The effect of dexmedetomidine on the firing properties of STN neurons in Parkinson's disease.

Dexmedetomidine (an alpha-2 adrenergic agonist) sedation is commonly used during subthalamic nucleus (STN) deep-brain stimulation (DBS). Its effects on the electrophysiological characteristics of human STN neurons are largely unknown. We hypothesised that dexmedetomidine modulates the firing rates and bursting of human STN neurons. We analysed microelectrode recording (MER) data from patients with Parkinson's disease who underwent STN DBS. A 'Dex bolus' group (dexmedetomidine bolus prior to MER; 27 cells from seven patients) was compared with a 'no sedation' group (29 cells from 11 patients). We also performed within-patient comparisons with varying dexmedetomidine states. Cells were classified as dorsal half or ventral half based on their relative location in the STN. Neuronal burst and oscillation characteristics were analysed using the Kaneoke-Vitek methodology and local field potential (LFP) oscillatory activity was also investigated. Dexmedetomidine was associated with a slight increase in firing rate (41.1 ± 9.9 vs. 34.5 ± 10.6 Hz, P = 0.02) but a significant decrease in burstiness (number of bursts, P = 0.02; burst index, P < 0.001; percentage of spikes in burst, P = 0.002) of dorsal but not ventral STN neurons. This was not associated with modulation of beta oscillations in the spike-oscillations analysis(beta peak, P = 0.4; signal-to-noise ratio in the beta range for spikes and bursts, P = 0.3 and P = 0.5, respectively) and LFP analysis (Beta power, P = 0.17). As bursting pattern is often used to identify STN and guide electrode placement, we recommend that high-dose dexmedetomidine should be avoided during DBS surgery.

Respiration organizes gamma synchrony in the prefronto-thalamic network.

Multiple cognitive operations are associated with the emergence of gamma oscillations in the medial prefrontal cortex (mPFC) although little is known about the mechanisms that control this rhythm. Using local field potential recordings from cats, we show that periodic bursts of gamma recur with 1 Hz regularity in the wake mPFC and are locked to the exhalation phase of the respiratory cycle. Respiration organizes long-range coherence in the gamma band between the mPFC and the nucleus reuniens the thalamus (Reu), linking the prefrontal cortex and the hippocampus. In vivo intracellular recordings of the mouse thalamus reveal that respiration timing is propagated by synaptic activity in Reu and likely underlies the emergence of gamma bursts in the prefrontal cortex. Our findings highlight breathing as an important substrate for long-range neuronal synchronization across the prefrontal circuit, a key network for cognitive operations.

Beta band oscillations in the motor thalamus are modulated by visuomotor coordination in essential tremor patients.

Introduction: Beta oscillations in sensorimotor structures contribute to the planning, sequencing, and stopping of movements, functions that are typically associated with the role of the basal ganglia. The presence of beta oscillations (13-30 Hz) in the cerebellar zone of the thalamus (the ventral intermediate nucleus - Vim) indicates that this rhythm may also be involved in cerebellar functions such as motor learning and visuomotor adaptation. Methods: To investigate the possible role of Vim beta oscillations in visuomotor coordination, we recorded local field potential (LFP) and multiunit activity from the Vim of essential tremor (ET) patients during neurosurgery for the implantation of deep brain stimulation (DBS) electrodes. Using a computer, patients performed a visuomotor adaptation task that required coordinating center-out movements with incongruent visual feedback imposed by inversion of the computer display. Results: The results show that, in ET, Vim beta oscillations of the LFP were lower during the incongruent center-out task than during the congruent orientation. Vim firing rates increased significantly during periods of low beta power, particularly on approach to the peripheral target. In contrast, beta power in the subthalamic nucleus of Parkinson's disease (PD) patients did not differ significantly between the incongruent and the congruent orientation of the center-out task. Discussion: The findings support the hypothesis that beta oscillations of the Vim are modulated by novel visuomotor tasks. The inverse relationship between the power of Vim-LFP beta oscillations and Vim firing rates suggest that the suppression of beta oscillations may facilitate information throughput to the thalamocortical circuit by modulation of Vim firing rates.

Neuronal activities during palatable food consumption in the reward system of binge-like eating female rats.

Binge eating disorder (BED), characterized by bingeing episodes and compulsivity, is the most prevalent eating disorder; however, little is known about its neurobiological underpinnings. In humans, BED is associated with desensitization of the reward system, specifically, the medial prefrontal cortex (mPFC), nucleus accumbens (Acb), and ventral tegmental area (VTA). Additionally, BED patients feel relieved during bingeing, suggesting that bingeing helps to decrease the negative emotions they were feeling prior to the binge episode. However, the mechanisms that underlie this feeling of relief in BED patients have not been well investigated. To investigate neuronal activity before and during palatable food consumption in BED, we performed in vivo electrophysiological recordings in a binge-like eating rat model (bingeing, n = 12 and non-bingeing, n = 14) and analyzed the firing rate of neurons in the mPFC, Acb, and VTA before and during access to sucrose solution. We also investigated changes in the firing rate of neurons in these regions during and between active bingeing, which may underlie the feeling of relief in BED patients. We found that neuronal firing rates of mPFC and VTA neurons in bingeing rats were lower than those in non-bingeing rats before and during sucrose consumption. Palatable food consumption increased neuronal firing rates during and between active bingeing in bingeing rats. Our results suggest a desynchronization in the activity of reward system regions, specifically in the mPFC, in bingeing rats, which may also contribute to BED. These results are consistent with those of functional magnetic resonance imaging (fMRI) studies that reported decreased activity in the reward system in BED patients. We propose that increased neuronal activity in the mPFC, Acb, or VTA produces an antidepressant effect in rats, which may underlie the sense of relief patients express during bingeing episodes.

Gamma oscillations in the somatosensory thalamus of a patient with a phantom limb: case report.

The amputation of an extremity is commonly followed by phantom sensations that are perceived to originate from the missing limb. The mechanism underlying the generation of these sensations is still not clear although the development of abnormal oscillatory bursting in thalamic neurons may be involved. The theory of thalamocortical dysrhythmia implicates gamma oscillations in phantom pathophysiology although this rhythm has not been previously observed in the phantom limb thalamus. In this study, the authors report the novel observation of widespread 38-Hz gamma oscillatory activity in spike and local field potential recordings obtained from the ventral caudal somatosensory nucleus of the thalamus (Vc) of a phantom limb patient undergoing deep brain stimulation (DBS) surgery. Interestingly, microstimulation near tonically firing cells in the Vc resulted in high-frequency, gamma oscillatory discharges coincident with phantom sensations reported by the patient. Recordings from the somatosensory thalamus of comparator groups (essential tremor and pain) did not reveal the presence of gamma oscillatory activity.

Predictors of deep brain stimulation outcome in tremor patients.

BACKGROUND: Deep brain stimulation of the ventro-intermedius nucleus of the thalamus is an established treatment for tremor of differing etiologies but factors that may predict the short- and especially long-term outcome of surgery are still largely unknown. METHODS: We retrospectively investigated the clinical, pharmacological, electrophysiological and anatomical features that might predict the initial response and preservation of benefit in all patients who underwent deep brain stimulation for tremor. Data were collected at the following time points: baseline (preoperative), one-year post-surgery, and most recent visit. Tremor severity was recorded using the Fahn-Tolosa-Marin Tremor Rating Scale and/or the Unified Parkinson's Disease Rating Scale. RESULTS: A total of 52 patients were included in the final analysis: 31 with essential tremor, 15 with cerebellar tremor of different etiologies, and 6 with Parkinson's disease. Long-term success (mean follow-up duration 34.7 months, range 1.7-121.1 months) was reported in 63.5%. Predictors of long-term benefit were: underlying tremor etiology (best outcome in Parkinson's disease, worst outcome in cerebellar tremor); age at surgery (the older the better); baseline tremor severity (the greater the better); lack of response to benzodiazepines; a more anterior electrode placement and single-unit beta power (the greater the better). CONCLUSIONS: Specific patients' features (including single unit beta activity) and electrode locations may predict the short- and long-term benefit of thalamic stimulation for tremor. Future prospective studies enrolling a much larger sample of patients are needed to substantiate the associations detected by this retrospective study.

Microelectrode recording findings within the tractography-defined ventral intermediate nucleus.

OBJECTIVE The ventral intermediate nucleus (VIM) of the thalamus is not visible on structural MRI. Therefore, direct VIM targeting methods for stereotactic tremor surgery are desirable. The authors previously described a direct targeting method for visualizing the VIM and its structural connectivity using deterministic tractography. In this combined electrophysiology and imaging study, the authors investigated the electrophysiology within this tractography-defined VIM (T-VIM). METHODS Thalamic neurons were classified based on their relative location to the T-VIM: dorsal, within, and ventral to the T-VIM. The authors identified the movement-responsive cells (kinesthetic and tremor cells), performed spike analysis (firing rate and burst index), and local field potential analysis (area under the curve for 13-30 Hz). Tremor efficacy in response to microstimulation along the electrode trajectory was also assessed in relation to the T-VIM. RESULTS Seventy-three cells from a total of 9 microelectrode tracks were included for this analysis. Movement-responsive cells (20 kinesthetic cells and 26 tremor cells) were identified throughout the electrode trajectories. The mean firing rate and burst index of cells (n = 27) within the T-VIM are 18.8 ± 9.8 Hz and 4.5 ± 5.4, respectively. Significant local field potential beta power was identified within the T-VIM (area under the curve for 13-30 Hz = 6.6 ± 7.7) with a trend toward higher beta power in the dorsal T-VIM. The most significant reduction in tremor was also observed in the dorsal T-VIM. CONCLUSIONS The electrophysiological findings within the VIM thalamus defined by tractography, or T-VIM, correspond with the known microelectrode recording characteristics of the VIM in patients with tremor.

Beta oscillatory neurons in the motor thalamus of movement disorder and pain patients.

Excessive beta oscillations (15-25Hz) in the basal ganglia have been linked to the akineto-rigid symptoms of Parkinson's disease (PD) although it remains unclear whether the underlying mechanism is causative or associative. While a number of studies have reported beta activity in the subthalamic nucleus and globus pallidus internus, relatively little is known about the beta rhythm of the motor thalamus and its relation to movement disorders. To test whether thalamic beta oscillations are related to parkinsonian symptoms, we examined the spectral properties of neuronal activity in the ventral thalamic nuclei of five Parkinson's disease patients (two female, age range 50-72years) and compared them to five essential tremor (three female, aged 41-75) and four central pain patients (one female, aged 38-60). Spike and local field potential recordings were obtained during microelectrode-guided localization of thalamic nuclei prior to the implantation of deep brain stimulating electrodes. A total of 118 movement-related neurons in the region of the ventral intermediate nucleus (Vim) were analyzed across all patient groups. Eighty of these neurons (68%) displayed significant oscillatory firing in the beta range with the limbs at rest. In contrast, only 5.7% of the ventral oral posterior (Vop) (χ(2) test, p<0.05) and only 7.2% of the ventral caudal (Vc) neurons fired rhythmically at beta frequency (χ(2) test, p<0.05). Beta power was significantly decreased during limb movements (ANOVA, p<0.05) and was inversely related to tremor-frequency power during tremor epochs in ET and PD (r(2)=0.44). Comparison between patient groups showed that Vim beta power was significantly higher in ET patients versus pain and PD groups (ANOVA, p<0.05). The findings suggest that beta oscillations are found predominantly in Vim and are involved in movement but are not enhanced in tremor-dominant Parkinson's patients.