A New Method for Quantitative Evaluation of Neurological Disorders based on EMG signals

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Diverse coordinate frames on sensorimotor areas in visuomotor transformation

The visuomotor transformation during a goal-directed movement may involve a coordinate transformation from visual ‘extrinsic’ to muscle-like ‘intrinsic’ coordinate frames, which might be processed via a multilayer network architecture composed of neural basis functions. This theory suggests that the postural change during a goal-directed movement task alters activity patterns of the neurons in the intermediate layer of the visuomotor transformation that recieves both visual and proprioceptive inputs, and thus influence the multi-voxel pattern of the blood oxygenation level dependent signal. Using a recently developed multi-voxel pattern decoding method, we found extrinsic, intrinsic and intermediate coordinate frames along the visuomotor cortical pathways during a visuomotor control task. The presented results support the hypothesis that, in human, the extrinsic coordinate frame was transformed to the muscle-like frame over the dorsal pathway from the posterior parietal cortex and the dorsal premotor cortex to the primary motor cortex

Dendritic retraction, but not atrophy, is consistent in amyotrophic lateral sclerosis-comparison between Onuf’s neurons and other sacral motor neurons-

BACKGROUND: Fundamental cytological changes of amyotrophic lateral sclerosis (ALS) were looked for by comparing relatively preserved Onuf’s nucleus (ON) and severely affected neighboring motor neuron groups (dorsolateral alpha motoneurons (DL) and other anterior horn neurons (OAH)). The second sacral segments from 11 ALS patients and 5 controls were initially quadruple-labeled for phosphorylated and non-phosphorylated TAR DNA-binding protein of 43 kDa (TDP43), and p62 with DAPI to identify TDP43-related changes. After digital recording of these fluorescence data encompassing the entire specimen at a high resolution, the same sections were stained with Klüver-Barrera method to obtain their exact bright-field counterparts. This novel approach facilitated exact identification of ON. Furthermore, this cell to cell comparison enabled to correlate quantitative indices of the neuronal cell bodies: perimeter, area and circularity index (CI) i.e. the ratio of (perimeter/2π) divided by the square root of (area/π), which decreases with dendritic retraction, overall number of neurons and inclusions. RESULTS: In addition to known preservation of ON neuron number relative to DL and OAH, size reduction of ON neurons was not significant even in the advanced stage. Significant size reduction in DL was counteracted in the presence of TDP43-positive inclusions. Early increase of neuronal size in OAH was further enhanced by the presence of TDP43-positive inclusions. Even with these heterogeneous cytopathological changes, a decrease in CI was consistent in all groups at an early phase and was correlated with neuronal loss. CONCLUSIONS: Among variable cytological changes of ALS, a decrease in CI is a consistent early feature shared between non-atrophic ON neurons and other anterior horn neurons with either decreased (DL) or even increased (OAH) size and profounder neuronal loss. This decrease in CI, representative of dendritic retraction, is fundamental to ALS pathogenesis, not necessarily linked to cell size and pathological inclusions

Class IA Phosphatidylinositol 3-Kinase in Pancreatic β Cells Controls Insulin Secretion by Multiple Mechanisms

SummaryType 2 diabetes is characterized by insulin resistance and pancreatic β cell dysfunction, the latter possibly caused by a defect in insulin signaling in β cells. Inhibition of class IA phosphatidylinositol 3-kinase (PI3K), using a mouse model lacking the pik3r1 gene specifically in β cells and the pik3r2 gene systemically (βDKO mouse), results in glucose intolerance and reduced insulin secretion in response to glucose. β cells of βDKO mice had defective exocytosis machinery due to decreased expression of soluble N-ethylmaleimide attachment protein receptor (SNARE) complex proteins and loss of cell-cell synchronization in terms of Ca2+ influx. These defects were normalized by expression of a constitutively active form of Akt in the islets of βDKO mice, preserving insulin secretion in response to glucose. The class IA PI3K pathway in β cells in vivo is important in the regulation of insulin secretion and may be a therapeutic target for type 2 diabetes

Improving Human Plateaued Motor Skill with Somatic Stimulation

Procedural motor learning includes a period when no substantial gain in performance improvement is obtained even with repeated, daily practice. Prompted by the potential benefit of high-frequency transcutaneous electrical stimulation, we examined if the stimulation to the hand reduces redundant motor activity that likely exists in an acquired hand motor skill, so as to further upgrade stable motor performance. Healthy participants were trained until their motor performance of continuously rotating two balls in the palm of their right hand became stable. In the series of experiments, they repeated a trial performing this cyclic rotation as many times as possible in 15 s. In trials where we applied the stimulation to the relaxed thumb before they initiated the task, most reported that their movements became smoother and they could perform the movements at a higher cycle compared to the control trials. This was not possible when the dorsal side of the wrist was stimulated. The performance improvement was associated with reduction of amplitude of finger displacement, which was consistently observed irrespective of the task demands. Importantly, this kinematic change occurred without being noticed by the participants, and their intentional changes of motor strategies (reducing amplitude of finger displacement) never improved the performance. Moreover, the performance never spontaneously improved during one-week training without stimulation, whereas the improvement in association with stimulation was consistently observed across days during training on another week combined with the stimulation. The improved effect obtained in stimulation trials on one day partially carried over to the next day, thereby promoting daily improvement of plateaued performance, which could not be unlocked by the first-week intensive training. This study demonstrated the possibility of effectively improving a plateaued motor skill, and pre-movement somatic stimulation driving this behavioral change

Neural Evidence of the Cerebellum as a State Predictor

We here provide neural evidence that the cerebellar circuit can predict future inputs from present outputs, a hallmark of an internal forward model. Recent computational studies hypothesize that the cerebellum performs state prediction known as a forward model. To test the forward-model hypothesis, we analyzed activities of 94 mossy fibers (inputs to the cerebellar cortex), 83 Purkinje cells (output from the cerebellar cortex to dentate nucleus), and 73 dentate nucleus cells (cerebellar output) in the cerebro-cerebellum, all recorded from a monkey performing step-tracking movements of the right wrist. We found that the firing rates of one population could be reconstructed as a weighted linear sum of those of preceding populations. We then went on to investigate if the current outputs of the cerebellum (dentate cells) could predict the future inputs of the cerebellum (mossy fibers). The firing rates of mossy fibers at time t + t_1 could be well reconstructed from as a weighted sum of firing rates of dentate cells at time t, thereby proving that the dentate activities contained predictive information about the future inputs. The average goodness-of-fit (R^2) decreased moderately from 0.89 to 0.86 when t_1 was increased from 20 to 100 ms, hence indicating that the prediction is able to compensate the latency of sensory feedback. The linear equations derived from the firing rates resembled those of a predictor known as Kalman filter composed of prediction and filtering steps. In summary, our analysis of cerebellar activities supports the forward-model hypothesis of the cerebellum