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Deep brain stimulation (DBS) is one of the most important clinical therapies for neurological disorders. DBS also has great potential to become a great tool for clinical neuroscience research. Recently, the National Engineering Laboratory for Neuromodulation at Tsinghua University held an international Deep Brain Stimulation Initiative workshop to discuss the cutting-edge technological achievements and clinical applications of DBS. We specifically addressed new clinical approaches and challenges in DBS for movement disorders (Parkinson's disease and dystonia), clinical application toward neurorehabilitation for stroke, and the progress and challenges toward DBS for neuropsychiatric disorders. This review highlighted key developments in (1) neuroimaging, with advancements in 3-Tesla magnetic resonance imaging DBS compatibility for exploration of brain network mechanisms; (2) novel DBS recording capabilities for uncovering disease pathophysiology; and (3) overcoming global healthcare burdens with online-based DBS programming technology for connecting patient communities. The successful event marks a milestone for global collaborative opportunities in clinical development of neuromodulation to treat major neurological disorders. [ABSTRACT FROM AUTHOR]

Background: The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) in Parkinson's disease (PD) and is believed to serve a role in sensorimotor integration. In addition to therapeutic neuromodulation, DBS facilitates the recording of local-field potentials (LFPs) in order to further understand the neurophysiological basis of disease. The capacity to wirelessly transmit these signals in real time has overcome the obstacle of externalization of electrodes during LFP recordings. Objective: Using the G102RS device (PINS Medical, China), we investigated the LFP changes in response to mechanical pain stimulation to further elucidate the representation of pain sensation in the basal ganglia. Methods: LFPs from 2 patients who had undergone bilateral STN-DBS were wirelessly recorded during no stimulation, low-frequency stimulation (60 and 90 Hz), and high-frequency stimulation (130 and 150 Hz) while introducing painful and nonpainful stimuli. Power spectral analysis was conducted to compare the changes in β frequency (13–30 Hz) during each stimulus. Results: During painful stimuli, STN power spectra (n = 4) revealed a significant increase in β activity compared to non-painful and no-stimulus epochs. Both low- and high-frequency stimulation produced a significant decrease in pain-related β activity. Conclusion: These 2 cases have demonstrated the potential for acute noxious stimuli to exacerbate pathologic β oscillatory activity in the STN. Our findings represent novel evidence of the neurophysiologic representation of pain in the STN of PD patients. [ABSTRACT FROM AUTHOR]

Purpose: Dysautonomia can be a debilitating feature of Parkinson disease (PD). Pedunculopontine nucleus (PPN) stimulation may improve gait disorders in PD, and may also result in changes in autonomic performance. Methods: To determine whether pedunculopontine nucleus stimulation improves cardiovascular responses to autonomic challenges of postural tilt and Valsalva manoeuver, eight patients with pedunculopontine nucleus deep brain stimulation were recruited to the study; two were excluded for technical reasons during testing. Participants underwent head up tilt and Valsalva manoeuver with stimulation turned ON and OFF. Continuous blood pressure and ECG waveforms were recorded during these tests. In a single patient, local field potential activity was recorded from the implanted electrode during tilt. Results: The fall in systolic blood pressure after tilt was significantly smaller with stimulation ON (mean − 8.3% versus − 17.2%, p = 0.044). Valsalva ratio increased with stimulation from median 1.15 OFF to 1.20 ON (p = 0.028). Baroreflex sensitivity increased during Valsalva compared to rest with stimulation ON versus OFF (p = 0.028). The increase in baroreflex sensitivity correlated significantly with the mean depth of PPN stimulating electrode contacts. This accounted for 89% of its variance (r = 0.943, p = 0.005). Conclusion: PPN stimulation can modulate the cardiovascular system in patients with PD. In this study, it reduced the postural fall in systolic blood pressure during head-up tilt and improved the cardiovascular response during Valsalva, presumably by altering the neural control of baroreflex activation. [ABSTRACT FROM AUTHOR]

Objective: Respiratory abnormalities such as upper airway obstruction are common in Parkinson's disease (PD) and are an important cause of mortality and morbidity. We tested the effect of pedunculopontine region (PPNr) stimulation on respiratory maneuvers in human participants with PD, and separately recorded PPNr neural activity reflected in the local field potential (LFP) during these maneuvers. Methods: Nine patients with deep brain stimulation electrodes in PPNr, and seven in globus pallidus interna (GPi) were studied during trials of maximal inspiration followed by forced expiration with stimulation OFF and ON. Local field potentials (LFPs) were recorded in the unstimulated condition. Results: PEFR increased from 6.41 ± 0.63 L/sec in the OFF stimulation state to 7.5 L ± 0.65 L/sec in the ON stimulation state (z = −2.666, df = 8, P = 0.024). Percentage improvement in PEFR was strongly correlated with proximity of the stimulated electrode contact to the mesencephalic locomotor region in the rostral PPN (r = 0.814, n = 9, P = 0.008). Mean PPNr LFP power increased within the alpha band (7–11 Hz) during forced respiratory maneuvers (1.63 ± 0.16 μV2/Hz) compared to resting breathing (0.77 ± 0.16 μV2/Hz; z = −2.197, df = 6, P = 0.028). No changes in alpha activity or spirometric indices were seen with GPi recording or stimulation. Percentage improvement in PEFR was strongly positively correlated with increase in alpha power (r = 0.653, n = 14 (7 PPNr patients recorded bilaterally), P = 0.0096). Interpretation: PPNr stimulation in PD improves indices of upper airway function. Increased alpha‐band activity is seen within the PPNr during forced respiratory maneuvers. Our findings suggest a link between the PPNr and respiratory performance in PD. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To differentiate physiological from harmonic components in coherence analysis of the tremor-related neural and muscular signals by comparing power, cross-power and coherence spectra. Methods: Influences of waveform, burst-width and additional noise on generating harmonic peaks in the power, cross-power and coherence spectra were studied using simulated signals. The local field potentials (LFPs) of the subthalamic nucleus (STN) and the EMGs of the contralateral forearm muscles in PD patients with rest tremor were analysed. Results: (1) Waveform had significant effect on generating harmonics; (2) noise significantly decreased the coherence values in a frequency-dependent fashion; and (3) cross-spectrum showed high resistance to harmonics. Among six examples of paired LFP–EMG signals, significant coherence appeared at the tremor frequency only, both the tremor and double tremor frequencies and the double-tremor frequency only. Conclusions: In coherence analysis of neural and muscular signals, distortion in waveform generates significant harmonic peaks in the coherence spectra and the coherence values of both physiological and harmonic components are modulated by extra noise or non-tremor related activity. Significance: The physiological or harmonic nature of a coherence peak at the double tremor frequency may be differentiated when the coherence spectra are compared with the power and in particular the cross-power spectra. [Copyright &y& Elsevier]

The quantitative characterization of movement disorders and their related neurophysiological signals is important for the management of Parkinson's disease (PD). The aim of this study is to develop a novel wearable system enabling the simultaneous measurement of both motion and other neurophysiological signals in PD patients. We designed a wearable system that consists of five motion sensors and three electrophysiology sensors to measure the motion signals of the body, electroencephalogram, electrocardiogram, and electromyography, respectively. The data captured by the sensors are transferred wirelessly in real time, and the outcomes are analyzed and uploaded to the cloud-based server automatically. We completed pilot studies to (1) test its validity by comparing outcomes to the commercialized systems, and (2) evaluate the deep brain stimulation (DBS) treatment effects in seven PD patients. Our results showed: (1) the motion and neurophysiological signals measured by this wearable system were strongly correlated with those measured by the commercialized systems (r > 0.94, p < 0.001); and (2) by completing the clinical supination and pronation frequency test, the frequency of motion as measured by this system increased when DBS was turned on. The results demonstrated that this multi-sensor wearable system can be utilized to quantitatively characterize and monitor motion and neurophysiological PD. [ABSTRACT FROM AUTHOR]

Neural oscillations are critical to understanding the synchronisation of neural activities and their relevance to neurological disorders. For instance, the amplitude of beta oscillations in the subthalamic nucleus has gained extensive attention, as it has been found to correlate with medication status and the therapeutic effects of continuous deep brain stimulation in people with Parkinson's disease. However, the frequency stability of subthalamic nucleus beta oscillations, which has been suggested to be associated with dopaminergic information in brain states, has not been well explored. Moreover, the administration of medicine can have inverse effects on changes in frequency and amplitude. In this study, we proposed a method based on the stationary wavelet transform to quantify the amplitude and frequency stability of subthalamic nucleus beta oscillations and evaluated the method using simulation and real data for Parkinson's disease patients. The results suggest that the amplitude and frequency stability quantification has enhanced sensitivity in distinguishing pathological conditions in Parkinson's disease patients. Our quantification shows the benefit of combining frequency stability information with amplitude and provides a new potential feedback signal for adaptive deep brain stimulation. • The new quantification AFS comprehensively captures variations in amplitude and frequency stability of neural oscillations. • AFS quantification indicates better correlation than amplitude or frequency stability with symptom alleviation. • AFS can be implemented in real-time for adaptive deep brain stimulation. [ABSTRACT FROM AUTHOR]

Summary: Practice makes perfect, but the neural substrates of trial-to-trial learning in motor tasks remain unclear. There is some evidence that the basal ganglia process feedback-related information to modify learning in essentially cognitive tasks , but the evidence that these key motor structures are involved in offline feedback-related improvement of performance in motor tasks is paradoxically limited. Lesion studies in adult zebra finches suggest that the avian basal ganglia are involved in the transmission or production of an error signal during song . However, patients with Huntington''s disease, in which there is prominent basal ganglia dysfunction, are not impaired in error-dependent modulation of future trial performance . By directly recording from the subthalamic nucleus in patients with Parkinson''s disease, we demonstrate that this nucleus processes error in trial performance at short latency. Local evoked activity is greatest in response to smallest errors and influences the programming of subsequent movements. Accordingly, motor parameters are least likely to change after the greatest evoked responses so that accurately performed trials tend to precede other accurate trials. This relationship is disrupted by electrical stimulation of the nucleus at high frequency. Thus, the human subthalamic nucleus is involved in feedback-based learning. [Copyright &y& Elsevier]

• The study provides a coding approach of multiple temporally varying oscillations. • Motor symptoms are associated with the neural states coded with multi-oscillations. • Dynamic neural states cloud be biomarkers for closed-loop deep brain stimulation. This study aims to discriminate the dynamic synchronization states from the subthalamic local field potentials and investigate their correlations with the motor symptoms in Parkinson's Disease (PD). The resting-state local field potentials of 10 patients with PD were recorded from the subthalamic nucleus. The dynamic neural states of multiple oscillations were discriminated and analyzed. The Spearman correlation was used to investigate the correlations between occurrence rate or duration of dynamic neural states and the severity of motor symptoms. The proportion of long low-beta and theta synchronized state was significantly correlated with the general motor symptom and tremor, respectively. The duration of combined low/high-beta state was significantly correlated with rigidity, and the duration of combined alpha/high-beta state was significantly correlated with bradykinesia. This study provides evidence that motor symptoms are associated with the neural states coded with multiple oscillations in PD. This study may advance the understanding of the neurophysiological mechanisms of the motor symptoms and provide potential biomarkers for closed-loop deep brain stimulation in PD. [ABSTRACT FROM AUTHOR]

Background: Subcortical structures, including the basal ganglia, have been proposed to be crucial for arousal, consciousness, and behavioural responsiveness. How the basal ganglia contribute to the loss and recovery of consciousness during anaesthesia has, however, not yet been well characterised.Methods: Twelve patients with advanced Parkinson's disease, who were undergoing deep brain stimulation (DBS) electrode implantation in the subthalamic nucleus (STN), were included in this study. Local field potentials (LFPs) were recorded from the DBS electrodes and EEG was recorded from the scalp during induction of general anaesthesia (with propofol and sufentanil) and during tracheal intubation. Neural signatures of loss of consciousness and of the expected arousal during intubation were sought in the STN and EEG recordings.Results: Propofol-sufentanil anaesthesia resulted in power increases in delta, theta, and alpha frequencies, and broadband power decreases in higher frequencies in both STN and frontal cortical areas. This was accompanied by increased STN-frontal cortical coherence only in the alpha frequency band (119 [68]%; P=0.0049). We observed temporal activity changes in STN after tracheal intubation, including power increases in high-beta (22-40 Hz) frequency (98 [123]%; P=0.0064) and changes in the power-law exponent in the power spectra at lower frequencies (2-80 Hz), which were not observed in the frontal cortex. During anaesthesia, the dynamic changes in the high-gamma power in STN LFPs correlated with the power-law exponent in the power spectra at lower frequencies (2-80 Hz).Conclusions: Apart from similar activity changes in both STN and cortex associated with anaesthesia-induced unresponsiveness, we observed specific neuronal activity changes in the STN in response to the anaesthesia and tracheal intubation. We also show that the power-law exponent in the power spectra in the STN was modulated by tracheal intubation in anaesthesia. Our results support the hypothesis that subcortical nuclei may play an important role in the loss and return of responsiveness. [ABSTRACT FROM AUTHOR]

Objectives Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been successfully used to treat both Parkinson's disease (PD) and dystonia. Local field potentials (LFPs) recorded from the STN of PD patients demonstrate prominent beta frequency band activity. It is unclear whether such activity occurs in the STN in dystonia, and, if not, whether dystonia has another distinctive neural population activity in the STN. Methods Twelve patients with PD, and eight patients with dystonia underwent DBS electrode implantation targeting the STN. Seven dystonia patients were off medication and one was on aripiprazole and clonazepam. LFPs were recorded from the DBS electrodes in PD in the on/off medication states and in dystonia. Power spectra and temporal dynamics measured by the with Lempel-Ziv complexity of the LFPs were compared among these states. Results Normalised power spectra and Lempel-Ziv complexity of subthalamic LFPs differed between dystonia off and PD on/off, and between PD off and on over the low frequency, beta and high gamma bands. Patients with dystonia and off medication had lower beta power but higher low frequency and high gamma power than PD. Spectral power in the low beta frequency (11–20 Hz) range was attenuated in medicated PD. Conclusion The results suggest that dystonia and PD are characterized by different patterns of oscillatory activities even within the same nucleus, and exaggerated beta activity may relate to hypo-dopaminergic status. [ABSTRACT FROM AUTHOR]