Neurosurgical and pharmacological management of dystonia.

Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements, often with repetitive or sustained contraction resulting in abnormal posturing. Different types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given intervention. For most patients afflicted with these disorders, an exact cause is rarely identified, so treatment mainly focuses on symptomatic alleviation. Pharmacological agents, such as oral anticholinergic administration and botulinum toxin injection, play a major role in the initial treatment of patients. In more severe and/or refractory cases, focal areas for neurosurgical intervention are identified and targeted to improve quality of life. Deep brain stimulation (DBS) targets these anatomical locations to minimize dystonia symptoms. Surgical ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to DBS. These management options grant providers and patients the ability to weigh the benefits and risks for each individual patient profile. This review article explores these pharmacological and neurosurgical management modalities for dystonia, providing a comprehensive assessment of each of their benefits and shortcomings.

Accelerating input-output model estimation with parallel computing for testing hippocampal memory prostheses in human.

BACKGROUND: Hippocampal memory prosthesis is defined as a closed-loop biomimetic system that can be used for restoration and enhancement of memory functions impaired in diseases or injuries. To build such a prosthesis, we have developed two types of input-output models, i.e., a multi-input multi-output (MIMO) model for predicting output spike trains based on input spikes, and a double-layer multi-resolution memory decoding (MD) model for classifying spatio-temporal patterns of spikes into memory categories. Both models can achieve high prediction accuracy using human hippocampal spikes data and can be used to derive electrical stimulation patterns to test the hippocampal memory prosthesis. METHODS: However, testing hippocampal memory prostheses in human epilepsy patients with such models has to be performed within a much shorter time window (48-72 h) due to clinical limitations. To solve this problem, we have developed parallelization strategies to decompose the overall model estimation task into multiple independent sub-tasks involving different outputs and cross-validation folds. These sub-tasks are then accomplished in parallel on different computer nodes to reduce model estimation time. RESULTS: Implementing both parallel schemes with a high-performance computer cluster, we successfully reduced the computing time of model estimations from hundreds of hours to tens of hours. COMPARISON WITH EXISTING METHOD: We have tested the two parallel computing schemes for both MIMO and MD models with data collected from 11 human subjects. The performances of the parallel schemes are compared with the performance of the non-parallel scheme. CONCLUSION: Such strategies allow us to complete the modeling procedure within the required time frame to further test input-output model-driven electrical stimulations for the hippocampal memory prosthesis. It has important implications to test the model-based DBS intraoperatively and developing clinically viable hippocampal memory prostheses.

Independent representations of self-motion and object location in barrel cortex output.

During active tactile exploration, the dynamic patterns of touch are transduced to electrical signals and transformed by the brain into a mental representation of the object under investigation. This transformation from sensation to perception is thought to be a major function of the mammalian cortex. In primary somatosensory cortex (S1) of mice, layer 5 (L5) pyramidal neurons are major outputs to downstream areas that influence perception, decision-making, and motor control. We investigated self-motion and touch representations in L5 of S1 with juxtacellular loose-seal patch recordings of optogenetically identified excitatory neurons. We found that during rhythmic whisker movement, 54 of 115 active neurons (47%) represented self-motion. This population was significantly more modulated by whisker angle than by phase. Upon active touch, a distinct pattern of activity was evoked across L5, which represented the whisker angle at the time of touch. Object location was decodable with submillimeter precision from the touch-evoked spike counts of a randomly sampled handful of these neurons. These representations of whisker angle during self-motion and touch were independent, both in the selection of which neurons were active and in the angle-tuning preference of coactive neurons. Thus, the output of S1 transiently shifts from a representation of self-motion to an independent representation of explored object location during active touch.