Bursting with Potential: How Sensorimotor Beta Bursts Develop from Infancy to Adulthood.

Beta activity is thought to play a critical role in sensorimotor processes. However, little is known about how activity in this frequency band develops. Here, we investigated the developmental trajectory of sensorimotor beta activity from infancy to adulthood. We recorded EEG from 9-month-old, 12-month-old, and adult humans (male and female) while they observed and executed grasping movements. We analyzed "beta burst" activity using a novel method that combines time-frequency decomposition and principal component analysis. We then examined the changes in burst rate and waveform motifs along the selected principal components. Our results reveal systematic changes in beta activity during action execution across development. We found a decrease in beta burst rate during movement execution in all age groups, with the greatest decrease observed in adults. Additionally, we identified three principal components that defined waveform motifs that systematically changed throughout the trial. We found that bursts with waveform shapes closer to the median waveform were not rate-modulated, whereas those with waveform shapes further from the median were differentially rate-modulated. Interestingly, the decrease in the rate of certain burst motifs occurred earlier during movement and was more lateralized in adults than in infants, suggesting that the rate modulation of specific types of beta bursts becomes increasingly refined with age.SIGNIFICANCE STATEMENT We demonstrate that, like in adults, sensorimotor beta activity in infants during reaching and grasping movements occurs in bursts, not oscillations like thought traditionally. Furthermore, different beta waveform shapes were differentially modulated with age, including more lateralization in adults. Aberrant beta activity characterizes various developmental disorders and motor difficulties linked to early brain injury, so looking at burst waveform shape could provide more sensitivity for early identification and treatment of affected individuals before any behavioral symptoms emerge. More generally, comparison of beta burst activity in typical versus atypical motor development will also be instrumental in teasing apart the mechanistic functional roles of different types of beta bursts.

Volitional control of beta activities in Parkinson's disease patients.

Patients diagnosed with Parkinson's disease (PD) have difficulty initiating and executing movements due to an acquired imbalance of the basal ganglia thalamocortical circuit secondary to loss of dopaminergic input into the striatum. The unbalanced circuit is hyper-synchronized, presenting as larger and longer bursts of beta-band (13-30 Hz) oscillations in the subthalamic nucleus (STN). As a first step toward a novel PD therapy that aims to improve symptoms through beta desynchronization, we sought to determine if individuals with PD could acquire volitional control of STN beta power in a neurofeedback task. We found a significant difference in STN beta power between task conditions, and relevant brain signal features could be detected and decoded in real time. This demonstration of volitional control of STN beta motivates development of a neurofeedback therapy to modulate PD symptom severity.

Spatiotemporal organisation of human sensorimotor beta burst activity.

Beta oscillations in human sensorimotor cortex are hallmark signatures of healthy and pathological movement. In single trials, beta oscillations include bursts of intermittent, transient periods of high-power activity. These burst events have been linked to a range of sensory and motor processes, but their precise spatial, spectral, and temporal structure remains unclear. Specifically, a role for beta burst activity in information coding and communication suggests spatiotemporal patterns, or travelling wave activity, along specific anatomical gradients. We here show in human magnetoencephalography recordings that burst activity in sensorimotor cortex occurs in planar spatiotemporal wave-like patterns that dominate along two axes either parallel or perpendicular to the central sulcus. Moreover, we find that the two propagation directions are characterised by distinct anatomical and physiological features. Finally, our results suggest that sensorimotor beta bursts occurring before and after a movement can be distinguished by their anatomical, spectral, and spatiotemporal characteristics, indicating distinct functional roles.

Long-Term Recording of Subthalamic Aperiodic Activities and Beta Bursts in Parkinson's Disease.

BACKGROUND: Local field potentials (LFPs) represent the summation of periodic (oscillations) and aperiodic (fractal) signals. Although previous studies showed changes in beta band oscillations and burst characteristics of the subthalamic nucleus (STN) in Parkinson's disease (PD), how aperiodic activity in the STN is related to PD pathophysiology is unknown. OBJECTIVES: The study aimed to characterize the long-term effects of STN-deep brain stimulation (DBS) and dopaminergic medications on aperiodic activities and beta bursts. METHODS: A total of 10 patients with PD participated in this longitudinal study. Simultaneous bilateral STN-LFP recordings were conducted in six separate visits during a period of 18 months using the Activa PC + S device in the off and on dopaminergic medication states. We used irregular-resampling auto-spectral analysis to separate oscillations and aperiodic components (exponent and offset) in the power spectrum of STN-LFP signals in beta band. RESULTS: Our results revealed a systematic increase in both the exponent and the offset of the aperiodic spectrum over 18 months following the DBS implantation, independent of the dopaminergic medication state of patients with PD. In contrast, beta burst durations and amplitudes were stable over time and were suppressed by dopaminergic medications. CONCLUSIONS: These findings indicate that oscillations and aperiodic activities reflect at least partially distinct yet complementary neural mechanisms, which should be considered in the design of robust biomarkers to optimize adaptive DBS. Given the link between increased gamma-aminobutyric acidergic (GABAergic) transmission and higher aperiodic activity, our findings suggest that long-term STN-DBS may relate to increased inhibition in the basal ganglia. © 2022 International Parkinson and Movement Disorder Society.

Cortical beta burst dynamics are altered in Parkinson's disease but normalized by deep brain stimulation.

Exaggerated subthalamic beta oscillatory activity and increased beta range cortico-subthalamic synchrony have crystallized as the electrophysiological hallmarks of Parkinson's disease. Beta oscillatory activity is not tonic but occurs in 'bursts' of transient amplitude increases. In Parkinson's disease, the characteristics of these bursts are altered especially in the basal ganglia. However, beta oscillatory dynamics at the cortical level and how they compare with healthy brain activity is less well studied. We used magnetoencephalography (MEG) to study sensorimotor cortical beta bursting and its modulation by subthalamic deep brain stimulation in Parkinson's disease patients and age-matched healthy controls. We show that the changes in beta bursting amplitude and duration typical of Parkinson's disease can also be observed in the sensorimotor cortex, and that they are modulated by chronic subthalamic deep brain stimulation, which, in turn, is reflected in improved motor function at the behavioural level. In addition to the changes in individual beta bursts, their timing relative to each other was altered in patients compared to controls: bursts were more clustered in untreated Parkinson's disease, occurring in 'bursts of bursts', and re-burst probability was higher for longer compared to shorter bursts. During active deep brain stimulation, the beta bursting in patients resembled healthy controls' data. In summary, both individual bursts' characteristics and burst patterning are affected in Parkinson's disease, and subthalamic deep brain stimulation normalizes some of these changes to resemble healthy controls' beta bursting activity, suggesting a non-invasive biomarker for patient and treatment follow-up.

Neuronal biomarkers of Parkinson's disease are present in healthy aging.

The prevalence of Parkinson's disease (PD) increases with aging and both processes share similar cellular mechanisms and alterations in the dopaminergic system. Yet it remains to be investigated whether aging can also demonstrate electrophysiological neuronal signatures typically associated with PD. Previous work has shown that phase-amplitude coupling (PAC) between the phase of beta oscillations and the amplitude of gamma oscillations as well as beta bursts features can serve as electrophysiological biomarkers for PD. Here we hypothesize that these metrics are also present in apparently healthy elderly subjects. Using resting state multichannel EEG measurements, we show that PAC between beta oscillation and broadband gamma activity (50-150 Hz) is elevated in a group of elderly (59-77 years) compared to young volunteers (20-35 years) without PD. Importantly, the increase of PAC is statistically significant even after ruling out confounds relating to changes in spectral power and non-sinusoidal shape of beta oscillation. Moreover, a trend for a higher percentage of longer beta bursts (> 0.2 s) along with the increase in their incidence rate is also observed for elderly subjects. Using inverse modeling, we further show that elevated PAC and longer beta bursts are most pronounced in the sensorimotor areas. Moreover, we show that PAC and longer beta bursts might reflect distinct mechanisms, since their spatial patterns only partially overlap and the correlation between them is weak. Taken together, our findings provide novel evidence that electrophysiological biomarkers of PD may already occur in apparently healthy elderly subjects. We hypothesize that PAC and beta bursts characteristics in aging might reflect a pre-clinical state of PD and suggest their predictive value to be tested in prospective longitudinal studies.

Spontaneous activity competes with externally evoked responses in sensory cortex.

The interaction between spontaneous and externally evoked neuronal activity is fundamental for a functional brain. Increasing evidence suggests that bursts of high-power oscillations in the 15- to 30-Hz beta-band represent activation of internally generated events and mask perception of external cues. Yet demonstration of the effect of beta-power modulation on perception in real time is missing, and little is known about the underlying mechanism. Here, we used a closed-loop stimulus-intensity adjustment system based on online burst-occupancy analyses in rats involved in a forepaw vibrotactile detection task. We found that the masking influence of burst occupancy on perception can be counterbalanced in real time by adjusting the vibration amplitude. Offline analysis of firing rates (FRs) and local field potentials across cortical layers and frequency bands confirmed that beta-power in the somatosensory cortex anticorrelated with sensory evoked responses. Mechanistically, bursts in all bands were accompanied by transient synchronization of cell assemblies, but only beta-bursts were followed by a reduction of FR. Our closed loop approach reveals that spontaneous beta-bursts reflect a dynamic state that competes with external stimuli.

A Single Case Feasibility Study of Sensorimotor Rhythm Neurofeedback in Parkinson's Disease.

Electroencephalographic activity over the sensorimotor cortex has been one of the best studied targets for neurofeedback therapy. Parkinson's disease patients display abnormal brain rhythms in the motor cortex caused by increased synchrony in the basal ganglia-cortical pathway. Few studies have examined the effects of sensorimotor-based neurofeedback therapy in humans with PD. In this pilot study, one patient, diagnosed with Parkinson's disease 10 years prior, participated in two consecutive days of EEG neurofeedback training to increase sensorimotor rhythm (SMR) power over the motor cortex. Using a visual display connected to ongoing EEG, the patient voluntarily manipulated SMR power, and he/she was awarded with points to positively reinforce successful increases over a predefined threshold. Recorded EEG data were source localized and analyzed for the occurrence of high amplitude bursts of SMR activity as well as bursts in the beta frequency band in the precentral cortex. The rate of SMR bursts increased with each subsequent training session, while the rate of beta bursts only increased on the final session. Relative power in the beta band, a marker of PD symptom severity, decreased over the motor cortex in the later session. These results provide first evidence for the feasibility of SMR neurofeedback training as a non-invasive therapy for reducing Parkinson's disease related activity and upregulating SMR in the human motor cortex.

Parkinsonism Alters Beta Burst Dynamics across the Basal Ganglia-Motor Cortical Network.

Elevated synchronized oscillatory activity in the beta band has been hypothesized to be a pathophysiological marker of Parkinson's disease (PD). Recent studies have suggested that parkinsonism is closely associated with increased amplitude and duration of beta burst activity in the subthalamic nucleus (STN). How beta burst dynamics are altered from the normal to parkinsonian state across the basal ganglia-thalamocortical (BGTC) motor network, however, remains unclear. In this study, we simultaneously recorded local field potential activity from the STN, internal segment of the globus pallidus (GPi), and primary motor cortex (M1) in three female rhesus macaques, and characterized how beta burst activity changed as the animals transitioned from normal to progressively more severe parkinsonian states. Parkinsonism was associated with an increased incidence of beta bursts with longer duration and higher amplitude in the low beta band (8-20 Hz) in both the STN and GPi, but not in M1. We observed greater concurrence of beta burst activity, however, across all recording sites (M1, STN, and GPi) in PD. The simultaneous presence of low beta burst activity across multiple nodes of the BGTC network that increased with severity of PD motor signs provides compelling evidence in support of the hypothesis that low beta synchronized oscillations play a significant role in the underlying pathophysiology of PD. Given its immersion throughout the motor circuit, we hypothesize that this elevated beta-band activity interferes with spatial-temporal processing of information flow in the BGTC network that contributes to the impairment of motor function in PD.SIGNIFICANCE STATEMENT This study fills a knowledge gap regarding the change in temporal dynamics and coupling of beta burst activity across the basal ganglia-thalamocortical (BGTC) network during the evolution from normal to progressively more severe parkinsonian states. We observed that changes in beta oscillatory activity occur throughout BGTC and that increasing severity of parkinsonism was associated with a higher incidence of longer duration, higher amplitude low beta bursts in the basal ganglia, and increased concurrence of beta bursts across the subthalamic nucleus, globus pallidus, and motor cortex. These data provide new insights into the potential role of changes in the temporal dynamics of low beta activity within the BGTC network in the pathogenesis of Parkinson's disease.

Subthalamic beta-targeted neurofeedback speeds up movement initiation but increases tremor in Parkinsonian patients.

Previous studies have explored neurofeedback training for Parkinsonian patients to suppress beta oscillations in the subthalamic nucleus (STN). However, its impacts on movements and Parkinsonian tremor are unclear. We developed a neurofeedback paradigm targeting STN beta bursts and investigated whether neurofeedback training could improve motor initiation in Parkinson's disease compared to passive observation. Our task additionally allowed us to test which endogenous changes in oscillatory STN activities are associated with trial-to-trial motor performance. Neurofeedback training reduced beta synchrony and increased gamma activity within the STN, and reduced beta band coupling between the STN and motor cortex. These changes were accompanied by reduced reaction times in subsequently cued movements. However, in Parkinsonian patients with pre-existing symptoms of tremor, successful volitional beta suppression was associated with an amplification of tremor which correlated with theta band activity in STN local field potentials, suggesting an additional cross-frequency interaction between STN beta and theta activities.

Eight cylindrical contact lead recordings in the subthalamic region localize beta oscillations source to the dorsal STN.

BACKGROUND: In Parkinson's disease (PD) patients, the subthalamic nucleus (STN) has prominent oscillatory activity in the beta band, which may be related to the motor symptoms severity. Local field potential (LFP) studies using standard four-contact deep brain stimulation (DBS) leads indicate that the source of beta activity in the STN region is the dorsolateral segment of the nucleus. However, these leads have few contacts outside of the STN, making the source localization of beta activity around the STN region uncertain. OBJECTIVE: This study aimed to investigate the electrophysiological characteristics of the STN and the surrounding area in PD to better locate the source of these oscillations and their clinical relevance. METHODS: Eight PD patients were bilaterally implanted in the STN with the eight ring-contact DBS lead (Boston Scientific Corporation). LFPs were recorded intra-operatively from each DBS contact in the off medication state at rest. Each contact location was normalized relative to the STN borders based on microelectrode recordings. For each recording, power spectral density was computed, averaged over multiple frequency bands and phase reversal analysis was used to localize the source of oscillatory activity. Beta burst, high-frequency activity (HFA), and phase-amplitude coupling (PAC) were also computed. Neurophysiological signatures were correlated with hemibody symptoms severity and clinical outcomes. RESULTS: Beta band power and phase reversal localized the beta oscillator to the dorsal STN and correlated with pre-operative off medication hemibody bradykinesia and rigidity score. The contact along the electrode with the largest beta oscillatory power co-localized with the independently chosen optimized contact used for long-term chronic DBS. Lastly, beta bursting, HFA, and Beta-HFA PAC co-localized with the beta oscillator at the dorsal STN, and Beta-HFA PAC correlated with DBS effect. CONCLUSIONS: Our findings support the hypothesis that the primary source of beta oscillations is located in dorsal STN, and argue against the alternative hypothesis that beta activity in the STN region arises from volume conduction from other sources. We demonstrate intrinsic STN beta-HFA PAC as an independent marker of DBS effect.

Temporal cascade of frontal, motor and muscle processes underlying human action-stopping.

Action-stopping is a canonical executive function thought to involve top-down control over the motor system. Here we aimed to validate this stopping system using high temporal resolution methods in humans. We show that, following the requirement to stop, there was an increase of right frontal beta (~13 to 30 Hz) at ~120 ms, likely a proxy of right inferior frontal gyrus; then, at 140 ms, there was a broad skeletomotor suppression, likely reflecting the impact of the subthalamic nucleus on basal ganglia output; then, at ~160 ms, suppression was detected in the muscle, and, finally, the behavioral time of stopping was ~220 ms. This temporal cascade supports a physiological model of action-stopping, and partitions it into subprocesses that are isolable to different nodes and are more precise than the behavioral latency of stopping. Variation in these subprocesses, including at the single-trial level, could better explain individual differences in impulse control.

Parkinsonian Beta Dynamics during Rest and Movement in the Dorsal Pallidum and Subthalamic Nucleus.

In Parkinson's disease (PD), pathologically high levels of beta activity (12-30 Hz) reflect specific symptomatology and normalize with pharmacological or surgical intervention. Although beta characterization in the subthalamic nucleus (STN) of PD patients undergoing deep brain stimulation (DBS) has now been translated into adaptive DBS paradigms, a limited number of studies have characterized beta power in the globus pallidus internus (GPi), an equally effective DBS target. Our objective was to compare beta power in the STN and GPi during rest and movement in people with PD undergoing DBS. Thirty-seven human female and male participants completed a simple behavioral experiment consisting of periods of rest and button presses, leading to local field potential recordings from 19 (15 participants) STN and 26 (22 participants) GPi nuclei. We examined overall beta power as well as beta time-domain dynamics (i.e., beta bursts). We found higher beta power during rest and movement in the GPi, which also had more beta desynchronization during movement. Beta power was positively associated with bradykinesia and rigidity severity; however, these clinical associations were present only in the GPi cohort. With regards to beta dynamics, bursts were similar in duration and frequency in the GPi and STN, but GPi bursts were stronger and correlated to bradykinesia-rigidity severity. Beta dynamics therefore differ across basal ganglia nuclei. Relative to the STN, beta power in the GPi may be readily detected, modulates more with movement, and relates more to clinical impairment. Together, this could point to the GPi as a potentially effective target for beta-based adaptive DBS.SIGNIFICANCE STATEMENT It is known that subthalamic nucleus (STN) beta activity is linked to symptom severity in Parkinson's disease (PD), but few studies have characterized beta activity in the globus pallidus internus (GPi), another effective target for deep brain stimulation (DBS). We compared beta power in the STN and GPi during rest and movement in 37 people with PD undergoing DBS. We found that beta dynamics differed across basal ganglia nuclei. Our results show that, relative to the STN, beta power in the GPi may be readily detected, modulates more with movement, and relates more to clinical impairment. Together, this could point to the GPi as a potentially effective target for beta-based adaptive DBS.

Continuous deep brain stimulation of the subthalamic nucleus may not modulate beta bursts in patients with Parkinson's disease.

BACKGROUND: Neural oscillations represent synchronous neuronal activation and are ubiquitous throughout the brain. Oscillatory activity often includes brief high-amplitude bursts in addition to background oscillations, and burst activity may predict performance on working memory, motor, and comprehension tasks. OBJECTIVE: We evaluated beta burst activity as a possible biomarker for motor symptoms in Parkinson's disease (PD). The relationship between beta amplitude dynamics and motor symptoms is critical for adaptive DBS for treatment of PD. METHODS: We applied threshold-based and support vector machine (SVM) analyses of burst parameters to a defined on/off oscillator and to intraoperative recordings of local field potentials from the subthalamic nucleus of 16 awake patients with PD. RESULTS: Filtering and time-frequency analysis techniques critically influenced the accuracy of identifying burst activity. Threshold-based analysis lead to biased results in the presence of changes in long-term beta amplitude and accurate quantification of bursts with thresholds required unknowable a priori knowledge of the time in bursts. We therefore implemented an SVM analysis, and we did not observe changes in burst fraction, rate, or duration with the application of cDBS in the participant data, even though SVM analysis was able to correctly identify bursts of the defined on/off oscillator. CONCLUSION: Our results suggest that cDBS of the STN may not change beta burst activity. Additionally, threshold-based analysis can bias the fraction of time spent in bursts. Improved analysis strategies for continuous and adaptive DBS may achieve improved symptom control and reduce side-effects.