with Subthalamic Nucleus Activity Parkinsonian Beta Oscillations in the External Globus Pallidus and Their Relationship (original) (raw)
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NeuroImage: Clinical
To investigate the spatial and temporal pattern of cortical responses evoked by deep brain stimulation (DBS) of the subthalamic nucleus (STN) and ventral intermediate nucleus of the thalamus (VIM). Methods: We investigated 7 patients suffering from Essential tremor (ET) and 7 patients with Parkinson's Disease (PD) following the implantation of DBS electrodes (VIM for ET patients, STN for PD patients). Magnetoencephalography (MEG) was used to record cortical responses evoked by electric stimuli that were applied via the DBS electrode in trains of 5 Hz. Dipole fitting was applied to reconstruct the origin of evoked responses. Results: Both VIM and STN DBS led to short latency cortical responses at about 1 ms. The pattern of medium and long latency cortical responses following VIM DBS consisted of peaks at 13, 40, 77, and 116 ms. The associated equivalent dipoles were localized within the central sulcus, 3 patients showed an additional response in the cerebellum at 56 ms. STN DBS evoked cortical responses peaking at 4 ms, 11 ms, and 27 ms, respectively. While most dipoles were localized in the pre-or postcentral gyrus, the distribution was less homogenous compared to VIM stimulation and partially included prefrontal brain areas. Conclusion: MEG enables localization of cortical responses evoked by DBS of the VIM and the STN, especially in the sensorimotor cortex. Short latency responses of 1 ms suggest cortical modulation which bypasses synaptic transmission, i.e. antidromic activation of corticofugal fiber pathways.
Brain, 2008
The emergence of oscillations and synchrony among neurons of the basal ganglia is a well-known characteristic of Parkinson's disease. In this study we used intra-operative microelectrode recording to investigate this interrelationship between these two phenomena in the subthalamic nucleus (STN) neurons of 39 human Parkinson's disease patients undergoing deep brain stimulation surgery. From the recorded neuronal traces both neuronal spike trains and their background activity were extracted, and their spectral characteristics were evaluated. We have used the background oscillations as a marker for synchronized activity in the local population in the neuron vicinity and studied its relation to single neuron oscillations. Spike train background oscillations were evaluated using a procedure of background reconstruction that consisted of spikes removal from the original traces and full wave rectification followed by standard spectral analysis. Coherence and phase analysis between oscillatory spike trains and their oscillatory background were also conducted to study the phase relationship between the two. Of the 231 neuronal spike-trains which were sorted offline, 82 (35%) showed significant oscillatory activity.These neurons were found to oscillate mostly in two bands; 3^7 Hz, termed theTremor Frequency Band (TFB), and 8^20 Hz, termed the High-Frequency Band (HFB). While HFB neurons oscillated for longer periods and always coherently with their background activity, TFB neurons oscillated more episodically and only a half were coherent with their background. These findings indicate that the two neuronal populations are the outcome of very different oscillatory drives deriving from different local functional neuronal organizations.
Neuroscience, 2004
In Parkinson's disease the neurones of the subthalamic nucleus show increased synchrony and oscillatory burst discharge, thought to reflect a breakdown of parallel processing in basal ganglia circuitry. To understand better the mechanisms underlying this transition, we sought to mimic this change in firing pattern within sagittal slices of rat midbrain. The firing patterns of up to four simultaneously extracellularly recorded subthalamic nucleus (STN) neurones were analysed using burst and oscillation detection programs, and correlated activity between pairs of neurones assessed.
Functional neuronal activity and connectivity within the subthalamic nucleus in Parkinson’s disease
Clinical Neurophysiology, 2013
h i g h l i g h t s Significantly different firing behavior of single units has been demonstrated in the sensorimotor part of the STN compared to the remaining part in PD patients. This includes increased mean firing rate, more bursty behavior of neurons and increased interneuronal coherences in the beta band. Postoperative evaluation of target stimulation areas in the investigated PD patients with DBS shows a significant preference for the sensorimotor part of the STN. a b s t r a c t Objective: Characterization of the functional neuronal activity and connectivity within the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). Methods: Single units were extracted from micro-electrode recording (MER) of 18 PD patients who underwent STN deep brain stimulation (DBS) surgery. The firing rate and pattern of simultaneously recorded spike trains and their coherence were analyzed. To provide a precise functional assignment of position to the observed activities, for each patient we mapped its classified multichannel STN MERs to a generic atlas representation with a sensorimotor part and a remaining part. Results: Within the sensorimotor part we found significantly higher mean firing rate (P < 0.05) and significantly more burst-like activity (P < 0.05) than within the remaining part. The proportion of significant coherence in the beta band (13-30 Hz) is significantly higher in the sensorimotor part of the STN than elsewhere (P = 0.015). Conclusions: The STN sensorimotor part distinguishes itself from the remaining part with respect to beta coherence, firing rate and burst-like activity and postoperatively was found as the preferred target area. Significance: Our firing behavior analysis may help to discriminate the STN sensorimotor part for the placement of the DBS electrode.
Journal of Computational Neuroscience, 2010
Deep brain stimulation (DBS) of the subthlamic nucleus (STN) represents an effective treatment for medically refractory Parkinson's disease; however, understanding of its effects on basal ganglia network activity remains limited. We constructed a computational model of the subthalamopallidal network, trained it to fit in vivo recordings from parkinsonian monkeys, and evaluated its response to STN DBS. The network model was created with synaptically connected single compartment biophysical models of STN and pallidal neurons, and stochastically defined inputs driven by cortical beta rhythms. A least mean square error training algorithm was developed to parameterize network connections and minimize error when compared to experimental spike and burst rates in the parkinsonian condition. The output of the trained network was then compared to experimental data not used in the training process. We found that reducing the influence of the cortical beta input on the model generated activity that agreed well with recordings from normal monkeys. Further, during STN DBS in the parkinsonian condition the simulations reproduced the reduction in GPi bursting found in existing experimental data. The model also provided the opportunity to greatly expand analysis of GPi bursting activity, generating three major predictions. First, its reduction was proportional to the volume of STN activated by DBS. Second, GPi bursting decreased in a stimulation frequency dependent manner, saturating at values consistent with clinically therapeutic DBS. And third, ablating STN neurons, reported to generate similar therapeutic outcomes as STN DBS, also reduced GPi bursting. Our theoretical analysis of stimulation induced network activity suggests that regularization of GPi firing is dependent on the volume of STN tissue activated and a threshold level of burst reduction may be necessary for therapeutic effect.
The Journal of Neuroscience, 2000
One of the functions of the excitatory subthalamic nucleus (STN) is to relay cortical activity to other basal ganglia structures. The response of the STN to cortical input is shaped by inhibition from the reciprocally connected globus pallidus (GP). To examine the activity in the STN–GP network in relation to cortical activity, we recorded single and multiple unit activity in STN and/or GP together with cortical electroencephalogram in anesthetized rats during various states of cortical activation.During cortical slow-wave activity (SWA), STN and GP neurons fired bursts of action potentials at frequencies that were similar to those of coincident slow (∼1 Hz) and spindle (7–14 Hz) cortical oscillations. Spontaneous or sensory-driven global activation was associated with a reduction of SWA and a shift in STN–GP activity from burst- to tonic- or irregular-firing. Rhythmic activity in STN and GP neurons was lost when the cortex was inactivated by spreading depression and did not resume ...
Stopping an initiated response could be implemented by a fronto-basal-ganglia circuit, including the right inferior frontal cortex (rIFC) and the subthalamic nucleus (STN). Intracranial recording studies in humans reveal an increase in beta-band power (ϳ16 -20 Hz) within the rIFC and STN when a response is stopped. This suggests that the beta-band could be important for communication in this network. If this is the case, then altering one region should affect the electrophysiological response at the other. We addressed this hypothesis by recording scalp EEG during a stop task while modulating STN activity with deep brain stimulation. We studied 15 human patients with Parkinson's disease and 15 matched healthy control subjects. Behaviorally, patients OFF stimulation were slower than controls to stop their response. Moreover, stopping speed was improved for ON compared to OFF stimulation. For scalp EEG, there was greater beta power, around the time of stopping, for patients ON compared to OFF stimulation. This effect was stronger over the right compared to left frontal cortex, consistent with the putative right lateralization of the stopping network. Thus, deep brain stimulation of the STN improved behavioral stopping performance and increased the beta-band response over the right frontal cortex. These results complement other evidence for a structurally connected functional circuit between right frontal cortex and the basal ganglia. The results also suggest that deep brain stimulation of the STN may improve task performance by increasing the fidelity of information transfer within a fronto-basalganglia circuit.
Journal of Neurophysiology, 1996
1. The neural activity associated with 20- to 40-Hz oscillations in sensorimotor cortex of awake monkeys was investigated by recording action potentials of single and multiple units. At a given site, activity of many units became synchronized with local field potential (LFP) oscillations. Cycle-triggered histograms (CTHs) of unit spikes aligned on cycles of LFP oscillations indicated that about two thirds of the recorded units (n = 268) were entrained with LFP oscillations. On average, units had the highest probability of spiking 2.7 ms before peak LFP negativity, corresponding to a -27.6 degrees phase shift relative to the negative peak of the LFP. 2. The average relative modulation amplitude (RMA), defined as the ratio of amplitude of oscillatory component of CTH and the baseline multiplied by 100, was 45 +/- 27% (mean +/- SD). The RMAs of single units did not differ significantly from those of multiple units. 3. Phase shifts and RMAs did not vary systematically with the cortical ...