From Parkinsonian thalamic activity to restoring thalamic relay using deep brain stimulation: new insights from computational modeling.

We present a computational model of a thalamocortical relay neuron for exploring basal ganglia thalamocortical loop behavior in relation to Parkinson's disease and deep brain stimulation (DBS). Previous microelectrode, single-unit recording studies demonstrated that oscillatory interaction within and between basal ganglia nuclei is very often accompanied by synchronization at Parkinsonian rest tremor frequencies (3-10 Hz). These oscillations have a profound influence on thalamic projections and impair the thalamic relaying of cortical input by generating rebound action potentials. Our model describes convergent inhibitory input received from basal ganglia by the thalamocortical cells based on characteristics of normal activity, and/or low-frequency oscillations (activity associated with Parkinson's disease). In addition to simulated input, we also used microelectrode recordings as inputs for the model. In the resting state, and without additional sensorimotor input, pathological rebound activity is generated for even mild Parkinsonian input. We have found a specific stimulation window of amplitudes and frequencies for periodic input, which corresponds to high-frequency DBS, and which also suppresses rebound activity for mild and even more prominent Parkinsonian input. When low-frequency pathological rebound activity disables the thalamocortical cell's ability to relay excitatory cortical input, a stimulation signal with parameter settings corresponding to our stimulation window can restore the thalamocortical cell's relay functionality.

Spatial steering of deep brain stimulation volumes using a novel lead design.

OBJECTIVE: To investigate steering the volume of activated tissue (VTA) with deep brain stimulation (DBS) using a novel high spatial-resolution lead design. METHODS: We examined the effect of asymmetric current-injection across the DBS-array on the VTA. These predictions were then evaluated acutely in a non-human primate implanted with the DBS-array, using motor side-effect thresholds as the metric for estimating VTA asymmetries. RESULTS: Simulations show the DBS-array, with electrodes arranged together in a cylindrical configuration, can generate field distributions equivalent to commercial DBS leads, and these field distributions can be modulated using field-steering methods. Stimulation with implanted DBS-arrays showed directionally-selective muscle activation, presumably through spread of stimulation fields into portions of the corticospinal tract lying in the internal capsule. CONCLUSIONS: Our computational and experimental studies demonstrate that the DBS-array is capable of spatially selective stimulation. Displacing VTAs away from the lead's axis can be achieved using a single simple and intuitive control parameter. SIGNIFICANCE: Optimal DBS likely requires non-uniform VTAs that may differentially affect a nucleus or fiber pathway. The DBS-array allows positioning VTAs with sub-millimeter precision, which is especially relevant for those patients with DBS leads placed in sub-optimal locations. This may present clinicians with an additional degree of freedom to optimize the DBS therapy.

Automatic noise-level detection for extra-cellular micro-electrode recordings.

Extra-cellular neuro-recording signals used for functional mapping in deep brain stimulation (DBS) surgery and invasive brain computer interfaces, may suffer from poor signal to noise ratio. Therefore, a reliable automatic noise estimate is essential to extract spikes from recordings. We show that current methods are biased toward overestimation of noise-levels with increasing neuronal activity or artifacts. An improved and novel method is proposed that is based on an estimate of the mode of the distribution of the signal envelope. Our method makes use of the inherent characteristics of the noise distribution. For band-limited Gaussian noise the envelope of the signal is known to follow the Rayleigh distribution. The location of the peak of this distribution provides a reliable noise-level estimate. It is demonstrated that this new 'envelope' method gives superior performance both on simulated data, and on actual micro-electrode recordings made during the implantation surgery of DBS electrodes for the treatment of Parkinson's disease.

Delocalization in weakly coupled disordered wires: application to conjugated polymers.

It is well known that even for minimal disorder one-dimensional wires are insulators: all 1D electron states are localized. Here, the influence of interwire coupling on delocalization of 1D states is examined. Based on perturbation theoretic arguments for the formation of 3D states in coupled wires and subsequent scaling analysis, practical expressions for the microscopic conditions of electronic delocalization and coherent conductivity of coupled 1D wires are obtained. The model quantitatively explains the temperature dependent dc conductivity in conducting polymers at both sides of the metal-insulator transition and links the experimental data to microscopic material parameters.

Carrier dynamics in conducting polymers: case of PF6 doped polypyrrole.

The carrier dynamics in PF6 doped polypyrrole has been probed by dielectric spectroscopy (from 10(-4) to 4 eV), down to 4.2 K. The phase-sensitive sub-THz data have assisted to resolve the discrepancies in Kramers-Kronig analysis in earlier studies. Even in metallic samples, just 1% of the carriers are delocalized, at 300 K; the fraction drops down considerably as a function of disorder, carrier density, and temperature. This subtle metallic feature and the anomalies in carrier dynamics are attributed to coherent and incoherent transport between short conjugated segments.