Oscillatory and non-oscillatory features of the magnetoencephalic sensorimotor rhythm in Parkinson's disease.

Parkinson's disease (PD) is associated with changes in neural activity in the sensorimotor alpha and beta bands. Using magnetoencephalography (MEG), we investigated the role of spontaneous neuronal activity within the somatosensory cortex in a large cohort of early- to mid-stage PD patients (N = 78) on Parkinsonian medication and age- and sex-matched healthy controls (N = 60) using source reconstructed resting-state MEG. We quantified features of the time series data in terms of oscillatory alpha power and central alpha frequency, beta power and central beta frequency, and 1/f broadband characteristics using power spectral density. Furthermore, we characterised transient oscillatory burst events in the mu-beta band time-domain signals. We examined the relationship between these signal features and the patients' disease state, symptom severity, age, sex, and cortical thickness. PD patients and healthy controls differed on PSD broadband characteristics, with PD patients showing a steeper 1/f exponential slope and higher 1/f offset. PD patients further showed a steeper age-related decrease in the burst rate. Out of all the signal features of the sensorimotor activity, the burst rate was associated with increased severity of bradykinesia, whereas the burst duration was associated with axial symptoms. Our study shows that general non-oscillatory features (broadband 1/f exponent and offset) of the sensorimotor signals are related to disease state and oscillatory burst rate scales with symptom severity in PD.

The Swedish National Facility for Magnetoencephalography Parkinson's disease dataset.

Parkinson's disease (PD) is characterised by a loss of dopamine and dopaminergic cells. The consequences hereof are widespread network disturbances in brain function. It is an ongoing topic of investigation how the disease-related changes in brain function manifest in PD relate to clinical symptoms. We present The Swedish National Facility for Magnetoencephalography Parkinson's Disease Dataset (NatMEG-PD) as an Open Science contribution to identify the functional neural signatures of Parkinson's disease and contribute to diagnosis and treatment. The dataset contains whole-head magnetoencephalographic (MEG) recordings from 66 well-characterised PD patients on their regular dose of dopamine replacement therapy and 68 age- and sex-matched healthy controls. NatMEG-PD contains three-minute eyes-closed resting-state MEG, MEG during an active movement task, and MEG during passive movements. The data includes anonymised MRI for source analysis and clinical scores. MEG data is rich in nature and can be used to explore numerous functional features. By sharing these data, we hope other researchers will contribute to advancing our understanding of the relationship between brain activity and disease state or symptoms.

EEGManyPipelines: A Large-scale, Grassroots Multi-analyst Study of Electroencephalography Analysis Practices in the Wild.

The ongoing reproducibility crisis in psychology and cognitive neuroscience has sparked increasing calls to re-evaluate and reshape scientific culture and practices. Heeding those calls, we have recently launched the EEGManyPipelines project as a means to assess the robustness of EEG research in naturalistic conditions and experiment with an alternative model of conducting scientific research. One hundred sixty-eight analyst teams, encompassing 396 individual researchers from 37 countries, independently analyzed the same unpublished, representative EEG data set to test the same set of predefined hypotheses and then provided their analysis pipelines and reported outcomes. Here, we lay out how large-scale scientific projects can be set up in a grassroots, community-driven manner without a central organizing laboratory. We explain our recruitment strategy, our guidance for analysts, the eventual outputs of this project, and how it might have a lasting impact on the field.

A Brain-To-Brain Mechanism for Social Transmission of Threat Learning.

Survival and adaptation in environments require swift and efficacious learning about what is dangerous. Across species, much of such threat learning is acquired socially, e.g., through the observation of others' ("demonstrators'") defensive behaviors. However, the specific neural mechanisms responsible for the integration of information shared between demonstrators and observers remain largely unknown. This dearth of knowledge is addressed by performing magnetoencephalography (MEG) neuroimaging in demonstrator-observer dyads. A set of stimuli are first shown to a demonstrator whose defensive responses are filmed and later presented to an observer, while neuronal activity is recorded sequentially from both individuals who never interacted directly. These results show that brain-to-brain coupling (BtBC) in the fronto-limbic circuit (including insula, ventromedial, and dorsolateral prefrontal cortex) within demonstrator-observer dyads predict subsequent expressions of learning in the observer. Importantly, the predictive power of BtBC magnifies when a threat is imminent to the demonstrator. Furthermore, BtBC depends on how observers perceive their social status relative to the demonstrator, likely driven by shared attention and emotion, as bolstered by dyadic pupillary coupling. Taken together, this study describes a brain-to-brain mechanism for social threat learning, involving BtBC, which reflects social relationships and predicts adaptive, learned behaviors.

Cortex-wide topography of 1/f-exponent in Parkinson's disease.

Parkinson's disease (PD) is a progressive and debilitating brain disorder. Besides the characteristic movement-related symptoms, the disease also causes decline in sensory and cognitive processing. The extent of symptoms and brain-wide projections of neuromodulators such as dopamine suggest that many brain regions are simultaneously affected in PD. To characterise brain-wide disease-related changes in neuronal function, we analysed resting state magnetoencephalogram (MEG) from two groups: PD patients and healthy controls. Besides standard spectral analysis, we quantified the aperiodic components (κ, λ) of the neural activity by fitting a power law κ/fλ - f is the frequency, κ and λ are the fitting parameters-to the MEG power spectrum and studied its relationship with age and Unified Parkinson's Disease Rating Scale (UPDRS). Consistent with previous results, the most significant spectral changes were observed in the high theta/low-alpha band (7-10 Hz) in all brain regions. Furthermore, analysis of the aperiodic part of the spectrum showed that in all but frontal regions λ was significantly larger in PD patients than in control subjects. Our results indicate that PD is associated with significant changes in aperiodic activity across the whole neocortex. Surprisingly, even early sensory areas showed a significantly larger λ in patients than in healthy controls. Moreover, λ was not affected by the Levodopa medication. Finally, λ was positively correlated with patient age but not with UPDRS-III. Because λ is closely associated with excitation-inhibition balance, our results propose new hypotheses about neural correlates of PD in cortical networks.

Task requirements affect the neural correlates of consciousness.

In the search for the neural correlates of consciousness, it is often assumed that there is a stable set within the relevant sensory modality. Within the visual modality, the debate has centred upon whether frontal or occipital activations are the best predictors of perceptual awareness. Although not accepted by all as definitive evidence, no-report and decoding studies have indicated that occipital activity is the most consistently correlated with perceptual awareness whereas frontal activity might be closely related to aspects of cognition typically related to reports. However, perception is rarely just passive perception of something, but more or less always perception for something. That is, the task at hand for the perceiver may influence what is being perceived. This suggests an alternative view: that consciousness is not one specific 'function' that can be localized consistently to one area or event-related component and that the specific attributes of the neural correlates of consciousness depend on the task at hand. To investigate whether and how tasks may influence the neural correlates of consciousness, we here contrasted two tasks, a perceptual task and a conceptual task, using identical stimuli in both tasks. Using magnetoencephalography, we found that the perceptual task recruited more occipital resources than the conceptual task. Furthermore, we found that between the two conditions, the amount of frontal resources recruited differed between different gradations of perceptual awareness partly in an unexpected manner. These findings support a view of task affecting the neural correlates of consciousness.

Changes in emotion processing in early Parkinson's disease reflect disease progression.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder which can substantially affect nonmotor functions related to emotional processing. We aimed to examine the underlying differences in emotional processing in PD by comparing how early-stage PD patients recognize, rate, and react to facial, bodily, and vocal emotional stimuli to that of healthy controls (HC). METHOD: We compared emotion recognition, emotional rating bias, and emotional response range between a PD patient group (n = 33) and a HC group (n = 29). Pearson's correlations were conducted to evaluate the relationship between emotion processing measures and clinical outcome measures in each group. RESULTS: PD patients showed an enhanced emotion processing as compared to HC. They were overall more accurate than HC's at identifying correct emotions and furthermore showed an increase in emotional ratings and reactions to both positive and negative stimuli that scaled with increased symptom severity, thereby yielding significant correlations between clinical outcomes and emotional range in the PD patient group. CONCLUSION: Our results suggest that alterations in emotional processing reflect disease progression in early PD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Sharing individualised template MRI data for MEG source reconstruction: A solution for open data while keeping subject confidentiality.

The increasing requirements for adoption of FAIR data management and sharing original research data from neuroimaging studies can be at odds with protecting the anonymity of the research participants due to the person-identifiable anatomical features in the data. We propose a solution to this dilemma for anatomical MRIs used in MEG source analysis. In MEG analysis, the channel-level data is reconstructed to the source-level using models derived from anatomical MRIs. Sharing data, therefore, requires sharing the anatomical MRI to replicate the analysis. The suggested solution is to replace the individual anatomical MRIs with individualised warped templates that can be used to carry out the MEG source analysis and that provide sufficient geometrical similarity to the original participants' MRIs. First, we demonstrate how the individualised template warping can be implemented with one of the leading open-source neuroimaging analysis toolboxes. Second, we compare results from four different MEG source reconstruction methods performed with an individualised warped template to those using the participant's original MRI. While the source reconstruction results are not numerically identical, there is a high similarity between the results for single dipole fits, dynamic imaging of coherent sources beamforming, and atlas-based virtual channel beamforming. There is a moderate similarity between minimum-norm estimates, as anticipated due to this method being anatomically constrained and dependent on the exact morphological features of the cortical sheet. We also compared the morphological features of the warped template to those of the original MRI. These showed a high similarity in grey matter volume and surface area, but a low similarity in the average cortical thickness and the mean folding index within cortical parcels. Taken together, this demonstrates that the results obtained by MEG source reconstruction can be preserved with the warped templates, whereas the anatomical and morphological fingerprint is sufficiently altered to protect the anonymity of research participants. In cases where participants consent to sharing anatomical MRI data, it remains preferable to share the original defaced data with an appropriate data use agreement. In cases where participants did not consent to share their MRIs, the individualised warped MRI template offers a good compromise in sharing data for reuse while retaining anonymity for research participants.

Neural correlates of impaired response inhibition in the antisaccade task in Parkinson's disease.

Deficits in response inhibition are a central feature of the highly prevalent dysexecutive syndrome found in Parkinson's disease (PD). Such deficits are related to a range of common clinically relevant symptoms including cognitive impairment as well as impulsive and compulsive behaviors. In this study, we explored the cortical dynamics underlying response inhibition during the mental preparation for the antisaccade task by recording magnetoencephalography (MEG) and eye-movements in 21 non-demented patients with early to mid-stage Parkinson's disease and 21 age-matched healthy control participants (HC). During the pre-stimulus preparatory period for antisaccades we observed: Taken together, the results indicate that alterations in pre-stimulus prefrontal alpha and beta activity hinder proactive response inhibition and in turn result in higher error rates and prolonged response latencies in PD.

Volition in prospective Memory: Evidence against differences between free and fixed target events.

Volition is the extent to which actions are generated as a result of internal states in contrast to responses to external conditions or dictated by external events. Delayed intentions about future action are stored in prospective memory until the intended action has to be formed at a later point in time. It is unknown how voluntary choice affects prospective memory. We compared the difference between freely chosen and fixed targets on the reaction times and task performance in the ongoing task and for the target stimuli in a prospective memory task. The task performance and the reaction time was modelled using a Bayesian hierarchical drift-diffusion model. The analysis showed no differences between self-chosen and fixed prospective memory cues on task responses. The result suggests that volition in choosing the cue to act upon or given a fixed cue does not make a difference for prospective memory task performance.

Reduction of spontaneous cortical beta bursts in Parkinson's disease is linked to symptom severity.

Parkinson's disease is characterized by a gradual loss of dopaminergic neurons, which is associated with altered neuronal activity in the beta-band (13-30 Hz). Assessing beta-band activity typically involves transforming the time-series to get the power of the signal in the frequency domain. Such transformation assumes that the time-series can be reduced to a combination of steady-state sine- and cosine waves. However, recent studies have suggested that this approach masks relevant biophysical features in the beta-band-for example, that the beta-band exhibits transient bursts of high-amplitude activity. In an exploratory study, we used magnetoencephalography to record beta-band activity from the sensorimotor cortex, to characterize how spontaneous cortical beta bursts manifest in Parkinson's patients on and off dopaminergic medication, and compare this to matched healthy controls. We extracted the time-course of beta-band activity from the sensorimotor cortex and characterized bursts in the signal. We then compared the burst rate, duration, inter-burst interval and peak amplitude between the Parkinson's patients and healthy controls. Our results show that Parkinson's patients off medication had a 5-17% lower beta bursts rate compared to healthy controls, while both the duration and the amplitude of the bursts were the same for healthy controls and medicated state of the Parkinson's patients. These data thus support the view that beta bursts are fundamental underlying features of beta-band activity, and show that changes in cortical beta-band power in Parkinson's disease can be explained-primarily by changes in the underlying burst rate. Importantly, our results also revealed a relationship between beta burst rate and motor symptom severity in Parkinson's disease: a lower burst rate scaled with increased severity of bradykinesia and postural/kinetic tremor. Beta burst rate might thus serve as a neuromarker for Parkinson's disease that can help in the assessment of symptom severity in Parkinson's disease or in the evaluation of treatment effectiveness.

Attenuated beta rebound to proprioceptive afferent feedback in Parkinson's disease.

Motor symptoms are defining traits in the diagnosis of Parkinson's disease (PD). A crucial component in motor function is the integration of afferent proprioceptive sensory feedback. Previous studies have indicated abnormal movement-related cortical oscillatory activity in PD, but the role of the proprioceptive afference on abnormal oscillatory activity in PD has not been elucidated. We examine the cortical oscillations in the mu/beta-band (8-30 Hz) in the processing of proprioceptive stimulation in PD patients, ON/OFF levodopa medication, as compared to that of healthy controls (HC). We used a proprioceptive stimulator that generated precisely controlled passive movements of the index finger and measured the induced cortical oscillatory responses following the proprioceptive stimulation using magnetoencephalography. Both PD patients and HC showed a typical beta-band desynchronization during the passive movement. However, the subsequent beta rebound after the passive movement that was almost absent in PD patients compared to HC. Furthermore, we found no difference in the degree of beta rebound attenuation between patients ON and OFF levodopa medication. The results demonstrate a disease-related deterioration in cortical processing of proprioceptive afference in PD.

Mice Knocked Out for the Primary Brain Calcification-Associated Gene Slc20a2 Show Unimpaired Prenatal Survival but Retarded Growth and Nodules in the Brain that Grow and Calcify Over Time.

Brain calcification of especially the basal ganglia characterizes primary familial brain calcification (PFBC). PFBC is a rare neurodegenerative disorder with neuropsychiatric and motor symptoms, and only symptomatic treatment is available. Four PFBC-associated genes are known; approximately 40% of patients carry mutations in the gene SLC20A2, which encodes the type III sodium-dependent inorganic phosphate transporter PiT2. To investigate the role of PiT2 in PFBC development, we studied Slc20a2-knockout (KO) mice using histology, microcomputed tomography, electron microscopy, and energy-dispersive X-ray spectroscopy. Slc20a2-KO mice showed histologically detectable nodules in the brain already at 8 weeks of age, which contained organic material and were weakly calcified. In 15-week-old mice, the nodules were increased in size and number and were markedly more calcified. The major minerals in overt calcifications were Ca and P, but Fe, Zn, and Al were also generally present. Electron microscopy suggested that the calcifications initiate intracellularly, mainly in pericytes and astrocytes. As the calcification grew, they incorporated organic material. Furthermore, endogenous IgG was detected around nodules, suggesting local increased blood-brain barrier permeabilities. Nodules were found in all 8-week-old Slc20a2-KO mice, but no prenatal or marked postnatal lethality was observed. Thus, besides allowing for the study of PFBC development, the Slc20a2-KO mouse is a potential solid preclinical model for evaluation of PFBC treatments.

Delta and gamma oscillations in operculo-insular cortex underlie innocuous cold thermosensation.

Cold-sensitive and nociceptive neural pathways interact to shape the quality and intensity of thermal and pain perception. Yet the central processing of cold thermosensation in the human brain has not been extensively studied. Here, we used magnetoencephalography and EEG in healthy volunteers to investigate the time course (evoked fields and potentials) and oscillatory activity associated with the perception of cold temperature changes. Nonnoxious cold stimuli consisting of Δ3°C and Δ5°C decrements from an adapting temperature of 35°C were delivered on the dorsum of the left hand via a contact thermode. Cold-evoked fields peaked at around 240 and 500 ms, at peak latencies similar to the N1 and P2 cold-evoked potentials. Importantly, cold-related changes in oscillatory power indicated that innocuous thermosensation is mediated by oscillatory activity in the range of delta (1-4 Hz) and gamma (55-90 Hz) rhythms, originating in operculo-insular cortical regions. We suggest that delta rhythms coordinate functional integration between operculo-insular and frontoparietal regions, while gamma rhythms reflect local sensory processing in operculo-insular areas.NEW & NOTEWORTHY Using magnetoencephalography, we identified spatiotemporal features of central cold processing, with respect to the time course, oscillatory profile, and neural generators of cold-evoked responses in healthy human volunteers. Cold thermosensation was associated with low- and high-frequency oscillatory rhythms, both originating in operculo-insular regions. These results support further investigations of central cold processing using magnetoencephalography or EEG and the clinical utility of cold-evoked potentials for neurophysiological assessment of cold-related small-fiber function and damage.

The time between intention and action affects the experience of action.

We present a study investigating how the delay between the intention to act and the following action, influenced the experience of action. In experiments investigating sense of agency and experience of action, the contrast is most often between voluntary and involuntary actions. It is rarely asked whether different types of intentions influence the experience of action differently. To investigate this we distinguished between proximal intentions (i.e., intentions for immediate actions) and delayed intentions (i.e., intentions with a temporal delay between intention and action). The distinction was implemented in an intentional binding paradigm, by varying the delay between the time where participants formed the intention to act and the time at which they performed the action. The results showed that delayed intentions were followed by a stronger binding effect for the tone following the action compared to proximal intentions. The actions were reported to have occurred earlier for delayed intentions than for proximal intentions. This effect was independent of the binding effect usually found in intentional binding experiments. This suggests that two perceptual shifts occurred in the contrast between delayed intentions and proximal intentions: The first being the binding effect, the second a general shift in the perceived time of action. Neither the stronger binding effect for tone, nor the earlier reports of action, differed across delays for delayed intentions. The results imply that delayed intentions and proximal intentions have a different impact on the experience of action.

Distinct electrophysiological potentials for intention in action and prior intention for action.

The role of conscious intention in relation to motoric movements has become a major topic of investigation in neuroscience. Traditionally, reports of conscious intention have been compared to various features of the readiness-potential (RP)--an electrophysiological signal that appears before voluntary movements. Experiments, however, tend to study intentions in immediate relation to movements (proximal intentions), thus ignoring other aspects of intentions such as planning or deciding in advance of movement (distal intentions). The current study examines the difference in electrophysiological activity between proximal intention and distal intention, using electroencephalography (EEG). Participants had to form an intention to move and then wait 2.5 sec before performing the actual movement. In this way, the electrophysiological activity related to forming a conscious intention was separated from any confounding activity related to automated motor activity. This was compared to conditions in which participants had to act as soon as they had the intention and a condition where participants acted upon an external cue 2.5 sec prior to movement. We examined the RP for the three conditions. No difference was found in early RP, but late RP differed significantly depending on the type of intention. In addition, we analysed signals during a longer time-interval starting before the time of distal intention formation until after the actual movement concluded. Results showed a slow negative electrophysiological "intention potential" above the mid-frontal areas at the time participants formed a distal intention. This potential was only found when the distal intention was self-paced and not when the intention was formed in response to an external cue.

Unravelling intention: distal intentions increase the subjective sense of agency.

Experimental studies investigating the contribution of conscious intention to the generation of a sense of agency for one's own actions tend to rely upon a narrow definition of intention. Often it is operationalized as the conscious sensation of wanting to move right before movement. Existing results and discussion are therefore missing crucial aspects of intentions, namely intention as the conscious sensation of wanting to move in advance of the movement. In the present experiment we used an intentional binding paradigm, in which we distinguished between immediate (proximal) intention, as usually investigated, and longer standing (distal) intention. The results showed that the binding effect was significantly enhanced for distal intentions compared to proximal intentions, indicating that the former leads to stronger sense of agency. Our finding provides empirical support for a crucial distinction between at least two types of intention when addressing the efficacy of conscious intentions.