LocalAnesth406_2011

LocalAnesth406_2011 - Local Anesthetics Local anesthesia...

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Unformatted text preview: Local Anesthetics Local anesthesia History - cocaine (Niemann 1860), procaine (Einhorn 1905), lidocaine (Löfgren 1943) Cerebral cortex Pain Pathways The role of nerve conduction in sensory & motor function Significance of blocking nerve conduction Blockade of nerve conduction by blockade of channels Blockade of voltage-gated sodium channels Administration - local injection or topical LEARNING AND MEMORY, SPEECH AND LANGUAGE. BASAL GANGLIA Structures believed to be imporand memor y include the cerebral cortex, amygdala, hippocampus, cerebellum and basal ganglia. Areas of the left be active in speech and lan- tant for various kinds of learning Caudate nucleus Putamen Globus pallidus Lack of selectivity hemisphere (inset) are known to guage. The form and meaning of an utterance is believed to arise in Wernicke’s area and then Broca’s area, which is related to vocalization. Wernicke’s area is also important for language comprehension. Amygdaloid nucleus AREAS OF SPEECH AND L ANGUAGE Amygdala Hippocampus Broca’s area Wernicke’s area Angular gyrus Cerebellum Cerebral cortex BASAL GANGLIA Effective on various sensory and motor neurons LEARNING AND MEMORY, SPEECH AND LANGUAGE. Structures believed to be imporand memor y include the cerebral cortex, amygdala, hippocampus, cerebellum and basal ganglia. Areas of the left tant for various kinds of learning Caudate nucleus Putamen of cortical processing systems involved in the perception, processing and anal y sis of the mater ial being learned. In shor t, each part of the brain most likely contributes di∑erently to permanent memor y storage. One ofcorhe most prominent intellectual activities depenCerebral t tex dent on memor y is language. W hile the neural basis of language is not full y understood, scientists have learned much about this feature of the brain from studies of patients who have lost speech and language abilities dueHippocampus, and from behavto stroke Amygdala ioral and functional neuroimaging studies of normal people. Cerebellum A prominent and influential model, based on studies of these patients, proposes that the underlying structure of speech comprehension arises in Wernicke’s area, a portion of the lef t hemisphere of the brain. This temporal lobe region is connected with Broca’s area in the frontal lobe where a program for vocal expression is created. This program is then transmitted to a near by area of the motor cor tex that activates the mouth, tongue and lar ynx. This same model proposes that, when we read a word, the Hippocampus Amygdala information is transmitted from the primar y visual cortex to the angular g yrus where the message is somehow matched Cerith the w ebellum sounds of processing s hen spoken. The uditor y form o t oof cortical the words wystems involved inathe perception, fprhe cessing and anal y sis of the mater ial being learned. In shor t, each part of the brain most likely contributes di∑erently to permanent memor y storage. One of the most prominent intellectual activities dependent on memor y is language. W hile the neural basis of language is not full y understood, scientists have learned much about this feature of the brain from studies of patients who have lost speech and language abilities due to stroke, and from behavioral and functional neuroimaging studies of normal people. A prominent and influential model, based on studies of of cortical processing systems involved in the perception, prothese patients, proposes that the underlying structure of speech cessing and anal y sis of the mater ial being learned. In shor t, comprehension arises in Wernicke’s area, a portion of the lef t each part of the brain most likely contributes di∑erently to perhemisphere of the brain. This temporal lobe region is connected manent memor y storage. with Broca’s area in the frontal lobe where a program for vocal One of the most prominent intellectual activities depenexpression is created. This program is then transmitted to a dent on memor y is language. W hile the neural basis of lannear by area of the motor cor tex that activates the mouth, guage is not full y understood, scientists have learned much tongue and lar ynx. about this feature of the brain from studies of patients who have This same model proposes that, when we read a word, the lost speech and language abilities due to stroke, and from behavinformation is transmitted from the primar y visual cortex to the ioral and functional neuroimaging studies of normal people. angular g yrus where the message is somehow matched with the A prominent and influential model, based on studies of sounds of the words when spoken. The auditor y form of the these patients, proposes that the underlying structure of speech comprehension arises in Wernicke’s area, a portion of the lef t hemisphere of the brain. This temporal lobe region is connected with Broca’s area in the frontal lobe where a program for vocal expression is created. This program is then transmitted to a near by area of the motor cor tex that activates the mouth, tongue and lar ynx. This same model proposes that, when we read a word, the information is transmitted from the primar y visual cortex to the angular g yrus where the message is somehow matched with the sounds of the words when spoken. The auditor y form of the word is then pprallidus ocessed for comprehensionei(inset)rare ke’swnrea hemispher n We nic kno a to as if the word Amygdaloid heard. Writing en rspeech and lan- oral had been be activ i in esponse to an nucleus instruction requires information guage.passed alongmeaning of to be The form and the same LEARNING AND MEMORY, pathways in the opposite direction—from the believedy carise an utterance is auditor to ortex SPEECH AND LANGUAGE. to Wernicke’s aBASALtGANGLIA angularin Wrernicke’s amodel accounts rea o the g y us. This rea and then Structures believed to be imporAREAS OF SPEECH for much of the Ldata AGE m patients, and’sis rea, which widely used f ro AND ANGU Broca a the most is related to tant for various kinds of learning model for c linic al diagnosis andvocalization. Wernicke’s area is prognosis. Howe ver, some and memor y include the cererefinements toCaudatemodel may be also important foro both recent this necessar y due t language Broca’s area bral cortex, amygdala, hipnucleus studies with Wernicke’s areand functiocomprehension. patients a nal neuroimaging studies in pocampus, cerebellum and Pu Angular n normal people. tamegyrus basal ganglia. Areas of the left Globus For example, using an imaging technique c alled posit ron pallidus hemisphere (inset) are known to emission tomography (PET), scientists have demonstrated that Amygdaloid be active in speech and lansome reading tnucleusperformed by normal people activated neiasks guage. The form and meaning of ther Wernicke’s area nor the angular g yrus. These results sugan utterance is believed to arise gest that there is a direct reading route that does not involve in Wernicke’s area and then speech sound Secoding of the visual stimulus before the proAREA r OF SPEECH AND L ANGUAGE Broca’s area, which is related to cessing of either meaning or speaking. O ther studies with vocalization. Wernicke’s area is patients also have indicated that it is likely that familiar words also important for language area need notBroca’sWernicke’s area sound before they can be understood. be recoded into comprehension. Although theAngular understanding of how language is implegyrus mented in the brain is far from complete, there are now several techniques that ocessed used omprehensiontantWernicke’s area word is then pr may be for c to gain impor in insights. as if the word had been heard. Writing in response to an oral 19 instruction requires information to be passed along the same pathways in the opposite direction—from the auditor y cortex to Wernicke’s area to the angular g yrus. This model accounts for much of the data from patients, and is the most widely used model for c linic al diagnosis and prognosis. Howe ver, some refinements to this model may be necessar y due to both recent studies with patients and functional neuroimaging studies in normal people. For example, using an imaging technique c alled posit ron word is then processed for comprehension in Wernicke’s area emission tomography (PET), scientists have demonstrated that as if the word had been heard. Writing in response to an oral some reading tasks performed by normal people activated neiinstruction requires information to be passed along the same ther Wernicke’s area nor the angular g yrus. These results sugpathways in the opposite direction—from the auditor y cortex gest that there is a direct reading route that does not involve to Wernicke’s area to the angular g yrus. This model accounts speech sound recoding of the visual stimulus before the profor much of the data from patients, and is the most widely used cessing of either meaning or speaking. O ther studies with model for c linic al diagnosis and prognosis. Howe ver, some patients also have indicated that it is likely that familiar words refinements to this model may be necessar y due to both recent need not be recoded into sound before they can be understood. studies with patients and functional neuroimaging studies in Although the understanding of how language is implenormal people. mented in the brain is far from complete, there are now several For example, using an imaging technique c alled posit ron techniques that may be used to gain important insights. emission tomography (PET), scientists have demonstrated that some reading tasks performed by normal people activated nei19 ther Wernicke’s area nor the angular g yrus. These results suggest that there is a direct reading route that does not involve speech sound recoding of the visual stimulus before the processing of either meaning or speaking. O ther studies with patients also have indicated that it is likely that familiar words need not be recoded into sound before they can be understood. Although the understanding of how language is implemented in the brain is far from complete, there are now several techniques that may be used to gain important insights. 19 Mechanism of action Blockade of Na+ channels Blockade of nerve conduction Globus 1 2 A Primer on Membrane Potentials Na+ channel, influx, depolarization, increased excitability Ca2+ channel, influx, depolarization, increased excitability K+ channel, efflux, hyperpolarization, decreased excitability Cl- channel, influx, hyperpolarization, decreased excitability 3 4 HUBNET - SUNY Buffalo -- Goodman & Gilman's The Pharmacological Basis of Therapeutics - 11th Ed. (2006) 1/17/10 8:02 PM Sodium Channels Figure 14-2. Structure and function of voltage-gated Na+ channels. A. A two-dimensional representation of the ! (center), " 1 (left), and " 2 (right) subunits of the voltage-gated Na + channel from mammalian brain. The polypeptide chains are represented by continuous lines with length approximately proportional to the actual length of each segment of the channel protein. Cylinders represent regions of transmembrane ! helices. indicates sites of demonstrated N-linked glycosylation. Note the repeated structure of the four homologous domains (I through IV) of the ! subunit. Voltage Sensing. The S4 transmembrane segments in each homologous domain of the ! subunit serve as voltage sensors. (+) represents the positively charged amino acid residues at every third position 5 6 Local Anesthetics & Sodium Channels http://online.statref.com/Document/Document.aspx?password=suny%24hub&FxId=75&docId=152&SessionId=115AB00GSTRAIJPM Page 1 of 3 Mechanisms of Action Resting, closed, open and inactivated states of the sodium channel State specific binding and blockade - higher affinity for specific states Delay in recovery from inactivation: 50-100 fold Cerebral cortex Dependence of blockade on the frequency of impulses BASAL GANGLIA LEARNING AND MEMORY, SPEECH AND LANGUAGE. Structures believed to be imporand memor y include the cerebral cortex, amygdala, hippocampus, cerebellum and tant for various kinds of learning Caudate nucleus Putamen Globus pallidus basal ganglia. Areas of the left be active in speech and lan- hemisphere (inset) are known to guage. The form and meaning of an utterance is believed to arise in Wernicke’s area and then Broca’s area, which is related to vocalization. Wernicke’s area is also important for language comprehension. Amygdaloid nucleus AREAS OF SPEECH AND L ANGUAGE Amygdala Hippocampus Broca’s area Wernicke’s area Angular gyrus Cerebellum Higher frequency; stronger blockade word is then processed for comprehension in Wernicke’s area as if the word had been heard. Writing in response to an oral instruction requires information to be passed along the same pathways in the opposite direction—from the auditor y cortex to Wernicke’s area to the angular g yrus. This model accounts for much of the data from patients, and is the most widely used model for c linic al diagnosis and prognosis. Howe ver, some refinements to this model may be necessar y due to both recent studies with patients and functional neuroimaging studies in normal people. For example, using an imaging technique c alled posit ron emission tomography (PET), scientists have demonstrated that some reading tasks performed by normal people activated neither Wernicke’s area nor the angular g yrus. These results suggest that there is a direct reading route that does not involve speech sound recoding of the visual stimulus before the processing of either meaning or speaking. O ther studies with patients also have indicated that it is likely that familiar words need not be recoded into sound before they can be understood. Although the understanding of how language is implemented in the brain is far from complete, there are now several techniques that may be used to gain important insights. 19 of cortical processing systems involved in the perception, processing and anal y sis of the mater ial being learned. In shor t, each part of the brain most likely contributes di∑erently to permanent memor y storage. One of the most prominent intellectual activities dependent on memor y is language. W hile the neural basis of language is not full y understood, scientists have learned much about this feature of the brain from studies of patients who have lost speech and language abilities due to stroke, and from behavioral and functional neuroimaging studies of normal people. A prominent and influential model, based on studies of these patients, proposes that the underlying structure of speech comprehension arises in Wernicke’s area, a portion of the lef t hemisphere of the brain. This temporal lobe region is connected with Broca’s area in the frontal lobe where a program for vocal expression is created. This program is then transmitted to a near by area of the motor cor tex that activates the mouth, tongue and lar ynx. This same model proposes that, when we read a word, the information is transmitted from the primar y visual cortex to the angular g yrus where the message is somehow matched with the sounds of the words when spoken. The auditor y form of the Use dependent inhibition 7 8 Use Dependent Inhibition Use Dependent Inhibition 9 10 Action of Local Anesthetics Blockade of voltage-activated sodium channels From blockade of channels to blockade of nerve conduction LEARNING AND MEMORY, SPEECH AND LANGUAGE. BASAL GANGLIA LEARNING AND MEMORY, Cerebral cortex BASAL GANGLIA SPEECH AND LANGUAGE. Structures believed to be imporand memor y include the cerebral cortex, amygdala, hippocampus, cerebellum and basal ganglia. Areas of the left be active in speech and lan- tant for various kinds of learning Caudate nucleus Putamen Globus pallidus Action of Local Anesthetics Selectivity of anesthetic effects hemisphere (inset) are known to guage. The form and meaning of an utterance is believed to arise in Wernicke’s area and then Broca’s area, which is related to vocalization. Wernicke’s area is also important for language comprehension. LEARNING AND MEMORY, SPEECH AND LANGUAGE. Structures believed to be imporand memor y include the cerebral cortex, amygdala, hippocampus, cerebellum and tant for various kinds of learning Amygdaloid nucleus AREAS OF SPEECH AND L ANGUAGE Amygdala Hippocampus Broca’s area Wernicke’s area Angular gyrus BASAL GANGLIA Cerebral cortex Cerebellum Caudate nucleus Putamen Globus pallidus Amygdaloid nucleus Cerebral cortex Structures believed to be imporand memor y include the cerebral cortex, amygdala, hippocampus, cerebellum and basal ganglia. Areas of the left be active in speech and lan- tant for various kinds of learning Caudate nucleus Putamen Globus pallidus Cerebral cortex Time course of Local anesthesia hemisphere (inset) are known to guage. The AND MEMORY, of LEARNING form and meaning an utterance is ANGUAGE. arise SPEECH AND L believed to in Wernicke’s area and then Structures believed to be imporAmygdaloid nucleus BASAL GANGLIA AREAS OF SPEECH AND L ANGUAGE Amygdala Hippocampus Caudate Broca’s area nucleus Wernicke’s area Putamen Angular Cerebellum gyrus Globus pallidus Amygdaloid nucleus Broca’s aarious kinds of learning tant for vrea, which is related to vocalization. Wernicke’s cereand memor y include the area is also cortex, amygdala, hipbral important for language comprehension. pocampus, cerebellum and basal ganglia. Areas of the left AREAS OF SPEECH AND L ANGUAGE Rapid onset ! 2-5 min., !10-15 min. be active in speech and language. The form and meaning of an utterance is believed to arise in Wernicke’s area and then Broca’s area, which is related to vocalization. Wernicke’s area is also important for language comprehension. hemisphere (inset) are known to Amygdala Hippocampus Broca’s area Wernicke’s area Angular gyrus Cerebellum of cortical processing systems involved in the perception, processing and anal y sis of the mater ial being learned. In shor t, each part of the brain most likely contributes di∑erently to permanent memor y storage. One of the most prominent intellectual activities dependent on memor y is language. W hile the neural basis of language is not full y understood, scientists have learned much about this feature of the brain from studies of patients who have lost speech and language abilities due to stroke, and from behavioral and functional neuroimaging studies of normal people. A p o processing i stems involved in based ception, pr of of corticralminent andsynfluential model, the peron studies othese p and a pr y sis of he the underl eing earned. In peech cessingatients,naloposes tthat mater ial bying sltructure of sshor t, comprehension a ises in W ikely contr ea, a di∑erentl he ef t each part of the brain most lernicke’s aributesportion ofytto plerhemisphere of t y brain. This temporal lobe region is connected manent memorhestorage. with Broca’stheea iostherorminent intelhere a pactivities orepenOne of ar m n t p f ontal lobe wlectual rogram f d vocal expr on m is cr y is language. W am s then transmitted o a dentession emoreated. This progrhile ithe neural basis of ltannear by a not full y motor cor scientists have learned outh, guage is rea of theunderstood,tex that activates the mmuch tongue and lar y e o about this featurnx.f the brain from studies of patients who have lost This same model proposes that, whenowe, readfaoword, the speech and language abilities due to str k e and r m behavinfor and functional neuroimaging primar of normal tex to t ioral mation is transmitted from thestudies y visual corpeople.he angular rominent and influential smomehow matchedtudiesthe A p g yrus where the message i s odel, based on s with of sounds of the proposes that poken. The auditor y f e m peech these patients, words when sthe underlying structurorof sof the comprehension arises in Wernicke’s area, a portion of the lef t hemisphere of the brain. This temporal lobe region is connected with Broca’s area in the frontal lobe where a program for vocal expression is created. This program is then transmitted to a near by area of the motor cor tex that activates the mouth, tongue and lar ynx. This same model proposes that, when we read a word, the information is transmitted from the primar y visual cortex to the angular g yrus where the message is somehow matched with the sounds of the words when spoken. The auditor y form of the word is then processed for comprehension in Wernicke’s area as if the word had been heard. Writing in response to an oral instruction requires information to be passed along the same pathways in the opposite direction—from the auditor y cortex to Wernicke’s area to the angular g yrus. This model accounts for much of the data from patients, and is the most widely used model for c linic al diagnosis and prognosis. Howe ver, some refinements to this model may be necessar y due to both recent studies with patients and functional neuroimaging studies in normal people. F is example, using or i omprehension in c ernic posit rea word or then processed fan cmaging techniqueWalled ke’s aron emission tomograad been heard. Writingave rdemonstrated that as if the word h phy (PET), scientists h in esponse to an oral some reading tasks pinformation to be passed along the same instruction requires erformed by normal people activated neither Wernicke’s arpposite tdirection—from the auditor y corugpathways in the o ea nor he angular g yrus. These results s tex gest ternicke’seais a tdirtect aeading goute tThisdmodel accounts to W hat ther rea o he r ngular r yrus. hat oes not involve speecucsound recoding mfpatients, and is tulus before the used for mh h of the data fro o the visual stim he most widely processing for c linic almeaning orand prognosis. Hostudies some model of either diagnosis speaking. O ther we ver, with patients alsothave indicated that e tniecessar ytdue ftamiliar recent refinements o this model may b i s likely hat o both words need not be recoded into sound beforenteuroimagingnderstood. studies with patients and functional hey can be u studies in Although normal people.the understanding of how language is implemented in the br, usingar nromaging technique aralledwpseveral For exampleain is f a f i m complete, there c e no osit ron techniques that phy be used to gain impor demonstrated emission tomogramay (PET), scientists havetant insights. that some reading tasks performed by normal people activated nei19 ther Wernicke’s area nor the angular g yrus. These results suggest that there is a direct reading route that does not involve speech sound recoding of the visual stimulus before the processing of either meaning or speaking. O ther studies with patients also have indicated that it is likely that familiar words need not be recoded into sound before they can be understood. Although the understanding of how language is implemented in the brain is far from complete, there are now several techniques that may be used to gain important insights. 19 Slow and variable recovery ! 15-60 min., hours of cortical processing systems involved in the perception, processing and anal y sis of the mater ial being learned. In shor t, each part of the brain most likely contributes di∑erently to permanent memor y storage. Hippocampus Amygdala One of the most prominent intellectual activities dependent on memor y is language. W hile the neural basis of lanCerebellum guage is not full y understood, scientists have learned much about this feature of the brain from studies of patients who have lost speech and language abilities due to stroke, and from behavioral and functional neuroimaging studies of normal people. A prominent and influential model, based on studies of these patients, proposes that the underlying structure of speech comprehension arises in Wernicke’s area, a portion of the lef t hemisphere of the brain. This temporal lobe region is connected with Broca’s area in the frontal lobe where a program for vocal expression is created. This program is then transmitted to a near by area of the motor cor tex that activates the mouth, of cortical processing systems involved in the perception, protongue and lar ynx. cessing and anal y sis of the mater ial being learned. In shor t, This same model proposes that, when we read a word, the each part of the brain most likely contributes di∑erently to perinformation is transmitted from the primar y visual cortex to the manent memor y storage. angular g yrus where the message is somehow matched with the One of the most prominent intellectual activities depensounds of the words when spoken. The auditor y form of the dent on memor y is language. W hile the neural basis of language is not full y understood, scientists have learned much about this feature of the brain from studies of patients who have lost speech and language abilities due to stroke, and from behavioral and functional neuroimaging studies of normal people. A prominent and influential model, based on studies of these patients, proposes that the underlying structure of speech comprehension arises in Wernicke’s area, a portion of the lef t hemisphere of the brain. This temporal lobe region is connected with Broca’s area in the frontal lobe where a program for vocal expression is created. This program is then transmitted to a near by area of the motor cor tex that activates the mouth, tongue and lar ynx. This same model proposes that, when we read a word, the information is transmitted from the primar y visual cortex to the angular g yrus where the message is somehow matched with the sounds of the words when spoken. The auditor y form of the AREA rOF SPEECH word is then pS ocessed for comprehension in Wernicke’s area AND L ANGUAGE Broca’s area, which is related to as if the word had been heard. Writing in response to an oral vocalization. Wernicke’s area is instruction requires information to be passed along the same also important for language Broca’s area pathways in the opposite direction—from the auditor y cortex Wernicke’s area comprehension. Angular to Wernicke’s area to the angular g yrus. This model accounts gyrus for much of the data from patients, and is the most widely used model for c linic al diagnosis and prognosis. Howe ver, some refinements to this model may be necessar y due to both recent studies with patients and functional neuroimaging studies in normal people. For example, using an imaging technique c alled posit ron emission tomography (PET), scientists have demonstrated that some reading tasks performed by normal people activated neither Wernicke’s area nor the angular g yrus. These results suggest that there is a direct reading route that does not involve speech sound recoding of the visual stimulus before the processing of either meaning or speaking. O ther studies with word is then processed for comprehension in Wernicke’s area patients also have indicated that it is likely that familiar words as if the word had been heard. Writing in response to an oral need not be recoded into sound before they can be understood. instruction requires information to be passed along the same Although the understanding of how language is implepathways in the opposite direction—from the auditor y cortex mented in the brain is far from complete, there are now several to Wernicke’s area to the angular g yrus. This model accounts techniques that may be used to gain important insights. for much of the data from patients, and is the most widely used model for c linic al diagnosis and prognosis. Howe ver, some 19 refinements to this model may be necessar y due to both recent studies with patients and functional neuroimaging studies in normal people. For example, using an imaging technique c alled posit ron emission tomography (PET), scientists have demonstrated that some reading tasks performed by normal people activated neither Wernicke’s area nor the angular g yrus. These results suggest that there is a direct reading route that does not involve speech sound recoding of the visual stimulus before the processing of either meaning or speaking. O ther studies with patients also have indicated that it is likely that familiar words need not be recoded into sound before they can be understood. Although the understanding of how language is implemented in the brain is far from complete, there are now several techniques that may be used to gain important insights. Selectivity of effect mainly in terms of local nature of application basal ganglia. Areas of the left be active in speech and lanhemisphere (inset) are known to guage. The form and meaning of an utterance is believed to arise in Wernicke’s area and then Equally effective on most neurons - sensory or motor 19 11 12 Use with Vasoconstrictors Cerebral cortex Reduction in blood flow LEARNING AND MEMORY, SPEECH AND LANGUAGE. BASAL GANGLIA Structures believed to be imporand memor y include the cerebral cortex, amygdala, hippocampus, cerebellum and basal ganglia. Areas of the left be active in speech and lan- tant for various kinds of learning Caudate nucleus Putamen Globus pallidus Cerebral cortex Increase in local concentration hemisphere (inset) are known to guage. The AND MEMORY, of LEARNING form and meaning an utter AND L believed to SPEECHance is ANGUAGE. arise Amygdaloid nucleus BASAL GANGLIA AREAS OF SPEECH AND L ANGUAGE in Wernicke’s area and be imporStructures believed to then Broca’s vrea, which is related to tant for aarious kinds of learning vocalization. include the area is and memor y Wernicke’s cerealso important for language bral cortex, amygdala, hipcomprehension. pocampus, cerebellum and basal ganglia. Areas of the left Amygdala Hippocampus Caudate Broca’s area nucleus Wernicke’s area Putamen Angular Cerebellum gyrus Globus pallidus Amygdaloid nucleus AREAS OF SPEECH AND L ANGUAGE Increased duration of action be active in speech and language. The form and meaning of an utterance is believed to arise in Wernicke’s area and then Broca’s area, which is related to vocalization. Wernicke’s area is also important for language comprehension. hemisphere (inset) are known to Hydrophobicity of Local Anesthetics Amygdala Hippocampus Broca’s area Wernicke’s area Angular gyrus Cerebellum of cortical processing systems involved in the perception, processing and anal y sis of the mater ial being learned. In shor t, each part of the brain most likely contributes di∑erently to permanent memor y storage. Cerebral t tex One ofcorhe most prominent intellectual activities dependent on memor y is language. W hile the neural basis of language is not full y understood, scientists have learned much about this feature of the brain from studies of patients who have lost speech and language abilities due to stroke, and from behavioral and functional neuroimaging studies of normal people. A p o processing i stems involved in based ception, pr of of corticralminent andsynfluential model, the peron studies othese p and a pr y sis of he the underl eing earned. In peech cessingatients,naloposes tthat mater ial bying sltructure of sshor t, comprehension a ises in W ikely contr ea, a di∑erentl he ef t each part of the brain most lernicke’s aributesportion ofytto plerhemisphere of t y brain. This temporal lobe region is connected manent memorhestorage. with Broca’stheea iostherorminent intelhere a pactivities orepenOne of ar m n t p f ontal lobe wlectual rogram f d vocal expression emoreated. This progrhile ithe neural basis of ltandent on m is cr y is language. W am s then transmitted o a near by a not full y motor cor scientists have learned outh, guage is rea of theunderstood,tex that activates the mmuch tonguehis featurnx.f the brain from studies of patients who have about t and lar y e o r abilities lost This same model pAmygdala that, Hippocampus, readfaoword, the speech and languageoposes due whenowe and r m behavto str k e infor and functional neuroimaging primar of normal tex to t ioral mation is transmitted from thestudies y visual corpeople.he angular rominent and influential smomehow matchedtudiesthe w ebellum A p g yrus where the message i s odel, based on s Cerith of sounds of the proposes that poken. The auditor y f e m peech these patients, words when sthe underlying structurorof sof the comprehension arises in Wernicke’s area, a portion of the lef t hemisphere of the brain. This temporal lobe region is connected with Broca’s area in the frontal lobe where a program for vocal expression is created. This program is then transmitted to a near by area of the motor cor tex that activates the mouth, tongue and lar ynx. This same model proposes that, when we read a word, the information is transmitted from the primar y visual cortex to the angular g yrus where the message is somehow matched with the sounds of processing s hen spoken. The uditor y form o t oof cortical the words wystems involved inathe perception, fprhe cessing and anal y sis of the mater ial being learned. In shor t, each part of the brain most likely contributes di∑erently to permanent memor y storage. One of the most prominent intellectual activities dependent on memor y is language. W hile the neural basis of language is not full y understood, scientists have learned much about this feature of the brain from studies of patients who have lost speech and language abilities due to stroke, and from behavioral and functional neuroimaging studies of normal people. A prominent and influential model, based on studies of these patients, proposes that the underlying structure of speech comprehension arises in Wernicke’s area, a portion of the lef t hemisphere of the brain. This temporal lobe region is connected with Broca’s area in the frontal lobe where a program for vocal expression is created. This program is then transmitted to a near by area of the motor cor tex that activates the mouth, tongue and lar ynx. This same model proposes that, when we read a word, the information is transmitted from the primar y visual cortex to the angular g yrus where the message is somehow matched with the sounds of the words when spoken. The auditor y form of the word is then processed for comprehension in Wernicke’s area as if the word had been heard. Writing in response to an oral instruction requires information to be passed along the same LEARNING AND MEMORY, pathways in the opposite direction—from the auditor y cortex SPEECH AND LANGUAGE. BASAL GANGLIA to Wernicke’s area to the angular g yrus. This model accounts Structures believed to be imporfor much of the data from patients, and is the most widely used tant for various kinds of learning model for c linic al diagnosis and prognosis. Howe ver, some and memor y include the cererefinements toCaudatemodel may be necessar y due to both recent this bral cortex, amygdala, hipnucleus studies with patients and functional neuroimaging studies in pocampus, cerebellum and Putamen normal people. basal ganglia. Areas of the left Globus F is example, using fan cmaging techniqueWalled ke’s aron c e nic posit word or then pprallidus ocessed or i omprehensionei(inset)rare knownrea hemispher n to emission tomogAmygdaloid ETeard. Writingave rdemonstrated that as if the word raad been h ), scientists h en speech and lan- oral h phy (P be activ i in esponse to an some reading tnucleuspinformation to be passed along the same asks normal p activated n instruction requires erformed by guage. Theeople and meaningeiform of ther Wernicke’s arpposite tdirection—from the auditor y corugus. These results s tex pathways in the o ea nor he angular g yrance is believed to arise an utter gest ternicke’seais a tdirtect aeading goute tThisdmodel accounts to W hat ther rea o he r ngularinrWrernicke’s aroesand then ve y us. hat ea not invol AREA r SPEE speecucsound Secoding mfpatients, and is tulus before the used h h of the OFata fCH o the visual stim he most widely profor m d ro AND L ANGUAGE Broca’s area, which is related to cessing for c linic almeaning orand prognosis. Hostudies some with model of either diagnosis speaking. O ther we ver,rea is vocalization. Wernicke’s a patients alsothave indicated that e tniecessar ytdue ftamiliar recent i s likely hat o both words refinements o ea model may b also important for language this Broca’s ar need not be rWernicke’s areand ound beforenteuroimagingnderstood. studies with ecoded into s functiocomprehension.be u studies in patients a nal hey can Although understanding of how language is implenormal people.theAngular gyrus mented in the br, usingar nromaging technique aralledwpseveral For exampleain is f a f i m complete, there c e no osit ron techniques that phy be used to gain impor demonstrated emission tomogramay (PET), scientists havetant insights. that some reading tasks performed by normal people activated nei19 ther Wernicke’s area nor the angular g yrus. These results suggest that there is a direct reading route that does not involve speech sound recoding of the visual stimulus before the processing of either meaning or speaking. O ther studies with patients also have indicated that it is likely that familiar words need not be recoded into sound before they can be understood. Although the understanding of how language is implemented in the brain is far from complete, there are now several techniques that ocessed used omprehensiontantWernicke’s area word is then pr may be for c to gain impor in insights. Need lower amounts Decreased concentration in systemic circulation Decreased toxicity as if the word had been heard. Writing in response to an oral 19 instruction requires information to be passed along the same pathways in the opposite direction—from the auditor y cortex to Wernicke’s area to the angular g yrus. This model accounts for much of the data from patients, and is the most widely used model for c linic al diagnosis and prognosis. Howe ver, some refinements to this model may be necessar y due to both recent studies with patients and functional neuroimaging studies in normal people. For example, using an imaging technique c alled posit ron emission tomography (PET), scientists have demonstrated that some reading tasks performed by normal people activated neither Wernicke’s area nor the angular g yrus. These results suggest that there is a direct reading route that does not involve speech sound recoding of the visual stimulus before the processing of either meaning or speaking. O ther studies with patients also have indicated that it is likely that familiar words need not be recoded into sound before they can be understood. Although the understanding of how language is implemented in the brain is far from complete, there are now several techniques that may be used to gain important insights. 19 Possibility of tissue hypoxia in areas of limited circulation 13 14 Anatomic Considerations Action on Nerves Effect of fiber diameter - smaller fibers blocked preferentially Effect of firing rate - better block at higher frequency Effect of action potential duration - better block with longer action potentials Effect of fiber position in the bundle - slower action on deeper fibers 15 16 ...
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