Attentional state-synchronous peripheral electrical stimulation during action observation induced distinct modulation of corticospinal plasticity after stroke.

Introduction: Brain computer interface-based action observation (BCI-AO) is a promising technique in detecting the user's cortical state of visual attention and providing feedback to assist rehabilitation. Peripheral nerve electrical stimulation (PES) is a conventional method used to enhance outcomes in upper extremity function by increasing activation in the motor cortex. In this study, we examined the effects of different pairings of peripheral nerve electrical stimulation (PES) during BCI-AO tasks and their impact on corticospinal plasticity. Materials and methods: Our innovative BCI-AO interventions decoded user's attentive watching during task completion. This process involved providing rewarding visual cues while simultaneously activating afferent pathways through PES. Fifteen stroke patients were included in the analysis. All patients underwent a 15 min BCI-AO program under four different experimental conditions: BCI-AO without PES, BCI-AO with continuous PES, BCI-AO with triggered PES, and BCI-AO with reverse PES application. PES was applied at the ulnar nerve of the wrist at an intensity equivalent to 120% of the sensory threshold and a frequency of 50 Hz. The experiment was conducted randomly at least 3 days apart. To assess corticospinal and peripheral nerve excitability, we compared pre and post-task (post 0, post 20 min) parameters of motor evoked potential and F waves under the four conditions in the muscle of the affected hand. Results: The findings indicated that corticospinal excitability in the affected hemisphere was higher when PES was synchronously applied with AO training, using BCI during a state of attentive watching. In contrast, there was no effect on corticospinal activation when PES was applied continuously or in the reverse manner. This paradigm promoted corticospinal plasticity for up to 20 min after task completion. Importantly, the effect was more evident in patients over 65 years of age. Conclusion: The results showed that task-driven corticospinal plasticity was higher when PES was applied synchronously with a highly attentive brain state during the action observation task, compared to continuous or asynchronous application. This study provides insight into how optimized BCI technologies dependent on brain state used in conjunction with other rehabilitation training could enhance treatment-induced neural plasticity.

Single-trial EEG analysis reveals burst structure during photic driving.

OBJECTIVE: Photic driving in the human visual cortex evoked by intermittent photic stimulation is usually characterized in averaged data by an ongoing oscillation showing frequency entrainment and resonance phenomena during the course of stimulation. We challenge this view of an ongoing oscillation by analyzing unaveraged data. METHODS: 64-channel EEGs were recorded during visual stimulation with light flashes at eight stimulation frequencies between 7.8 and 23 Hz for fourteen healthy volunteers. Time-frequency analyses were performed in averaged and unaveraged data. RESULTS: While we find ongoing oscillations in the averaged data during intermittent photic stimulation, we find transient events (bursts) of activity in the unaveraged data. Both resonance and entrainment occur for the ongoing oscillations in the averaged data and the bursts in the unaveraged data. CONCLUSIONS: We argue that the continuous oscillations in the averaged signal may be composed of brief, transient bursts in single trials. Our results can also explain previously observed amplitude fluctuations in averaged photic driving data. SIGNIFICANCE: Single-trial analyses might consequently improve our understanding of resonance and entrainment phenomena in the brain.

Dopamine D4 Receptor Agonist Drastically Increases Delta Activity in the Thalamic Nucleus Reuniens: Potential Role in Communication between Prefrontal Cortex and Hippocampus.

Network oscillations are essential for all cognitive functions. Oscillatory deficits are well established in psychiatric diseases and are recapitulated in animal models. They are significantly and specifically affected by pharmacological interventions using psychoactive compounds. Dopamine D4 receptor (D4R) activation was shown to enhance gamma rhythm in freely moving rats and to specifically affect slow delta and theta oscillations in the urethane-anesthetized rat model. The goal of this study was to test the effect of D4R activation on slow network oscillations at delta and theta frequencies during wake states, potentially supporting enhanced functional connectivity during dopamine-induced attention and cognitive processing. Network activity was recorded in the prefrontal cortex (PFC), hippocampus (HC) and nucleus reuniens (RE) in control conditions and after injecting the D4R agonist A-412997 (3 and 5 mg/kg; systemic administration). We found that A-412997 elicited a lasting (~40 min) wake state and drastically enhanced narrow-band delta oscillations in the PFC and RE in a dose-dependent manner. It also preferentially enhanced delta synchrony over theta coupling within the PFC-RE-HC circuit, strongly strengthening PFC-RE coupling. Thus, our findings indicate that the D4R may contribute to cognitive processes, at least in part, through acting on wake delta oscillations and that the RE, providing an essential link between the PFC and HC, plays a prominent role in this mechanism.

An autonomic mode of brain activity.

The relevance of interactions between autonomic and central nervous systems remains unclear for human brain function and health, particularly when both systems are challenged under sleep deprivation (SD). We measured brain activity (with fMRI), pulse and respiratory signals, and baseline brain amyloid beta burden (with PET) in healthy participants. We found that SD relative to rested wakefulness (RW) resulted in a significant increase in synchronized low frequency (LF, < 0.1 Hz) activity in an autonomically-related network (AN), including dorsal attention, visual, and sensorimotor regions, which we previously found to have consistent temporal coupling with LF pulse signal changes (regulated by sympathetic tone). SD resulted in a significant phase coherence between the LF component of the pulse signal and a medial network with peak effects in the midbrain reticular formation, and between LF component of the respiratory variations (regulated by respiratory motor output) and a cerebellar network. The LF power of AN during SD was significantly and independently correlated with pulse-medial network and respiratory-cerebellar network phase coherences (total adjusted R2 = 0.78). Higher LF power of AN during SD (but not RW) was associated with lower amyloid beta burden (Cohen's d = 0.8). In sum, SD triggered an autonomic mode of synchronized brain activity that was associated with distinct autonomic-central interactions. Findings highlight the direct relevance of global cortical synchronization to brain clearance mechanisms.

Decreased Gamma Auditory Steady-State Response Is Associated With Impaired Real-World Functioning in Unmedicated Patients at Clinical High Risk for Psychosis.

AIM: Deficits in synchronous, gamma-frequency neural oscillations may contribute to schizophrenia patients' real-world functional impairment and can be measured electroencephalographically using the auditory steady-state response (ASSR). Gamma ASSR deficits have been reported in schizophrenia patients and individuals at clinical high risk (CHR) for developing psychosis. We hypothesized that, in CHR patients, gamma ASSR would correlate with real-world functioning, consistent with a role for gamma synchrony deficits in functional impairment. METHODS: A total of 35 CHR patients rated on Global Functioning: Social and Role scales had EEG recorded while listening to 1-ms, 93-dB clicks presented at 40 Hz in 500-ms trains, in response to which 40-Hz evoked power and intertrial phase-locking factor (PLF) were measured. RESULTS: In CHR patients, lower 40-Hz PLF correlated with lower social functioning. CONCLUSIONS: Gamma synchrony deficits may be a biomarker of real-world impairment at early stages of the schizophrenia disease trajectory.

Prefrontal high gamma during a magnetoencephalographic working memory task.

In human electrophysiology research, the high gamma part of the power spectrum (~>60 Hz) is a relatively new area of investigation. Despite a low signal-to-noise ratio, evidence exists that it contains significant information about activity in local cortical networks. Here, using magnetoencephalography (MEG), we found high gamma activity when comparing data from an n-back working memory task to resting data in a large sample of normal volunteers. Initial analysis of power spectra from 0-back, 2-back, and rest trials showed three frequency bands exhibiting task-related differences: alpha, beta, and high gamma. Unlike alpha and beta, the high gamma spectrum was broad, without a peak at a single frequency. In addition, power in high gamma was highest for the 2-back and lowest during rest, while the opposite pattern occurred in the other bands. Beamformer source localization of each of the three frequency bands revealed a distinct set of sources for high gamma. These included several regions of prefrontal cortex that exhibited greater power when both n-back conditions were compared to rest. A subset of these regions had more power when the 2-back was compared to 0-back, which indicates a role in working memory performance. Our results show that high gamma will be important for understanding cortical processing during cognitive and other tasks. Furthermore, data from human intracortical recordings suggest that high gamma is the aggregate of spiking in local cortical networks, which implies that MEG could serve to bridge experimental modalities by noninvasively observing task-related modulation of spiking rates.

Neural network topology in ADHD; evidence for maturational delay and default-mode network alterations.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) has been associated with widespread brain abnormalities in white and grey matter, affecting not only local, but global functional networks as well. In this study, we explored these functional networks using source-reconstructed electroencephalography in ADHD and typically developing (TD) children. We expected evidence for maturational delay, with underlying abnormalities in the default mode network. METHODS: Electroencephalograms were recorded in ADHD (n=42) and TD (n=43) during rest, and functional connectivity (phase lag index) and graph (minimum spanning tree) parameters were derived. Dependent variables were global and local network metrics in theta, alpha and beta bands. RESULTS: We found evidence for a more centralized functional network in ADHD compared to TD children, with decreased diameter in the alpha band (ηp2=0.06) and increased leaf fraction (ηp2=0.11 and 0.08) in the alpha and beta bands, with underlying abnormalities in hub regions of the brain, including default mode network. CONCLUSIONS: The finding of a more centralized network is in line with maturational delay models of ADHD and should be replicated in longitudinal designs. SIGNIFICANCE: This study contributes to the literature by combining high temporal and spatial resolution to construct EEG network topology, and associates maturational-delay and default-mode interference hypotheses of ADHD.

Orexin and Epilepsy: Potential Role of REM Sleep.

Interest in orexin receptor antagonism as a novel mechanism of action against seizures and epilepsy has increased in recent years. Loss of orexinergic activity is associated with rapid eye movement (REM) sleep onset, and REM sleep is generally protective against seizures. This paper discusses the dynamic modulation of seizure threshold by orexin through a postulated "orexi-cortical" axis in which the specific type of orexinergic activity exquisitely regulates sleep-wake states to modify ascending subcortical influences on cortical synchronization with profound subsequent consequences on seizure threshold. This paper also explores the current state of research into experimental orexinergic modulation of seizure threshold and suggests possible future research directions to fully understand the promise and peril of orexinergic manipulation in seizures and epilepsy.

Atypical neural synchronization to speech envelope modulations in dyslexia.

A fundamental deficit in the synchronization of neural oscillations to temporal information in speech could underlie phonological processing problems in dyslexia. In this study, the hypothesis of a neural synchronization impairment is investigated more specifically as a function of different neural oscillatory bands and temporal information rates in speech. Auditory steady-state responses to 4, 10, 20 and 40Hz modulations were recorded in normal reading and dyslexic adolescents to measure neural synchronization of theta, alpha, beta and low-gamma oscillations to syllabic and phonemic rate information. In comparison to normal readers, dyslexic readers showed reduced non-synchronized theta activity, reduced synchronized alpha activity and enhanced synchronized beta activity. Positive correlations between alpha synchronization and phonological skills were found in normal readers, but were absent in dyslexic readers. In contrast, dyslexic readers exhibited positive correlations between beta synchronization and phonological skills. Together, these results suggest that auditory neural synchronization of alpha and beta oscillations is atypical in dyslexia, indicating deviant neural processing of both syllabic and phonemic rate information. Impaired synchronization of alpha oscillations in particular demonstrated to be the most prominent neural anomaly possibly hampering speech and phonological processing in dyslexic readers.

Basal ganglia impairments in autism spectrum disorder are related to abnormal signal gating to prefrontal cortex.

Research on the biological basis of autism spectrum disorder has yielded a list of brain abnormalities that are arguably as diverse as the set of behavioral symptoms that characterize the disorder. Among these are patterns of abnormal cortical connectivity and abnormal basal ganglia development. In attempts to integrate the existing literature, the current paper tests the hypothesis that impairments in the basal ganglia's function to flexibly select and route task-relevant neural signals to the prefrontal cortex underpins patterns of abnormal synchronization between the prefrontal cortex and other cortical processing centers observed in individuals with autism spectrum disorder (ASD). We tested this hypothesis using a Dynamic Causal Modeling analysis of neuroimaging data collected from 16 individuals with ASD (mean age=25.3 years; 6 female) and 17 age- and IQ-matched neurotypical controls (mean age=25.6, 6 female), who performed a Go/No-Go test of executive functioning. Consistent with the hypothesis tested, a random-effects Bayesian model selection procedure determined that a model of network connectivity in which basal ganglia activation modulated connectivity between the prefrontal cortex and other key cortical processing centers best fit the data of both neurotypicals and individuals with ASD. Follow-up analyses suggested that the largest group differences were observed for modulation of connectivity between prefrontal cortex and the sensory input region in the occipital lobe [t(31)=2.03, p=0.025]. Specifically, basal ganglia activation was associated with a small decrease in synchronization between the occipital region and prefrontal cortical regions in controls; however, in individuals with ASD, basal ganglia activation resulted in increased synchronization between the occipital region and the prefrontal cortex. We propose that this increased synchronization may reflect a failure in basal ganglia signal gating mechanisms, resulting in a non-selective copying of signals to prefrontal cortex. Such a failure to prioritize and filter signals to the prefrontal cortex could result in the pervasive impairments in cognitive flexibility and executive functioning that characterize autism spectrum disorder, and may offer a mechanistic explanation of some of the observed abnormalities in patterns of cortical synchronization in ASD.

Induced Gamma-Band Activity During Voluntary Movement: EEG Analysis for Clinical Purposes.

OBJECTIVE: Propose a simplified method applicable in routine clinical practice that uses EEG to assess induced gamma-band activity (GBA) in the 30-90 Hz frequency range in cerebral motor areas. DESIGN: EEG recordings (25 healthy subjects) of cerebral activity (at rest, motor task). GBA was obtained as power spectral density (PSD). GBA - defined as the gamma index (Iγ) - was calculated using the basal GBA (γB) and motor GBA (γMOV) PSD values. RESULTS: The mean values of Iγ were (IγR (right hand) = 1.30, IγL (left hand) = 1.22). Manual laterality showed a correlation with Iγ. CONCLUSIONS: Iγ may provide a useful way of indirectly assessing operation of activated motor neuronal circuits. It could be applied to diagnosis of motor area pathologies and as follow up in rehabilitation processes. Likewise, Iγ could enable the assessment of motor capacity, physical training and manual laterality in sport medicine.

An in vitro method to manipulate the direction and functional strength between neural populations.

We report the design and application of a Micro Electro Mechanical Systems (MEMs) device that permits investigators to create arbitrary network topologies. With this device investigators can manipulate the degree of functional connectivity among distinct neural populations by systematically altering their geometric connectivity in vitro. Each polydimethylsilxane (PDMS) device was cast from molds and consisted of two wells each containing a small neural population of dissociated rat cortical neurons. Wells were separated by a series of parallel micrometer scale tunnels that permitted passage of axonal processes but not somata; with the device placed over an 8 × 8 microelectrode array, action potentials from somata in wells and axons in microtunnels can be recorded and stimulated. In our earlier report we showed that a one week delay in plating of neurons from one well to the other led to a filling and blocking of the microtunnels by axons from the older well resulting in strong directionality (older to younger) of both axon action potentials in tunnels and longer duration and more slowly propagating bursts of action potentials between wells. Here we show that changing the number of tunnels, and hence the number of axons, connecting the two wells leads to changes in connectivity and propagation of bursting activity. More specifically, the greater the number of tunnels the stronger the connectivity, the greater the probability of bursting propagating between wells, and shorter peak-to-peak delays between bursts and time to first spike measured in the opposing well. We estimate that a minimum of 100 axons are needed to reliably initiate a burst in the opposing well. This device provides a tool for researchers interested in understanding network dynamics who will profit from having the ability to design both the degree and directionality connectivity among multiple small neural populations.

Electroencephalographic Changes of Brain Oscillatory Activity After Upper Limb Somatic Sensation Training in a Patient With Somatosensory Deficit After Stroke.

The development of an innovative functional assessment procedure based on the combination of electroencephalography (EEG) and robot-assisted upper limb devices may provide new insights into the dynamics of cortical reorganization promoted by rehabilitation. The aim of this study was to evaluate changes in event-related synchronization/desynchronization (ERS/ERD) in alpha and beta bands in a patient with pure sensory stroke who underwent a specific rehabilitation program for somatic sensation recovery. A 49-year-old, right-handed woman (time since stroke, 12 months) with severe upper limb somatic sensation deficits was tested using validated clinical scales and a standardized video-EEG system combined with the Bi-Manu-Track robot-assisted arm trainer protocol. The patient underwent a 3-month home-based rehabilitation program for promoting upper limb recovery (1 hour a day for 5 days a week). She was tested before treatment, at 1-month, and at 3-month during treatment. Results showed progressive recovery of upper limb function over time. These effects were associated with specific changes in the modulation of alpha and beta event-related synchronization/desynchronization. This unique study provides new perspectives for the assessment of functional deficits and changes in cortical activity promoted by rehabilitation in poststroke patients.

Electrophysiological indices of interference resolution covary with individual fluid intelligence: investigating reactive control processes in a 3-back working memory task.

It has been proposed that the well-established relationship between working memory (WM) and fluid intelligence (gf) is mediated by executive mechanisms underlying interference control. The latter relies upon the integrity of a frontoparietal brain network, whose activity is modulated by general cognition. In regards to the chronology of this activation, only few EEG studies investigated the topic, although none of them examined the regional interaction or the effects of individual differences in gf. The current investigation sought at extending previous research by characterizing the EEG markers (temporal activation and regional coupling) of interference control and the effects of the individual variation in gf. To this end, we recorded the EEG activity of 33 participants while performing verbal and spatial versions of a 3-back WM task. In a separate session, participants were administered with a test of fluid intelligence. Interference-inducing trials were associated with an increased negativity in the frontal scalp region occurring in two separate time windows and probably reflecting two different stages of the underlying cognitive process. In addition, we found that scalp distribution of such activity differed among individuals, being the strongest activation of the left and right frontolateral sites related to high gf level. Finally, high- and low-gf participants showed different patterns in the modulation of regional connectivity (electrodes coherence in the range of 4.5-7.5Hz) according to changes in attention load among types of trials. Our findings suggest that high-gf participants may rely upon effective engagement and modulation of attention resources to face interference.

Topographical organization of mu and Beta band activity associated with hand and foot movements in patients with perirolandic lesions.

To study the topographical organization of mu and beta band event-related desynchronization (ERD) associated with voluntary hand and foot movements, we used magnetoencephalographic (MEG) recordings from 19 patients with perirolandic lesions. Synthetic aperture magnetometry (SAM) was used to detect and localize changes in the mu (7 - 11 Hz) and beta (13 - 30 Hz) frequency bands associated with repetitive movements of the hand and foot and overlaid on individual coregistered magnetic resonance (MR) images. Hand movements showed homotopic and contralateral ERD at the sensorimotor (S/M) cortex in the majority of cases for mu and to a lesser extent for beta rhythms. Foot movements showed an increased heterotopic distribution with bilateral and ipsilateral ERD compared to hand movements. No systematic topographical segregation between mu and beta ERD could be observed. In patients with perirolandic lesions, the mu and beta band spatial characteristics associated with hand movements retain the expected functional-anatomical boundaries to a large extent. Foot movements have altered patterns of mu and beta band ERD, which may give more insight into the differential functional role of oscillatory activity in different voluntary movements.