Considerable evidence suggests a role of beta-band oscillations in voluntary movements. However, most of the studies linking beta power to motor performance are based on data averaged across trials that ignore the fast dynamics of oscillatory activity and trial-to-trial variations in motor responses. Recently, emphasis has shifted from the functional implications of the mean beta power to the presence and nature of episodic bursts of beta activity. Here we test the hypothesis that beta bursts, though short in duration in more physiological state, may help explain spontaneous variations in motor behavior of human adults at the single-trial level. To this end, we recorded local field potential activity from the subthalamic nucleus of parkinsonian patients of both genders whose motor behavior had been normalized as far as possible through treatment with the dopamine prodrug, levodopa. We found that beta bursts present in a time-limited window well before movement onset in the contralateral subthalamic nucleus reduce the peak velocity of that movement and that this effect is further amplified by the amplitude of the burst. Additionally, prolonged reaction times are observed when bursts occur immediately after the GO cue. Together, these results suggest that the modulation of the timing and amplitude of beta bursts might serve to dynamically adapt motor performance. These results offer new insight in the pathology of Parkinson's disease, and suggest that beta bursts whose presence and nature are modulated by context may have a physiological role in modulating behavior.SIGNIFICANCE STATEMENTBeta oscillations (∼13–30 Hz) have been increasingly interpreted as transient bursts rather than as rhythmically sustained oscillations (Feingold et al., 2015). Prolonged and increased probability of beta bursts in the subthalamic nucleus correlates with the severity of motor impairment in Parkinson's disease (Tinkhauser et al., 2017a, b). However, it remains unclear whether beta bursts act to modify motor performance on a trial-by-trial basis under more physiological condition. Here, we found that, according to the time window in which they fall, beta bursts reduced the velocity of the forthcoming movement or prolonged the reaction time. These results offer new insight in the pathology of Parkinson's disease and also suggest that the modulation of beta bursts might serve to dynamically adapt motor performance.

Deep brain stimulation (DBS) for Parkinson’s disease is a highly effective treatment in controlling otherwise debilitating symptoms. Yet the underlying brain mechanisms are currently not well understood. Whole-brain computational modeling was used to disclose the effects of DBS during resting-state functional Magnetic Resonance Imaging in ten patients with Parkinson’s disease. Specifically, we explored the local and global impact that DBS has in creating asynchronous, stable or critical oscillatory conditions using a supercritical bifurcation model. We found that DBS shifts global brain dynamics of patients towards a Healthy regime. This effect was more pronounced in very specific brain areas such as the thalamus, globus pallidus and orbitofrontal regions of the right hemisphere (with the left hemisphere not analyzed given artifacts arising from the electrode lead). Global aspects of integration and synchronization were also rebalanced. Empirically, we found higher communicability and coherence brain measures during DBS-ON compared to DBS-OFF. Finally, using our model as a framework, artificial in silico DBS was applied to find potential alternative target areas for stimulation and whole-brain rebalancing. These results offer important insights into the underlying large-scale effects of DBS as well as in finding novel stimulation targets, which may offer a route to more efficacious treatments.

Gait disturbances in Parkinson's disease are commonly refractory to current treatment options and majorly impair patient's quality of life. Auditory cues facilitate gait and prevent motor blocks. We investigated how neural dynamics in the human subthalamic nucleus of Parkinsons's disease patients (14 male, 2 female) vary during stepping and whether rhythmic auditory cues enhance the observed modulation. Oscillations in the beta band were suppressed after ipsilateral heel strikes, when the contralateral foot had to be raised, and reappeared after contralateral heel strikes, when the contralateral foot rested on the floor. The timing of this 20–30 Hz beta modulation was clearly distinct between the left and right subthalamic nucleus, and was alternating within each stepping cycle. This modulation was similar, whether stepping movements were made while sitting, standing, or during gait, confirming the utility of the stepping in place paradigm. During stepping in place, beta modulation increased with auditory cues that assisted patients in timing their steps more regularly. Our results suggest a link between the degree of power modulation within high beta frequency bands and stepping performance. These findings raise the possibility that alternating deep brain stimulation patterns may be superior to constant stimulation for improving parkinsonian gait.SIGNIFICANCE STATEMENTGait disturbances in Parkinson's disease majorly reduce patients' quality of life and are often refractory to current treatment options. We investigated how neural activity in the subthalamic nucleus of patients who received deep brain stimulation surgery covaries with the stepping cycle. 20–30 Hz beta activity was modulated relative to each step, alternating between the left and right STN. The stepping performance of patients improved when auditory cues were provided, which went along with enhanced beta modulation. This raises the possibility that alternating stimulation patterns may also enhance beta modulation and may be more beneficial for gait control than continuous stimulation, which needs to be tested in future studies.

Chronic intractable pain is debilitating for those touched, affecting 5% of the population. Deep brain stimulation (DBS) has fallen out of favour as the centrally implantable neurostimulation of choice for chronic pain since the 1970–1980s, with some neurosurgeons favouring motor cortex stimulation as the ‘last chance saloon’. This article reviews the available data and professional opinion of the current state of DBS as a treatment for chronic pain, placing it in the context of other neuromodulation therapies. We suggest DBS, with its newer target, namely anterior cingulate cortex (ACC), should not be blacklisted on the basis of a lack of good quality study data, which often fails to capture the merits of the treatment.

High frequency Deep brain stimulation (DBS) targeting motor thalamus is an effective therapy for essential tremor (ET). However, conventional continuous stimulation may deliver unnecessary current to the brain since tremor mainly affects voluntary movements and sustained postures in ET. We aim to decode both voluntary movements and the presence of postural tremor from the Local field potentials (LFPs) recorded from the electrode implanted in motor thalamus for stimulation, in order to close the loop for DBS so that stimulation could be delivered on demand, without the need for peripheral sensors or additional invasive electrodes. LFPs from the motor thalamus, surface electromyographic (EMG) signals and/or behavioural measurements were simultaneously recorded in seven ET patients during temporary lead externalisation 3-5 days after the first surgery for DBS when they performed different voluntary upper limb movements. Nine different patients were recorded during the surgery, when they were asked to lift their arms to trigger postural tremor. A machine learning based binary classifier was used to detect voluntary movements and postural tremor based on features extracted from thalamic LFPs. Cross-validation demonstrated that both voluntary movements and postural tremor can be decoded with an average sensitivity of 0.8 and false detection rate of 0.2. Oscillatory activities in the beta frequency bands (13-23 Hz) and the theta frequency bands (4-7 Hz) contributed most to the decoding of movements and postural tremor, respectively, though incorporating features in different frequency bands using a machine learning approach increased the accuracy of decoding.

The autonomic nervous system (ANS) is involved in the regulation of physiologic and homeostatic parameters relating particularly to the visceral organs and the co-ordination of physiological responses to threat. Blood pressure and heart rate, respiration, pupillomotor reactivity, sexual function, gastrointestinal secretions and motility, and urine storage and micturition are all under a degree of ANS control. Furthermore, there is close integration between the ANS and other neural functions such as emotion and cognition, and thus brain regions that are known to be important for autonomic control are also implicated in emotional functions. In this review we explore the role of the central ANS in the control of the bladder, and the implications of this for bladder dysfunction in diseases of the ANS.