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Memory loss is one of the first symptoms of typical Alzheimer's disease (AD), for which there are no effective therapies available. The precuneus (PC) has been recently emphasized as a key area for the memory impairment observed in early AD, likely due to disconnection mechanisms within large-scale networks such as the default mode network (DMN). Using a multimodal approach we investigated in a two-week, randomized, sham-controlled, double-blinded trial the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the PC on cognition, as measured by the Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite in 14 patients with early AD (7 females). TMS combined with electroencephalography (TMS-EEG) was used to detect changes in brain connectivity. We found that rTMS of the PC induced a selective improvement in episodic memory, but not in other cognitive domains. Analysis of TMS-EEG signal revealed an increase of neural activity in patients' PC, an enhancement of brain oscillations in the beta band and a modification of functional connections between the PC and medial frontal areas within the DMN. Our findings show that high-frequency rTMS of the PC is a promising, non-invasive treatment for memory dysfunction in patients at early stages of AD. This clinical improvement is accompanied by modulation of brain connectivity, consistently with the pathophysiological model of brain disconnection in AD. •The precuneus is a key area for memory impairment in Alzheimer’s disease (AD).•We investigated the effects of precuneus-rTMS on memory in patients with early AD.•Precuneus-rTMS induced a selective improvement in episodic memory.•Precuneus-rTMS enhance precuneus activity and connectivity with frontal areas.•Precuneus-rTMS is a promising treatment for memory dysfunction in early AD patients.

The EEG/MEG signal is generated primarily by the summation of the post-synaptic potentials of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons and cortical oscillations are thought to be dependent on the balance of excitation and inhibition between these cell types. To investigate the dependence of movement-related cortical oscillations on excitation–inhibition balance, we pharmacologically manipulated the GABA system using tiagabine, which blocks GABA Transporter 1(GAT-1), the GABA uptake transporter and increases endogenous GABA activity. In a blinded, placebo-controlled, crossover design, in 15 healthy participants we administered either 15mg of tiagabine or a placebo. We recorded whole-head magnetoencephalograms, while the participants performed a movement task, prior to, one hour post, three hour post and five hour post tiagabine ingestion. Using time-frequency analysis of beamformer source reconstructions, we quantified the baseline level of beta activity (15–30Hz), the post-movement beta rebound (PMBR), beta event-related desynchronisation (beta-ERD) and movement-related gamma synchronisation (MRGS) (60–90Hz). Our results demonstrated that tiagabine, and hence elevated endogenous GABA levels causes, an elevation of baseline beta power, enhanced beta-ERD and reduced PMBR, but no modulation of MRGS. Comparing our results to recent literature (Hall et al., 2011) we suggest that beta-ERD may be a GABAA receptor mediated process while PMBR may be GABAB receptor mediated. ► Recorded MEG during a movement task before and after tiagabine or placebo ► Tiagabine elevates the activity of endogenous GABA. ► Results showed increased beta-ERD, decreased PMBR and no change in MRGS. ► It is suggested that beta-ERD depends on GABAA while PMBR depends on GABAB.

Neurofeedback of self-regulated brain activity in circumscribed cortical regions is used as a novel strategy to facilitate functional restoration following stroke. Basic knowledge about its impact on motor system oscillations and functional connectivity is however scarce. Specifically, a direct comparison between different feedback modalities and their neural signatures is missing. We assessed a neurofeedback training intervention of modulating β-activity in circumscribed sensorimotor regions by kinesthetic motor imagery (MI). Right-handed healthy participants received two different feedback modalities contingent to their MI-associated brain activity in a cross-over design: (I) visual feedback with a brain–computer interface (BCI) and (II) proprioceptive feedback with a brain–robot interface (BRI) orthosis attached to the right hand. High-density electroencephalography was used to examine the reactivity of the cortical motor system during the training session of each task by studying both local oscillatory power entrainment and distributed functional connectivity. Both feedback modalities activated a distributed functional connectivity network of coherent oscillations. A significantly higher skill and lower variability of self-controlled sensorimotor β-band modulation could, however, be achieved in the BRI condition. This gain in controlling regional motor oscillations was accompanied by functional coupling of remote β-band and θ-band activity in bilateral fronto-central regions and left parieto-occipital regions, respectively. The functional coupling of coherent θ-band oscillations correlated moreover with the skill of regional β-modulation thus revealing a motor learning related network. Our findings indicate that proprioceptive feedback is more suitable than visual feedback to entrain the motor network architecture during the interplay between motor imagery and feedback processing thus resulting in better volitional control of regional brain activity. [Display omitted] •Proprioceptive input is superior to visual input to entrain the motor network during neurofeedback.•Proprioceptive feedback increases self-control of regional β-band modulation.•Proprioceptive feedback entrains motor functional connectivity in the θ- and β-band.•Large-scale functional connectivity in θ-band correlates with regional β-band control.

The development of neural circuits has long-lasting effects on brain function, yet our understanding of early circuit development in humans remains limited. Here, periodic EEG power features and aperiodic components were examined from longitudinal EEGs collected from 592 healthy 2–44 month-old infants, revealing age-dependent nonlinear changes suggestive of distinct milestones in early brain maturation. Developmental changes in periodic peaks include (1) the presence and then absence of a 9-10 Hz alpha peak between 2-6 months, (2) nonlinear changes in high beta peaks (20-30 Hz) between 4-18 months, and (3) the emergence of a low beta peak (12-20 Hz) in some infants after six months of age. We hypothesized that the emergence of the low beta peak may reflect maturation of thalamocortical network development. Infant anesthesia studies observe that GABA-modulating anesthetics do not induce thalamocortical mediated frontal alpha coherence until 10-12 months of age. Using a small cohort of infants ( n  = 23) with EEG before and during GABA-modulating anesthesia, we provide preliminary evidence that infants with a low beta peak have higher anesthesia-induced alpha coherence compared to those without a low beta peak. Using longitudinal EEG data from 592 infants and toddlers, the authors identify age-dependent nonlinear changes in periodic alpha and beta peaks suggestive of distinct milestones in early brain maturation, including thalamocortical network development.

Spontaneous brain activity at rest is highly organized even when the brain is not explicitly engaged in a task. Functional connectivity (FC) in the alpha frequency band (α, 8–12 Hz) during rest is associated with improved performance on various cognitive and motor tasks. In this study we explored how FC is associated with visuo-motor skill learning and offline consolidation. We tested two hypotheses by which resting-state FC might achieve its impact on behavior: preparing the brain for an upcoming task or consolidating training gains. Twenty-four healthy participants were assigned to one of two groups: The experimental group (n = 12) performed a computerized mirror-drawing task. The control group (n = 12) performed a similar task but with concordant cursor direction. High-density 156-channel resting-state EEG was recorded before and after learning. Subjects were tested for offline consolidation 24h later. The Experimental group improved during training and showed offline consolidation. Increased α-FC between the left superior parietal cortex and the rest of the brain before training and decreased α-FC in the same region after training predicted learning. Resting-state FC following training did not predict offline consolidation and none of these effects were present in controls. These findings indicate that resting-state alpha-band FC is primarily implicated in providing optimal neural resources for upcoming tasks. •Learning and offline consolidation of mirror-drawing skills are evaluated.•EEG resting-state predicts learning but not offline consolidation.•Modulations of resting state are apparent at the alpha-band in left parietal areas.•Alpha-band resting-state provides the optimal neural resources for upcoming tasks.

•Randomized, sham-controlled, within-subject study of β-tACS in younger adults.•Fixed 20 Hz-, individualized β-, and sham EEG-tACS during a bimanual motor task.•Individualized β-tACS improved bimanual motor control versus fixed- and sham tACS.•Individualized β-tACS enhanced N β desynchronization during planning.•β desynchronization was only related to motor control improvements during planning. To unveil if 3 mA peak-to-peak high-definition β transcranial alternating current stimulation (tACS) applied over C4 –the area overlaying the right sensorimotor cortex–enhances bimanual motor control and affects movement-related β desynchronization (MRβD), thereby providing causal evidence for the polymorphic role of MRβD in motor control. In this sham-controlled, crossover study, 36 participants underwent 20 min of fixed 20 Hz tACS; tACS individualized to peak β activity during motor planning at baseline; and sham tACS randomized over three consecutive days. Each participant underwent all three conditions for a total of 108 sessions, ensuring within-subject comparisons. Before, during, and after tACS, participants performed a bimanual tracking task (BTT) and 64-channel electroencephalography (EEG) data was measured. Spatiotemporal and temporal clustering statistics with underlying linear mixed effect models were used to test our hypotheses. Individualized tACS significantly improved bimanual motor control, both online and offline, and increased online MRβD during motor planning compared to fixed tACS. No offline effects of fixed and individualized tACS on MRβD were found compared to sham, although tACS effects did trend towards the hypothesized MRβD increase. Throughout the course of the study, MRβD and bimanual motor performance increased. Exclusively during motor planning, MRβD was positively associated to bimanual motor performance improvements, emphasizing the functionally polymorphic role of MRβD. tACS was well tolerated and no side-effects occurred. Individualized β-tACS improves bimanual motor control and enhances motor planning MRβD online. These findings provide causal evidence for the importance of MRβD when planning complex motor behavior. [Display omitted]

Enhanced oscillations at beta frequencies (8–30 Hz) are a signature neural dynamic pathology in the basal ganglia and cortex of Parkinson's disease patients. The mechanisms underlying these pathological beta oscillations remain elusive. Here, using mathematical models, we find that robust beta oscillations can emerge from inhibitory interactions between striatal medium spiny neurons. The interaction of the synaptic GABAa currents and the intrinsic membrane M-current promotes population oscillations in the beta frequency range. Increased levels of cholinergic drive, a condition relevant to the parkinsonian striatum, lead to enhanced beta oscillations in the striatal model. We show experimentally that direct infusion of the cholinergic agonist carbachol into the striatum, but not into the neighboring cortex, of the awake, normal rodent induces prominent beta frequency oscillations in the local field potential. These results provide evidence for amplification of normal striatal network dynamics as a mechanism responsible for the enhanced beta frequency oscillations in Parkinson's disease.

•PAPTO disambiguates transient events from aperiodic neural activity.•PAPTO is highly sensitive to neocortical beta oscillations.•Sensorimotor beta event rate almost doubles over the adult lifespan.•Findings may explain age-related decline in sensory perception. Two techniques for analyzing human extracranial neurophysiological signals, namely the periodic/aperiodic parameterization of neural power spectra and the transient events framework of oscillatory activity, have recently emerged in the scientific literature. In this work, we integrate these two analysis perspectives to analyze extracranial neurophysiological signals as a series of transient rhythmic events disambiguated from the background aperiodic activity. We call this novel technique the periodic/aperiodic parametrization of transient oscillations (PAPTO). We demonstrate PAPTO by investigating resting-state sensorimotor magnetoencephalography recordings from the Cambridge Center for Ageing and Neuroscience cross-sectional study on healthy ageing (n = 600, ages 18–88). We show that PAPTO is more sensitive to neocortical transient beta rhythms compared to more conventional transient event detection algorithms and captures more variance in the resting-state occurrence rate of beta events across participants. The improved sensitivity of PAPTO reveals that the beta occurrence rate almost doubles over the adult lifespan which we discuss in terms of thalamocortical beta generation in the somatosensory cortex and the age-related decline of sensory perception.

Our recent study demonstrated that prefrontal transcranial photobiomodulation (tPBM) with 1064-nm laser enables significant changes in EEG rhythms, but these changes might result from the laser-induced heat rather than tPBM. This study hypothesized that tPBM-induced and heat-induced alterations in EEG power topography were significantly distinct. We performed two sets of measurements from two separate groups of healthy humans under tPBM (n = 46) and thermal stimulation (thermo_stim; n = 11) conditions. Each group participated in the study twice under true and respective sham stimulation with concurrent recordings of 64-channel EEG before, during, and after 8-min tPBM at 1064 nm or thermo_stim with temperature of 33–41 °C, respectively. After data preprocessing, EEG power spectral densities (PSD) per channel per subject were quantified and normalized by respective baseline PSD to remove the power-law effect. At the group level for each group, percent changes of EEG powers per channel were statistically compared between (1) tPBM vs light-stimulation sham, (2) thermo_stim vs heat-stimulation sham, and (3) tPBM vs thermo_stim after sham exclusion at five frequency bands using the non-parametric permutation tests. By performing the false discovery rate correction for multi-channel comparisons, we showed by EEG power change topographies that (1) tPBM significantly increased EEG alpha and beta powers, (2) the thermal stimulation created opposite effects on EEG power topographic patterns, and (3) tPBM and thermal stimulations induced significantly different topographies of changes in EEG alpha and beta power. Overall, this study provided evidence to support our hypothesis, showing that the laser-induced heat on the human forehead is not a mechanistic source causing increases in EEG power during and after tPBM.

Understanding and improving memory are vital to enhance human life. Theta rhythm is associated with memory consolidation and coding, but the trainability and effects on long-term memory of theta rhythm are unknown. This study investigated the ability to improve long-term memory using a neurofeedback (NFB) technique reflecting the theta/low-beta power ratio on an electroencephalogram (EEG). Our study consisted of three stages. First, the long-term memory of participants was measured. In the second stage, the participants in the NFB group received 3 days of theta/low-beta NFB training. In the third stage, the long-term memory was measured again. The NFB group had better episodic and semantic long-term memory than the control group and significant differences in brain activity between episodic and semantic memory during the recall tests were revealed. These findings suggest that it is possible to improve episodic and semantic long-term memory abilities through theta/low-beta NFB training.