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Idiopathic inflammatory myopathy (IIM) summarizes rare, systemic autoimmune conditions primarily characterized by inflammatory damage to the skeletal muscle. Although primary damage occurs to the muscle, these IIM-related conditions involve other organs, including the skin, lungs, upper gastrointestinal tract, joints, and heart. While many patients have an adequate response to immunosuppressive treatment, some patients develop rapidly progressive and treatment-resistant life-threatening courses. Treatment-resistant IIM is challenging for the treating physician and requires interdisciplinary and individualized treatment approaches. Extracorporeal therapy is one option for rescue therapy, with immunoadsorption (IA) having proven more effective than plasma exchange regarding the removal of circulating antibodies. Despite its efficacy and desirable safety profile, the clinical value of IA use in IIM is understudied with no controlled trials reported. Here, we present a review of the current knowledge regarding the management of treatment-resistant IIM and the cases of three patients with treatment-resistant IIM (two with dermatomyositis and one with immune-mediated necrotizing myopathy) who have successfully been treated with IA. All patients responded well to the therapy and experienced no IA-related complications. Taken together, we found IA to be a safe and effective treatment option in treatment-resistant IIM.
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Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic cause of kidney failure. Tolvaptan, a vasopressin 2 receptor antagonist, is the first drug with proven disease-modifying activity. Long-term treatment adherence is crucial, but a considerable fraction of patients discontinue treatment, because of aquaretic side effects. Methods: Twenty-four-hour urine was collected in 75 patients with ADPKD during up-titration of tolvaptan and, in combination with clinical characteristics, examined to identify factors influencing urine volume. Patient-reported outcomes were analyzed using the Short Form-12 (SF-12) and patient-reported outcomes questionnaires reporting micturition frequency and burden of urine volume. Results: Initiation of therapy led to a large increase in urine volume followed by only minor further increase during up-dosing. Younger patients and patients with better kidney function experienced a larger relative rise. Twenty-four-hour urine osmolality dropped by about 50% after therapy initiation independently of dose, with a considerable proportion of patients achieving adequate suppression. Sodium and potassium intake turned out to be the only significant modifiable factors for urine volume after multivariate linear regression models, whereas age and weight could be identified as non-modifiable factors. No change in quality of life (QoL) was detected in relation to treatment or urine volume using SF-12 questionnaires, a finding that was further supported by the results of the patient-reported outcomes assessment. Conclusion: This study provides an in-detail analysis of factors associated with the degree of polyuria on tolvaptan and puts them into the context of QoL. These findings will contribute to optimized patient counseling regarding this treatment option in ADPKD.
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Objective: Gait dysfunction is one of the most difficult motor signs to treat in patients with Parkinson's disease (PD). Understanding its pathophysiology and developing more effective therapies for parkinsonian gait dysfunction will require preclinical studies that can quantitatively and objectively assess the spatial and temporal features of gait. Design: We developed a novel system for measuring volitional, naturalistic gait patterns in non-human primates, and then applied the approach to characterize the progression of parkinsonian gait dysfunction across a sequence of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatments that allowed for intrasubject comparisons across mild, moderate, and severe stages. Results: Parkinsonian gait dysfunction was characterized across treatment levels by a slower stride speed, increased time in both the stance and swing phase of the stride cycle, and decreased cadence that progressively worsened with overall parkinsonian severity. In contrast, decreased stride length occurred most notably in the moderate to severe parkinsonian state. Conclusion: The results suggest that mild parkinsonism in the primate model of PD starts with temporal gait deficits, whereas spatial gait deficits manifest after reaching a more severe parkinsonian state overall. This study provides important context for preclinical studies in non-human primates studying the neurophysiology of and treatments for parkinsonian gait.
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Elevated synchronized oscillatory activity in the beta band has been hypothesized to be a pathophysiological marker of Parkinson's disease (PD). Recent studies have suggested that parkinsonism is closely associated with increased amplitude and duration of beta burst activity in the subthalamic nucleus (STN). How beta burst dynamics are altered from the normal to parkinsonian state across the basal ganglia-thalamocortical (BGTC) motor network, however, remains unclear. In this study, we simultaneously recorded local field potential activity from the STN, internal segment of the globus pallidus (GPi), and primary motor cortex (M1) in three female rhesus macaques, and characterized how beta burst activity changed as the animals transitioned from normal to progressively more severe parkinsonian states. Parkinsonism was associated with an increased incidence of beta bursts with longer duration and higher amplitude in the low beta band (8-20 Hz) in both the STN and GPi, but not in M1. We observed greater concurrence of beta burst activity, however, across all recording sites (M1, STN, and GPi) in PD. The simultaneous presence of low beta burst activity across multiple nodes of the BGTC network that increased with severity of PD motor signs provides compelling evidence in support of the hypothesis that low beta synchronized oscillations play a significant role in the underlying pathophysiology of PD. Given its immersion throughout the motor circuit, we hypothesize that this elevated beta-band activity interferes with spatial-temporal processing of information flow in the BGTC network that contributes to the impairment of motor function in PD.SIGNIFICANCE STATEMENT This study fills a knowledge gap regarding the change in temporal dynamics and coupling of beta burst activity across the basal ganglia-thalamocortical (BGTC) network during the evolution from normal to progressively more severe parkinsonian states. We observed that changes in beta oscillatory activity occur throughout BGTC and that increasing severity of parkinsonism was associated with a higher incidence of longer duration, higher amplitude low beta bursts in the basal ganglia, and increased concurrence of beta bursts across the subthalamic nucleus, globus pallidus, and motor cortex. These data provide new insights into the potential role of changes in the temporal dynamics of low beta activity within the BGTC network in the pathogenesis of Parkinson's disease.
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Ganglios Basales/fisiopatología , Corteza Motora/fisiopatología , Red Nerviosa/fisiopatología , Trastornos Parkinsonianos/fisiopatología , Animales , Femenino , Macaca mulattaRESUMEN
Many studies suggest that Parkinson's disease (PD) is associated with changes in neuronal activity patterns throughout the basal ganglia-thalamocortical motor circuit. There are limited electrophysiological data, however, describing how parkinsonism impacts the presupplementary motor area (pre-SMA) and SMA proper (SMAp), cortical areas known to be involved in movement planning and motor control. In this study, local field potentials (LFPs) were recorded in the pre-SMA/SMAp of a nonhuman primate during a visually cued reaching task. Recordings were made in the same subject in both the naive and parkinsonian state using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of parkinsonism. We found that in the naive animal, well before a go-cue providing instruction of reach onset and direction was given, LFP activity was dynamically modulated in both high (20-30 Hz) and low beta (10-20 Hz) bands, and the magnitude of this modulation (e.g., decrease/increase in beta amplitude for each band, respectively) correlated linearly with reaction time (RT) on a trial-to-trial basis, suggesting it may predictively encode for RT. Consistent with this hypothesis, we observed that this activity was more prominent within the pre-SMA compared with SMAp. In the parkinsonian state, however, pre-SMA/SMAp beta band modulation was disrupted, particularly in the high beta band, such that the predictive encoding of RT was significantly diminished. In addition, the predictive encoding of RT preferentially within pre-SMA over SMAp was lost. These findings add to our understanding of the role of pre-SMA/SMAp in motor behavior and suggest a fundamental role of these cortical areas in early preparatory and premovement processes that are altered in parkinsonism. NEW & NOTEWORTHY Goal-directed movements, such as reaching for an object, necessitate temporal preparation and organization of information processing within the basal ganglia-thalamocortical motor network. Impaired movement in parkinsonism is thought to be the result of pathophysiological activity disrupting information flow within this network. This work provides neurophysiological evidence linking altered motor preplanning processes encoded in pre-SMA/SMAp beta band modulation to the pathogenesis of motor disturbances in parkinsonism.
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Corteza Motora/fisiopatología , Movimiento , Neuronas/fisiología , Trastornos Parkinsonianos/fisiopatología , Desempeño Psicomotor , Animales , Ritmo beta , Señales (Psicología) , Femenino , Macaca mulatta , Tiempo de ReacciónRESUMEN
OBJECTIVE: Using the Medtronic Activa® PC + S system, this study investigated how passive joint manipulation, reaching behavior, and deep brain stimulation (DBS) modulate local field potential (LFP) activity in the subthalamic nucleus (STN) and globus pallidus (GP). APPROACH: Five non-human primates were implanted unilaterally with one or more DBS leads. LFPs were collected in montage recordings during resting state conditions and during motor tasks that facilitate the expression of parkinsonian motor signs. These recordings were made in the naïve state in one subject, in the parkinsonian state in two subjects, and in both naïve and parkinsonian states in two subjects. MAIN RESULTS: LFPs measured at rest were consistent over time for a given recording location and parkinsonian state in a given subject; however, LFPs were highly variable between subjects, between and within recording locations, and across parkinsonian states. LFPs in both naïve and parkinsonian states across all recorded nuclei contained a spectral peak in the beta band (10-30 Hz). Moreover, the spectral content of recorded LFPs was modulated by passive and active movement of the subjects' limbs. LFPs recorded during a cued-reaching task displayed task-related beta desynchronization in STN and GP. The bidirectional capabilities of the Activa® PC + S also allowed for recording LFPs while delivering DBS. The therapeutic effect of STN DBS on parkinsonian rigidity outlasted stimulation for 30-60 s, but there was no correlation with beta band power. SIGNIFICANCE: This study emphasizes (1) the variability in spontaneous LFPs amongst subjects and (2) the value of using the Activa® PC + S system to record neural data in the context of behavioral tasks that allow one to evaluate a subject's symptomatology.
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Estimulación Encefálica Profunda/métodos , Modelos Animales de Enfermedad , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapia , Animales , Estimulación Encefálica Profunda/instrumentación , Femenino , Macaca mulatta , PrimatesRESUMEN
Hand shaping during prehension involves intricate coordination of a complex system of bones, joints, and muscles. It is widely hypothesized that the motor system uses strategies to reduce the degrees of independent control. Both biomechanical constraints that result in coupling of the fingers and joints and neural synergies act to simplify the control problem. Synergies in hand shaping are typically defined using principal component-like analyses to define orthogonal patterns of movement. Although much less examined, joint angle velocities are also important parameters governing prehension. The primary goal of this study was to evaluate joint angles and joint angle velocities during prehension in monkeys. Fourteen joint angles and angular velocities were measured as monkeys reached to and grasped a set of objects designed to systematically vary hand shapes. Hand shaping patterns in joint angles and velocities were examined using singular value decomposition (SVD). Highly correlated patterns of movements were observed in both joint angles and joint angle velocities, but there was little correlation between the two, suggesting that velocities are controlled separately. Joint angles and velocities can be defined by a small number of eigenvectors by SVD. The unresolved question of the functional relevance of higher-order eigenvectors was also evaluated. Results support that higher-order components are not easily distinguished from noise and are likely not of physiological significance.
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Articulaciones de la Mano/fisiología , Fuerza de la Mano/fisiología , Mano/inervación , Movimiento/fisiología , Desempeño Psicomotor/fisiología , Animales , Fenómenos Biomecánicos , Macaca mulattaRESUMEN
Dystonia has generally been considered a basal ganglia (BG) disorder. Early models hypothesized that dystonia occurred as the result of reduced mean discharge rates in the internal segment of the globus pallidus (GPi). Increasing evidence suggests a more systemwide disruption of the basal ganglia thalamic circuit (BGTC) resulting in altered firing patterns, synchronized oscillations, and widened receptive fields. A model of dystonia incorporating these changes within the BGTC is presented in which we postulate that this pathophysiology arises from disruptions within the striatum. Alterations in the cerebellothalamocortical (CBTC) pathway to the development of dystonia may also play a role. However, the contribution of CBTC abnormalities to dystonia remains unclear and may vary with different etiologies of dystonia. Finally, the relevance of established and emerging theories related to the pathophysiology of dystonia is addressed within the context of improving conventional approaches for deep brain stimulation (DBS) treatment strategies.
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Distonía/fisiopatología , Modelos Neurológicos , Red Nerviosa/fisiología , Vías Nerviosas/fisiología , Ganglios Basales/fisiopatología , Tronco Encefálico/fisiopatología , Cerebelo/fisiopatología , Estimulación Encefálica Profunda/métodos , Distonía/terapia , Globo Pálido/fisiopatología , Humanos , Tálamo/fisiopatologíaRESUMEN
Encoding of movement kinematics in Purkinje cell simple spike discharge has important implications for hypotheses of cerebellar cortical function. Several outstanding questions remain regarding representation of these kinematic signals. It is uncertain whether kinematic encoding occurs in unpredictable, feedback-dependent tasks or kinematic signals are conserved across tasks. Additionally, there is a need to understand the signals encoded in the instantaneous discharge of single cells without averaging across trials or time. To address these questions, this study recorded Purkinje cell firing in monkeys trained to perform a manual random tracking task in addition to circular tracking and center-out reach. Random tracking provides for extensive coverage of kinematic workspaces. Direction and speed errors are significantly greater during random than circular tracking. Cross-correlation analyses comparing hand and target velocity profiles show that hand velocity lags target velocity during random tracking. Correlations between simple spike firing from 120 Purkinje cells and hand position, velocity, and speed were evaluated with linear regression models including a time constant, τ, as a measure of the firing lead/lag relative to the kinematic parameters. Across the population, velocity accounts for the majority of simple spike firing variability (63 ± 30% of R(adj)(2)), followed by position (28 ± 24% of R(adj)(2)) and speed (11 ± 19% of R(adj)(2)). Simple spike firing often leads hand kinematics. Comparison of regression models based on averaged vs. nonaveraged firing and kinematics reveals lower R(adj)(2) values for nonaveraged data; however, regression coefficients and τ values are highly similar. Finally, for most cells, model coefficients generated from random tracking accurately estimate simple spike firing in either circular tracking or center-out reach. These findings imply that the cerebellum controls movement kinematics, consistent with a forward internal model that predicts upcoming limb kinematics.
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Potenciales de Acción/fisiología , Extremidades/inervación , Extremidades/fisiología , Modelos Neurológicos , Actividad Motora/fisiología , Células de Purkinje/fisiología , Animales , Fenómenos Biomecánicos/fisiología , Condicionamiento Psicológico/fisiología , Electrodos Implantados , Electrofisiología/métodos , Femenino , Macaca mulatta , Masculino , Movimiento/fisiología , Análisis de RegresiónRESUMEN
A fundamental question is how the CNS controls the hand with its many degrees of freedom. Several motor cortical areas, including the dorsal premotor cortex (PMd) and primary motor cortex (M1), are involved in reach to grasp. Although neurons in PMd are known to modulate in relation to the type of grasp and neurons in M1 in relation to grasp force and finger movements, whether specific parameters of whole hand shaping are encoded in the discharge of these cells has not been studied. In this study, two monkeys were trained to reach and grasp 16 objects varying in shape, size, and orientation. Grasp force was explicitly controlled, requiring the monkeys to exert either three or five levels of grasp force on each object. The animals were unable to see the objects or their hands. Single PMd and M1 neurons were recorded during the task, and cell firing was examined for modulation with object properties and grasp force. The firing of the vast majority of PMd and M1 neurons varied significantly as a function of the object presented as well as the object grasp dimension. Grasp dimension of the object was an important determinant of the firing of cells in both PMd and M1. A smaller percentage of PMd and M1 neurons were modulated by grasp force. Linear encoding was prominent with grasp force but less so with grasp dimension. The correlations with grasp dimension and grasp force were stronger in the firing of M1 than PMd neurons and across both regions the modulation with these parameters increased as reach to grasp proceeded. All PMd and M1 neurons that signaled grasp force also signaled grasp dimension, yet the two signals showed limited interactions, providing a neural substrate for the independent control of these two parameters at the behavioral level.
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Potenciales de Acción/fisiología , Fuerza de la Mano/fisiología , Macaca mulatta/fisiología , Corteza Motora/citología , Neuronas Motoras/fisiología , Movimiento/fisiología , Desempeño Psicomotor/fisiología , Animales , Mapeo Encefálico , Electromiografía , Femenino , Lateralidad Funcional , Masculino , Corteza Motora/fisiología , Tiempo de Reacción/fisiología , Análisis de Regresión , Factores de Tiempo , TactoRESUMEN
The tottering mouse is an autosomal recessive disorder involving a missense mutation in the gene encoding P/Q-type voltage-gated Ca2+ channels. The tottering mouse has a characteristic phenotype consisting of transient attacks of dystonia triggered by stress, caffeine, or ethanol. The neural events underlying these episodes of dystonia are unknown. Flavoprotein autofluorescence optical imaging revealed transient, low-frequency oscillations in the cerebellar cortex of anesthetized and awake tottering mice but not in wild-type mice. Analysis of the frequencies, spatial extent, and power were used to characterize the oscillations. In anesthetized mice, the dominant frequencies of the oscillations are between 0.039 and 0.078 Hz. The spontaneous oscillations in the tottering mouse organize into high power domains that propagate to neighboring cerebellar cortical regions. In the tottering mouse, the spontaneous firing of 83% (73/88) of cerebellar cortical neurons exhibit oscillations at the same low frequencies. The oscillations are reduced by removing extracellular Ca2+ and blocking L-type Ca2+ channels. The oscillations are likely generated intrinsically in the cerebellar cortex because they are not affected by blocking AMPA receptors or by electrical stimulation of the parallel fiber-Purkinje cell circuit. Furthermore, local application of an L-type Ca2+ agonist in the tottering mouse generates oscillations with similar properties. The beam-like response evoked by parallel fiber stimulation is reduced in the tottering mouse. In the awake tottering mouse, transcranial flavoprotein imaging revealed low-frequency oscillations that are accentuated during caffeine-induced attacks of dystonia. During dystonia, oscillations are also present in the face and hindlimb electromyographic (EMG) activity that become significantly coherent with the oscillations in the cerebellar cortex. These low-frequency oscillations and associated cerebellar cortical dysfunction demonstrate a novel abnormality in the tottering mouse. These oscillations are hypothesized to be involved in the episodic movement disorder in this mouse model of episodic ataxia type 2.
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Corteza Cerebelosa/fisiología , Animales , Agonistas de los Canales de Calcio/farmacología , Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/fisiología , Corteza Cerebelosa/anatomía & histología , Corteza Cerebelosa/efectos de los fármacos , Electromiografía , Electrofisiología , Femenino , Flavoproteínas/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes Neurológicos , Microscopía Fluorescente , Trastornos del Movimiento/genética , Trastornos del Movimiento/fisiopatología , Red Nerviosa/anatomía & histología , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiología , Neuronas/efectos de los fármacosRESUMEN
The cerebellar cortex and nuclei play important roles in the learning, planning, and execution of reach-to-grasp and prehensile movements. However, few studies have investigated the signals carried by cerebellar neurons during reach-to-grasp, particularly signals relating to target object properties, hand shape, and grasp force. In this study, the simple spike discharge of 77 Purkinje cells was recorded as two rhesus monkeys reached and grasped 16 objects. The objects varied systematically in volume, shape, and orientation and each was grasped at five different force levels. Linear multiple regression analyses showed the simple spike discharge was significantly modulated in relation to objects and force levels. Object related modulation occurred preferentially during reach or early in the grasp and was linearly related to grasp aperture. The simple spike discharge was positively correlated with grasp force during both the reach and the grasp. There was no significant interaction between object and grasp force modulation, supporting previous kinematic findings that grasp kinematics and force are signaled independently. Singular value decomposition (SVD) was used to quantify the temporal patterns in the simple spike discharge. Most cells had a predominant discharge pattern that remained relatively constant across object grasp dimensions and force levels. A single predominant simple spike discharge pattern that spans reach and grasp and accounts for most of the variation (>60%) is consistent with the concept that the cerebellum is involved with synergies underlying prehension. Therefore Purkinje cells are involved with the signaling of prehension, providing independent signals for hand shaping and grasp force.
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Potenciales de Acción/fisiología , Fuerza de la Mano/fisiología , Mano/anatomía & histología , Mano/fisiología , Movimiento/fisiología , Contracción Muscular/fisiología , Células de Purkinje/fisiología , Animales , Femenino , Macaca mulatta , Masculino , Desempeño Psicomotor/fisiología , Estrés MecánicoRESUMEN
To reduce the complexity of controlling hand-shaping, recent evidence suggests that the central nervous system uses synergies. In this study, two Rhesus monkeys reached-to-grasp 15 objects, varying in geometric properties, at five grasp force levels. Hand kinematics were recorded using a video-based tracking system. Individual finger movements were described as vectors varying in length and angle. Inflection points (i.e., stereotypic minima/maxima in the temporal profile of each finger vector) exhibited a temporal synchrony for individual fingers and in the coupling across fingers. Inflection point amplitudes varied significantly across objects grasped, scaling linearly with the object grasp dimension. Thus, differences in the vectors as a function of the objects were in the relative scaling of the vector parameters over time rather than a change in the temporal structure. Mahalanobis distance analysis of the inflection points confirmed that changes in inflection point amplitude as a function of objects were greater than changes in timing. Inflection points were independent of the grasp force, consistent with the observation that reach-to-grasp kinematics and grasp force are controlled independently. In summary, the shaping of the hand during reach-to-grasp involves scaling the amplitude of highly stereotypic temporal movements of the fingers.
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Dedos , Fuerza de la Mano/fisiología , Movimiento/fisiología , Propiocepción , Desempeño Psicomotor/fisiología , Animales , Conducta Animal , Fenómenos Biomecánicos , Análisis por Conglomerados , Lateralidad Funcional/fisiología , Macaca mulatta , Postura/fisiología , Tiempo de Reacción/fisiologíaRESUMEN
Spreading acidification and depression (SAD) is a form of propagated activity in the cerebellar cortex characterized by acidification and a transient depression in excitability. This study investigated the role of Kv1 potassium channels in SAD using neutral red, flavoprotein autofluorescence, and voltage-sensitive dye optical imaging in the mouse cerebellar cortex, in vivo. The probability of evoking SAD was greatly increased by blocking Kv1.1 as well as Kv1.2 potassium channels by their specific blockers dendrotoxin K (DTX-K) and tityustoxin (TsTX), respectively. DTX-K not only greatly lowered the threshold for evoking SAD but also resulted in multiple cycles of spread and spontaneous SAD. The occurrence of spontaneous SAD originating from spontaneous parallel fiber-like beams of activity suggests that blocking Kv1 channels increased parallel fiber excitability. This was confirmed by the generation of parallel fiber-like beams with the microinjection of glutamate into the upper molecular layer in the presence of DTX-K. The dramatic effects of DTX-K suggest a possible connection between SAD and episodic ataxia type 1 (EA1), a Kv1.1 potassium channelopathy. The threshold for evoking SAD was significantly lowered in the Kv1.1 heterozygous knockout mouse compared with wild-type littermates. Carbamazepine and acetazolamide, both effective in the treatment of EA1, significantly decreased the likelihood of evoking SAD. Blocking GABAergic neurotransmission did not alter the effectiveness of DTX-K. The cyclin D2 null mouse, which lacks cerebellar stellate cells, also exhibited SAD. Therefore blocking Kv1 potassium channels establishes the conditions needed to generate SAD. Furthermore, the results are consistent with the hypothesis that SAD may underlie the transient attacks of ataxia characterizing EA1.
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Ácidos/metabolismo , Corteza Cerebral/fisiología , Depresión de Propagación Cortical/fisiología , Canales de Potasio/fisiología , Acetazolamida/farmacología , Animales , Anticonvulsivantes/farmacología , Baclofeno/análogos & derivados , Baclofeno/farmacología , Bicuculina/farmacología , Carbamazepina/farmacología , Corteza Cerebral/efectos de los fármacos , Depresión de Propagación Cortical/efectos de los fármacos , Ciclina D2 , Ciclinas/genética , Diagnóstico por Imagen/métodos , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Interacciones Farmacológicas , Estimulación Eléctrica/métodos , Femenino , Antagonistas del GABA/farmacología , Ácido Glutámico/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Rojo Neutro/metabolismo , Péptidos/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio/deficiencia , Tiempo de Reacción/efectos de los fármacos , Venenos de Escorpión/farmacología , Canales de Potasio de la Superfamilia Shaker , Factores de TiempoRESUMEN
Understanding how the CNS controls reach-to-grasp will require behavioral and neurophysiological studies of reach-to-grasp in the monkey, including the evaluation of whole-hand grasp with explicit force requirements. In this study, monkeys performed a reach-to-grasp task in which the size, shape, and orientation of the objects were varied. The monkeys were required to grasp each object at five force levels based on visual feedback. Seventeen positions on the wrist and hand were monitored to quantify kinematics. Hand shaping began with initiation of reach and continued throughout the reach, matching object properties even without vision of the hand or object. Grasp aperture scaled to object size. Singular value decomposition analysis of the marker positions identified two dominant hand postures. The first eigenvector or "eigenposture" consisted of an open hand configuration midway between flexion and extension that explained >93% of the variance. The second eigenposture consisted of hyperextension of all joints that accounted for another 4-5% of the variance. The two eigenpostures were similar across force levels and between monkeys. Reach kinematics consisted of a U-shaped hand path with a bell-shaped velocity profile. Trajectory and speed were independent of grasp force and object properties. In summary, hand shaping during the reach occurred without vision of the hand or object, and hand kinematics were not dependent on grasp force. Furthermore, the reach was independent of grasp force and object properties. These observations imply that the kinematics of reach-to-grasp and grasp force are controlled independently. Similar to humans, monkeys may use a simplifying strategy to reduce the degrees of freedom of the hand during reach-to-grasp.