By M. Thorek. University of Newport.
The importance of these ﬁndings is that they demonstrated purchase 100 mg caverta, as a proof of principle buy generic caverta 100 mg on-line, that TMS can modulate human cortical plasticity. These ﬁndings led to the investigation of the effects of cortical stimulation on use- dependent plasticity (UDP), fundamentally relevant in neurorehabilitation. A recent study demonstrated for the ﬁrst time that cortical stimulation can enhance human cortical plasticity elicited by motor training. These results demonstrated that UDP can be promoted by synchronous Hebbian stimulation of the motor cortex. Performance time of each subtest with cortical stimulation (black bars) and placebo stimulation (grey bars) relative to baseline (white bars) is shown in a representative patient. Subtests consist of turning cards (exemplarily shown in the lower row), picking up small objects, mimicking feeding by putting beans with a spoon in a can, stacking checkers, and lifting light and heavy cans is shown. Note the improvement of performance time during tDCS compared to placebo stim- ulation, indicating that cortical stimulation of the affected hemisphere improved functional motor skills of the paretic hand in this particular patient (modiﬁed from Hummel et al. Results depicted so far have demonstrated that cortical stimulation applied to one site can enhance excitability or plasticity at that site. Additionally, cortical stimulation applied to one site can induce distant effects on cortical function and behavior. It has been proposed that this balance may be disturbed in patients with cortical lesions such as stroke. Indeed, an abnormally high interhemispheric inhibitory drive from M1 in the intact hemisphere to M1 in the affected hemisphere has been documented during generation of a voluntary movement by the paretic hand. Therefore, it is conceivable that one way to improve motor function in the paretic hand is to decrease motor cortical excitability in the ipsilateral, intact motor cortex (with the purpose of reducing abnormal inhibition from the intact to the affected hemisphere), a hypothesis under investigation. In summary, animal models and human studies in healthy volunteers and stroke patients suggest that cortical stimulation may potentially become an adjuvant to improve motor function and enhance the beneﬁcial effects of motor training in patients with brain lesions. Improved understanding of the way in which somatosensory input inﬂuences motor function led to the development of novel rehabilitative interventions. One example is constraint-induced movement therapy, a strategy consisting of immobi- lization of the intact hand of stroke patients associated with intensive practice performed with the weak hand. This intervention may enhance functional recovery in patients with motor deﬁcits following a stroke. The combination of constraint and practice in these patients may result in a reduction of exaggerated interhemispheric inhibition from M1 in the intact hemisphere to M1 in the affected hemisphere. CONCLUSIONS The somatosensory and motor cortices are highly interconnected, operate in var- ious settings of learning and skill acquisition, and experience constant reorgani- zation in response to environmental challenges or lesions. Acute and chronic deafferentation, somatosensory stimulation, and cortical stimulation can modulate plasticity in both cerebral hemispheres. Improved understanding of these plastic changes has recently raised the exciting hypothesis of utilizing these tools to modify function after brain lesions such as stroke, hopefully evolving to the development of new strategies in neurorehabilitation. Adkins-Muir DL, Jones TA (2003) Cortical electrical stimulation combined with rehabilitative training: enhanced functional recovery and dendritic plasticity following focal cortical ischemia in rats. Ahissar E, Abeles M, Ahissar M, Haidarliu S, Vaadia E (1998) Hebbian-like functional plasticity in the auditory cortex of the behaving monkey. Ahissar E, Vaadia E, Ahissar M, Bergman H, Arieli A, Abeles M (1992) Dependence of cortical plasticity on correlated activity of single neurons and on behavioral context. Asanuma H, Larsen KD, Zarzecki P (1979) Peripheral input pathways projecting to the motor cortex in the cat. Asanuma H, Rosen I (1972) Functional role of afferent inputs to the monkey motor cortex. Bartoletti A, Medini P, Berardi N, Maffei L (2004) Environmental enrichment pre- vents effects of dark-rearing in the rat visual cortex. Bear MF, Rittenhouse CD (1999) Molecular basis for induction of ocular dominance plasticity. Birbaumer N, Lutzenberger W, Montoya P, Larbig W, Unertl K, Topfner S, Grodd W, Taub E, Flor H (1997) Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization. Brasil-Neto J, Cohen LG, Pascual-Leone A, Jabir FK, Wall RT, Hallett M (1992) Rapid reversible modulation of human motor outputs after transient deafferentation of the forearm: a study with transcranial magnetic stimulation. Brasil-Neto J, Valls-Sole J, Pascual-Leone A, Cammarota A, Amassian VE, Cracco R, Maccabee P, Cracco J, Hallett M, Cohen LG (1993) Rapid modulation of human cortical motor outputs following ischaemic nerve block. Bueteﬁsch CM, Khurana V, Kopylev L, Cohen LG (2004) Enhancing encoding of a motor memory in the primary motor cortex by cortical stimulation. Calford MB, Tweedale R (1990) Interhemispheric transfer of plasticity in the cerebral cortex. Canavero S, Bonicalzi V, Paolotti R, Castellano G, Greco-Crasto S, Rizzo L, Davini O, Maina R (2003) Therapeutic extradural cortical stimulation for movement disor- ders: a review. Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, Cohen LG (1997) Depression of motor cortex excitability by low-frequency transcranial mag- netic stimulation. Chen R, Corwell B, Yaseen Z, Hallett M, Cohen LG (1998) Mechanisms of cortical reorganization in lower-limb amputees. Cohen LG, Bandinelli S, Findley TW, Hallett M (1991a) Motor reorganization after upper limb amputation in man. Cohen LG, Celnik P, Pascual-Leone A, Corwell B, Falz L, Dambrosia J, Honda M, Sadato N, Gerloff C, Catala MD, Hallett M (1997) Functional relevance of cross- modal plasticity in blind humans. Cohen LG, Topka H, Cole RA, Hallett M (1991b) Leg paresthesias induced by magnetic brain stimulation in patients with thoracic spinal cord injury. Cohen LG, Ziemann U, Chen R, Classen J, Hallett M, Gerloff C, Buteﬁsch C (1998) Studies of neuroplasticity with transcranial magnetic stimulation. Conforto AB, Kaelin-Lang A, Cohen LG (2002) Increase in hand muscle strength of stroke patients after somatosensory stimulation. Darian-Smith C, Gilbert CD (1994) Axonal sprouting accompanies functional reor- ganization in adult cat striate cortex. Darian-Smith C, Gilbert CD (1995) Topographic reorganization in the striate cortex of the adult cat and monkey is cortically mediated.
Persistent deﬁcits were identiﬁed by physiological recording from single cells in layer IV barrels with a history of normal activity during development (normal or intact whisker barrels) buy 100 mg caverta with mastercard, or barrels that received abnormally low activity during development (deprived barrels) caverta 100 mg low price. The animals were anesthetized with pentobarbital and maintained with fentanyl coupled with paralysis produced by pancuronium bromide. When Simons and Land recorded cortical responses after restricted SD, the deprived barrel cells showed quite different response properties from non-deprived barrel neurons. The deprived barrel cells showed: 1) elevated spontaneous activity, 2) greater responses to both principal and surround whisker stimulation (spontaneous activity was not subtracted from the total spikes), 3) enlarged receptive ﬁelds (more whiskers produced a response), and 4) reduced directional tuning. Population responses to principal whiskers showed that both onset and offset responses to the 200 msec duration deﬂections were greater in the deprived barrels than in adjacent nondeprived barrel columns (or in normally reared animals). They proposed that the SD led to an increased whisker drive on cortical cells from thalamic inputs (increased excitation) coupled with a decreased efﬁcacy of intracortical inhib- itory mechanisms in the deprived barrels (see below). One of the questions that these results raise is whether there is a critical period, and if so, does the sensitive period for SD end at the same time for cells in all corticaI layers. Fox122 reported that SD changes could be produced by raising rat pups with all whiskers plucked except one intact whisker (the D1 whisker) on one side of the face. Then, with a minimal recovery period only long enough to let the whiskers elongate to apply test stimuli, cortical cell responses were recorded to whisker stimulation. In this paradigm, the one intact whisker is used during daily exploration by the animal throughout the period when all surrounding whiskers are producing levels of neural activity well below normal. This result suggested that SD leads to different effects in different layers, with layer IV stabilizing during the ﬁrst postnatal week in a way that layers II/III do not. A follow-up study by the same author92 provided evidence that the expanded cortical domains dominated by the single intact whisker when SD was initiated at PND 0 were diminished by small lesions placed in the D1 barrel at the end of the deprivation period, leading to the suggestion that the expansion depended upon intra- cortical connections rather than synaptic reorganization at the thalamic or brainstem levels. Curiously, although latencies changed, response magnitudes showed no changes for the preserved D1 whisker. Plasticity in layer IV was greatly diminished at later onsets of deprivation when only one whisker was left intact, which is © 2005 by Taylor & Francis Group. Another important question is whether a short period of neonatal deprivation degrades the plasticity of cortical function to sensory challenges throughout life. In a recent study, 3-week periods of trimming two whiskers starting just after birth impaired the ability of the deprived cortex to produce plastic changes at maturity. After a 2-month recovery period, all whiskers were trimmed except for D2 and D3 which normally induces whisker pairing plasticity (WPP)88 and cells were analyzed in the D2 (a deprived) barrel column. The two whiskers left intact (paired) could either be the previously deprived whiskers D2 and D3 or one deprived (D2) and one spared (D1) whisker. Cells in the layer IV D2 barrel showed elevated responses to principal D2 whisker stimulation, but reduced responses to the early-intact D1 and particularly low responses to the early-deprived D3 surround whisker. The interesting ﬁnding was that the plasticity associated with WPP was normal in layer IV of the deprived barrel columns, but greatly reduced and delayed in the supragranular layers II/III that receive driving inputs from layer IV. The whisker with normal early experience developed a stronger inﬂuence on the deprived D2 neurons than did the deprived whisker D3 on the other side of D2. Removing all but one whisker in animals just after weaning (roughly 1 month old) for 7, 20 or 60 d does not reduce neuronal responses to the intact whisker in layer IV neurons surrounding the intact barrel cells. Here again, with SD starting at this rather mature age, the deprivation effect on response magnitude in the deprived barrel columns is most pronounced in layers II/III. The recovery of responses is consistent with earlier results in normal adult rats by Armstrong-James, et al. Comparison of Partial with Global Sensory Deprivation The essential difference between restricted and global SD is that global trimming reduces activity uniformly throughout the whisker barrel ﬁeld domain, while partial trimming creates epicenters of high activity competing with adjacent barrel columns that have low sensory input activity. The distance over which competitive interactions occur is not known completely, since most studies were recorded in the barrels adjacent to the deprived or intact barrel, but Glazewski and colleagues125,126 have provided evidence that potentiation of a spared whisker response and depression of responses to deprived whiskers decrease with distance from an active barrel column in cases of late (PND 28) onset plucking. In fact, if every other whisker is plucked in a checkerboard pattern for 7 d beginning at PND 28, then responses to deprived © 2005 by Taylor & Francis Group. In certain cases, such as prenatal alcohol exposure, barrel cortex circuits never develop normal responsive or spontaneous activity in the early postnatal period and cannot reach the threshold to be up-regulated by experi- ence after the animals mature. In 1987 some, but not all whiskers were trimmed on one side (C-row or all but C-row trimmed), while the behavioral deﬁcits were the result of trimming all whiskers on both sides of the face starting at birth. But a reasonable prediction is that total long term bilateral SD cortex would show a marked reduction in spontaneous as well as evoked activity throughout the barrel cortex, with reduced response levels similar to the results above where all of the whiskers on one side of the face were trimmed from PNDo to PND3o. The behavioral deﬁcit in roughness discrimination produced by the global bilateral SD could be interpreted as a degra- dation of frequency discrimination, in that the animals could still discriminate grossly different discriminanda, but not ﬁne differences. Effects of Sensory Deprivation on the Adult Brain As stated earlier, the concept of a critical period of receptive ﬁeld plasticity in the barrel cortex has required much reassessment in the face of multiple studies showing activity-dependent response plasticity in adult rat barrel cortex (>2 months of age). Plasticity of neurons to acute partial SD is produced robustly in all layers of the barrel cortex in normal adult rats by trimming all but two whiskers at maturity on one side of the face (the whisker pairing (WP) paradigm; Diamond, et al. Layer IV neurons in the barrel column receiving input from one of the intact whiskers show a signiﬁcant increase in response to stimulation of their principal whisker and also to the weaker surround whisker that remains intact on one side of the principal whisker, but a decrease in response to the cut, adjacent, surround row whisker on the other side of the principal whisker. The WPP response modiﬁcations develop signiﬁcance in 2–4 h in awake ani- mals,131 and are detected easily under urethane anesthesia using single-unit anal- ysis. Under similar conditions of testing and anesthesia used in our studies, surround receptive ﬁelds (SRFs) in layers I–IV have been shown by a number of criteria to depend for their expression on intracortical column to column relay, initiated by principal whisker discharges. Either route would be expected to depend upon excitatory glutamatergic synapses and NMDA receptor activation,79 and indeed, blocking NMDA receptors at the time of adult whisker trimming prevents WPP. Hence, with adult cortex the WPP paradigm generates Hebbian potentiation and competitive inhibition in at least the ﬁrst four layers of the barrel cortex.
Several day-to-day decisions in patient care are based on changing regulations and practice guidelines generic 50 mg caverta amex. In order to expedite such decision rule changes buy discount caverta 50mg on line, it is important to maintain the rules themselves in databases, thus making the model database a meta-database. These third party objects may or may not include the model database bundled within the object. If they are bundled, it would become a direct interface with the decision support subsystem and the data management system. If they are not bundled, then the data is carefully placed either in the model database or in the medical database as appropriate. Decision support subsystems are independent decision support systems that can interface with any external subsystem directly or through the decision support user interface. The medical decision support system generally consists of both automated and interactive subsystems. The automated decision support subsystems may use the automated engine to integrate the automated decision making capabilities with existing automated functions. For decision support functions that require user interaction, the decision support system flexible interface is called from the user interface layer and presented to the decision maker. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. These decision support systems generally address the medical decision support functions listed in Table 1 (Raghavan, Ladik, & Meyer, 2005). These functions are generic in nature, while the knowledge base of the decision support systems is generally specific to a medical domain area like oncology, nephrology, pediatrics, and so on. The most common decision support function found in medical decision support systems is alerts and reminders. In a real time environment, these decision support functions are attached to the monitoring devices to provide immediate alerts as and when the trigger condition occurs. In a chronic setting, a simple scan of laboratory results and an email or pager alert to the corresponding decision maker are valuable decision support functions. A few medical decision support systems can provide image recognition and interpretation functions. These are extremely helpful in large hospitals where various radiology reports can be interpreted and alerts can be generated to gain the attention of the experts. Diagnostic support is a key function that several medical decision support systems attempt to offer to help the physicians in detecting the problem based on symptoms and etiology. Such systems are commonly used to detect rare diseases and also as an aid for inexperienced practitioners. A few medical decision support systems offer care plan Copyright © 2005, Idea Group Inc. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Medical Decision Support Systems and Knowledge Sharing Standards 205 critiques by looking at data inconsistencies, errors, and omissions against practice guidelines. In the next section, the problem domain, and the decision support functions provided by various popular medical decision support systems will be discussed. While there are close to hundred known medical decision support systems in use, the most popular medical decision support systems based on the existing literature and usage will be discussed in this chapter. M edical Decision Support Systems HELP (Health Evaluation through Logical Processes) This is the most successful and popular medical decision support system in the United States. The HELP system of the Latter Day Saints Hospital in Salt Lake City is a hospital- based medical information system that gives practitioners a comprehensive patient record with decision support capabilities. HELP is a comprehensive medical information system with full fledged medical records, physician order entry, charges, radiology, pharmacy, ICU monitoring, laboratory, and robust decision support functions (MedExpert- HELP, 2004). The success of HELP information system was due to the fact that the decision support functions were integrated with the hospital information system. The availability of required data and the knowledge base makes this a powerful system. The decision support capabilities made available to the decision makers at the point of care made this an effective product. The HELP information system supports the following decision support functions: alerts and reminders, decision critiquing, patient diagnosis, care suggestions, and protocols. The integrated laboratory information system allows automatic monitoring and alerts for abnormalities or out of range values. The critiquing feature is integrated within the transfusion ordering module to critique the reason provided against the strict guidelines. The system also includes modules such as automated surveillance system that uses various data elements to diagnose nosocomial infections. As an extension of this module, the antibiotic assistant recommends the antibiotics that can produce optimal benefit to the patient. DXplain Dxplain is a diagnostic decision support system that is owned by Massachusetts General Hospital and can be licensed and accessed over the internet as well. The power of DXplain is its knowledge base that can diagnose close to 2000 diseases emphasizing the signs and Copyright © 2005, Idea Group Inc. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. This system was developed during the early 1990s by Massachusetts General Hospital and has been used by thousands of physicians and medical students. DXplain uses a set of signs, symptoms, and laboratory results to produce a ranked list of diagnoses which might explain the clinical manifestations. DXplain uses Bayesian logic to derive the clinical diagnosis interpretation (MedExpert-DxPlain, 2004). It is important to note that the system only provides suggestion and not definitive conclu- sions.
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