Motor cortex oscillates at its intrinsic post-movement beta rhythm following real (but not sham) single pulse, rhythmic and arrhythmic transcranial magnetic stimulation.

We aimed to test the idea that rhythmic transcranial magnetic stimulation (TMS) entrains cortical oscillations. To do this, we examined oscillatory responses in the electroencephalogram (EEG) to TMS over primary motor cortex. In particular, we contrasted responses to real TMS with those to sham TMS in order to dissociate the contributions of direct (transcranial) activation and indirect activation (via auditory/sensory input) of the brain. We first showed that real single pulse TMS elicited a brief (∼200 ms) increase in sensorimotor beta power whose frequency closely matched that of each individual's post-movement beta rebound (PMBR, ∼18 Hz). Sham TMS triggered minimal oscillatory activity. Together this implies that real TMS interacts with endogenous oscillations via direct brain activation. We then showed that although trains of real rhythmic TMS delivered at each individuals PMBR frequency produced a brief increase in beta power at the same frequency, real arrhythmic TMS also elicited an equivalent increase in beta. The implication is that the oscillatory response is independent of the rhythm of stimulation. By contrast, sham stimulation elicited minimal activity in the beta band, and the responses to rhythmic and arrhythmic sham TMS were broadly similar, showing that sham rhythmic stimulation did not produce entrainment via sensory rhythms. Together, the data demonstrate that the beta oscillatory response of M1 to real TMS predominantly reflects direct activation of the underlying cortex. However, the data do not support the notion of rhythmic TMS enhancing oscillatory activity via entrainment-like mechanisms, at least within the constraints of the current experimental set-up.

Entraining Stepping Movements of Parkinson's Patients to Alternating Subthalamic Nucleus Deep Brain Stimulation.

Patients with advanced Parkinson's can be treated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). This affords a unique opportunity to record from this nucleus and stimulate it in a controlled manner. Previous work has shown that activity in the STN is modulated in a rhythmic pattern when Parkinson's patients perform stepping movements, raising the question whether the STN is involved in the dynamic control of stepping. To answer this question, we tested whether an alternating stimulation pattern resembling the stepping-related modulation of activity in the STN could entrain patients' stepping movements as evidence of the STN's involvement in stepping control. Group analyses of 10 Parkinson's patients (one female) showed that alternating stimulation significantly entrained stepping rhythms. We found a remarkably consistent alignment between the stepping and stimulation cycle when the stimulation speed was close to the stepping speed in the five patients that demonstrated significant individual entrainment to the stimulation cycle. Our study suggests that the STN is causally involved in dynamic control of step timing and motivates further exploration of this biomimetic stimulation pattern as a potential basis for the development of DBS strategies to ameliorate gait impairments.SIGNIFICANCE STATEMENT We tested whether the subthalamic nucleus (STN) in humans is causally involved in controlling stepping movements. To this end, we studied patients with Parkinson's disease who have undergone therapeutic deep brain stimulation (DBS), as in these individuals we can stimulate the STNs in a controlled manner. We developed an alternating pattern of stimulation that mimics the pattern of activity modulation recorded in this nucleus during stepping. The alternating DBS (altDBS) could entrain patients' stepping rhythm, suggesting a causal role of the STN in dynamic gait control. This type of stimulation may potentially form the basis for improved DBS strategies for gait.

Local entrainment of α oscillations by visual stimuli causes cyclic modulation of perception.

Prestimulus oscillatory neural activity in the visual cortex has large consequences for perception and can be influenced by top-down control from higher-order brain regions. Making a causal claim about the mechanistic role of oscillatory activity requires that oscillations be directly manipulated independently of cognitive instructions. There are indications that a direct manipulation, or entrainment, of visual alpha activity is possible through visual stimulation. However, three important questions remain: (1) Can the entrained alpha activity be endogenously maintained in the absence of continuous stimulation?; (2) Does entrainment of alpha activity reflect a global or a local process?; and (3) Does the entrained alpha activity influence perception? To address these questions, we presented human subjects with rhythmic stimuli in one visual hemifield, and arhythmic stimuli in the other. After rhythmic entrainment, we found a periodic pattern in detection performance of near-threshold targets specific to the entrained hemifield. Using magnetoencephalograhy to measure ongoing brain activity, we observed strong alpha activity contralateral to the rhythmic stimulation outlasting the stimulation by several cycles. This entrained alpha activity was produced locally in early visual cortex, as revealed by source analysis. Importantly, stronger alpha entrainment predicted a stronger phasic modulation of detection performance in the entrained hemifield. These findings argue for a cortically focal entrainment of ongoing alpha oscillations by visual stimulation, with concomitant consequences for perception. Our results support the notion that oscillatory brain activity in the alpha band provides a causal mechanism for the temporal organization of visual perception.

The Short-Term Effects of Rhythmic Vibrotactile and Auditory Biofeedback on the Gait of Individuals After Weight-Induced Asymmetry.

BACKGROUND: Biofeedback (BFB), the practice of providing real-time sensory feedback has been shown to improve gait rehabilitation outcomes. BFB training through rhythmic stimulation has the potential to improve spatiotemporal gait asymmetries while minimizing cognitive load by encouraging a synchronization between the user's gait cycle and an external rhythm. OBJECTIVE: The purpose of this work was to evaluate if rhythmic stimulation can improve the stance time symmetry ratio (STSR) and to compare vibrotactile to auditory stimulation. Gait parameters including velocity, cadence, stride length, double support time, and step length symmetry, were also examined. METHODOLOGY: An experimental rhythmic stimulation system was developed, and twelve healthy adults (5 males), age 28.42 ± 10.93 years, were recruited to participate in walking trials. A unilateral ankle weight was used to induce a gait asymmetry to simulate asymmetry as commonly exhibited by individuals with lower limb amputation and other clinical disorders. Four conditions were evaluated: 1) No ankle weight baseline, 2) ankle weight without rhythmic stimulation, 3) ankle weight + rhythmic vibrotactile stimulation (RVS) using alternating motors and 4) ankle weight + rhythmic auditory stimulation (RAS) using a singletone metronome at the participant's self-selected cadence. FINDINGS: As expected the STSR became significantly more asymmetrical with the ankle weight (i.e. induced asymmetry condition). STSR improved significantly with RVS and RAS when compared to the ankle weight without rhythmic stimulation. Cadence also significantly improved with RVS and RAS compared to ankle weight without rhythmic stimulation. With the exception of double support time, the other gait parameters were unchanged from the ankle weight condition. There were no statistically significant differences between RVS and RAS. CONCLUSION: This study found that rhythmic stimulation can improve the STSR when an asymmetry is induced. Moreover, RVS is at least as effective as auditory stimulation in improving STSR in healthy adults with an induced gait asymmetry. Future work should be extended to populations with mobility impairments and outside of laboratory settings.

Benefits in Alzheimer's Disease of Sensory and Multisensory Stimulation.

Alzheimer's disease (AD) is a serious neurodegenerative disease, which seriously affects the behavior, cognition, and memory of patients. Studies have shown that sensory stimulation can effectively improve the cognition and memory of AD patients, and its role in brain plasticity and neural regulation is initially revealed. This paper aims to review the effect of various sensory stimulation and multisensory stimulation for AD, and to explain the possible mechanism, so as to provide some new ideas for further research in this field. We searched the Web of Science and PubMed databases (from 2000 to October 27, 2020) for literature on the treatment of AD with sensory and multisensory stimulation, including music therapy, aromatherapy, rhythmic (e.g., visual or acoustic) stimulation, light therapy, multisensory stimulation, and virtual reality assisted therapy, then conducted a systematic analysis. Results show these sensory and multisensory stimulations can effectively ameliorate the pathology of AD, arouse memory, and improve cognition and behaviors. What's more, it can cause brain nerve oscillation, enhance brain plasticity, and regulate regional cerebral blood flow. Sensory and multisensory stimulation are very promising therapeutic methods, and they play an important role in the improvement and treatment of AD, but their potential mechanism and stimulation parameters need to be explored and improved.

Modulation of gamma oscillations as a possible therapeutic tool for neuropsychiatric diseases: A review and perspective.

Gamma oscillations (30-80 Hz) are well-known for their role in cortical signal transmission and cognitive brain functions. Aberrant gamma activity has been observed in various neuropsychiatric disorders, but the clinical potential of restoring gamma oscillations via noninvasive brain stimulation has been widely neglected. Only recently, therapeutic effects of gamma entrainment were documented in mouse models of Alzheimer's dementia (AD) using rhythmic sensory stimulation. In the present review, we first summarize the current status of the research on gamma entrainment in mouse models of AD and human AD patients. Then, we suggest transcranial alternating current stimulation (tACS) as an alternative brain stimulation technique and review the recent literature on the effects of gamma tACS in healthy volunteers and neuropsychiatric diseases to document the efficacy of gamma tACS in improving cognitive functions. We discuss several advantages of tACS compared to rhythmic sensory stimulation for the entrainment of gamma oscillations in the human brain and emphasize the need for more clinical studies applying tACS to drive gamma oscillations and, in turn, to improve cognitive functioning not only in AD but also in patients suffering from other neuropsychiatric disorders.

Rocking Promotes Sleep in Mice through Rhythmic Stimulation of the Vestibular System.

Rocking has long been known to promote sleep in infants and, more recently, also in adults, increasing NREM sleep stage N2 and enhancing EEG slow waves and spindles. Nevertheless, whether rocking also promotes sleep in other species, and what the underlying mechanisms are, has yet to be explored. In the current study, C57BL/6J mice equipped with EEG and EMG electrodes were rocked laterally during their main sleep period, i.e., the 12-h light phase. We observed that rocking affected sleep in mice with a faster optimal rate than in humans (1.0 versus 0.25 Hz). Specifically, rocking mice at 1.0 Hz increased time spent in NREM sleep through the shortening of wake episodes and accelerated sleep onset. Although rocking did not increase EEG activity in the slow-wave and spindle-frequency ranges in mice, EEG theta activity (6-10 Hz) during active wakefulness shifted toward slower frequencies. To test the hypothesis that the rocking effects are mediated through the vestibular system, we used the otoconia-deficient tilted (tlt) mouse, which cannot encode linear acceleration. Mice homozygous for the tlt mutation were insensitive to rocking at 1.0 Hz, while the sleep and EEG response of their heterozygous and wild-type littermates resembled those of C57BL/6J mice. Our findings demonstrate that rocking also promotes sleep in the mouse and that this effect requires input from functional otolithic organs of the vestibule. Our observations also demonstrate that the maximum linear acceleration applied, and not the rocking rate per se, is key in mediating the effects of rocking on sleep.

Gait-Assist Wearable Robot Using Interactive Rhythmic Stimulation to the Upper Limbs.

Many power-assist wearable exoskeletons have been developed to provide walking support and gait rehabilitation for elderly subjects and gait-disorder patients. Most designers have focused on a direct power-assist to the wearer's lower limbs. However, gait is a coordinated rhythmic movement of four limbs controlled intrinsically by central pattern generators, with the upper limbs playing an important role in walking. Maintaining a normal gait can become difficult as a person ages, because of decreases in limb coordination, stride length, and gait speed. It is known that coordination mechanisms can be governed by the principle of mutual entrainment, in which synchronization develops through the interaction between nonlinear phase oscillators in biological systems. This principle led us to hypothesize that interactive rhythmic stimulation to upper-limb movements might compensate for the age-related decline in coordination, thereby improving the gait in the elderly. To investigate this hypothesis, we developed a gait-assist wearable exoskeleton that employs interactive rhythmic stimulation to the upper limbs. In particular, we investigated the effects on spatial (i.e., hip-swing amplitude) and temporal (i.e., hip-swing period) gait parameters by conducting walking experiments with 12 healthy elderly subjects under one control condition and five upper-limb-assist conditions, where the output motor torque was applied at five different upper-limb swing positions. The results showed a statistically significant increase in the mean hip-swing amplitude, with a mean increment of about 7% between the control and upper-limb-assist conditions. They also showed a statistically significant decrease in the mean hip-swing period, with a mean decrement of about 2.3% between the control and one of the upper-limb-assist conditions. Although the increase in the hip-swing amplitude and the decrease in the hip-swing period were both small, the results indicate the possibility that interactive rhythmic stimulation to the upper limbs might have a positive effect on the gait of the elderly.