +In all Sperry and his colleagues showed that language, mathematical, and logical reasoning is dominant in the left hemisphere and that shape recognition, spatial attention, emotional processing, and creativity in more dominant in the right hemisphere. + +*right hemisphere: 'coloring' language with emotive tonal variation, 'prosody'. Adds additional meaning to verbal communication. Mandarin chinese. Monotone professor lecture*. Evidence suggest similar areas of the right hemisphere associate with this emotive coloring of language. + +Similar areas used in sign language thus this constellation of brain regions specializes in symbolic representation and communication, rather than just spoken language. + + +PET: +: positron emission tomography +: detects pairs of gamma rays emitted indirectly by a radioactive tracer injected into bloodstream (positron-emitting radionuclide) + +CT: +: computerized tomography +: a series of X-ray images from different angles +: computer processing to create cross-sectional images + + +Babbling sounds from a baby shows that there is a pattern of sounds produced sequentially that are related to the phones necessary for producing spoken language. Language imitation follows other imitations (mirror neurons?) during developmental learning and behavioral acquistion. Brain is continuously simulating the future based on past experienced training patterns. + + + + +-- + + +## Mapping brain activity with fMRI + +
Neuroscience 5e Fig. 27.6
+ + +Note: + +- functional magnetic resonance imaging +- different patterns of brain activity localization depending on what the task is +- Actually sitting inside a small space magnet + +--- diff --git a/neurophysiology1.md b/neurophysiology1.md index 5d2e674..4fd82ba 100644 --- a/neurophysiology1.md +++ b/neurophysiology1.md @@ -538,17 +538,18 @@ For CaCl₂: (58/2)log10(10/1) = +29 mV Since the Nernst equation is really just a linear equation of the form y = mx, you can think of this first term at the slope and the equilibrium potential for an ion varies linearly with the log of the concentration gradient. In other words there is 58 mV per tenfold change in the concentration gradient when we are talking about our potassium examples above, which is depicted here --> ---- + + + --- ## Electrochemical equilibrium summary @@ -596,22 +597,17 @@ If our hypothetical battery holds the membrane at -58 mV, the equilbrium potenti At more negative membrane potentials than the nernst equilbrium potential we get net inward flow due to the stronger electrical driving force which in the case of potassium here is causing it to move against its chemical gradient. ---- - + - ---- - -## Both direction and magnitude of ion flux depend on the membrane potential + --- @@ -680,16 +675,6 @@ For a typical neuron at rest, pK : pNa : pCl = 1 : 0.05 : 0.45. Note that becaus - *"Expansion of the constant field equation to include both divalent and monovalent ions." (Spangler, S.G., Ala J Med Sci, 9: 218-223, 1972)* - [http://www.nernstgoldman.physiology.arizona.edu/using/](http://www.nernstgoldman.physiology.arizona.edu/using/) ---- - -## Resting membrane and action potentials entail permeabilities to different ions - -
Neuroscience 5e Fig. 2.7
- - -Note: - -And as we will soon lecarn, the resting membrane potential and action potential voltage is mostly due to changes in K permeability and Na permeability across the neuronal membrane. As you can see in this figure, the resting membrane potential for a neuron is close to the EK eq potential due to much greater permeability for K. During an action potential Na permeability initially increases, until the Vm approaches the ENa and then Na permeability decreases until the Vm again approaches the resting membrane potential and Pk increases. --- @@ -727,7 +712,7 @@ Cells are a bit like a semipermeable bag of electrolytes with different concentr | calcium (Ca2+), squid | 0.0001 | 10 | 100000 | | calcium (Ca2+), mammal | 0.0001 | 1–2 | 10000 | -
see also Neuroscience Table 2.1
+
see also Neuroscience 5e Table 2.1
@@ -770,12 +755,16 @@ Note: * Hypothesis– if axon resting potential (-65 mV) is predominantly due to K⁺ permeability then changing [K⁺]out should change the resting potential in a manner predicted by the Nernst equation * Experiment– stick an electrode inside axon, one outside axon (in bath). Change the concentration of K⁺ in the bath and measure new membrane potential. Assume intracellular K⁺ is unchanged during experiment. - * Nernst equation prediction– resting potential will depolarize with a slope of 58 mV per tenfold change in K⁺ gradient + + + Note: Alan Hodgkin, Andrew Huxley, Bernard Katz + + --- ## K⁺ concentration gradient determines resting membrane potential @@ -795,7 +784,6 @@ However it deviates from this expected relationship (shown by the black line), e **Because other ions, particularly Cl⁻ and Na⁺, are also slightly permeable and the contribution of these other ions is more evident at low K⁺ concentrations.** - --- ## Hodgkin and Katz– 1949 conclusions 1 @@ -874,41 +862,71 @@ As you can see on the left here changing extracellular [Na] changes the action p * During depolarization membrane becomes super permeable to Na⁺ * There must be Na⁺ channels that are closed during rest but become open during an action potential, and closed again at the end of an action potential -
Neuroscience 5e Fig. 2.7
+ Note: So a summary of the Hodgkin and Katz experiment conclusions... + --- + + +## Resting membrane and action potentials entail permeabilities to different ions + +
Neuroscience 5e Fig. 2.7
+ + +Note: + +And as we will soon lecarn, the resting membrane potential and action potential voltage is mostly due to changes in K permeability and Na permeability across the neuronal membrane. As you can see in this figure, the resting membrane potential for a neuron is close to the EK eq potential due to much greater permeability for K. During an action potential Na permeability initially increases, until the Vm approaches the ENa and then Na permeability decreases until the Vm again approaches the resting membrane potential and Pk increases. + + +--- + +## The action potential– summary + +
+ + +Note: + +And this is just a overall summary of what we have been discussing + + + + + --- - -## The action potential– summary - -
- - -Note: - -And this is just a overall summary of what we have been discussing diff --git a/neurophysiology2.md b/neurophysiology2.md index 3a834bb..d3a1f63 100644 --- a/neurophysiology2.md +++ b/neurophysiology2.md @@ -354,6 +354,7 @@ Note: Note: + @@ -366,7 +367,7 @@ Note:
* Question– Why do APs exhibit an all-or-nothing threshold? - * Answer– When membrane potential (Vm) is below threshold there is not enough Na⁺ channels open to raise Vm high enough to open more channels. When Vm is above threshold the action potential cycle is activated. + * Answer– When membrane potential (Vm) is below threshold there is not enough Na⁺ channels open to raise Vm high enough to open more channels. When Vm is above threshold the 'explosive' action potential cycle is activated. * Question– Why to APs exhibit an undershoot? * Answer– During the AP voltage-gated K⁺ conductance slowly increases (delayed activation of voltage-gated K⁺ channels) and during the falling phase these K⁺ channels are still open and active whereas voltage-gated Na⁺ channels are inactivated… as Vm approaches Ek there is briefly more K⁺ flowing out than at rest and the hyperpolarization inactivates voltage-gated K⁺ channels. K⁺ leak channels and ion transporters bring back cell to resting potential. @@ -423,7 +424,7 @@ Note: bottom graph shows the peak Vm ---- + - -Note: +
Neuroscience 5e Fig. 3.10
Active and Passive current flow. @@ -445,6 +444,8 @@ Active and Passive current flow. * Local passive depolarization causes nearby Na chan to open and another AP is generated * Na chan upstream inactivate and K chan open. Vm repolarizes and is refractory to further AP generation upstream * Process repeated downstream, propagating AP along the axon + --> + --- @@ -502,27 +503,26 @@ Note: Note: +saltatory action potential condution along a myelinated axon - ---- + --- ## Speed of action potential conduction in unmyelinated versus myelinated axons -
Neuroscience 5e Fig. 3.12
+
Neuroscience 5e Fig. 3.12
Note: @@ -592,5 +592,3 @@ ultimate cause of MS remains unclear. Immune system contributes to damage and is * women to men ratio 3/2 * Genetic component is likely the effect of multiple genes - ----