Human Subthalamic Nucleus Theta and Beta Oscillations Entrain Neuronal Firing During Sensorimotor Conflict.
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ABSTRACT:
SUBMITTER: Zavala B
PROVIDER: S-EPMC5390852 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Parkinson's disease is a neurodegenerative disorder characterized by progressive loss of dopaminergic cells in the central nervous system, in particular the substantia nigra, resulting in an unrelenting loss of motor and nonmotor function. Animal models of Parkinson's disease reveal hyperactive neurons in the subthalamic nucleus that have increased firing rates and bursting activity compared with controls. Although subthalamic nucleus activity has been characterized in patients with advanced-stage Parkinson's disease, it has not been described in patients with early-stage Parkinson's disease. Here we present the results of subthalamic nucleus neuronal recordings from patients with early-stage Parkinson's disease (Hoehn and Yahr stage II) enrolled in an ongoing clinical trial compared with recordings from age- and sex-matched patients with advanced Parkinson's disease. Subthalamic nucleus neurons had a significantly lower firing rate in early versus advanced Parkinson's disease (28.7 vs 36.3 Hz; P<.01). The overall activity of the subthalamic nucleus was also significantly lower in early versus late Parkinson's disease, as measured by background neuronal noise (12.4 vs 14.0 mV; P<.05). No significant difference was identified between groups in the bursting or variability of neuronal firing in the subthalamic nucleus, as measured by a burst index or the interspike interval coefficient of variability. The results suggest that neuronal firing in the subthalamic nucleus increases with Parkinson's disease progression.
| S-EPMC3151310 | biostudies-literature
Project description:Performance and cognitive effort in humans have recently been related to amplitude and multisite coherence of alpha (7-12 Hz) and theta (4-7 Hz) band electroencephalogram oscillations. I examined this phenomenon in rats by using theta band oscillations of the local field potential to signify sniffing as a sensorimotor process. Olfactory bulb (OB) theta oscillations are coherent with those in the dorsal hippocampus (HPC) during odor sniffing in a two-odor olfactory discrimination task. Coherence is restricted to the high-frequency theta band (6-12 Hz) associated with directed sniffing in the OB and type 1 theta in the HPC. Coherence and performance fluctuate on a time scale of several minutes. Coherence magnitude is positively correlated with performance in the two-odor condition but not in extended runs of single odor conditional-stimulus-positive trials. Simultaneous with enhanced OB-HPC theta band coherence during odor sniffing is a significant decrease in lateral entorhinal cortex (EC)-HPC and OB-EC coherence, suggesting that linkage of the olfactory and hippocampal theta rhythms is not through the synaptic relay from OB to HPC in the lateral EC. OB-HPC coupling at the sniffing frequency is proposed as a mechanism underlying olfactory sensorimotor effort as a cognitive process.
| S-EPMC553293 | biostudies-literature
Project description:It is unclear how subthalamic nucleus activity is modulated by the cerebral cortex. Here we investigate the effect of transcranial magnetic stimulation (TMS) of the cortex on oscillatory subthalamic local field potential activity in the 8-35 Hz (alpha/beta) band, as exaggerated synchronization in this band is implicated in the pathophysiology of parkinsonism. We studied nine patients with Parkinson's disease (PD) to test whether cortical stimulation can modulate synchronized oscillations in the human subthalamic nucleus. With patients at rest, single-pulse TMS was delivered every 5 s over each primary motor area and supplementary motor area at intensities of 85-115% resting motor threshold. Subthalamic local field potentials were recorded from deep brain stimulation electrodes implanted into this nucleus for the treatment of PD. Motor cortical stimulation suppressed beta activity in the subthalamic nucleus from approximately 0.2 to 0.6 s after TMS (repeated measures anova; main effect of time, P < 0.01; main effect of side, P = 0.03), regardless of intensity. TMS over the supplementary motor area also reduced subthalamic beta activity at 95% (P = 0.05) and 115% resting motor threshold (P = 0.01). The oscillatory activity decreased to 80 +/- 26% of baseline (averaged across sites and stimulation intensities). Suppression with subthreshold stimuli confirmed that these changes were centrally driven and not due to peripheral afference. The results may have implications for mechanisms underlying the reported therapeutic benefits of cortical stimulation.
| S-EPMC2695156 | biostudies-literature
Project description:The medial prefrontal cortex (mPFC) is thought to control the shift from automatic to controlled action selection when conflict is present or when mistakes have been recently committed. Growing evidence suggests that this process involves frequency specific communication in the theta (4-8Hz) band between the mPFC and the subthalamic nucleus (STN), which is the main target of deep brain stimulation (DBS) for Parkinson's disease. Key in this hypothesis is the finding that DBS can lead to impulsivity by disrupting the correlation between higher mPFC oscillations and slower reaction times during conflict. In order to test whether theta band coherence between the mPFC and the STN underlies adjustments to conflict and to errors, we simultaneously recorded mPFC and STN electrophysiological activity while DBS patients performed an arrowed flanker task. These recordings revealed higher theta phase coherence between the two sites during the high conflict trials relative to the low conflict trials. These differences were observed soon after conflicting arrows were displayed, but before a response was executed. Furthermore, trials that occurred after an error was committed showed higher phase coherence relative to trials that followed a correct trial, suggesting that mPFC-STN connectivity may also play a role in error related adjustments in behavior. Interestingly, the phase coherence we observed occurred before increases in theta power, implying that the theta phase and power may influence behavior at separate times during cortical monitoring. Finally, we showed that pre-stimulus differences in STN theta power were related to the reaction time on a given trial, which may help adjust behavior based on the probability of observing conflict during a task.
| S-EPMC4927260 | biostudies-literature
Project description:Parkinsonian bradykinesia and rigidity are typically associated with excessive beta band oscillations in the subthalamic nucleus. Recently another spectral peak has been identified that might be implicated in the pathophysiology of the disease: high-frequency oscillations (HFO) within the 150-400 Hz range. Beta-HFO phase-amplitude coupling (PAC) has been found to correlate with severity of motor impairment. However, the neuronal origin of HFO and its usefulness as a potential target for deep brain stimulation remain to be established. For example, it is unclear whether HFO arise from the same neural populations as beta oscillations. We intraoperatively recorded local field potentials from the subthalamic nucleus while advancing DBS electrodes in 2 mm steps from 4 mm above the surgical target point until 2 mm below, resulting in 4 recording sites. Data from 26 nuclei from 14 patients were analysed. For each trajectory, we identified the recording site with the largest spectral peak in the beta range (13-30 Hz), and the largest peak in the HFO range separately. In addition, we identified the recording site with the largest beta-HFO PAC. Recording sites with largest beta power and largest HFO power coincided in 50% of cases. In the other 50%, HFO was more likely to be detected at a more superior recording site in the target area. PAC followed more closely the site with largest HFO (45%) than beta power (27%). HFO are likely to arise from spatially close, but slightly more superior neural populations than beta oscillations. Further work is necessary to determine whether the different activities can help fine-tune deep brain stimulation targeting.
| S-EPMC5540829 | biostudies-other
Project description:IntroductionSubthalamic nucleus (STN) is an effective target for deep brain stimulation (DBS) to reduce the motor symptoms of Parkinson's disease (PD). It is important to identify firing patterns within the structure for a better understanding of the electro-pathophysiology of the disease. Using recently established metrics, our study aims to autonomously identify the discharge patterns of individual cells and examine their spatial distribution within the STN.MethodsWe recorded single unit activity (SUA) from 12 awake PD patients undergoing a standard clinical DBS surgery. Three extracted features from raw SUA (local variation, bursting index and prominence of peak) were used with k-means clustering to achieve the aforementioned unsupervised grouping of firing patterns.Results279 neurons were isolated and four distinct firing patterns were identified across patients: tonic (11%), irregular (55%), periodic (9%) and non-periodic bursts (25%). The mean firing rates for irregular discharges were significantly lower (p < 0.05) than the rest. Tonic firings were significantly ventral (p < 0.05) while periodic (p < 0.05) and non-periodic (p < 0.01) bursts were dorsal. The percentage of periodically bursting neurons in dorsal region and entire STN were significantly correlated with off state UPDRS tremor scores (r = 0.51, p = 0.04) and improvement in bradykinesia and rigidity (r = 0.57, p = 0.02) respectively.ConclusionStrengthening the application of unsupervised clustering for firing patterns of individual cells, this study shows a unique spatial affinity of tonic activity towards the ventral and bursting activity towards the dorsal region of STN in PD patients. This spatial preference, together with the correlation of clinical scores, can provide a clue towards understanding Parkinsonian symptom generation.
| S-EPMC8298773 | biostudies-literature
Project description:Inappropriately synchronized beta (beta) oscillations (15-30 Hz) in the subthalamic nucleus (STN) accompany movement difficulties in idiopathic Parkinson's disease (PD). The cellular and network substrates underlying these exaggerated beta oscillations are unknown but activity in the external globus pallidus (GP), which forms a candidate pacemaker network with STN, might be of particular importance. Using a clinically relevant rat model of PD, we demonstrate that oscillatory activity in GP neuronal networks becomes excessively and selectively synchronized at beta frequencies in a spatially widespread and brain state-dependent manner after lesion of dopamine neurons. Although synchronization of GP unit activity increased by almost 100-fold during beta oscillations, the mean firing rate of GP neurons decreased compared with controls. Importantly, in parkinsonian animals, two main types of GP neuron were identified according to their distinct and inversely related firing rates and patterns. Moreover, neurons of the same type tended to fire together, with small phase differences, whereas different types of neuron tended not to do so. This functional dichotomy in temporal coupling persisted across extreme brain states, suggesting that maladaptive interactions are dominated by hardwiring. Finally, the precisely timed discharges of GP and STN neurons indicated that rhythmic sequences of recurrent excitation and inhibition in the STN-GP network, and lateral inhibition between GP neurons, could actively support abnormal beta oscillations. We propose that GP neurons, by virtue of their spatiotemporal synchronization, widespread axon collaterals and feed-back/feed-forward mechanisms, are well placed to orchestrate and propagate exaggerated beta oscillations throughout the entire basal ganglia in PD.
| S-EPMC4243385 | biostudies-literature
Project description:The subthalamic nucleus (STN) occupies a strategic position in the motor network, slowing down responses in situations with conflicting perceptual input. Recent evidence suggests a role of the STN in emotion processing through strong connections with emotion recognition structures. As deep brain stimulation (DBS) of the STN in patients with Parkinson's disease (PD) inhibits monitoring of perceptual and value-based conflict, STN DBS may also interfere with emotional conflict processing. To assess a possible interference of STN DBS with emotional conflict processing, we used an emotional Stroop paradigm. Subjects categorized face stimuli according to their emotional expression while ignoring emotionally congruent or incongruent superimposed word labels. Eleven PD patients ON and OFF STN DBS and eleven age-matched healthy subjects conducted the task. We found conflict-induced response slowing in healthy controls and PD patients OFF DBS, but not ON DBS, suggesting STN DBS to decrease adaptation to within-trial conflict. OFF DBS, patients showed more conflict-induced slowing for negative conflict stimuli, which was diminished by STN DBS. Computational modelling of STN influence on conflict adaptation disclosed DBS to interfere via increased baseline activity.
| S-EPMC5647801 | biostudies-literature
Project description:Neuronal oscillations comprise a fundamental mechanism by which distant neural structures establish and express functional connectivity. Long-range functional connectivity between the hippocampus and other forebrain structures is enabled by theta oscillations. Here, we show for the first time that the infant rat red nucleus (RN)-a brainstem sensorimotor structure-exhibits theta (4-7 Hz) oscillations restricted primarily to periods of active (REM) sleep. At postnatal day 8 (P8), theta is expressed as brief bursts immediately following myoclonic twitches; by P12, theta oscillations are expressed continuously across bouts of active sleep. Simultaneous recordings from the hippocampus and RN at P12 show that theta oscillations in both structures are coherent, co-modulated, and mutually interactive during active sleep. Critically, at P12, inactivation of the medial septum eliminates theta in both structures. The developmental emergence of theta-dependent functional coupling between the hippocampus and RN parallels that between the hippocampus and prefrontal cortex. Accordingly, disruptions in the early expression of theta could underlie the cognitive and sensorimotor deficits associated with neurodevelopmental disorders such as autism and schizophrenia.
| S-EPMC5446093 | biostudies-literature
Project description:Neuronal oscillations at beta frequencies (20-50 Hz) in the cortico-basal ganglia circuits have long been the leading theory for bradykinesia, the slow movements that are cardinal symptoms in Parkinson's disease (PD). The beta oscillation theory helped to drive a frequency-based design in the development of deep brain stimulation therapy for PD. However, in contrast to this theory, here we have found that bradykinesia can be completely dissociated from beta oscillations in rodent models. Instead, we observed that bradykinesia is causatively regulated by the burst-firing pattern of the subthalamic nucleus (STN) in a feed-forward, or efferent-only, mechanism. Furthermore, STN burst-firing and beta oscillations are two independent mechanisms that are regulated by different NMDA receptors in STN. Our results shift the understanding of bradykinesia pathophysiology from an interactive oscillatory theory toward a feed-forward mechanism that is coded by firing patterns. This distinct mechanism may improve understanding of the fundamental concepts of motor control and enable more selective targeting of bradykinesia-specific mechanisms to improve PD therapy.
| S-EPMC5127676 | biostudies-literature