Closed-loop recruitment of striatal parvalbumin interneurons prevents the onset of compulsive behaviors

A prominent electrophysiological feature of compulsive behaviours is striatal hyperactivity; but its underlying dysfunctional cellular mechanisms still need to be characterized. Within the striatum, parvalbumin-positive interneurons (PVI) exert a powerful feedforward inhibition essential for the regulation of striatal activity. To investigate the potential implication of striatal PVI in aberrant repetitive behaviors, we used the Sapap3 mutant mice which exhibit compulsive-like behaviours characterized by excessive self-grooming. When striatal PVI in the centromedial striatum of Sapap3 mice were we optogenetically activated, we first showed that the number of compulsive-like events were greatly reduced. To investigate further the critical time-window when striatal PVI needed to be recruited for the behavioural regulation of compulsive-like grooming, we then designed a novel closed-loop stimulation pipeline. We identified a transient 1-4 Hz oscillations in the orbitofrontal cortex that temporally predicted grooming onsets. Exploiting this delta band signal as a biomarker, we were able to provide on-demand stimulation of striatal PVI shortly before predicted grooming events. This targeted closed-loop optogenetics approach greatly reduced grooming events and demonstrated that the recruitment of striatal PVI regulated the initiations of compulsive-like behaviours.

Alteration of Behavioral Inhibitory Control in High-Altitude Immigrants

Behavioral inhibitory control (BIC) acts as a key cognitive ability, which is essential for humans to withhold inappropriate behaviors. Meanwhile, many studies reported that long-term exposure to high altitude (HA) may affect cognitive ability. However, it is not clear whether long-term exposure to HAs may affect the BIC of an individual. To clarify the role of altitude in the behavioral control of adults and the underlying neural mechanism, we explored the BIC neural activity profiles of healthy immigrants from low-altitude (LA) regions to HA regions. Combining a two-choice oddball paradigm and electrophysiological techniques, this study monitored the N2 and P3 event-related components and neural oscillations across LA and HA groups. Results showed longer reaction times (RTs) for the HA group than the LA group. Relative to the LA group, lower N2 and P3 amplitudes were observed for the HA group. Significant positive correlations were also found between P3 amplitude and theta/delta band power across both groups. Importantly, lower theta/delta band powers were only observed for the HA group under the deviant condition. Collectively, these findings suggest that long-term exposure to HAs may attenuate BIC during the response inhibition stage and provide valuable insights into the neurocognitive implications of environmental altitude on BIC.

Decoding speech information from EEG data with 4, 7 and 11 month-old infants: Contrasting convolutional neural network, mutual information-based and backward linear models

Computational models that successfully translate neural activity into speech are multiplying in the adult literature, with non-linear convolutional neural network (CNN) approaches joining the more frequently-employed linear and mutual information (MI) models. Despite the promise of these methods for uncovering the neural basis of language acquisition by the human brain, similar studies with infants are rare. Existing infant studies rely on simpler cross-correlation and other linear techniques and aim only to establish neural tracking of the broadband speech envelope. Here, three novel computational models were applied to measure whether low-frequency speech envelope information was encoded in infant neural activity. Backward linear and CNN models were applied to estimate speech information from neural activity using linear versus nonlinear approaches, and a MI model measured how well the acoustic stimuli were encoded in infant neural responses. Fifty infants provided EEG recordings when aged 4, 7, and 11 months, while listening passively to natural speech (sung nursery rhymes) presented by video with a female singer. Each model computed speech information for these nursery rhymes in two different frequency bands, delta (1 – 4 Hz) and theta (4 – 8 Hz), thought to provide different types of linguistic information. All three models demonstrated significant levels of performance for delta-band and theta-band neural activity from 4 months of age. All models also demonstrated higher accuracy for the delta-band neural response in the infant brain. However, only the linear and MI models showed developmental (age-related) effects, and these developmental effects differed by model. Accordingly, the choice of algorithm used to decode speech envelope information from neural activity in the infant brain may determine the developmental conclusions that can be drawn. Better understanding of the strengths and weaknesses of each modelling approach will be fundamental to improving our understanding of how the human brain builds a language system.

Prefrontal, striatal, and VTA subnetwork dynamics during novelty and exploration

Multiple distinct brain areas have been implicated in memory including the prefrontal cortex (PFC), striatum (STR), and ventral tegmental area (VTA). Information-exchange across these widespread networks requires flexible coordination at a fine time-scale. In the present study, we collected high-density recordings from the PFC, STR, and VTA of male rats during baseline, encoding, consolidation, and retrieval stages of memory formation. Novel sub-regional clustering analyses identified patterns of spatially restricted, temporally coherent, and frequency specific signals that were reproducible across days and were modulated by behavioral states. Clustering identified miniscule patches of neural tissue. Generalized eigen decomposition (GED) reduced each cluster to a single time series. Amplitude envelope correlation of the cluster time series was used to assess functional connectivity between clusters. Dense intra- and inter regional functional connectivity characterized the baseline period, with delta oscillations playing an outsized role. There was a dramatic pruning of network connectivity during encoding. Connectivity rebounded during consolidation, but connections in the theta band became stronger, and those in the delta band were weaker. Finally, during retrieval, connections were not as severely reduced as they had been during encoding, and specifically theta and higher-frequency connections were stronger. Underlying these connectivity changes, the anatomical extent of clusters observed in the gamma band in the PFC and in both the gamma and delta bands in the VTA changed markedly across behavioral conditions. These results demonstrate the brain's ability to reorganize functionally at both the intra- and inter-regional levels during different stages of memory processing.

Altered Effective Connectivity in Migraine Patients During Emotional Stimuli: a Multi-frequency Magnetoencephalography Study.

Background: Migraine is a common and disabling primary headache associated with a wide range of psychiatric comorbidities. However, the mechanisms of emotion processing in migraine are not fully understood yet. The present study was designed to investigate the neural network during neutral, positive，and negative emotional stimuli in migraine suffers.Methods: We enrolled 24 migraine suffers and 24 age- and sex-matched controls in this study. Neuromagnetic brain activity was recorded by using a whole-head magnetoencephalography (MEG) system towards human faces expression pictures. MEG data were analyzed in the multi-frequency band of 1–100 Hz.Results: Migraine patients exhibited significantly enhanced effective connectivity from the prefrontal lobe to the temporal cortex during negative emotional stimuli in the gamma band(30-90Hz). Graph theory analysis revealed that patients had (1) an increased degree and clustering coefficient of connectivity in the delta band(1-4Hz) during positive emotional stimuli; (2) an increased degree of connectivity in the delta band(1-4Hz) during negative emotional stimuli.Conclusion: The results suggested individuals with migraine showed deviant effective connectivity when viewing human facial expressions in multi-frequency. The prefrontal-temporal pathway might be related to the altered negative emotion modulation in migraine. These findings may contribute to understanding the mechanism of the comorbidity of depression and anxiety in migraine and provide references for the comprehensive therapeutic plan.

Reorganization of Brain Functional Connectivity Network and Vision Restoration Following Combined tACS-tDCS Treatment After Occipital Stroke

Objective: Non-invasive brain stimulation (NIBS) is already known to improve visual field functions in patients with optic nerve damage and partially restores the organization of brain functional connectivity networks (FCNs). However, because little is known if NIBS is effective also following brain damage, we now studied the correlation between visual field recovery and FCN reorganization in patients with stroke of the central visual pathway.Method: In a controlled, exploratory trial, 24 patients with hemianopia were randomly assigned to one of three brain stimulation groups: transcranial direct current stimulation (tDCS)/transcranial alternating current stimulation (tACS) (ACDC); sham tDCS/tACS (AC); sham tDCS/sham tACS (Sham), which were compared to age-matched controls (n = 24). Resting-state electroencephalogram (EEG) was collected at baseline, after 10 days stimulation and at 2 months follow-up. EEG recordings were analyzed for FCN measures using graph theory parameters, and FCN small worldness of the network and long pairwise coherence parameter alterations were then correlated with visual field performance.Result: ACDC enhanced alpha-band FCN strength in the superior occipital lobe of the lesioned hemisphere at follow-up. A negative correlation (r = −0.80) was found between the intact visual field size and characteristic path length (CPL) after ACDC with a trend of decreased alpha-band centrality of the intact middle occipital cortex. ACDC also significantly decreased delta band coherence between the lesion and the intact occipital lobe, and coherence was enhanced between occipital and temporal lobe of the intact hemisphere in the low beta band. Responders showed significantly higher strength in the low alpha band at follow-up in the intact lingual and calcarine cortex and in the superior occipital region of the lesioned hemisphere.Conclusion: While ACDC decreases delta band coherence between intact and damaged occipital brain areas indicating inhibition of low-frequency neural oscillations, ACDC increases FCN connectivity between the occipital and temporal lobe in the intact hemisphere. When taken together with the lower global clustering coefficient in responders, these findings suggest that FCN reorganization (here induced by NIBS) is adaptive in stroke. It leads to greater efficiency of neural processing, where the FCN requires fewer connections for visual processing.

Sequential Temporal Anticipation Characterized by Neural Power Modulation and in Recurrent Neural Networks

Complex human behaviors involve perceiving continuous stimuli and planning actions at sequential time points, such as in perceiving/producing speech and music. To guide adaptive behavior, the brain needs to internally anticipate a sequence of prospective moments. How does the brain achieve this sequential temporal anticipation without relying on any external timing cues? To answer this question, we designed a premembering task: we tagged three temporal locations in white noise by asking human listeners to detect a tone presented at one of the temporal locations. We selectively probed the anticipating processes guided by memory in trials with only flat noise using novel modulation analyses. A multiscale anticipating scheme was revealed: the neural power modulation in the delta band encodes noise duration on a supra-second scale; the modulations in the alpha-beta band range mark the tagged temporal locations on a subsecond scale and correlate with tone detection performance. To unveil the functional role of those neural observations, we turned to recurrent neural networks (RNNs) optimized for the behavioral task. The RNN hidden dynamics resembled the neural modulations; further analyses and perturbations on RNNs suggest that the neural power modulations in the alpha/beta band emerged as a result of selectively suppressing irrelevant noise periods and increasing sensitivity to the anticipated temporal locations. Our neural, behavioral, and modelling findings convergingly demonstrate that the sequential temporal anticipation involves a process of dynamic gain control: to anticipate a few meaningful moments is also to actively ignore irrelevant events that happen most of the time.

Functional Connectivity Alterations Based on the Weighted Phase Lag Index: An Exploratory Electroencephalography Study on Alzheimer’s Disease

Objectives: Numerous electroencephalography (EEG) studies focus on the alteration of electrical activity in patients with Alzheimer’s Disease (AD), but there are no consistent results es- pecially regarding functional connectivity. We supposed that the weighted Phase Lag Index (w- PLI), as phase-based measures of functional connectivity, may be used as an auxiliary diagnostic method for AD. Methods: We enrolled 30 patients with AD, 30 patients with Mild Cognitive Impairment (MCI), and 30 Healthy Controls (HC). EEGs were recorded in all participants at baseline during relaxed wakefulness. Following EEG preprocessing, Power Spectral Density (PSD) and wPLI parameters were determined to further analyze whether they were correlated to cognitive scores. Results: In the patients with AD, the increased PSD in theta band was presented compared with MCI and HC groups, which was associated with disturbances of the directional, computational, and delayed memory capacity. Furthermore, the wPLI revealed a distinctly lower connection strength between frontal and distant areas in the delta band and a higher connection strength of the central and temporo-occipital region in the theta band for AD patients. Moreover,we found a significant negative correlation between theta functional connectivity and cognitive scores. Conclusions: Increased theta PSD and decreased delta wPLI may be one of the earliest changes in AD and associated with disease severity. The parameter wPLI is a novel measurement of phase synchronization and has potentials in understanding underlying functional connectivity and aiding in the diagnostics of AD.

Amphetamine alters the Reward Positivity in humans and mice

The development of pro-cognitive therapeutics for psychiatric disorders has been beset with difficulties. This is in part due to the absence of pharmacologically-sensitive cognitive biomarkers common to humans and rodents. Here, we describe a cross-species translational measure of reward processing that is sensitive to the dopamine agonist, d-amphetamine. Motivated by human electroencephalographic (EEG) findings, we recently reported that frontal midline delta-band power is also an electrophysiological biomarker of reward surprise in mice. Here, we determined the impact on this reward-related EEG response from humans (n=23) and mice (n=28) performing a probabilistic learning task under parametric doses of d-amphetamine (human: placebo, 10 mg, 20 mg; mice: placebo, 0.1 mg/kg, 0.3 mg.kg, 1.0 mg/kg). In humans, d-amphetamine boosted the Reward Positivity event-related potential (ERP) component as well as the spectral delta-band representation of this signal. In mice, only the Reward Positivity ERP component was significantly boosted by d-amphetamine. In sum, the present results confirm the role of dopamine in the generation of the Reward Positivity, and support the first pharmacologically valid biomarker of reward sensitivity across species.

Classification of Body Position During Muslim Prayer Using the Convolutional Neural Network

Background: Muslim prayer (Namaz) is the most important obligatory religious duty in Islam that is regularly performed five times per day at specific prescribed times by Muslims. Due to the fact that change of body position affects brain activity, Namaz can be considered as a suitable model to assess the effect of quick changes of the body position on brain activity measured by electroencephalography (EEG). Methods: Forty Muslim participants performed a four-cycle Namaz while their brain activity was being recorded using a 14-channel EEG recorder. The brain connectivity (as defined by a mutual correlation between EEG channels in this study) in different frequency bands (delta, theta, alpha, beta, and gamma) was measured in various positions of Namaz including standing, bowing, prostration, and sitting. Results: The results indicated that the delta band demonstrates the most changes in cross-correlation between the recorded channels, and finally, the accuracy of 73.8% was obtained in the data classification.