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The value associated with reward is sensitive to external factors, such as the time between the choice and reward delivery as classically manipulated in temporal discounting tasks. Subjective preference for two reward options is dependent on objective variables of reward magnitude and reward delay. Single neuron correlates of reward value have been observed in regions, including ventral striatum, orbital, and medial prefrontal cortex. Brain imaging studies show cortico-striatal-limbic network activity related to subjective preferences. To explore how oscillatory dynamics represent reward processing across brain regions, we measured local field potentials of rats performing a temporal discounting task. Our goal was to use a data-driven approach to identify an electrophysiological marker that correlates with reward preference. We found that reward-locked oscillations at beta frequencies signaled the magnitude of reward and decayed with longer temporal delays. Electrodes in orbitofrontal/medial prefrontal cortex, anterior insula, ventral striatum, and amygdala individually increased power and were functionally connected at beta frequencies during reward outcome. Beta power during reward outcome correlated with subjective value as defined by a computational model fit to the discounting behavior. These data suggest that cortico-striatal beta oscillations are a reward signal correlated, which may represent subjective value and hold potential to serve as a biomarker and potential therapeutic target.

Deep brain stimulation (DBS) is a common therapy for managing Parkinson's disease (PD) in clinical practice. However, a complete understanding of its mode of action is still needed. DBS is believed to work primarily through electrical and neurochemical pathways. Furthermore, DBS has other mechanisms of action. This review explores the fundamental concepts and applications of DBS in treating PD, including its mechanisms, clinical implications, and recent research. [ABSTRACT FROM AUTHOR]

The value associated with reward is sensitive to external factors, such as the time between the choice and reward delivery as classically manipulated in temporal discounting tasks. Subjective preference for two reward options is dependent on objective variables of reward magnitude and reward delay. Single neuron correlates of reward value have been observed in regions, including ventral striatum, orbital, and medial prefrontal cortex. Brain imaging studies show cortico-striatal-limbic network activity related to subjective preferences. To explore how oscillatory dynamics represent reward processing across brain regions, we measured local field potentials of rats performing a temporal discounting task. Our goal was to use a data-driven approach to identify an electrophysiological marker that correlates with reward preference. We found that reward-locked oscillations at beta frequencies signaled the magnitude of reward and decayed with longer temporal delays. Electrodes in orbitofrontal/medial prefrontal cortex, anterior insula, ventral striatum, and amygdala individually increased power and were functionally connected at beta frequencies during reward outcome. Beta power during reward outcome correlated with subjective value as defined by a computational model fit to the discounting behavior. These data suggest that cortico-striatal beta oscillations are a reward signal correlated, which may represent subjective value and hold potential to serve as a biomarker and potential therapeutic target. [ABSTRACT FROM AUTHOR]

Summary: Motor adaptation reflects the ability of the brain's sensorimotor system to flexibly deal with environmental changes to generate effective motor behaviour. Whether sleep contributes to the consolidation of motor adaptation remains controversial. In this study, we investigated the impact of sleep on motor adaptation and its neurophysiological correlates in a novel motor adaptation task that leverages a highly automatised motor skill, that is, typing. We hypothesised that sleep‐associated memory consolidation would benefit motor adaptation and induce modulations in task‐related beta band (13–30 Hz) activity during adaptation. Healthy young male experts in typing on the regular computer keyboard were trained to type on a vertically mirrored keyboard while brain activity was recorded using electroencephalography. Typing performance was assessed either after a full night of sleep with polysomnography or a similar period of daytime wakefulness. Results showed improved motor adaptation performance after nocturnal sleep but not after daytime wakefulness, and decreased beta power: (a) during mirrored typing as compared with regular typing; and (b) in the post‐sleep versus the pre‐sleep mirrored typing sessions. Furthermore, the slope of the electroencephalography signal, a measure of aperiodic brain activity, decreased during mirrored as compared with regular typing. Changes in the electroencephalography spectral slope from pre‐ to post‐sleep mirrored typing sessions were correlated with changes in task performance. Finally, increased fast sleep spindle density (13–15 Hz) during the night following motor adaptation training was predictive of successful motor adaptation. These findings suggest that post‐training sleep modulates neural activity supporting adaptive motor functions. [ABSTRACT FROM AUTHOR]

Brief beta bursts, rather than sustained oscillations, support cognition by providing transient, functional inhibition. Analyzing the timing of beta bursts helps establish neural correlates of cognitive behavior on a single trial level. The intermittent and nonlinear nature of beta bursts provides novel insights into interareal interactions. Diversity of beta burst types may reflect differences in circuit-level origins and may yield insights into the underlying activity motifs and function. We suggest that spatiotemporal patterns of beta bursting implement cognitive control operations underlying goal-directed behavior. Beta oscillations are linked to the control of goal-directed processing of sensory information and the timing of motor output. Recent evidence demonstrates they are not sustained but organized into intermittent high-power bursts mediating timely functional inhibition. This implies there is a considerable moment-to-moment variation in the neural dynamics supporting cognition. Beta bursts thus offer new opportunities for studying how sensory inputs are selectively processed, reshaped by inhibitory cognitive operations and ultimately result in motor actions. Recent method advances reveal diversity in beta bursts that provide deeper insights into their function and the underlying neural circuit activity motifs. We propose that brain-wide, spatiotemporal patterns of beta bursting reflect various cognitive operations and that their dynamics reveal nonlinear aspects of cortical processing. [ABSTRACT FROM AUTHOR]

Brain rhythms can facilitate neural communication for the maintenance of brain function. Beta rhythms (13–35 Hz) have been proposed to serve multiple domains of human ability, including motor control, cognition, memory, and emotion, but the overarching organisational principles remain unknown. To uncover the circuit architecture of beta oscillations, we leverage normative brain data, analysing over 30 hr of invasive brain signals from 1772 channels from cortical areas in epilepsy patients, to demonstrate that beta is the most distributed cortical brain rhythm. Next, we identify a shared brain network from beta-dominant areas with deeper brain structures, like the basal ganglia, by mapping parametrised oscillatory peaks to whole-brain functional and structural MRI connectomes. Finally, we show that these networks share significant overlap with dopamine uptake as indicated by positron emission tomography. Our study suggests that beta oscillations emerge in cortico-subcortical brain networks that are modulated by dopamine. It provides the foundation for a unifying circuit-based conceptualisation of the functional role of beta activity beyond the motor domain and may inspire an extended investigation of beta activity as a feedback signal for closed-loop neurotherapies for dopaminergic disorders.

Combining electrophysiological, anatomical and functional brain maps reveals networks of beta neural activity that align with dopamine uptake.

Beta band oscillations in the sensorimotor cortex and subcortical structures, such as the subthalamic nucleus (STN) and internal pallidum (GPi), are closely linked to motor control. Recent research suggests that low-beta (14.5–23.5 Hz) and high-beta (23.5–35 Hz) cortico-STN coherence arise through distinct networks, possibly reflecting indirect and hyperdirect pathways. In this study, we sought to probe whether low- and high-beta coherence also exhibit different functional roles in facilitating and inhibiting movement. Twenty patients with Parkinson's disease who had deep brain stimulation electrodes implanted in either STN or GPi performed a classical go/nogo task while undergoing simultaneous magnetoencephalography and local field potentials recordings. Subjects' expectations were manipulated by presenting go- and nogo-trials with varying probabilities. We identified a lateral source in the sensorimotor cortex for low-beta coherence, as well as a medial source near the supplementary motor area for high-beta coherence. Task-related coherence time courses for these two sources revealed that low-beta coherence was more strongly implicated than high-beta coherence in the performance of go-trials. Accordingly, average pre-stimulus low-beta but not high-beta coherence or spectral power correlated with overall reaction time across subjects. High-beta coherence during unexpected nogo-trials was higher compared to expected nogo-trials at a relatively long latency of 3 s after stimulus presentation. Neither low- nor high-beta coherence showed a significant correlation with patients' symptom severity at baseline assessment. While low-beta cortico-subcortical coherence appears to be related to motor output, the role of high-beta coherence requires further investigation.

Defining spatial synchronisation of pathological beta oscillations is important, given that many theories linking them to parkinsonian symptoms propose a reduction in the dimensionality of the coding space within and/or across cortico-basal ganglia structures. Such spatial synchronisation could arise from a single process, with widespread entrainment of neurons to the same oscillation. Alternatively, the partially segregated structure of cortico-basal ganglia loops could provide a substrate for multiple ensembles that are independently synchronized at beta frequencies. Addressing this question requires an analytical approach that identifies groups of signals with a statistical tendency for beta synchronisation, which is unachievable using standard pairwise measures. Here, we utilized such an approach on multichannel recordings of background unit activity (BUA) in the external globus pallidus (GP) and subthalamic nucleus (STN) in parkinsonian rats. We employed an adapted version of a principle and independent component analysis-based method commonly used to define assemblies of single neurons (i.e., neurons that are synchronized over short timescales). This analysis enabled us to define whether changes in the power of beta oscillations in local ensembles of neurons (i.e., the BUA recorded from single contacts) consistently covaried over time, forming a “beta ensemble”. Multiple beta ensembles were often present in single recordings and could span brain structures. Membership of a beta ensemble predicted significantly higher levels of short latency (

Clinical experiments have proven that the pedunculopontine nucleus (PPN) plays a crucial role in the modulation of beta oscillations in Parkinson’s disease (PD). Here, we propose a new computational framework by introducing the PPN and related synaptic connections to the classic basal ganglia-thalamo-cortical model. Fascinatingly, the improved model can not only simulate the basic saturated and beta activities mentioned in previous studies but also produce the normal alpha rhythm that is much closer to physiological phenomena. Specifically, the results show that Parkinsonian oscillation activities can be controlled and modulated by the connection strength between the PPN and the globus pallidus internal nucleus (GPi) and the subthalamic nucleus (STN), supporting the fact that PPN is overinhibited in PD. Meanwhile, the internal mechanism underlying these state transitions is further explained from the perspective of dynamics. Additionally, both deep brain stimulation (DBS) and optogenetic technology are considered effective in terms of abnormal oscillations. Especially when a low-frequency DBS is added to the PPN, beta oscillations can be suppressed, but it is excited again as the DBS’s frequency gradually increases to a larger value. These results coincide with the experimental results that low-frequency stimulation of the PPN is effective, and verify the rationality of the model. Furthermore, we show that optogenetic stimulation of the globus pallidus external (GPe) expressing excitatory channelrhodopsin (ChR2) can effectively inhibit beta oscillations, whereas exciting the STN and PPN has a limited effect. These results are consistent with experimental reports suggesting that the symptoms of PD’s movement disorder can be alleviated under the GPe-ChR2, but not STN-ChR2, situation. Although the functional role of the PPN and the feasibility of optogenetic stimulation remain to be clinically explored, the results obtained help us understand the mechanisms of beta oscillations in PD. [ABSTRACT FROM AUTHOR]

Due to the interconnected nature of the brain, changes in one region are likely to affect other structurally and functionally connected regions. Emerging evidence indicates that single-site transcranial alternating current stimulation (tACS) can modulate functional connectivity between stimulated and interconnected unstimulated brain regions. However, our understanding of the network response to tACS is incomplete. Here, we investigated the effect of beta tACS of different intensities on phase-based connectivity between the left and right primary motor cortices in 21 healthy young adults (13 female; mean age 24.30 ± 4.84 years). Participants underwent four sessions of 20 min of 20 Hz tACS of varying intensities (sham, 0.5 mA, 1.0 mA, or 1.5 mA) applied to the left primary motor cortex at rest. We recorded resting-state and event-related electroencephalography (EEG) before and after tACS, analyzing changes in sensorimotor beta (13–30 Hz) imaginary coherence (ImCoh), an index of functional connectivity. Event-related EEG captured movement-related beta activity as participants performed self-paced button presses using their right index finger. For resting-state connectivity, we observed intensity-dependent changes in beta ImCoh: sham and 0.5 mA stimulation resulted in an increase in beta ImCoh, while 1.0 mA and 1.5 mA stimulation decreased beta ImCoh. For event-related connectivity, 1.5 mA stimulation decreased broadband ImCoh (4–90 Hz) during movement execution. None of the other stimulation intensities significantly modulated event-related ImCoh during movement preparation, execution, or termination. Interestingly, changes in ImCoh during movement preparation following 1.0 mA and 1.5 mA stimulation were significantly associated with participants’ pre-tACS peak beta frequency, suggesting that the alignment of stimulation frequency and peak beta frequency affected the extent of neuromodulation. Collectively, these results suggest that beta tACS applied to a single site influences connectivity within the motor network in a manner that depends on the intensity and frequency of stimulation. These findings have significant implications for both research and clinical applications.

The ability to accurately encode the temporal information of sensory events and hence to make prompt action is fundamental to humans’ prompt behavioral decision-making. Here we examined the ability of ensemble coding (averaging multiple inter-intervals in a sound sequence) and subsequent immediate reproduction of target duration at half, equal, or double that of the perceived mean interval in a sensorimotor loop. With magnetoencephalography (MEG), we found that the contingent magnetic variation (CMV) in the central scalp varied as a function of the averaging tasks, with a faster rate for buildup amplitudes and shorter peak latencies in the “half” condition as compared to the “double” condition. ERD (event-related desynchronization) -to-ERS (event-related synchronization) latency was shorter in the ”half” condition. A robust beta band (15–23 Hz) power suppression and recovery between the final tone and the action of key pressing was found for time reproduction. The beta modulation depth (i.e., the ERD-to-ERS power difference) was larger in motor areas than in primary auditory areas. Moreover, results of phase slope index (PSI) indicated that beta oscillations in the left supplementary motor area (SMA) led those in the right superior temporal gyrus (STG), showing SMA to STG directionality for the processing of sequential (temporal) auditory interval information. Our findings provide the first evidence to show that CMV and beta oscillations predict the coupling between perception and action in time averaging.

Centromedian nucleus (CM) is one of several intralaminar nuclei of the thalamus and is thought to be involved in consciousness, arousal, and attention. CM has been suggested to play a key role in the control of attention, by regulating the flow of information to different brain regions such as the ascending reticular system, basal ganglia, and cortex. While the neurophysiology of attention in visual and auditory systems has been studied in animal models, combined single unit and LFP recordings in human have not, to our knowledge, been reported. Here, we recorded neuronal activity in the CM nucleus in 11 patients prior to insertion of deep brain stimulation electrodes for the treatment of epilepsy while subjects performed an auditory attention task. Patients were requested to attend and count the infrequent (p = 0.2) odd or ''deviant'' tones, ignore the frequent standard tones and report the total number of deviant tones at trial completion. Spikes were discriminated, and LFPs were band pass filtered (5–45 Hz). Average peri‑stimulus time histograms and spectra were constructed by aligning on tone onsets and statistically compared. The firing rate of CM neurons showed selective, multi-phasic responses to deviant tones in 81% of the tested neurons. Local field potential analysis showed selective beta and low gamma (13–45 Hz) modulations in response to deviant tones, also in a multi-phasic pattern. The current study demonstrates that CM neurons are under top-down control and participate in the selective processing during auditory attention and working memory. These results, taken together, implicate the CM in selective auditory attention and working memory and support a role of beta and low gamma oscillatory activity in cognitive processes. It also has potential implications for DBS therapy for epilepsy and non-motor symptoms of PD, such as apathy and other disorders of attention.

Background: Deep brain stimulation (DBS) of the thalamus can effectively reduce tics in severely affected patients with Tourette syndrome (TS). Its effect on cortical oscillatory activity is currently unknown. Objective: We assessed whether DBS modulates beta activity at fronto-central electrodes. We explored concurrent EEG sources and probabilistic stimulation maps. Methods: Resting state EEG of TS patients treated with thalamic DBS was recorded in repeated DBS-on and DBS-off states. A mixed linear model was employed for statistical evaluation. EEG sources were estimated with eLORETA. Thalamic probabilistic stimulation maps were obtained by assigning beta power difference scores (DBS-on minus DBS-off) to stimulation sites. Results: We observed increased beta power in DBS-on compared to DBS-off states. Modulation of cortical beta activity was localized to the midcingulate cortex. Beta modulation was more pronounced when stimulating the thalamus posteriorly, peaking in the ventral posterior nucleus. Conclusion: Thalamic DBS in TS patients modulates beta frequency oscillations presumably important for sensorimotor function and relevant to TS pathophysiology.

Synchronous neural oscillations within the beta frequency range are observed across the parkinsonian basal ganglia network, including within the subthalamic nucleus (STN) - globus pallidus (GPe) subcircuit. The emergence of pathological synchrony in Parkinson’s disease is often attributed to changes in neural properties or connection strength, and less often to the network topology, i.e. the structural arrangement of connections between neurons. This study investigates the relationship between network structure and neural synchrony in a model of the STN-GPe circuit comprised of conductance-based spiking neurons. Changes in net synaptic input were controlled for through a synaptic scaling rule, which facilitated separation of the effects of network structure from net synaptic input. Five topologies were examined as structures for the STN-GPe circuit: Watts-Strogatz, preferential attachment, spatial, stochastic block, k-regular random. Beta band synchrony generally increased as the number of connections increased, however the exact relationship was topology specific. Varying the wiring pattern while maintaining a constant number of connections caused network synchrony to be enhanced or suppressed, demonstrating the ability of purely structural changes to alter synchrony. This relationship was well-captured by the algebraic connectivity of the network, the second smallest eigenvalue of the network’s Laplacian matrix. The structure-synchrony relationship was further investigated in a network model designed to emulate the action selection role of the STN-GPe circuit. It was found that increasing the number of connections and/or the overlap of action selection channels could lead to a rapid transition to synchrony, which was also predicted by the algebraic connectivity.

Increasing evidence suggests slow-wave sleep (SWS) dysfunction in Parkinson's disease (PD) is associated with faster disease progression, cognitive impairment, and excessive daytime sleepiness. Beta oscillations (8-35 Hz) in the basal ganglia thalamocortical (BGTC) network are thought to play a role in the development of cardinal motor signs of PD. The role cortical beta oscillations play in SWS dysfunction in the early stage of parkinsonism is not understood, however. To address this question, we used a within-subject design in a nonhuman primate (NHP) model of PD to record local field potentials from the primary motor cortex (MC) during sleep across normal and mild parkinsonian states. The MC is a critical node in the BGTC network, exhibits pathological oscillations with depletion in dopamine tone, and displays high amplitude slow oscillations during SWS. The MC is therefore an appropriate recording site to understand the neurophysiology of SWS dysfunction in parkinsonism. We observed a reduction in SWS quantity (p = 0.027) in the parkinsonian state compared to normal. The cortical delta (0.5-3 Hz) power was reduced (p = 0.038) whereas beta (8-35 Hz) power was elevated (p = 0.001) during SWS in the parkinsonian state compared to normal. Furthermore, SWS quantity positively correlated with delta power (r=0.43, p = 0.037) and negatively correlated with beta power (r=-0.65, p< 0.001). Our findings support excessive beta oscillations as a mechanism for SWS dysfunction in mild parkinsonism and could inform the development of neuromodulation therapies for enhancing SWS in people with PD. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of the thalamus can effectively reduce tics in severely affected patients with Tourette syndrome (TS). Its effect on cortical oscillatory activity is currently unknown. We assessed whether DBS modulates beta activity at fronto-central electrodes. We explored concurrent EEG sources and probabilistic stimulation maps. Resting state EEG of TS patients treated with thalamic DBS was recorded in repeated DBS-on and DBS-off states. A mixed linear model was employed for statistical evaluation. EEG sources were estimated with eLORETA. Thalamic probabilistic stimulation maps were obtained by assigning beta power difference scores (DBS-on minus DBS-off) to stimulation sites. We observed increased beta power in DBS-on compared to DBS-off states. Modulation of cortical beta activity was localized to the midcingulate cortex. Beta modulation was more pronounced when stimulating the thalamus posteriorly, peaking in the ventral posterior nucleus. Thalamic DBS in TS patients modulates beta frequency oscillations presumably important for sensorimotor function and relevant to TS pathophysiology. • Thalamic deep brain stimulation increased cortical beta oscillations. • Increased beta power was localized to midcingulate cortex. • Peak beta modulation was related to stimulation of the ventral posterior nucleus. [ABSTRACT FROM AUTHOR]

• Strong beta suppression in diplegic cerebral palsy (CP) can reflect hyperexcitation/activation of the primary sensorimotor (SM1) cortex contralateral to the stimulation. • Weak beta rebound in the ipsilateral SM1 cortex may indicate broadly impaired control of cortical inhibition in diplegic CP. • Strong ipsilateral rebound in controls may reflect the importance of interhemispheric inhibitory regulation in fine-motor actions. Our objective was to clarify the primary sensorimotor (SM1) cortex excitatory and inhibitory alterations in hemiplegic (HP) and diplegic (DP) cerebral palsy (CP) by quantifying SM1 cortex beta power suppression and rebound with magnetoencephalography (MEG). MEG was recorded from 16 HP and 12 DP adolescents, and their 32 healthy controls during proprioceptive stimulation of the index fingers evoked by a movement actuator. The related beta power changes were computed with Temporal Spectral Evolution (TSE). Peak strengths of beta suppression and rebound were determined from representative channels over the SM1 cortex. Beta suppression was stronger contralateral to the stimulus and rebound was weaker ipsilateral to the stimulation in DP compared to controls. Beta modulation strengths did not differ significantly between HP and the control group. The emphasized beta suppression in DP suggests less efficient proprioceptive processing in the SM1 contralateral to the stimulation. Their weak rebound further indicates reduced intra- and/or interhemispheric cortical inhibition, which is a potential neuronal mechanism for their bilateral motor impairments. The excitation-inhibition balance of the SM1 cortex related to proprioception is impaired in diplegic CP. Therefore, the cortical and behavioral proprioceptive deficits should be better diagnosed and considered to better target individualized effective rehabilitation in CP. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) is an invasive treatment option for patients with Parkinson's disease. Recently, adaptive DBS (aDBS) systems have been developed, which adjust stimulation timing and amplitude in real-time. However, it is unknown how changes in parameters, movement states and the controllability of subthalamic beta activity affect aDBS performance. To characterize how parameter choice, movement state and controllability interactively affect the electrophysiological and behavioral response to single threshold aDBS. We recorded subthalamic local field potentials in 12 patients with Parkinson's disease receiving single threshold aDBS in the acute post-operative state. We investigated changes in two aDBS parameters: the onset time and the smoothing of real-time beta power. Electrophysiological patterns and motor performance were assessed while patients were at rest and during a simple motor task. We further studied the impact of controllability on aDBS performance by comparing patients with and without beta power modulation during continuous stimulation. Our findings reveal that changes in the onset time control the extent of beta power suppression achievable with single threshold adaptive stimulation during rest. Behavioral data indicate that only specific parameter combinations yield a beneficial effect of single threshold aDBS. During movement, action induced beta power suppression reduces the responsivity of the closed loop algorithm. We further demonstrate that controllability of beta power is a prerequisite for effective parameter dependent modulation of subthalamic beta activity. Our results highlight the interaction between single threshold aDBS parameter selection, movement state and controllability in driving subthalamic beta activity and motor performance. By this means, we identify directions for the further development of closed-loop DBS algorithms. • Adaptive DBS in Parkinson's disease was delivered in externalized patients. • Suppression of subthalamic beta power by adaptive DBS was dependent on onset time. • Movement reduced the responsivity of adaptive DBS. • Diminished controllability lowered the sensitivity to parameter changes. • Parameters, movement and controllability interacted in driving adaptive DBS performance. [ABSTRACT FROM AUTHOR]

Inhibitory control has been linked to beta oscillations in the fronto-basal ganglia network. Here we aim to investigate the functional role of the phase of this oscillatory beta rhythm for successful motor inhibition. We applied 20 Hz transcranial alternating current stimulation (tACS) to the pre-supplementary motor area (pre-SMA) while presenting stop signals at 4 (Experiment 1) and 8 (Experiment 2) equidistant phases of the tACS entrained beta oscillations. Participants showed better inhibitory performance when stop signals were presented at the trough of the beta oscillation whereas their inhibitory control performance decreased with stop signals being presented at the oscillatory beta peak. These results are consistent with the communication through coherence theory, in which postsynaptic effects are thought to be greater when an input arrives at an optimal phase within the oscillatory cycle of the target neuronal population. The current study provides mechanistic insights into the neural communication principles underlying successful motor inhibition and may have implications for phase-specific interventions aimed at treating inhibitory control disorders such as PD or OCD.

Bradykinesia, a debilitating symptom characterized by impaired movement initiation and reduced speed in Parkinson’s disease (PD), is associated with abnormal oscillatory activity in the motor cortex-basal ganglia circuit. We investigated the interplay between abnormal beta and gamma oscillations in relation to bradykinesia in parkinsonian rats. Our findings showed reduced movement activities in parkinsonian rats, accompanied by enhanced high beta oscillations in the motor cortex, which are closely associated with movement transitional difficulties. Additionally, gamma oscillations correlated with movement velocity in control rats but not in parkinsonian rats. We observed selective coupling between high beta oscillation phase and gamma oscillation amplitude in PD, as well as cortical high beta-broadband gamma phase-amplitude coupling (PAC) negatively influencing locomotor activities in control and PD rats. These findings suggest a collaborative role of cortical beta and gamma oscillations in facilitating movement execution, with beta oscillations being linked to movement initiation and gamma oscillations associated with movement speed. Importantly, the aberrant alterations of these oscillations are closely related to the development of bradykinesia. Furthermore, PAC hold promise as a biomarker for comprehensive assessment of movement performance in PD.

Abstract Background Neural motor control rests on the dynamic interaction of cortical and subcortical regions, which is reflected in the modulation of oscillatory activity and connectivity in multiple frequency bands. Motor control is thought to be compromised in developmental stuttering, particularly involving circuits in the left hemisphere that support speech, movement initiation, and timing control. However, to date, evidence comes from adult studies, with a limited understanding of motor processes in childhood, closer to the onset of stuttering. Methods We investigated the neural control of movement initiation in children who stutter and children who do not stutter by evaluating transient changes in EEG oscillatory activity (power, phase locking to button press) and connectivity (phase synchronization) during a simple button press motor task. We compared temporal changes in these oscillatory dynamics between the left and right hemispheres and between children who stutter and children who do not stutter, using mixed-model analysis of variance. Results We found reduced modulation of left hemisphere oscillatory power, phase locking to button press and phase connectivity in children who stutter compared to children who do not stutter, consistent with previous findings of dysfunction within the left sensorimotor circuits. Interhemispheric connectivity was weaker at lower frequencies (delta, theta) and stronger in the beta band in children who stutter than in children who do not stutter. Conclusions Taken together, these findings indicate weaker engagement of the contralateral left motor network in children who stutter even during low-demand non-speech tasks, and suggest that the right hemisphere might be recruited to support sensorimotor processing in childhood stuttering. Differences in oscillatory dynamics occurred despite comparable task performance between groups, indicating that an altered balance of cortical activity might be a core aspect of stuttering, observable during normal motor behavior.

Abstract Background Obsessive-compulsive disorder (OCD) is related to working memory impairment. Since patients with OCD have difficulty controlling their obsessive thoughts, removal of irrelevant information might be important in the pathophysiology of OCD. However, little is known about brain activity during the removal of information from working memory in patients with OCD. Our goal was to explore potential deficits in inhibitory function related to working memory processes in patients with OCD. Methods Sixteen OCD patients and 20 healthy controls (HCs) were recruited. We compared in prefrontal alpha and beta band activity derived from magnetoencephalography (MEG) between patients with OCD and HCs during multiple phases of information processing associated with working memory, especially in post-trial period of the visuospatial working memory task (the delayed matching-to‐sample task), which is presumed to be related to the information removal process of working memory. Results Prefrontal post-trial beta power change (presumed to occur at high levels during the post-trial period) exhibited significant reductions in patients with OCD compared to HCs. In addition, the post-trial beta power change was negatively correlated with Obsessive-Compulsive Inventory–Revised total scores in patients with OCD. Conclusions These findings suggest that impairment in the removal of information from working memory might be a key mechanism underlying the inability of OCD patients to rid themselves of their obsessions.

Increasing evidence suggests slow-wave sleep (SWS) dysfunction in Parkinson’s disease (PD) is associated with faster disease progression, cognitive impairment, and excessive daytime sleepiness. Beta oscillations (8–35 Hz) in the basal ganglia thalamocortical (BGTC) network are thought to play a role in the development of cardinal motor signs of PD. The role cortical beta oscillations play in SWS dysfunction in the early stage of parkinsonism is not understood, however. To address this question, we used a within-subject design in a nonhuman primate (NHP) model of PD to record local field potentials from the primary motor cortex (MC) during sleep across normal and mild parkinsonian states. The MC is a critical node in the BGTC network, exhibits pathological oscillations with depletion in dopamine tone, and displays high amplitude slow oscillations during SWS. The MC is therefore an appropriate recording site to understand the neurophysiology of SWS dysfunction in parkinsonism. We observed a reduction in SWS quantity (p = 0.027) in the parkinsonian state compared to normal. The cortical delta (0.5–3 Hz) power was reduced (p = 0.038) whereas beta (8–35 Hz) power was elevated (p = 0.001) during SWS in the parkinsonian state compared to normal. Furthermore, SWS quantity positively correlated with delta power (r = 0.43, p = 0.037) and negatively correlated with beta power (r = −0.65, p

IntroductionProtocols for noninvasive brain stimulation (NIBS) are generally categorized as “excitatory” or “inhibitory” based on their ability to produce short-term modulation of motor-evoked potentials (MEPs) in peripheral muscles, when applied to motor cortex. Anodal and cathodal stimulation are widely considered excitatory and inhibitory, respectively, on this basis. However, it is poorly understood whether such polarity-dependent changes apply for neural signals generated during task performance, at rest, or in response to sensory stimulation.MethodsTo characterize such changes, we measured spontaneous and movement-related neural activity with magnetoencephalography (MEG) before and after high-definition transcranial direct-current stimulation (HD-TDCS) of the left motor cortex (M1), while participants performed simple finger movements with the left and right hands.ResultsAnodal HD-TDCS (excitatory) decreased the movement-related cortical fields (MRCF) localized to left M1 during contralateral right finger movements while cathodal HD-TDCS (inhibitory), increased them. In contrast, oscillatory signatures of voluntary motor output were not differentially affected by the two stimulation protocols, and tended to decrease in magnitude over the course of the experiment regardless. Spontaneous resting state oscillations were not affected either.DiscussionMRCFs are thought to reflect reafferent proprioceptive input to motor cortex following movements. Thus, these results suggest that processing of incoming sensory information may be affected by TDCS in a polarity-dependent manner that is opposite that seen for MEPs—increases in cortical excitability as defined by MEPs may correspond to reduced responses to afferent input, and vice-versa.

Understanding encoded languages, such as written script or Morse code, requires nonlexical and lexical processing components that act in a parallel and interactive fashion. Decoding written script—as for example in reading—is typically very fast, making the investigation of the lexical and nonlexical components and their underlying neural mechanisms challenging. In the current study, we aimed to accomplish this problem by using Morse code as a model for language decoding. The decoding of Morse code is slower and thus allows a better and more fine‐grained investigation of the lexical and nonlexical components of language decoding. In the current study, we investigated the impact of various components of nonlexical decoding of Morse code using magnetoencephalography. For this purpose, we reconstructed the time–frequency responses below 40 Hz in brain regions significantly involved in Morse code decoding and word comprehension that were identified in a previous study. Event‐related reduction in beta‐ and alpha‐band power were found in left inferior frontal cortex and angular gyrus, respectively, while event‐related theta‐band power increase was found at frontal midline. These induced oscillations reflect working‐memory encoding, long‐term memory retrieval as well as demanding cognitive control, respectively. In sum, by using Morse code and MEG, we were able to identify a cortical network underlying language decoding in a time‐ and frequency‐resolved manner. [ABSTRACT FROM AUTHOR]

Excessive neural synchronization of neural populations in the beta (β) frequency range (12–35 Hz) is intimately related to the symptoms of hypokinesia in Parkinson's disease (PD). Studies have shown that delayed feedback stimulation strategies can interrupt excessive neural synchronization and effectively alleviate symptoms associated with PD dyskinesia. Work on optimizing delayed feedback algorithms continues to progress, yet it remains challenging to further improve the inhibitory effect with reduced energy expenditure. Therefore, we first established a neural mass model of the cortex-basal ganglia-thalamus-pedunculopontine nucleus (CBGTh-PPN) closed-loop system, which can reflect the internal properties of cortical and basal ganglia neurons and their intrinsic connections with thalamic and pedunculopontine nucleus neurons. Second, the inhibitory effects of three delayed feedback schemes based on the external globus pallidum (GPe) on β oscillations were investigated separately and compared with those based on the subthalamic nucleus (STN) only. Our results show that all four delayed feedback schemes achieve effective suppression of pathological β oscillations when using the linear delayed feedback algorithm. The comparison revealed that the three GPe-based delayed feedback stimulation strategies were able to have a greater range of oscillation suppression with reduced energy consumption, thus improving control performance effectively, suggesting that they may be more effective for the relief of Parkinson's motor symptoms in practical applications. [ABSTRACT FROM AUTHOR]

Background: Neural motor control rests on the dynamic interaction of cortical and subcortical regions, which is reflected in the modulation of oscillatory activity and connectivity in multiple frequency bands. Motor control is thought to be compromised in developmental stuttering, particularly involving circuits in the left hemisphere that support speech, movement initiation, and timing control. However, to date, evidence comes from adult studies, with a limited understanding of motor processes in childhood, closer to the onset of stuttering. Methods: We investigated the neural control of movement initiation in children who stutter and children who do not stutter by evaluating transient changes in EEG oscillatory activity (power, phase locking to button press) and connectivity (phase synchronization) during a simple button press motor task. We compared temporal changes in these oscillatory dynamics between the left and right hemispheres and between children who stutter and children who do not stutter, using mixed-model analysis of variance. Results: We found reduced modulation of left hemisphere oscillatory power, phase locking to button press and phase connectivity in children who stutter compared to children who do not stutter, consistent with previous findings of dysfunction within the left sensorimotor circuits. Interhemispheric connectivity was weaker at lower frequencies (delta, theta) and stronger in the beta band in children who stutter than in children who do not stutter. Conclusions: Taken together, these findings indicate weaker engagement of the contralateral left motor network in children who stutter even during low-demand non-speech tasks, and suggest that the right hemisphere might be recruited to support sensorimotor processing in childhood stuttering. Differences in oscillatory dynamics occurred despite comparable task performance between groups, indicating that an altered balance of cortical activity might be a core aspect of stuttering, observable during normal motor behavior. [ABSTRACT FROM AUTHOR]

Studies have shown that beta band activity is not tonically elevated but comprises exaggerated phasic bursts of varying durations and magnitudes, for Parkinson's disease (PD) patients. Current methods for detecting beta bursts target a single frequency peak in beta band, potentially ignoring bursts in the wider beta band. In this study, we propose a new robust framework for beta burst identification across wide frequency ranges. Chronic local field potential at-rest recordings were obtained from seven PD patients implanted with Medtronic SenSight™ deep brain stimulation (DBS) electrodes. The proposed method uses wavelet decomposition to compute the time–frequency spectrum and identifies bursts spanning multiple frequency bins by thresholding, offering an additional burst measure, ∆f, that captures the width of a burst in the frequency domain. Analysis included calculating burst duration, magnitude, and ∆f and evaluating the distribution and likelihood of bursts between the low beta (13–20 Hz) and high beta (21–35 Hz). Finally, the results of the analysis were correlated to motor impairment (MDS-UPDRS III) med off scores. We found that low beta bursts with longer durations and larger width in the frequency domain (∆f) were positively correlated, while high beta bursts with longer durations and larger ∆f were negatively correlated with motor impairment. The proposed method, finding clear differences between bursting behavior in high and low beta bands, has clearly demonstrated the importance of considering wide frequency bands for beta burst behavior with implications for closed-loop DBS paradigms. [ABSTRACT FROM AUTHOR]

Neural oscillations in alpha (8–12 Hz) and beta (13–30 Hz) frequency bands are thought to reflect feedback/reentrant loops and large-scale cortical interactions. In the last decades a main effort has been made in linking perception with alpha-band oscillations, with converging evidence showing that alpha oscillations have a key role in the temporal and featural binding of visual input, configuring the alpha rhythm a key determinant of conscious visual experience. Less attention has been historically dedicated to link beta oscillations and visual processing. Nonetheless, increasing studies report that task conditions that require to segregate/integrate stimuli in space, to disentangle local/global shapes, to spatially reorganize visual inputs, and to achieve motion perception or form-motion integration, rely on the activity of beta oscillations, with a main hub in parietal areas. In the present review, we summarize the evidence linking oscillations within the beta band and visual perception. We propose that beta oscillations represent a neural code that supports the functionality of the magnocellular-dorsal (M-D) visual pathway, serving as a fast primary neural code to exert top-down influences on the slower parvocellular-ventral visual pathway activity. Such M-D-related beta activity is proposed to act mainly pre-consciously, providing the spatial coordinates of vision and guiding the conscious extraction of objects identity that are achieved with slower alpha rhythms in ventral areas. Finally, within this new theoretical framework, we discuss the potential role of M-D-related beta oscillations in visuo-spatial attention, oculo-motor behavior and reading (dis)abilities.

The medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) are involved in the regulation of defensive behavior under threat, but their engagement in flexible behavior shifts remains unclear. Here, we report the oscillatory activities of mPFC-BLA circuit in reaction to a naturalistic threat, created by a predatory robot in mice. Specifically, we found dynamic frequency tuning among two different theta rhythms (~5 or ~10 Hz) was accompanied by agile changes of two different defensive behaviors (freeze-or-flight). By analyzing flight trajectories, we also found that high beta (~30 Hz) is engaged in the top-down process for goal-directed flights and accompanied by a reduction in fast gamma (60 to 120 Hz, peak near 70 Hz). The elevated beta nested the fast gamma activity by its phase more strongly. Our results suggest that the mPFC-BLA circuit has a potential role in oscillatory gear shifting allowing flexible information routing for behavior switches. [ABSTRACT FROM AUTHOR]

To form a perceptual decision, the brain must acquire samples of evidence from the environment and incorporate them in computations that mediate choice behavior. While much is known about the neural circuits that process sensory information and those that form decisions, less is known about the mechanisms that establish the functional linkage between them. We trained monkeys of both sexes to make difficult decisions about the net direction of visual motion under conditions that required trial-by-trial control of functional connectivity. In one condition, the motion appeared at different locations on different trials. In the other, two motion patches appeared, only one of which was informative. Neurons in the parietal cortex produced brief oscillations in their firing rate at the time routing was established: upon onset of the motion display when its location was unpredictable across trials, and upon onset of an attention cue that indicated in which of two locations an informative patch of dots would appear. The oscillation was absent when the stimulus location was fixed across trials. We interpret the oscillation as a manifestation of the mechanism that establishes the source and destination of flexibly routed information, but not the transmission of the information per se. [ABSTRACT FROM AUTHOR]

Background: Obsessive-compulsive disorder (OCD) is related to working memory impairment. Since patients with OCD have difficulty controlling their obsessive thoughts, removal of irrelevant information might be important in the pathophysiology of OCD. However, little is known about brain activity during the removal of information from working memory in patients with OCD. Our goal was to explore potential deficits in inhibitory function related to working memory processes in patients with OCD. Methods: Sixteen OCD patients and 20 healthy controls (HCs) were recruited. We compared in prefrontal alpha and beta band activity derived from magnetoencephalography (MEG) between patients with OCD and HCs during multiple phases of information processing associated with working memory, especially in post-trial period of the visuospatial working memory task (the delayed matching-to‐sample task), which is presumed to be related to the information removal process of working memory. Results: Prefrontal post-trial beta power change (presumed to occur at high levels during the post-trial period) exhibited significant reductions in patients with OCD compared to HCs. In addition, the post-trial beta power change was negatively correlated with Obsessive-Compulsive Inventory–Revised total scores in patients with OCD. Conclusions: These findings suggest that impairment in the removal of information from working memory might be a key mechanism underlying the inability of OCD patients to rid themselves of their obsessions. [ABSTRACT FROM AUTHOR]

• We investigate effects of different theta/beta neurofeedback (NF) protocols on mechanisms underlying response inhibition in ADHD. • Different NF protocols lead to response inhibition improvements via different neurophysiological mechanisms. • The interactive relationship of theta and beta band activity extends the understanding of oscillatory dynamics in the brain. In attention deficit/hyperactivity disorder (ADHD), impaired response inhibition is frequently observed. A promising non-pharmacological treatment is electroencephalography (EEG)-neurofeedback (NF) training. However, the widely used theta-down/beta-up regulation (↓θ↑β) NF protocol may not be optimal for targeting these deficits. We examined how neurofeedback protocols training the upregulation of theta and/or beta power affect inhibitory control in children and adolescents with ADHD. 64 patients with ADHD took part in the three NF trainings. Aside from parent-reported ADHD symptoms and behavioural performance data, neurophysiological parameters collected via a Go/Nogo task and corrected to account for intraindividual variability were compared in a pre-post design and to an ADHD (n = 20) as well as a typically developing control group (n = 24). The examined NF protocols resulted in similar improvements in response inhibition with the neurophysiological mechanisms differing substantially. The upregulation of theta led to a specific Nogo-P3 increase, while training beta upregulation as well as the combined protocol resulted in less specific effects. This study shows distinct effects of different theta/beta-neurofeedback protocols on the neural mechanisms underlying improvements in response inhibition in patients with ADHD. These effects shed further light on the oscillatory dynamics underlying cognitive control in ADHD and how these may be targeted in neurofeedback treatments. [ABSTRACT FROM AUTHOR]

Cognitive processing relies on the functional refinement of the limbic circuitry during the first two weeks of life. During this developmental period, when the auditory, somatosensory and visual systems are still largely immature, the sense of olfaction acts as 'door to the world', providing an important source of environmental inputs. However, it is unknown whether early olfactory processing shapes the activity in the limbic circuitry during neonatal development. Here, we address this question by combining simultaneous in vivo recordings from the olfactory bulb (OB), lateral entorhinal cortex (LEC), hippocampus (HP) and prefrontal cortex (PFC) with olfactory stimulation as well as opto‐ and chemogenetic manipulations of mitral/tufted cells in the OB of non‐anaesthetized neonatal mice of both sexes. We show that the neonatal OB synchronizes the limbic circuity in the beta frequency range. Moreover, it drives neuronal and network activity in LEC, as well as subsequently, HP and PFC via long‐range projections from mitral cells to HP‐projecting LEC neurons. Thus, OB activity shapes the communication within limbic circuits during neonatal development. Key points: During early postnatal development, oscillatory activity in the olfactory bulb synchronizes the limbic circuit.Olfactory stimulation boosts firing and beta synchronization along the olfactory bulb–lateral entorhinal cortex–hippocampal–prefrontal pathway.Mitral cells drive neuronal and network activity in the lateral entorhinal cortex (LEC), as well as subsequently, the hippocampus (HP) and the prefrontal cortex (PFC) via long‐range projections from mitral cells to HP‐projecting LEC neurons.Inhibition of vesicle release on LEC targeting mitral cell axons reveals direct involvement of LEC in the olfactory bulb‐driven oscillatory entrainment of the limbic circuitry. [ABSTRACT FROM AUTHOR]

BackgroundBeta-based adaptive Deep Brain Stimulation (aDBS) is effective in Parkinson's disease (PD), when assessed in the immediate post-implantation phase. However, the potential benefits of aDBS in patients with electrodes chronically implanted, in whom changes due to the microlesion effect have disappeared, are yet to be assessed.MethodsTo determine the acute effectiveness and side-effect profile of aDBS in PD compared to conventional continuous DBS (cDBS) and no stimulation (NoStim), years after DBS implantation, 13 PD patients undergoing battery replacement were pseudo-randomised in a crossover fashion, into three conditions (NoStim, aDBS or cDBS), with a 2-min interval between them. Patient videos were blindly evaluated using a short version of the Unified Parkinson's Disease Rating Scale (subUPDRS), and the Speech Intelligibility Test (SIT).ResultsMean disease duration was 16 years, and the mean time since DBS-implantation was 6.9 years. subUPDRS scores (11 patients tested) were significantly lower both in aDBS (p=

A pillar of systems neuroscience has been the study of neural oscillations. Research into these oscillations spans brain areas, species, and disciplines, giving us common ground for discussing typically disparate fields of neuroscience. In this review, we aim to strengthen the dialog between sensory systems research and learning and memory systems research by examining a 15-40 Hz oscillation known as the beta rhythm. Starting with foundational observations based largely in olfactory systems neuroscience, we review evidence suggesting beta-based activity may extend across sensory systems generally, as well as into the hippocampus and areas well known for coordinating decisions and memoryguided behaviors. After evaluating this work, we propose a framework wherein the hippocampal beta oscillation and its diverse coupling with other brain areas can support both sensory learning and memory-guided decision-making. Using this framework, we also propose circuitries that may support these processes, and experiments to test our hypothesis. [ABSTRACT FROM AUTHOR]

Background: Pallidal deep brain stimulation (DBS) effectively alleviates symptoms in dystonia patients, but may induce movement slowness as a side‐effect. In Parkinson's disease, hypokinetic symptoms have been associated with increased beta oscillations (13–30 Hz). We hypothesize that this pattern is symptom‐specific, thus accompanying DBS‐induced slowness in dystonia. Methods: In 6 dystonia patients, pallidal rest recordings with a sensing‐enabled DBS device were performed and tapping speed was assessed using marker‐less pose estimation over 5 time points following cessation of DBS. Results: After cessation of pallidal stimulation, movement speed increased over time (P < 0.01). A linear mixed‐effects model revealed that pallidal beta activity explained 77% of the variance in movement speed across patients (P = 0.01). Conclusions: The association between beta oscillations and slowness across disease entities provides further evidence for symptom‐specific oscillatory patterns in the motor circuit. Our findings might help DBS therapy improvements, as DBS‐devices able to adapt to beta oscillations are already commercially available. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Both passive tactile stimulation and motor actions result in dynamic changes in beta band (15-30 Hz Hz) oscillations over somatosensory cortex. Similar to alpha band (8-12 Hz) power decrease in the visual system, beta band power also decreases following stimulation of the somatosensory system. This relative suppression of α and β oscillations is generally interpreted as an increase in cortical excitability. Here, next to traditional single-pulse stimuli, we used a random intensity continuous right index finger tactile stimulation (white noise), which enabled us to uncover an impulse response function of the somatosensory system. Contrary to previous findings, we demonstrate a burst-like initial increase rather than decrease of beta activity following white noise stimulation (human participants, N = 18, 8 female). These β bursts, on average, lasted for 3 cycles, and their frequency was correlated with resonant frequency of somatosensory cortex, as measured by a multifrequency steady-state somatosensory evoked potential paradigm. Furthermore, beta band bursts shared spectro-temporal characteristics with evoked and resting-state β oscillations. Together, our findings not only reveal a novel oscillatory signature of somatosensory processing that mimics the previously reported visual impulse response functions, but also point to a common oscillatory generator underlying spontaneous β bursts in the absence of tactile stimulation and phase-locked β bursts following stimulation, the frequency of which is determined by the resonance properties of the somatosensory system. [ABSTRACT FROM AUTHOR]

Simple Summary: Memory is a fundamental cognitive function we need for everyday life. Since we process so much information each day, it is believed that our memory system selects only relevant information to encode in order to avoid overload. In this work, we study the molecular mechanism supporting this selective memory encoding. It is believed that memory encoding occurs mainly when we encounter a new unexpected condition: a novel context. In a novel context, the hippocampus, which is crucial for memory function, intensifies a specific rhythmic activity called beta oscillations. While these beta oscillations are believed to support memory encoding, the molecular mechanisms underlying this increase in beta oscillations are not yet understood. We demonstrate that a specific type of membrane ionic channel called transient receptor potential canonical 4 (TRPC4) supports the modulation of beta oscillation in the hippocampus, indicating that TRPC4 channels play a role in novelty-related memory encoding. Hippocampal local field potentials (LFP) are highly related to behavior and memory functions. It has been shown that beta band LFP oscillations are correlated with contextual novelty and mnemonic performance. Evidence suggests that changes in neuromodulators, such as acetylcholine and dopamine, during exploration in a novel environment underlie changes in LFP. However, potential downstream mechanisms through which neuromodulators may alter the beta band oscillation in vivo remain to be fully understood. In this paper, we study the role of the membrane cationic channel TRPC4, which is modulated by various neuromodulators through G-protein-coupled receptors, by combining shRNA-mediated TRPC4 knockdown (KD) with LFP measurements in the CA1 region of the hippocampus in behaving mice. We demonstrate that the increased beta oscillation power seen in the control group mice in a novel environment is absent in the TRPC4 KD group. A similar loss of modulation was also seen in the low-gamma band oscillations in the TRPC4 KD group. These results demonstrate that TRPC4 channels are involved in the novelty-induced modulation of beta and low-gamma oscillations in the CA1 region. [ABSTRACT FROM AUTHOR]

The brain processes short-interval timing but also allows people to project themselves into the past and the future (i.e., mental time travel [MTT]). Beta oscillations index seconds-long-interval timing (i.e., higher beta power is associated with longer durations). Here, we used parietal transcranial alternating current stimulation (tACS) to investigate whether MTT is also supported by parietal beta oscillations and to test the link between MTT and short intervals. Thirty adults performed a novel MTT task while receiving beta and alpha tACS, in addition to no stimulation. Beta tACS corresponded to a temporal underestimation in past but not in future MTT. Furthermore, participants who overestimated seconds-long intervals also overestimated temporal distances in the past-projection MTT condition and showed a stronger effect of beta tACS. These data provide a unique window into temporal perception, showing how beta oscillations may be a common mechanism for short intervals and MTT. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder characterized by midbrain dopaminergic neuronal loss and subsequent physical impairments. Levodopa manages symptoms best, while deep brain stimulation (DBS) is effective for advanced PD patients; however, side effects occur with the diminishing therapeutic window. Recently, Lactiplantibacillus plantarum PS128 (PS128) was found to elevate dopamine levels in rodent brains, suggesting its potential to prevent PD. Here, the therapeutic efficacy of PS128 was examined in the 6-hydroxydopamine rat PD model. Suppression of the power spectral density of beta oscillations (beta PSD) in the primary motor cortex (M1) was recorded as the indicator of disease progression. We found that 6 weeks of daily PS128 supplementation suppressed M1 beta PSD as well as did levodopa and DBS. Long-term normalization of M1 beta PSD was found in PS128-fed rats, whereas levodopa and DBS showed only temporal effects. PS128 + levodopa and PS128 + DBS exhibited better therapeutic effects than did levodopa + DBS or either alone. Significantly improved motor functions in PS128-fed rats were correlated with normalization of M1 beta PSD. Brain tissue analyses further demonstrated the role of PS128 in dopaminergic neuroprotection and the enhanced availability of neurotransmitters. These findings suggest that psychobiotic PS128 might be used alongside conventional therapies to treat PD patients. [ABSTRACT FROM AUTHOR]

The external globus pallidus (GPe), a subcortical nucleus located in the indirect pathway of the basal ganglia, is widely considered to have tight associations with abnormal beta oscillations (13–30 Hz) observed in Parkinson's disease (PD). Despite that many mechanisms have been put forward to explain the emergence of these beta oscillations, however, it is still unclear the functional contributions of the GPe, especially, whether the GPe itself can generate beta oscillations. To investigate the role played by the GPe in producing beta oscillations, we employ a well described firing rate model of the GPe neural population. Through extensive simulations, we find that the transmission delay within the GPe–GPe pathway contributes significantly to inducing beta oscillations, and the impacts of the time constant and connection strength of the GPe–GPe pathway on generating beta oscillations are non-negligible. Moreover, the GPe firing patterns can be significantly modulated by the time constant and connection strength of the GPe–GPe pathway, as well as the transmission delay within the GPe–GPe pathway. Interestingly, both increasing and decreasing the transmission delay can push the GPe firing pattern from beta oscillations to other firing patterns, including oscillation and non-oscillation firing patterns. These findings suggest that if the transmission delays within the GPe are at least 9.8 ms, beta oscillations can be produced originally in the GPe neural population, which also may be the origin of PD-related beta oscillations and should be regarded as a promising target for treatments for PD. [ABSTRACT FROM AUTHOR]

IntroductionAdaptive deep brain stimulation (aDBS), based on the detection of increased beta oscillations in the subthalamic nucleus (STN), has been assessed in patients with Parkinson's disease (PD) during the immediate postoperative setting. In these studies, aDBS was shown to be at least as effective as conventional DBS (cDBS), while stimulation time and side effects were reduced. However, the effect of aDBS on motor symptoms and stimulation-induced side effects during the chronically implanted phase (after the stun effect of DBS placement has disappeared) has not yet been determined.Methods and analysisThis protocol describes a single-centre clinical study in which aDBS will be tested in 12 patients with PD undergoing battery replacement, with electrodes implanted in the STN, and as a proof of concept in the internal globus pallidus. Patients included will be allocated in a pseudo-randomised fashion to a three-condition (no stimulation/cDBS/ aDBS), cross-over design. A battery of tests will be conducted and recorded during each condition, which aim to measure the severity of motor symptoms and side effects. These tests include a tablet-based tapping test, a subscale of the Movement Disorder Society-unified Parkinson's disease rating scale (subMDS-UPDRS), the Speech Intelligibility Test (SIT) and a tablet-based version of the Stroop test. SubMDS-UPDRS and SIT recordings will be blindly assessed by independent raters. Data will be analysed using a linear mixed-effects model.Ethics and disseminationThis protocol was approved by the Ethical Committee of the University Medical Centre Groningen, where the study will be carried out. Data management and compliance to research policies and standards of our centre, including data privacy, storage and veracity, will be controlled by an independent monitor. All the scientific findings derived from this protocol are aimed to be made public through publication of articles in international journals.Trial registration numberNTR 5456; Pre-results.

Synchronized oscillations within and between brain areas facilitate normal processing, but are often amplified in disease. A prominent example is the abnormally sustained beta-frequency (∼20 Hz) oscillations recorded from the cortex and subthalamic nucleus of Parkinson's disease patients. Computational modeling suggests that the amplitude of such oscillations could be modulated by applying stimulation at a specific phase. Such a strategy would allow selective targeting of the oscillation, with relatively little effect on other activity parameters. Here, activity was recorded from 10 awake, parkinsonian patients (6 male, 4 female human subjects) undergoing functional neurosurgery. We demonstrate that stimulation arriving on a particular patient-specific phase of the beta oscillation over consecutive cycles could suppress the amplitude of this pathophysiological activity by up to 40%, while amplification effects were relatively weak. Suppressive effects were accompanied by a reduction in the rhythmic output of subthalamic nucleus (STN) neurons and synchronization with the mesial cortex. While stimulation could alter the spiking pattern of STN neurons, there was no net effect on firing rate, suggesting that reduced beta synchrony was a result of alterations to the relative timing of spiking activity, rather than an overall change in excitability. Together, these results identify a novel intrinsic property of cortico-basal ganglia synchrony that suggests the phase of ongoing neural oscillations could be a viable and effective control signal for the treatment of Parkinson's disease. This work has potential implications for other brain diseases with exaggerated neuronal synchronization and for probing the function of rhythmic activity in the healthy brain.SIGNIFICANCE STATEMENT In Parkinson's disease (PD), movement impairment is correlated with exaggerated beta frequency oscillations in the cerebral cortex and subthalamic nucleus (STN). Using a novel method of stimulation in PD patients undergoing neurosurgery, we demonstrate that STN beta oscillations can be suppressed when consecutive electrical pulses arrive at a specific phase of the oscillation. This effect is likely because of interrupting the timing of neuronal activity rather than excitability, as stimulation altered the firing pattern of STN spiking without changing overall rate. These findings show the potential of oscillation phase as an input for "closed-loop" stimulation, which could provide a valuable neuromodulation strategy for the treatment of brain disorders and for elucidating the role of neuronal oscillations in the healthy brain.

Background: Neural oscillations in the primary motor cortex (M1) shape corticospinal excitability. Power and phase of ongoing mu (8–13 Hz) and beta (14–30 Hz) activity may mediate motor cortical output. However, the functional dynamics of both mu and beta phase and power relationships and their interaction, are largely unknown. Objective: Here, we employ recently developed real-time targeting of the mu and beta rhythm, to apply phase-specific brain stimulation and probe motor corticospinal excitability non-invasively. For this, we used instantaneous read-out and analysis of ongoing oscillations, targeting four different phases (0°, 90°, 180°, and 270°) of mu and beta rhythms with suprathreshold single-pulse transcranial magnetic stimulation (TMS) to M1. Ensuing motor evoked potentials (MEPs) in the right first dorsal interossei muscle were recorded. Twenty healthy adults took part in this double-blind randomized crossover study. Results: Mixed model regression analyses showed significant phase-dependent modulation of corticospinal output by both mu and beta rhythm. Strikingly, these modulations exhibit a double dissociation. MEPs are larger at the mu trough and rising phase and smaller at the peak and falling phase. For the beta rhythm we found the opposite behavior. Also, mu power, but not beta power, was positively correlated with corticospinal output. Power and phase effects did not interact for either rhythm, suggesting independence between these aspects of oscillations. Conclusion: Our results provide insights into real-time motor cortical oscillation dynamics, which offers the opportunity to improve the effectiveness of TMS by specifically targeting different frequency bands.

Patients with Parkinson's disease (PD) show impaired short-term potentiation (STP) mechanisms in the primary motor cortex (M1). However, the role played by this neurophysiological abnormality in bradykinesia pathophysiology is unknown. In this study, we used a multimodal neuromodulation approach to test whether defective STP contributes to bradykinesia. We evaluated STP by measuring motor-evoked potential facilitation during 5 Hz-repetitive transcranial magnetic stimulation (rTMS) and assessed repetitive finger tapping movements through kinematic techniques. Also, we used transcranial alternating current stimulation (tACS) to drive M1 oscillations and experimentally modulate bradykinesia. STP was assessed during tACS delivered at beta (β) and gamma (γ) frequency, and during sham-tACS. Data were compared to those recorded in a group of healthy subjects. In PD, we found that STP was impaired during sham- and γ-tACS, while it was restored during β-tACS. Importantly, the degree of STP impairment was associated with the severity of movement slowness and amplitude reduction. Moreover, β-tACS-related improvements in STP were linked to changes in movement slowness and intracortical GABA-A-ergic inhibition during stimulation, as assessed by short-interval intracortical inhibition (SICI). Patients with prominent STP amelioration had greater SICI reduction (cortical disinhibition) and less slowness worsening during β-tACS. Dopaminergic medications did not modify β-tACS effects. These data demonstrate that abnormal STP processes are involved in bradykinesia pathophysiology and return to normal levels when β oscillations increase. STP changes are likely mediated by modifications in GABA-A-ergic intracortical circuits and may represent a compensatory mechanism against β-induced bradykinesia in PD.