Firing Patterns In Subthalamic Nucleus Research Articles

Subthalamic Nucleus Activity during Cognitive Load and Gait Dysfunction in Parkinson's Disease.

Gait freezing is a common, disabling symptom of Parkinson's disease characterized by sudden motor arrest during walking. Adaptive deep brain stimulation devices that detect freezing and deliver real-time, symptom-specific stimulation are a potential treatment strategy. Real-time alterations in subthalamic nucleus firing patterns have been demonstrated with lower limb freezing, however, whether similar abnormal signatures occur with freezing provoked by cognitive load, is unknown. We obtained subthalamic nucleus microelectrode recordings from eight Parkinson's disease patients performing a validated virtual reality gait task, requiring responses to on-screen cognitive cues while maintaining motor output. Signal analysis during 15 trials containing freezing or significant motor output slowing precipitated by dual-tasking demonstrated reduced θ frequency (3-8 Hz) firing compared to 18 unaffected trials. These preliminary results reveal a potential neurobiological basis for the interplay between cognitive factors and gait disturbances including freezing in Parkinson's disease, informing development of adaptive deep brain stimulation protocols. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Grouping Neuronal Spiking Patterns in the Subthalamic Nucleus of Parkinsonian Patients.

The subthalamic nucleus (STN) is a commonly used target in deep brain stimulation (DBS) to control the motor symptoms of Parkinson's Disease (PD). Identification of the spiking patterns in the STN is important in order to understand the neuropathophysiology of PD and can also assist in electrophysiological mapping of the structure. This study aims to provide a tool for grouping these firing patterns based on several extracted features from the spiking data. Single neuronal activity from the STN of PD subjects was detected and sorted to compute the binary spike trains. Several features including loca variation, bursting index and the prominence of the peak frequency of the power spectrum were extracted. Clustering of spike train segments was performed based on combination of features in 3D space to scrutinize how well they describe different firing regimes. The results show that this approach could be used to automate the grouping of stereotypic firing patterns in STN.

Correlation between spike statistics and T-type calcium channel activation in simulated subthalamic nucleus neurons

Firing patterns of subthalamic nucleus (STN) neurons are closely related to behavioral functions such as motor controls. In the patients of the Parkinson disease, which is a representative of basal ganglia disorders, STN neurons show a distinctive firing pattern, rebound bursts. To understand the relation between the STN firing patterns and their functional roles, it is useful to characterize the firing patterns, especially the burst firings. Although several methods have been proposed so far, an objective definition of burst firings is still unclear. On the other hand, the mechanism for the rebound bursts is attributed to the low-voltage-activated calcium channels, also known as T-type calcium channels [1]. The channels are activated by strong inhibitory synaptic inputs from globus pallidal neurons that have reciprocal connections with STN. If we could observed directly T-type calcium currents, the observation could be a criterion to determine whether the firing activity is a burst firing or not. Here we investigated to what degree spike statistics correlate with an activation level of the T-type calcium currents by simulating an STN neuron model [2]. We employed the following spike statistics of interspike intervals (ISIs) of STN neural activities: (i) coefficient of variation (Cv), (ii) time-local variation (Lv) [3], (iii) chisquared test statistic between a spike count histogram and a Poisson distribution [4], and (iv)-(vi) KolmogorovSmirnov (K-S) statistics in K-S test between an observed and hypothesized ISI distributions (Gaussian, exponential, and gamma distributions). By comparing multiple correlation coefficients between these statistics and temporally-averaged conductances of the T-type calcium channels under different conditions including burst-preferred parameter sets, we found that the K-S statistic between the observed ISI distribution and the hypothesized exponential one (v) showed the highest correlation with the averaged T-type calcium currents among them under any condition. This would provide a more objective criterion, which is linked to the generation mechanism, to define rebound bursts observed in pathological STN.

Dopamine lesion‐induced changes in subthalamic nucleus activity are not associated with alterations in firing rate or pattern in layer V neurons of the anterior cingulate cortex in anesthetized rats

Dysfunctional activity in the subthalamic nucleus (STN) is thought to underlie movement deficits of patients with Parkinson's disease. Alterations in STN firing patterns are also evident in the anesthetized rat model of Parkinson's disease, where studies show that loss of striatal dopamine and concomitant changes in the indirect pathway are associated with bursty and oscillatory firing patterns in STN output. However, the extent to which alterations in cortical activity contribute to changes in STN activity is unclear. As pyramidal neurons in the cingulate cortex project directly to the STN, cingulate output was assessed after dopamine lesion by simultaneously recording single-unit and local field potential (LFP) activities in STN and anterior cingulate cortex in control, dopamine-lesioned and non-lesioned hemispheres of urethane-anesthetized rats. Correlated oscillations were observed in cross-correlograms of spike trains from STN and cingulate layer V neurons with broad waveforms indicative of pyramidal neurons. One-2 weeks after dopamine cell lesion, firing rate, incidence of bursty and 0.3-2.5 Hz oscillatory activity of neurons and LFP power in the STN all increased significantly. In contrast, firing rate, incidence of bursty and 0.3-2.5 Hz oscillatory activity of cingulate layer V putative pyramidal neurons and power in cingulate LFPs did not differ significantly between dopamine-lesioned, non-lesioned or control hemispheres, despite significant loss of dopamine in the lesioned cingulate cortex. Data show that alterations in STN activity in the dopamine-lesioned hemisphere are not associated with alterations in neuronal activity in layer V of the anterior cingulate cortex in anesthetized rats.