Applications of OPM-MEG for translational neuroscience: a perspective.

Magnetoencephalography (MEG) allows the non-invasive measurement of brain activity at millisecond precision combined with localization of the underlying generators. So far, MEG-systems consisted of superconducting quantum interference devices (SQUIDS), which suffer from several limitations. Recent technological advances, however, have enabled the development of novel MEG-systems based on optically pumped magnetometers (OPMs), offering several advantages over conventional SQUID-MEG systems.

Modulation of subthalamic beta oscillations by movement, dopamine, and deep brain stimulation in Parkinson's disease.

Subthalamic beta band activity (13-35 Hz) is known as a real-time correlate of motor symptom severity in Parkinson's disease (PD) and is currently explored as a feedback signal for closed-loop deep brain stimulation (DBS). Here, we investigate the interaction of movement, dopaminergic medication, and deep brain stimulation on subthalamic beta activity in PD patients implanted with sensing-enabled, implantable pulse generators. We recorded subthalamic activity from seven PD patients at rest and during repetitive movements in four conditions: after withdrawal of dopaminergic medication and DBS, with medication only, with DBS only, and with simultaneous medication and DBS.

Invasive neurophysiology and whole brain connectomics for neural decoding in patients with brain implants.

Brain computer interfaces (BCI) provide unprecedented spatiotemporal precision that will enable significant expansion in how numerous brain disorders are treated. Decoding dynamic patient states from brain signals with machine learning is required to leverage this precision, but a standardized framework for identifying and advancing novel clinical BCI approaches does not exist. Here, we developed a platform that integrates brain signal decoding with connectomics and demonstrate its utility across 123 hours of invasively recorded brain data from 73 neurosurgical patients treated for movement disorders, depression and epilepsy.

Pallidal Beta Activity Is Linked to Stimulation-Induced Slowness in Dystonia.

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.

Christmas-Related Reduction in Beta Activity in Parkinson's Disease.

Background: Subthalamic nucleus (STN) beta (13 - 35 Hz) activity is a biomarker reflecting motor state in Parkinson's disease (PD). Adaptive deep brain stimulation (DBS) aims to use beta activity for therapeutic adjustments, but many aspects of beta activity in real-life situations are unknown.

Objective: The aim was to investigate Christmas-related influences on beta activity in PD.

Subthalamic beta bursts correlate with dopamine-dependent motor symptoms in 106 Parkinson's patients.

Pathologically increased beta power has been described as a biomarker for Parkinson's disease (PD) and related to prolonged bursts of subthalamic beta synchronization. Here, we investigate the association between subthalamic beta dynamics and motor impairment in a cohort of 106 Parkinson's patients in the ON- and OFF-medication state, using two different methods of beta burst determination. We report a frequency-specific correlation of low beta power and burst duration with motor impairment OFF dopaminergic medication.

Interrater reliability of deep brain stimulation electrode localizations.

Lead-DBS is an open-source, semi-automatized and widely applied software tool facilitating precise localization of deep brain stimulation electrodes both in native as well as in standardized stereotactic space. While automatized preprocessing steps within the toolbox have been tested and validated in previous studies, the interrater reliability in manual refinements of electrode localizations using the tool has not been objectified so far. Here, we investigate the variance introduced in this processing step by different raters when localizing electrodes based on postoperative CT or MRI.

Spectral and spatial distribution of subthalamic beta peak activity in Parkinson's disease patients.

Current efforts to optimise subthalamic deep brain stimulation in Parkinson's disease patients aim to harness local oscillatory activity in the beta frequency range (13-35 Hz) as a feedback-signal for demand-based adaptive stimulation paradigms. A high prevalence of beta peak activity is prerequisite for this approach to become routine clinical practice. In a large dataset of postoperative rest recordings from 106 patients we quantified occurrence and identified determinants of spectral peaks in the alpha, low and high beta bands.

A translational perspective on pathophysiological changes of oscillatory activity in dystonia and parkinsonism.

Intracerebral recordings from movement disorders patients undergoing deep brain stimulation have allowed the identification of pathophysiological patterns in oscillatory activity that correlate with symptom severity. Changes in oscillatory synchrony occur within and across brain areas, matching the classification of movement disorders as network disorders. However, the underlying mechanisms of oscillatory changes are difficult to assess in patients, as experimental interventions are technically limited and ethically problematic.

Toward therapeutic electrophysiology: beta-band suppression as a biomarker in chronic local field potential recordings.

Adaptive deep brain stimulation (aDBS) is a promising concept for feedback-based neurostimulation, with the potential of clinical implementation with the sensing-enabled Percept neurostimulator. We aim to characterize chronic electrophysiological activity during stimulation and to validate beta-band activity as a biomarker for bradykinesia. Subthalamic activity was recorded during stepwise stimulation amplitude increase OFF medication in 10 Parkinson's patients during rest and finger tapping.

Brain oscillatory dysfunctions in dystonia.

Dystonia is a hyperkinetic movement disorder associated with loss of inhibition, abnormal plasticity, dysfunctional sensorimotor integration, and brain oscillatory dysfunctions at cortical and subcortical levels of the central nervous system. Hence, dystonia is considered a network disorder that can, in many cases, be efficiently treated by pallidal deep brain stimulation (DBS). Abnormal oscillatory activity has been identified across the motor circuit of patients with dystonia.

Subthalamic beta band suppression reflects effective neuromodulation in chronic recordings.

Background And Purpose: Biomarkers for future adaptive deep brain stimulation still need evaluation in clinical routine. Here, we aimed to assess stimulation-induced modulation of beta-band activity and clinical symptoms in a Parkinson's disease patient during chronic neuronal sensing using a novel implantable pulse generator.

Methods: Subthalamic activity was recorded OFF and ON medication during a stepwise increase of stimulation amplitude.

Subthalamic stimulation impairs stopping of ongoing movements.

The subthalamic nucleus is part of a global stopping network that also includes the presupplementary motor area and inferior frontal gyrus of the right hemisphere. In Parkinson's disease, subthalamic deep brain stimulation improves movement initiation and velocity, but its effect on stopping of ongoing movement is unknown. Here, we examine the relation between movement stopping and connectivity of stimulation volumes to the stopping network.

Pallidal low-frequency activity in dystonia after cessation of long-term deep brain stimulation.

Objective: This study investigates the association between pallidal low-frequency activity and motor sign severity in dystonia after chronic deep brain stimulation for several months.

Methods: Local field potentials were recorded in 9 dystonia patients at 5 timepoints (T1-T5) during an OFF-stimulation period of 5 to 7 hours in parallel with clinical assessment using Burke-Fahn-Marsden Dystonia Rating Scale. A linear mixed effects model was used to investigate the potential association of motor signs with local field potential activity in the low frequency (3-12 Hz) and beta range (13-30 Hz).

Beta bursts during continuous movements accompany the velocity decrement in Parkinson's disease patients.

Bradykinesia is reported to correlate with subthalamic beta power (13-35 Hz) recorded at rest in Parkinson's disease (PD). Pilot studies suggest adaptive deep brain stimulation triggered by amplitude threshold crossings of beta activity defined at rest is effective. This is puzzling, given that beta is suppressed during repetitive movements when bradykinesia becomes apparent.

Pallidal beta bursts in Parkinson's disease and dystonia.

Background: Exaggerated beta power has been discussed as a disease-specific biomarker for Parkinson's disease (PD) and has recently been suggested to rely on prolonged bursts of subthalamic beta synchronization.

Objective: In this study, we test whether prolonged bursts are disease specific for beta activity in PD by comparison to oscillatory activity in dystonia.

Methods: Pallidal local field potentials were recorded from 5 PD patients ON and OFF dopaminergic medication and 5 dystonia patients.

Pallidal and thalamic neural oscillatory patterns in tourette's syndrome.

Objective: Aberrant oscillatory activity has been hypothesized to play a role in the pathophysiology of Tourette's syndrome (TS). Deep brain stimulation (DBS) has recently been established as an effective treatment for severe TS. Modulation of symptom-specific oscillations may underlie the mechanism of action of DBS and could be used for adaptive neuromodulation to improve therapeutic efficacy.

Dopamine-dependent scaling of subthalamic gamma bursts with movement velocity in patients with Parkinson's disease.

Gamma synchronization increases during movement and scales with kinematic parameters. Here, disease-specific characteristics of this synchronization and the dopamine-dependence of its scaling in Parkinson's disease are investigated. In 16 patients undergoing deep brain stimulation surgery, movements of different velocities revealed that subthalamic gamma power peaked in the sensorimotor part of the subthalamic nucleus, correlated positively with maximal velocity and negatively with symptom severity.

Laminar Localization and Projection-Specific Properties of Presubicular Neurons Targeting the Lateral Mammillary Nucleus, Thalamus, or Medial Entorhinal Cortex.

The presubiculum (PrS) is part of an interconnected network of distributed brain regions where individual neurons signal the animals heading direction. PrS sends axons to medial entorhinal cortex (MEC), it is reciprocally connected with anterior thalamic nuclei (ATNs), and it sends feedback projections to the lateral mammillary nucleus (LMN), involved in generating the head direction signal. The intrinsic properties of projecting neurons will influence the pathway-specific transmission of activity.

Diversity and overlap of parvalbumin and somatostatin expressing interneurons in mouse presubiculum.

The presubiculum, located between hippocampus and entorhinal cortex, plays a fundamental role in representing spatial information, notably head direction. Little is known about GABAergic interneurons of this region. Here, we used three transgenic mouse lines, Pvalb-Cre, Sst-Cre, and X98, to examine distinct interneurons labeled with tdTomato or green fluorescent protein.