Re-emergent Tremor in Parkinson's Disease: Evidence of Pathologic ß and Prokinetic γ Activity.

BACKGROUND: Re-emergent tremor is characterized as a continuation of resting tremor and is often highly therapy refractory. This study examines variations in brain activity and oscillatory responses between resting and re-emergent tremors in Parkinson's disease. METHODS: Forty patients with Parkinson's disease (25 males, mean age, 66.78 ± 5.03 years) and 40 age- and sex-matched healthy controls were included in the study. Electroencephalogram and electromyography signals were simultaneously recorded during resting and re-emergent tremors in levodopa on and off states for patients and mimicked by healthy controls. Brain activity was localized using the beamforming technique, and information flow between sources was estimated using effective connectivity. Cross-frequency coupling was used to assess neuronal oscillations between tremor frequency and canonical frequency oscillations. RESULTS: During levodopa on, differences in brain activity were observed in the premotor cortex and cerebellum in both the patient and control groups. However, Parkinson's disease patients also exhibited additional activity in the primary sensorimotor cortex. On withdrawal of levodopa, different source patterns were observed in the supplementary motor area and basal ganglia area. Additionally, levodopa was found to suppress the strength of connectivity (P < 0.001) between the identified sources and influence the tremor frequency-related coupling, leading to a decrease in ß (P < 0.001) and an increase in γ frequency coupling (P < 0.001). CONCLUSIONS: Distinct variations in cortical-subcortical brain activity are evident in tremor phenotypes. The primary sensorimotor cortex plays a crucial role in the generation of re-emergent tremor. Moreover, oscillatory neuronal responses in pathological ß and prokinetic γ activity are specific to tremor phenotypes. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

When Maturation is Not Linear: Brain Oscillatory Activity in the Process of Aging as Measured by Electrophysiology.

Changes in brain oscillatory activity are commonly used as biomarkers both in cognitive neuroscience and in neuropsychiatric conditions. However, little is known about how its profile changes across maturation. Here we use regression models to characterize magnetoencephalography power changes within classical frequency bands in a sample of 792 healthy participants, covering the range 13 to 80 years old. Our findings unveil complex, non-linear power trajectories that defy the traditional linear paradigm, with notable cortical region variations. Interestingly, slow wave activity increases correlate with improved cognitive performance throughout life and larger gray matter volume in the elderly. Conversely, fast wave activity diminishes in adulthood. Elevated low-frequency activity during aging, traditionally seen as compensatory, may also signify neural deterioration. This dual interpretation, highlighted by our study, reveals the intricate dynamics between brain oscillations, cognitive performance, and aging. It advances our understanding of neurodevelopment and aging by emphasizing the regional specificity and complexity of brain rhythm changes, with implications for cognitive and structural integrity.

Age-related changes of deep-brain neurophysiological activity.

Cognitive decline with age is associated with brain atrophy and reduced brain activations, but the underlying neurophysiological mechanisms are unclear, especially in deeper brain structures primarily affected by healthy aging or neurodegenerative processes. Here, we characterize time-resolved, resting-state magnetoencephalography activity of the hippocampus and subcortical brain regions in a large cohort of healthy young (20-30 years) and older (70-80 years) volunteers from the Cam-CAN (Cambridge Centre for Ageing and Neuroscience) open repository. The data show age-related changes in both rhythmic and arrhythmic signal strength in multiple deeper brain regions, including the hippocampus, striatum, and thalamus. We observe a slowing of neural activity across deeper brain regions, with increased delta and reduced gamma activity, which echoes previous reports of cortical slowing. We also report reduced occipito-parietal alpha peak associated with increased theta-band activity in the hippocampus, an effect that may reflect compensatory processes as theta activity, and slope of arrhythmic activity were more strongly expressed when short-term memory performances were preserved. Overall, this study advances the understanding of the biological nature of inter-individual variability in aging. The data provide new insight into how hippocampus and subcortical neurophysiological activity evolve with biological age, and highlight frequency-specific effects associated with cognitive decline versus cognitive maintenance.

CPT1C is required for synaptic plasticity and oscillatory activity that supports motor, associative and non-associative learning.

Carnitine palmitoyltransferase 1c (CPT1C) is a neuron-specific protein widely distributed throughout the CNS and highly expressed in discrete brain areas including the hypothalamus, hippocampus, amygdala and different motor regions. Its deficiency has recently been shown to disrupt dendritic spine maturation and AMPA receptor synthesis and trafficking in the hippocampus, but its contribution to synaptic plasticity and cognitive learning and memory processes remains mostly unknown. Here, we aimed to explore the molecular, synaptic, neural network and behavioural role of CPT1C in cognition-related functions by using CPT1C knockout (KO) mice. CPT1C-deficient mice showed extensive learning and memory deficits. The CPT1C KO animals exhibited impaired motor and instrumental learning that seemed to be related, in part, to locomotor deficits and muscle weakness but not to mood alterations. In addition, CPT1C KO mice showed detrimental hippocampus-dependent spatial and habituation memory, most probably attributable to inefficient dendritic spine maturation, impairments in long-term plasticity at the CA3-CA1 synapse and aberrant cortical oscillatory activity. In conclusion, our results reveal that CPT1C is not only crucial for motor function, coordination and energy homeostasis, but also has a crucial role in the maintenance of learning and memory cognitive functions. KEY POINTS: CPT1C, a neuron-specific interactor protein involved in AMPA receptor synthesis and trafficking, was found to be highly expressed in the hippocampus, amygdala and various motor regions. CPT1C-deficient animals exhibited energy deficits and impaired locomotion, but no mood changes were found. CPT1C deficiency disrupts hippocampal dendritic spine maturation and long-term synaptic plasticity and reduces cortical γ oscillations. CPT1C was found to be crucial for motor, associative and non-associative learning and memory.

Metabolic cues impact non-oscillatory intergeniculate leaflet and ventral lateral geniculate nucleus: standard versus high-fat diet comparative study.

The intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/VLG) are subcortical structures involved in entrainment of the brain's circadian system to photic and non-photic (e.g. metabolic and arousal) cues. Both receive information about environmental light from photoreceptors, exhibit infra-slow oscillations (ISO) in vivo, and connect to the master circadian clock. Although current evidence demonstrates that the IGL/VLG communicate metabolic information and are crucial for entrainment of circadian rhythms to time-restricted feeding, their sensitivity to food intake-related peptides has not been investigated yet. We examined the effect of metabolically relevant peptides on the spontaneous activity of IGL/VLG neurons. Using ex vivo and in vivo electrophysiological recordings as well as in situ hybridisation, we tested potential sensitivity of the IGL/VLG to anorexigenic and orexigenic peptides, such as cholecystokinin, glucagon-like peptide 1, oxyntomodulin, peptide YY, orexin A and ghrelin. We explored neuronal responses to these drugs during day and night, and in standard vs. high-fat diet conditions. We found that IGL/VLG neurons responded to all the substances tested, except peptide YY. Moreover, more neurons responded to anorexigenic drugs at night, while a high-fat diet affected the IGL/VLG sensitivity to orexigenic peptides. Interestingly, ISO neurons responded to light and orexin A, but did not respond to the other food intake-related peptides. In contrast, non-ISO cells were activated by metabolic peptides, with only some being responsive to light. Our results show for the first time that peptides involved in the body's energy homeostasis stimulate the thalamus and suggest functional separation of the IGL/VLG cells. KEY POINTS: The intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/VLG) of the rodent thalamus process various signals and participate in circadian entrainment. In both structures, cells exhibiting infra-slow oscillatory activity as well as non-rhythmically firing neurons being observed. Here, we reveal that only one of these two groups of cells responds to anorexigenic (cholecystokinin, glucagon-like peptide 1 and oxyntomodulin) and orexigenic (ghrelin and orexin A) peptides. Neuronal responses vary depending on the time of day (day vs. night) and on the diet (standard vs. high-fat diet). Additionally, we visualised receptors to the tested peptides in the IGL/VLG using in situ hybridisation. Our results suggest that two electrophysiologically different subpopulations of IGL/VLG neurons are involved in two separate functions: one related to the body's energy homeostasis and one associated with the subcortical visual system.

Tactile expectancy modulates occipital alpha oscillations in early blindness.

Alpha oscillatory activity is thought to contribute to visual expectancy through the engagement of task-relevant occipital regions. In early blindness, occipital alpha oscillations are systematically reduced, suggesting that occipital alpha depends on visual experience. However, it remains possible that alpha activity could serve expectancy in non-visual modalities in blind people, especially considering that previous research has shown the recruitment of the occipital cortex for non-visual processing. To test this idea, we used electroencephalography to examine whether alpha oscillations reflected a differential recruitment of task-relevant regions between expected and unexpected conditions in two haptic tasks (texture and shape discrimination). As expected, sensor-level analyses showed that alpha suppression in parieto-occipital sites was significantly reduced in early blind individuals compared with sighted participants. The source reconstruction analysis revealed that group differences originated in the middle occipital cortex. In that region, expected trials evoked higher alpha desynchronization than unexpected trials in the early blind group only. Our results support the role of alpha rhythms in the recruitment of occipital areas in early blind participants, and for the first time we show that although posterior alpha activity is reduced in blindness, it remains sensitive to expectancy factors. Our findings therefore suggest that occipital alpha activity is involved in tactile expectancy in blind individuals, serving a similar function to visual anticipation in sighted populations but switched to the tactile modality. Altogether, our results indicate that expectancy-dependent modulation of alpha oscillatory activity does not depend on visual experience. SIGNIFICANCE STATEMENT: Are posterior alpha oscillations and their role in expectancy and anticipation dependent on visual experience? Our results show that tactile expectancy can modulate posterior alpha activity in blind (but not sighted) individuals through the engagement of occipital regions, suggesting that in early blindness, alpha oscillations maintain their proposed role in visual anticipation but subserve tactile processing. Our findings bring a new understanding of the role that alpha oscillatory activity plays in blindness, contrasting with the view that alpha activity is task unspecific in blind populations.

Neurophysiological time course of timbre-induced music-like perception.

Traditionally, pitch variation in a sound stream has been integral to music identity. We attempt to expand music's definition, by demonstrating that the neural code for musicality is independent of pitch encoding. That is, pitchless sound streams can still induce music-like perception and a neurophysiological hierarchy similar to pitched melodies. Previous work reported that neural processing of sounds with no-pitch, fixed-pitch, and irregular-pitch (melodic) patterns, exhibits a right-lateralized hierarchical shift, with pitchless sounds favorably processed in Heschl's gyrus (HG), ascending laterally to nonprimary auditory areas for fixed-pitch and even more laterally for melodic patterns. The objective of this EEG study was to assess whether sound encoding maintains a similar hierarchical profile when musical perception is driven by timbre irregularities in the absence of pitch changes. Individuals listened to repetitions of three musical and three nonmusical sound-streams. The nonmusical streams were comprised of seven 200-ms segments of white, pink, or brown noise, separated by silent gaps. Musical streams were created similarly, but with all three noise types combined in a unique order within each stream to induce timbre variations and music-like perception. Subjects classified the sound streams as musical or nonmusical. Musical processing exhibited right dominant α power enhancement, followed by a lateralized increase in θ phase-locking and spectral power. The θ phase-locking was stronger in musicians than in nonmusicians. The lateralization of activity suggests higher-level auditory processing. Our findings validate the existence of a hierarchical shift, traditionally observed with pitched-melodic perception, underscoring that musicality can be achieved with timbre irregularities alone.NEW & NOTEWORTHY EEG induced by streams of pitchless noise segments varying in timbre were classified as music-like and exhibited a right-lateralized hierarchy in processing similar to pitched melodic processing. This study provides evidence that the neural-code of musicality is independent of pitch encoding. The results have implications for understanding music processing in individuals with degraded pitch perception, such as in cochlear-implant listeners, as well as the role of nonpitched sounds in the induction of music-like perceptual states.

Mini-review: Transcranial Alternating Current Stimulation and the Cerebellum.

Oscillatory activity in the cerebellum and linked networks is an important aspect of neuronal processing and functional implementation of behavior. So far, it was challenging to quantify and study cerebellar oscillatory signatures in human neuroscience due to the constraints of non-invasive cerebellar electrophysiological recording and interventional techniques. The emerging cerebellar transcranial alternating current stimulation technique (CB-tACS) is a promising tool, which may partially overcome this challenge and provides an exciting non-invasive opportunity to better understand cerebellar physiology.Several studies have successfully demonstrated that CB-tACS can modulate the cerebellar outflow and cerebellum-linked behavior. In the present narrative review, we summarize current studies employing the CB-tACS approach and discuss open research questions. Hereby, we aim to provide an overview on this emerging electrophysiological technique and strive to promote future research in the field. CB-tACS will contribute in the further deciphering of cerebellar oscillatory signatures and its role for motor, cognitive, or affective functions. In long term, CB-tACS could develop into a therapeutic tool for retuning disturbed oscillatory activity in cerebellar networks underlying brain disorders.

Neurophysiological MEG markers of cognitive impairment and performance validity in multiple sclerosis.

BACKGROUND: Suboptimal performance during neuropsychological testing frequently occurs in multiple sclerosis (MS), leading to unreliable cognitive outcomes. Neurophysiological alterations correlate with MS-related cognitive impairment, but studies have not yet considered performance validity. OBJECTIVES: To investigate neurophysiological markers of cognitive impairment in MS, while explicitly addressing performance validity. METHODS: Magnetoencephalography recordings, neuropsychological assessments, and performance validity testing were obtained from 90 MS outpatients with cognitive complaints. Spectral and resting-state functional connectivity (rsFC) properties were compared between cognitively impaired (CI), cognitively preserved (CP), and suboptimally performing (SUB) patients using regression models and permutation testing. RESULTS: CI had higher power in low-frequency bands and lower power in high bands compared to CP, indicating neuronal slowing. CI also showed lower beta power compared to SUB. Overall power spectra visually differed between CI and CP, and SUB showed overlap with both groups. CI had lower rsFC than CP and SUB patients. CP and SUB patients showed no differences. CONCLUSION: Neuronal slowing and altered rsFC can be considered cognitive markers in MS. Patients who performed suboptimally showed resemblance with patients with and without cognitive impairments, and although their overall neurophysiological profile was more similar to patients without impairments, it suggests heterogeneity regarding their pathophysiology.

A Dynamical Systems Approach to Characterizing Brain-Body Interactions during Movement: Challenges, Interpretations, and Recommendations.

Brain-body interactions (BBIs) have been the focus of intense scrutiny since the inception of the scientific method, playing a foundational role in the earliest debates over the philosophy of science. Contemporary investigations of BBIs to elucidate the neural principles of motor control have benefited from advances in neuroimaging, device engineering, and signal processing. However, these studies generally suffer from two major limitations. First, they rely on interpretations of 'brain' activity that are behavioral in nature, rather than neuroanatomical or biophysical. Second, they employ methodological approaches that are inconsistent with a dynamical systems approach to neuromotor control. These limitations represent a fundamental challenge to the use of BBIs for answering basic and applied research questions in neuroimaging and neurorehabilitation. Thus, this review is written as a tutorial to address both limitations for those interested in studying BBIs through a dynamical systems lens. First, we outline current best practices for acquiring, interpreting, and cleaning scalp-measured electroencephalography (EEG) acquired during whole-body movement. Second, we discuss historical and current theories for modeling EEG and kinematic data as dynamical systems. Third, we provide worked examples from both canonical model systems and from empirical EEG and kinematic data collected from two subjects during an overground walking task.

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.

Sex-specific response to whole-body vibration training: a randomized controlled trial.

A few studies have indicated that males and females respond differently to whole-body vibration (WBV) training. However, the existing insights are still insufficient and they cannot be transferred to sex-specific practice planning. To evaluate the effect of 5-week WBV training on neuromuscular [countermovement jump (CMJ), squat jump (SJ)] and cardiovascular [heart rate and blood pressure] data, taking into account sex-specific effects. This is a comparative experimental study including 96 healthy adults, divided into two groups: a WBV group (25 females and 24 males) and a control group (27 females and 20 males). The participants attended nine to ten training sessions (twice a week for 5 weeks), each lasting approximately 30 min. Both groups performed the same exercise routine on the vibration training device. For the WBV group, the training device was vibrating during the whole training session, including the breaks. For the control group, it was turned off. Maximum jump height (H, cm) and maximum relative power (MRP, kW/kg) were noted during CMJ and SJ performed on a force plate. Resting (sitting) heart rate (bpm) and blood pressure (mmHg) were measured twice, before and after the intervention. For each parameter, Δdata (= before - after) was calculated. Interactive effects of sex (2) vs group (2) vs session (2) were noted only in males and they only concerned ΔSJMPR and ΔCMJH: compared to the control group, the WBV group had better ΔSJMPR (1.39 ± 3.05 vs -2.69 ± 4.49 kW/kg, respectively) and ΔCMJH (0.50 ± 6.14 vs -4.42 ± 5.80 cm, respectively). No sex-specific effect of WBV on neuromuscular (CMJ and SJ) or cardiovascular (heart rate and blood pressure) data was found.

Pathomechanisms in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a frequent neuropsychiatric complication in patients with acute or chronic liver failure. Symptoms of HE in particular include disturbances of sensory and motor functions and cognition. HE is triggered by heterogeneous factors such as ammonia being a main toxin, benzodiazepines, proinflammatory cytokines and hyponatremia. HE in patients with liver cirrhosis is triggered by a low-grade cerebral edema and cerebral oxidative/nitrosative stress which bring about a number of functionally relevant alterations including posttranslational protein modifications, oxidation of RNA, gene expression changes and senescence. These alterations are suggested to impair astrocyte/neuronal functions and communication. On the system level, a global slowing of oscillatory brain activity and networks can be observed paralleling behavioral perceptual and motor impairments. Moreover, these changes are related to increased cerebral ammonia, alterations in neurometabolite and neurotransmitter concentrations and cortical excitability in HE patients.

Task-specific signatures in the expert brain: Differential correlates of translation and reading in professional interpreters.

Insights on the neurocognitive particularities of expert individuals have benefited from language studies on professional simultaneous interpreters (PSIs). Accruing research indicates that behavioral advantages in this population are restricted to those skills that are directly taxed during professional practice (e.g., translation as opposed to reading), but little is known about the neural signatures of such selective effects. To illuminate the issue, we recruited 17 PSIs and 15 non-interpreter bilinguals and compared behavioral and electrophysiological markers of word reading and translation from and into their native and non-native languages (L1 and L2, respectively). PSIs exhibited greater delta-theta (1-8 â€‹Hz) power across all tasks over varying topographies, but these were accompanied by faster performance only in the case of translation conditions. Moreover, neural differences in PSIs were most marked for L2-L1 translation (the dominant interpreting direction in their market), which exhibited maximally widespread modulations that selectively correlated with behavioral outcomes. Taken together, our results suggest that interpreting experience involves distinct neural signatures across reading and translation mechanisms, but that these are systematically related with processing efficiency only in domains that face elevated demands during everyday practice (i.e., L2-L1 translation). These findings can inform models of simultaneous interpreting, in particular, and expert cognitive processing, in general.

Methodological considerations for a better somatosensory gating paradigm: The impact of the inter-stimulus interval.

Sensory gating (SG) is a neurophysiological phenomenon whereby the response to the second stimulus in a repetitive pair is attenuated. This filtering of irrelevant or redundant information is thought to preserve neural resources for more behaviorally-relevant stimuli and thereby reflect the functional inhibition of sensory input. Developing a SG paradigm in which optimal suppression of sensory input is achieved requires investigators to consider numerous parameters such as stimulus intensity, time between stimulus pairs, and the inter-stimulus interval (ISI) within each pair. While these factors have been well defined for the interrogation of auditory gating, the precise parameters for eliciting optimal gating in the somatosensory domain are far less understood. To address this, we investigated the impact of varying the ISI within each identical pair of stimuli on gating using magnetoencephalography (MEG). Specifically, 25 healthy young adults underwent paired-pulse electrical stimulation of the median nerve with increasing ISIs between 100 and 1000 â€‹ms (in 100 â€‹ms increments). Importantly, for correspondence with previous studies of somatosensory gating, both time-domain and oscillatory neural responses to somatosensory stimulation were evaluated. Our results indicated that gating of somatosensory input was optimal (i.e., best suppression) for trials with an ISI of 200-220 â€‹ms, as evidenced by the smallest gating ratios and through statistical modeling estimations of optimal suppression. Importantly, this was true irrespective of whether oscillatory or evoked neural activity was used to calculate SG. Interestingly, oscillatory metrics of gating calculated using peak gamma (30-75 â€‹Hz) power and frequency revealed more robust gating (i.e., smaller ratios) than those calculated using time-domain neural responses, suggesting that high frequency oscillations may provide a more sensitive measure of SG. These findings have important implications for the development of optimal protocols and analysis pipelines to interrogate SG and inhibitory processing with a higher degree of sensitivity and accuracy.

Improving visuo-motor learning with cerebellar theta burst stimulation: Behavioral and neurophysiological evidence.

The cerebellum is strongly implicated in learning new motor skills. Theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation, can be used to influence cerebellar activity. Our aim was to explore the potential of cerebellar TBS in modulating visuo-motor adaptation, a form of motor learning, in young healthy subjects. Cerebellar TBS was applied immediately before the learning phase of a visuo-motor adaptation task (VAT), in two different experiments. Firstly, we evaluated the behavioral effects of continuous (cTBS), intermittent (iTBS) or sham TBS on the learning, re-adaptation and de-adaptation phases of VAT. Subsequently, we investigated the changes induced by iTBS or sham TBS on motor cortical activity related to each phase of VAT, as measured by concomitant TMS/EEG recordings. We found that cerebellar TBS induced a robust bidirectional modulation of the VAT performance. More specifically, cerebellar iTBS accelerated visuo-motor adaptation, by speeding up error reduction in response to a novel perturbation. This gain of function was still maintained when the novel acquired motor plan was tested during a subsequent phase of re-adaptation. On the other hand, cerebellar cTBS induced the opposite effect, slowing the rate of error reduction in both learning and re-adaptation phases. Additionally, TMS/EEG recordings showed that cerebellar iTBS induced specific changes of cortical activity in the interconnected motor networks. The improved performance was accompanied by an increase of TMS-evoked cortical activity and a generalized desynchronization of TMS-evoked cortical oscillations. Taken together, our behavioral and neurophysiological findings provide the first-time multimodal evidence of the potential efficacy of cerebellar TBS in improving motor learning, by promoting successful cerebellar-cortical reorganization.

The effect of STN DBS on modulating brain oscillations: consequences for motor and cognitive behavior.

In this review, we highlight Professor John Rothwell's contribution towards understanding basal ganglia function and dysfunction, as well as the effects of subthalamic nucleus deep brain stimulation (STN DBS). The first section summarizes the rate and oscillatory models of basal ganglia dysfunction with a focus on the oscillation model. The second section summarizes the motor, gait, and cognitive mechanisms of action of STN DBS. In the final section, we summarize the effects of STN DBS on motor and cognitive tasks. The studies reviewed in this section support the conclusion that high-frequency STN DBS improves the motor symptoms of Parkinson's disease. With respect to cognition, STN DBS can be detrimental to performance especially when the task is cognitively demanding. Consolidating findings from many studies, we find that while motor network oscillatory activity is primarily correlated to the beta-band, cognitive network oscillatory activity is not confined to one band but is subserved by activity in multiple frequency bands. Because of these findings, we propose a modified motor and associative/cognitive oscillatory model that can explain the consistent positive motor benefits and the negative and null cognitive effects of STN DBS. This is clinically relevant because STN DBS should enhance oscillatory activity that is related to both motor and cognitive networks to improve both motor and cognitive performance.

The strength of alpha and gamma oscillations predicts behavioral switch costs.

Cognitive flexibility is often examined using task-switch paradigms, whereby individuals either switch between tasks or repeat the same task on successive trials. The behavioral costs of switching in terms of accuracy and reaction time are well-known, but the oscillatory dynamics underlying such costs are poorly understood. Herein, we examined 25 healthy adults who performed a task-switching paradigm during magnetoencephalography (MEG). All MEG data were transformed into the time-frequency domain and significant oscillatory responses were imaged separately per condition (i.e., switch, repeat) using a beamformer. To determine the impact of task-switching on the neural dynamics, the resulting images were examined using paired-samples t-tests. Whole-brain correlations were also computed using the switch-related difference images (switch - repeat) and the switch-related behavioral data (i.e., switch costs). Our key results indicated stronger decreases in alpha and beta activity, and greater increases in gamma activity in nodes of the cingulo-opercular and fronto-parietal networks during switch relative to repeat trials. In addition, behavioral switch costs were positively correlated with switch-related differences in right frontal and inferior parietal alpha activity, and negatively correlated with switch effects in anterior cingulate and right temporoparietal gamma activity. In other words, participants who had a greater decrease in alpha or increase in gamma in these respective regions had smaller behavioral switch costs, which suggests that these oscillations are critical to supporting cognitive flexibility. In sum, we provide novel data linking switch effects and gamma oscillations, and employed a whole-brain approach to directly link switch-related oscillatory differences with switch-related performance differences.

Load effects on spatial working memory performance are linked to distributed alpha and beta oscillations.

Increasing spatial working memory (SWM) load is generally associated with declines in behavioral performance, but the neural correlates of load-related behavioral effects remain poorly understood. Herein, we examine the alterations in oscillatory activity that accompany such performance changes in 22 healthy adults who performed a two- and four-load SWM task during magnetoencephalography (MEG). All MEG data were transformed into the time-frequency domain and significant oscillatory responses were imaged separately per load using a beamformer. Whole-brain correlation maps were computed using the load-related beamformer difference images and load-related accuracy effects on the SWM task. The results indicated that load-related differences in left inferior frontal alpha activity during encoding and maintenance were negatively correlated with load-related accuracy differences on the SWM task. That is, individuals who had more substantial decreases in prefrontal alpha during high-relative to low-load SWM trials tended to have smaller performance decrements on the high-load condition (i.e., they performed more accurately). The same pattern of neurobehavioral correlations was observed during the maintenance period for right superior temporal alpha activity and right superior parietal beta activity. Importantly, this is the first study to employ a voxel-wise whole-brain approach to significantly link load-related oscillatory differences and load-related SWM performance differences.

Resting-state MEG measurement of functional activation as a biomarker for cognitive decline in MS.

BACKGROUND: Neurophysiological measures of brain function, such as magnetoencephalography (MEG), are widely used in clinical neurology and have strong relations with cognitive impairment and dementia but are still underdeveloped in multiple sclerosis (MS). OBJECTIVES: To demonstrate the value of clinically applicable MEG-measures in evaluating cognitive impairment in MS. METHODS: In eyes-closed resting-state, MEG data of 83 MS patients and 34 healthy controls (HCs) peak frequencies and relative power of six canonical frequency bands for 78 cortical and 10 deep gray matter (DGM) areas were calculated. Linear regression models, correcting for age, gender, and education, assessed the relation between cognitive performance and MEG biomarkers. RESULTS: Increased alpha1 and theta power was strongly associated with impaired cognition in patients, which differed between cognitively impaired (CI) patients and HCs in bilateral parietotemporal cortices. CI patients had a lower peak frequency than HCs. Oscillatory slowing was also widespread in the DGM, most pronounced in the thalamus. CONCLUSION: There is a clinically relevant slowing of neuronal activity in MS patients in parietotemporal cortical areas and the thalamus, strongly related to cognitive impairment. These measures hold promise for the application of resting-state MEG as a biomarker for cognitive disturbances in MS in a clinical setting.