High Beta Frequency Research Articles

Caffeine reverses the unconsciousness produced by light anesthesia in the continued presence of isoflurane in rats.

Currently no drugs are employed clinically to reverse the unconsciousness induced by general anesthetics. Our previous studies showed that caffeine, when given near the end of an anesthesia session, accelerated emergence from isoflurane anesthesia, likely caused by caffeine’s ability to elevate intracellular cAMP levels and to block adenosine receptors. These earlier studies showed that caffeine did not rouse either rats or humans from deep anesthesia (≥ 1 minimum alveolar concentration, MAC). In this current crossover study, we examined whether caffeine reversed the unconsciousness produced by light anesthesia (< 1 MAC) in the continued presence of isoflurane. The primary endpoint of this study was to measure isoflurane levels at the time of recovery of righting reflex, which was a proxy for consciousness. Rats were deeply anesthetized with 2% isoflurane (~1.5 MAC) for 20 minutes. Subsequently, isoflurane was reduced to 1.2% for 10 minutes, then by 0.2% every 10 min; animals were monitored until the recovery of righting reflex occurred, in the continued presence of isoflurane. Respiration rate, heart rate and electroencephalogram (EEG) were monitored. Our results show that caffeine-treated rats recovered their righting reflex at a significantly higher inspired isoflurane concentration, corresponding to light anesthesia, than the same rats treated with saline (control). Respiration rate and heart rate increased initially after caffeine injection but were then unchanged for the rest of the anesthesia session. Deep anesthesia is correlated with burst suppression in EEG recordings. Our data showed that caffeine transiently reduced the burst suppression time produced by deep anesthesia, suggesting that caffeine altered neuronal circuit function but not to a point where it caused arousal. In contrast, under light anesthesia, caffeine shifted the EEG power to high frequency beta and gamma bands. These data suggest that caffeine may represent a clinically viable drug to reverse the unconsciousness produced by light anesthesia.

Evaluation of the Effectiveness of a Novel Brain-Computer Interface Neuromodulative Intervention to Relieve Neuropathic Pain Following Spinal Cord Injury: Protocol for a Single-Case Experimental Design With Multiple Baselines.

BackgroundNeuropathic pain is a debilitating secondary condition for many individuals with spinal cord injury. Spinal cord injury neuropathic pain often is poorly responsive to existing pharmacological and nonpharmacological treatments. A growing body of evidence supports the potential for brain-computer interface systems to reduce spinal cord injury neuropathic pain via electroencephalographic neurofeedback. However, further studies are needed to provide more definitive evidence regarding the effectiveness of this intervention.ObjectiveThe primary objective of this study is to evaluate the effectiveness of a multiday course of a brain-computer interface neuromodulative intervention in a gaming environment to provide pain relief for individuals with neuropathic pain following spinal cord injury.MethodsWe have developed a novel brain-computer interface-based neuromodulative intervention for spinal cord injury neuropathic pain. Our brain-computer interface neuromodulative treatment includes an interactive gaming interface, and a neuromodulation protocol targeted to suppress theta (4-8 Hz) and high beta (20-30 Hz) frequency powers, and enhance alpha (9-12 Hz) power. We will use a single-case experimental design with multiple baselines to examine the effectiveness of our self-developed brain-computer interface neuromodulative intervention for the treatment of spinal cord injury neuropathic pain. We will recruit 3 participants with spinal cord injury neuropathic pain. Each participant will be randomly allocated to a different baseline phase (ie, 7, 10, or 14 days), which will then be followed by 20 sessions of a 30-minute brain-computer interface neuromodulative intervention over a 4-week period. The visual analog scale assessing average pain intensity will serve as the primary outcome measure. We will also assess pain interference as a secondary outcome domain. Generalization measures will assess quality of life, sleep quality, and anxiety and depressive symptoms, as well as resting-state electroencephalography and thalamic γ-aminobutyric acid concentration.ResultsThis study was approved by the Human Research Committees of the University of New South Wales in July 2019 and the University of Technology Sydney in January 2020. We plan to begin the trial in October 2020 and expect to publish the results by the end of 2021.ConclusionsThis clinical trial using single-case experimental design methodology has been designed to evaluate the effectiveness of a novel brain-computer interface neuromodulative treatment for people with neuropathic pain after spinal cord injury. Single-case experimental designs are considered a viable alternative approach to randomized clinical trials to identify evidence-based practices in the field of technology-based health interventions when recruitment of large samples is not feasible.Trial RegistrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000556943; https://bit.ly/2RY1jRx International Registered Report Identifier (IRRID)PRR1-10.2196/20979

Alterations of oscillatory neuronal activity during reward processing in schizophrenia

ObjectivesReward system dysfunctions are considered to be a pathophysiological mechanism in schizophrenia. Electrophysiological studies of reward system functions have identified frequency-specific brain networks for the processing of positive (high-beta frequency) and negative (theta frequency) events. Remarkably, midbrain dopaminergic signalling also includes theta and high-beta frequency modes, which have been assumed to reflect tonic and phasic dopamine responses, respectively. The aim of the present study was to identify alterations of oscillatory responses to reward feedback in patients with schizophrenia. MethodsSeventeen patients with schizophrenia and 18 healthy controls performed a gambling task during recording of 64-channel electroencephalography. The theta and high-beta band total power were investigated in response to feedback events depending on feedback valence (loss or gain) and magnitude (5 vs. 25 points). ResultsBoth the increase of theta oscillatory activity in response to loss feedback (compared to gain feedback) and the increase of high-beta oscillatory activity in response to gain feedback (compared to loss feedback) were reduced in patients. The difference in high-beta responses to gain versus loss feedback in patients was associated with the severity of negative symptoms. ConclusionsOur findings are consistent with current models of reward system dysfunction in schizophrenia, and indicate deficits in both cortical tonic and subcortical phasic dopamine activity, consistent with the complex dopaminergic abnormalities in schizophrenia.

Quantitative EEG Findings in Patients With Psychogenic Nonepileptic Seizures.

Objective. Psychogenic nonepileptic seizures (PNES), is one of the clinical manifestations of conversion disorder that epileptiform discharges do not accompany. Factors capable of increasing susceptibility to these seizures have not been adequately investigated yet. This study aims to investigate the quantitative electroencephalography (QEEG) findings for PNES by evaluating the resting EEG spectral power changes during the periods between seizures. Methods. Thirty-nine patients (29 females, 10 males) diagnosed with PNES (group 1) and 47 patients (23 females, 24 males) without any psychiatric diagnosis (group 2) were included in the study. The patients underwent a psychiatric examination at their first visit, were diagnosed and their EEGs were recorded. Using fast Fourier transformation (FFT), spectral power analysis was calculated for delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (15-30 Hz), high-beta (25-30 Hz), gamma-1 (31-40 Hz), gamma-2 (41-50 Hz), and gamma (30-80 Hz) frequency bands. Results. Six separate EEG band power, namely (C3-high beta, C3-gamma, C3-gamma-1, C3-gamma-2, P3-gamma, P3 gamma-1), were found to be higher in the patients diagnosed with PNES than in the control group. Conclusion. Our findings show that PNES correlate with high-frequency oscillations on central motor and somatosensory cortices.

Dynamic changes in rhythmic and arrhythmic neural signatures in the subthalamic nucleus induced by anaesthesia and tracheal intubation

BackgroundSubcortical structures, including the basal ganglia, have been proposed to be crucial for arousal, consciousness, and behavioural responsiveness. How the basal ganglia contribute to the loss and recovery of consciousness during anaesthesia has, however, not yet been well characterised. MethodsTwelve patients with advanced Parkinson's disease, who were undergoing deep brain stimulation (DBS) electrode implantation in the subthalamic nucleus (STN), were included in this study. Local field potentials (LFPs) were recorded from the DBS electrodes and EEG was recorded from the scalp during induction of general anaesthesia (with propofol and sufentanil) and during tracheal intubation. Neural signatures of loss of consciousness and of the expected arousal during intubation were sought in the STN and EEG recordings. ResultsPropofol–sufentanil anaesthesia resulted in power increases in delta, theta, and alpha frequencies, and broadband power decreases in higher frequencies in both STN and frontal cortical areas. This was accompanied by increased STN–frontal cortical coherence only in the alpha frequency band (119 [68]%; P=0.0049). We observed temporal activity changes in STN after tracheal intubation, including power increases in high-beta (22–40 Hz) frequency (98 [123]%; P=0.0064) and changes in the power-law exponent in the power spectra at lower frequencies (2–80 Hz), which were not observed in the frontal cortex. During anaesthesia, the dynamic changes in the high-gamma power in STN LFPs correlated with the power-law exponent in the power spectra at lower frequencies (2–80 Hz). ConclusionsApart from similar activity changes in both STN and cortex associated with anaesthesia-induced unresponsiveness, we observed specific neuronal activity changes in the STN in response to the anaesthesia and tracheal intubation. We also show that the power-law exponent in the power spectra in the STN was modulated by tracheal intubation in anaesthesia. Our results support the hypothesis that subcortical nuclei may play an important role in the loss and return of responsiveness.

Neurophysiological Correlates of Adaptation and Interference during Asymmetrical Bimanual Movements

In this study, we investigated brain dynamics during interference between hands during bimanual movements. Participants performed a bimanual center-out reaching task in which a visuomotor rotation was applied to the right hand while the left hand did not receive visual feedback of its movements. This manipulation resulted in interference from the adapting right hand to the kinesthetically guided left hand. Electroencephalography (EEG) recordings during the task showed that spectral power in the high and low beta frequency bands was elevated early in exposure, but decreased throughout learning. This may be representative of error-based updating of internal models of movement. Additionally, coherence, a measure of neural functional connectivity, was elevated both within and between hemispheres in the beta frequencies during the initial presentation of the visuomotor rotation, and then decreased throughout adaptation. This suggests that beta oscillatory neural activity may be marker for transmission of conflicting motor information between hemispheres, which manifests in interference between the hands during asymmetrical bimanual movements.

Abstract TMP42: Coherent Neural Oscillations Inform Early Stroke Motor Recovery

Introduction: Neural oscillations may contain valuable information for stroke rehabilitation. The objective of this study was to examine the predictive performance of neural oscillations in early stroke motor recovery using dense array electroencephalography (EEG). Since past work theorizes that neural oscillations underlie behavior, we hypothesized that coherent oscillations with ipsilesional primary motor cortex (M1) across a 1-30 Hz band would significantly predict early motor recovery post-stroke. Methods: Individuals with stroke admitted to an inpatient rehabilitation facility (IRF) completed a three-minute resting EEG recording and structural MRI around the time of IRF admission and motor testing (Functional Independence Measurement motor subscale (FIM-motor)) at IRF admission and discharge. We examined how well FIM-Motor change was predicted using EEG power and coherence with ipsilesional M1 across delta (1-3 Hz), theta (4-7 Hz), alpha (8-12 Hz), low beta (13-19 Hz), and high beta (20-30 Hz) frequency bands, along with corticospinal tract (CST) injury, in a lasso regression with K-fold cross-validation for deviance estimation. Results: Twenty-seven subjects (20 males, 58.3±14.6 years, 8-17 days post-stroke) with predominantly mild-moderate motor impairment participated. EEG ipsilesional M1 coherence with 16 leads overlying both hemispheres predicted 61.8% of FIM-motor change from IRF admission to discharge, with higher frequencies (alpha, high beta) positively relating to motor recovery. Lower frequencies overlying contralesional parietal (theta) and frontal (delta) regions inversely and positively related to motor recovery respectively. Coherence outperformed EEG power and CST injury measurements. Ipsilesional M1 coherence also predicted 55.2% of the variance in residuals derived from a predictive model containing only CST injury, suggesting that EEG coherence and CST injury contain unique information for motor recovery prediction. Conclusions: Early after stroke, coherence of neural oscillations with ipsilesional M1 across the entire brain through a wide frequency spectrum is best at predicting functional gains from inpatient rehabilitation and may be feasible as a bedside biomarker of motor recovery.

Cortical Tracking of Surprisal during Continuous Speech Comprehension.

Speech comprehension requires rapid online processing of a continuous acoustic signal to extract structure and meaning. Previous studies on sentence comprehension have found neural correlates of the predictability of a word given its context, as well as of the precision of such a prediction. However, they have focused on single sentences and on particular words in those sentences. Moreover, they compared neural responses to words with low and high predictability, as well as with low and high precision. However, in speech comprehension, a listener hears many successive words whose predictability and precision vary over a large range. Here, we show that cortical activity in different frequency bands tracks word surprisal in continuous natural speech and that this tracking is modulated by precision. We obtain these results through quantifying surprisal and precision from naturalistic speech using a deep neural network and through relating these speech features to EEG responses of human volunteers acquired during auditory story comprehension. We find significant cortical tracking of surprisal at low frequencies, including the delta band as well as in the higher frequency beta and gamma bands, and observe that the tracking is modulated by the precision. Our results pave the way to further investigate the neurobiology of natural speech comprehension.

Individualized Neurofeedback Training May Help Achieve Long-Term Improvement of Working Memory in Children With ADHD.

Background. Children with attention deficit hyperactivity disorder (ADHD) may suffer from working memory deficits, which can adversely affect their academic performance. Neurofeedback training may enhance working memory and provide a solution to this problem. Aim. To investigate the effect of frequency-neurofeedback on working memory in children with ADHD and to check if the effect is long-lasting. Method. Forty-eight children with ADHD (aged 6-12 years) were randomly assigned either to a neurofeedback with training parameters chosen to take into account each child's peak alpha frequency (PAF) or to a waiting list control group. Each trained child underwent 19-channel electroencephalography (EEG). All children had average intelligence and none were receiving treatment, such as medications, for ADHD. Prior to the training, MOXO and n-back tests were performed. Next, neurofeedback training sessions with frequency bands for theta and beta ranges determined using each child's PAF were carried out for 10 weeks. Training parameters were set to increase amplitudes in the low beta range and to decrease amplitudes in the theta and high beta frequency ranges. The n-back test was performed again right after the training and then a year later. Results. During the first n-back test, children from both groups responded correctly to more than 43% of the stimuli. During the second test, children from the waiting list responded correctly to an average of 49% of the stimuli, while children who underwent the neurofeedback training were correct, on average, 69% of the time (significant difference, P < .001). During the third n-back test a year later, children from the waiting list responded correctly to 53% of the stimuli, while those who underwent the neurofeedback training responded correctly to nearly 71%. Conclusion. This study found a statistically significant improvement in a measure of working memory in children who did 10 to 12 sessions of neurofeedback training with training frequency ranges for theta and beta defined according to each child's PAF. The beneficial effects were still present a year after training.

Oscillatory brain mechanisms supporting response cancellation in selective stopping strategies

Although considerable progress has been made in understanding the neural substrates of simple or global stopping, the neural mechanisms supporting selective stopping remain less understood. The selectivity of the stop process is often required in our everyday life in situations where responses must be suppressed to certain signals but not others. Here, we examined the oscillatory brain mechanisms of response cancellation in selective stopping by controlling for the different strategies adopted by participants (n = 54) to accomplish a stimulus selective stop-signal task. We found that successfully cancelling an initiated response was specifically associated with increased oscillatory activity in the high-beta frequency range in the strategy characterized by stopping selectively (the so called dependent Discriminate then Stop, dDtS), but not in the strategy characterized by stopping non-selectively (Stop then Discriminate, StD). Beamforming source reconstruction suggests that this high-beta activity was mainly generated in the superior frontal gyrus (including the pre-supplementary motor area) and the middle frontal gyrus. Present findings provide neural support for the existence of different strategies for solving selective stopping tasks. Specifically, differences between strategies were observed in the oscillatory activity associated with the stop process and were restricted to the high-beta frequency range. Moreover, current results provide important evidence suggesting that high-beta oscillations in superior and middle frontal cortices play an essential role in cancelling an initiated motor response.

0230 Preimmunization With a Non-pathogenic Bacterium Mycobacterium vaccae NCTC11659 Prevents the Development of Cortical Hyperarousal and a PTSD-like Sleep Phenotype Following Sleep Disruption Plus Acute Stress in Mice.

Because regular sleep disruption can increase vulnerability to stress-related psychiatric disorders, there is a need to explore novel countermeasures to increase stress resilience after inadequate sleep. Immunization with heat-killed Mycobacterium vaccae NCTC11659 (MV), an environmental bacterium and immunomodulator, can increase resilience to chronic stress in mice. We therefore tested the hypothesis that MV immunization would prevent the negative impacts of five days of sleep disruption on stress-induced changes in sleep in mice. 120 male C57BL/6N mice were implanted with EEG/EMG recording devices and given 3 weekly injections of either MV or vehicle before entering the experimental protocol (day 0). On days 1-5, sleep was disrupted by a slowly rotating bar, with an ad libitum sleep opportunity from ZT2-ZT6. At ZT4 of day 5, mice were exposed to a 1-hour episode of social defeat stress. Sleep recording continued for seven days after social defeat (day 12). Groups received just sleep disruption, just social defeat, both (‘double hit’), or neither. In vehicle-treated mice receiving just social defeat, an increase in NREM delta (0.5-4Hz) power compared to baseline was observed during the post-stress dark period (p=0.005, Wilcoxon signed rank test). However, this was absent in mice receiving the double hit, who instead had elevated power in the high frequency beta (15-30Hz) power band in both NREM (p=0.002) and REM (p=0.001). Mice receiving the double hit also had increased REM and sleep fragmentation compared to controls for at least 6 days post-stress (p<0.05, ANOVA). NREM beta power immediately post-stress correlated with REM sleep disturbances 6 days later. MV preimmunization prevented all double hit-induced sleep disturbances. These results suggest repeated sleep disruption may increase vulnerability to an acute stressor in part by shifting the adaptive increase in delta power to a maladaptive increase in beta power during post-stress sleep. Importantly, these data provide further evidence supporting microbiota-based countermeasures to promote health. Office of Naval Research Grant #N00014-15-1-2809; NIH Training Grant T32HL007909

Abstract TMP46: EEG is a Useful Biomarker of Motor Recovery in Early Stroke Rehabilitation

Introduction: The application of biomarkers to study and monitor stroke recovery mechanisms can potentially advance rehabilitation practice and research. This study examined the utility of dense-array electroencephalography (EEG) for predicting and capturing changes in brain function in early stroke rehabilitation. Hypothesis: Changes in EEG measures involving ipsi- and contralesional motor cortices (iM1 and cM1) in delta (1-3Hz) and high beta (20-30Hz) frequency bands [1] parallel and [2] predict motor recovery. Methods: Individuals with recent ischemic or hemorrhagic stroke admitted to an inpatient rehabilitation facility (IRF) completed a 3-minute resting-state EEG recording and behavioral testing (Upper Extremity Fugl-Meyer (FM) and Functional Independence Measurement motor subscale (FIM-motor)) during hospitalization and 90-days post-stroke. EEG power and coherence (connectivity) measures were computed from leads overlying iM1 and cM1. Results: Twenty-seven subjects (20 males, age 58.3±14.6 years, 14.7±12.8 days post-stroke) participated. Greater decrease in iM1-cM1 coherence in the delta band correlated significantly with larger (a) FIM-motor score improvement from IRF admission to discharge (r=-0.70, p=0.001, n=18) and (b) FM score improvement from IRF admission to 90-days post-stroke (r=-0.57, p=0.02, n=17). Baseline EEG measures did not predict motor recovery when examined across the entire group. Performance of biomarkers varies according to stroke severity, and so prediction was further examined in relation to baseline FM. In subjects with moderate-severe impairment (FM≤40), delta iM1-cM1 coherence at baseline correlated with FIM-motor gains (r=0.72, p=0.03, n=9), and delta power in leads over iM1 positively correlated with FM gains (a) from IRF admission to discharge (r=0.75, p=0.03, n=8) and (b) from IRF admission to 90-days post-stroke (r=0.73, p=0.04, n=8). Conclusions: Bedside EEG recording in the IRF provides neurophysiological insights that predict and parallel motor recovery, and so may be a valuable bedside tool in early stroke rehabilitation. EEG measures can predict motor recovery in individuals with moderate-severe motor impairment.

EEG Oscillations Response To Dual-Target rTMS Therapy of Parkinson Disease and Co-Occuring Depression

The approach intended evaluating neurophysiological concomitants of treatment response to dual-target navigated TMS in patients with Parkinson’s disease and co-occuring depression. Patients with PD (n=46) were initially enrolled for a placebo-controlled study and randomly assigned to either an actively treated (rTMS, n = 23) or a sham-stimulation (sTMS, n=23) groups. Every TMS session was performed sequentially over the primary motor cortex (20 min) followed by the DLPFC (20 min). The patients received a total of 20 sessions on 20 consecutive days. For every participant the main outcome measure included the MDS-UPDRS Motor Examination Part (Part 3) scale score, BDI-II and DASS depression scores as well as spectral parameters of the resting EEG (the last ones were available for fewer patients - rTMS, n=15; sTMS, n=16). After the stimulation course the Part 3 scale scores demonstrated clinically meaningful improvement which was larger in the rTMS group (GROUP by TIME: F1,88= 44,06 p<.001). The BDI-2 and DASS scores showed significantly attenuated negative affect for both groups (TIME: BDI-2 - F1,44=4.48, p <.040; DASS - F1,44=15.34, p <.000). According to sLORETA, beneficial treatment response to the TMS course was accounted by selective EEG power increase over the theta, high beta and gamma frequency bands and significantly locked only to the rTMS group. Using source analysis, the generators of this power difference were localized to somatosensory and visual functional networks, as well as to separate nodes of the salience and default mode networks. There was an increased frontal lobe activation (the 9thand 10thBrodman areas). The main EEG power differences were locked to the ranges of 18-30 Hz and 30-45 Hz (sLORETA statistics at p < .05).The findings demonstrate the beneficial effects of the dual-target TMS in PD and hints to some EEG oscillatory signatures as putative predictors of the treatment response.

Neural Correlates of Transmitted Light Experience during Meditation: A Pilot Hyperscanning Study

Certain individuals during deep meditative states can transmitt and give out an aura or ‘light, which is perceived by others through some unknown connections, visual, telepathic or other. Despite various anecdotal, historical accounts of such induced light experience (ILE), its underlying neural mechanism is not known. In this pilot study, we investigated the neural correlates of ILE by simultaneously recording the EEGs of an expert Teacher, who is claimed to elicit ILE, and his Pupil (N=2) during joint sessions under various instructions, given separately to the Teacher (transmit/ do not transmit) and to the Pupil (receive/ do not receive). In a further condition both teacher and pupil wear opaque goggles during transmit/receive instruction, limiting the visual/outputinput. We observed a robust increase in the high frequency beta (12-30 Hz) and gamma oscillations (30-70 Hz) in the Teacher’s brain whenever he was instructed to transmit. Electric field tomography analysis localized these effects over several brain regions including the fusiform gyrus, angular gyrus and the cerebellum. Finally, we found that the Teacher’s and Pupil’s brain responses were synchronized, especially in the alpha band (8-12 Hz) during transmit/receive condition, and the information flow was directional, i.e. from the Teacher to the Pupil; interestingly, this enhanced interbrain synchrony disappeared with opaque goggles. These results were interpreted in terms of heightened internally selective attention as manifested by high frequency beta-gamma oscillations and of joint attention as manifested by interbrain alpha synchrony. Altogether, our results provide the first neuroscientific evidence underlying the phenomenological experience of induced light.

Virtual Reality for Anxiety Reduction Demonstrated by Quantitative EEG: A Pilot Study.

While previous research has established that virtual reality (VR) can be successfully used in the treatment of anxiety disorders, including phobias and PTSD, no research has examined changes in brain patterns associated with the use of VR for generalized anxiety management. In the current study, we compared a brief nature-based mindfulness VR experience to a resting control condition on anxious participants. Self-reported anxiety symptoms and resting-state EEG were recorded across intervals containing quiet rest or the VR intervention. EEG activity was analyzed as a function of global power shifts in Alpha and Beta activity, and with sLORETA current source density estimates of cingulate cortex regions of interest. Results demonstrated that both a quiet rest control condition and the VR meditation significantly reduced subjective reports of anxiety and increased Alpha power. However, the VR intervention uniquely resulted in shifting proportional power from higher Beta frequencies into lower Beta frequencies, and significantly reduced broadband Beta activity in the anterior cingulate cortex. These effects are consistent with a physiological reduction of anxiety. This pilot study provides preliminary evidence supporting the therapeutic potential of VR for anxiety management and stress reduction programs.

Alternating Modulation of Subthalamic Nucleus Beta Oscillations during Stepping.

Gait disturbances in Parkinson's disease are commonly refractory to current treatment options and majorly impair patient's quality of life. Auditory cues facilitate gait and prevent motor blocks. We investigated how neural dynamics in the human subthalamic nucleus of Parkinsons's disease patients (14 male, 2 female) vary during stepping and whether rhythmic auditory cues enhance the observed modulation. Oscillations in the beta band were suppressed after ipsilateral heel strikes, when the contralateral foot had to be raised, and reappeared after contralateral heel strikes, when the contralateral foot rested on the floor. The timing of this 20–30 Hz beta modulation was clearly distinct between the left and right subthalamic nucleus, and was alternating within each stepping cycle. This modulation was similar, whether stepping movements were made while sitting, standing, or during gait, confirming the utility of the stepping in place paradigm. During stepping in place, beta modulation increased with auditory cues that assisted patients in timing their steps more regularly. Our results suggest a link between the degree of power modulation within high beta frequency bands and stepping performance. These findings raise the possibility that alternating deep brain stimulation patterns may be superior to constant stimulation for improving parkinsonian gait.SIGNIFICANCE STATEMENT Gait disturbances in Parkinson's disease majorly reduce patients' quality of life and are often refractory to current treatment options. We investigated how neural activity in the subthalamic nucleus of patients who received deep brain stimulation surgery covaries with the stepping cycle. 20–30 Hz beta activity was modulated relative to each step, alternating between the left and right STN. The stepping performance of patients improved when auditory cues were provided, which went along with enhanced beta modulation. This raises the possibility that alternating stimulation patterns may also enhance beta modulation and may be more beneficial for gait control than continuous stimulation, which needs to be tested in future studies.

Large-scale functional networks connect differently for processing words and symbol strings.

Reconfigurations of synchronized large-scale networks are thought to be central neural mechanisms that support cognition and behavior in the human brain. Magnetoencephalography (MEG) recordings together with recent advances in network analysis now allow for sub-second snapshots of such networks. In the present study, we compared frequency-resolved functional connectivity patterns underlying reading of single words and visual recognition of symbol strings. Word reading emphasized coherence in a left-lateralized network with nodes in classical perisylvian language regions, whereas symbol processing recruited a bilateral network, including connections between frontal and parietal regions previously associated with spatial attention and visual working memory. Our results illustrate the flexible nature of functional networks, whereby processing of different form categories, written words vs. symbol strings, leads to the formation of large-scale functional networks that operate at distinct oscillatory frequencies and incorporate task-relevant regions. These results suggest that category-specific processing should be viewed not so much as a local process but as a distributed neural process implemented in signature networks. For words, increased coherence was detected particularly in the alpha (8–13 Hz) and high gamma (60–90 Hz) frequency bands, whereas increased coherence for symbol strings was observed in the high beta (21–29 Hz) and low gamma (30–45 Hz) frequency range. These findings attest to the role of coherence in specific frequency bands as a general mechanism for integrating stimulus-dependent information across brain regions.

Abstract TP158: Neural Function and Injury Combined Best Predict Behavioral Gains During Inpatient Stroke Rehabilitation

Background: A better understanding of the mechanisms of recovery during rehabilitation could inform treatment decision-making. We tested two hypotheses: [1] a combination of neural function and injury measures is better than either measure alone for predicting motor gains during inpatient rehabilitation facility (IRF) admission; and [2] performance of prediction measures varies according to severity of baseline impairment. Methods: Fifteen patients with subacute stroke (56±12 yr, 16 days post-stroke) admitted to an IRF underwent EEG [3-min, resting-state, dense-array (256-lead)] and MRI [anatomical and diffusion tensor] at IRF admission; and serial behavioral testing. Neural function was assessed using EEG measures of coherence and power from electrodes overlying ipsilesional (M1 i ) and contralesional (M1 c ) primary motor cortex, in the Delta (1-3 Hz) and high Beta (20-30 Hz) frequency bands. Neural injury was assessed as integrity of white matter in corpus callosum (CC). Change in arm Fugl-Meyer (FM) and Functional Independent Measurement motor (FIM-m) scores served as primary and secondary behavioral recovery metrics, respectively. Results: In subjects with moderate or severe impairment (FM &lt;55, N=11), neither neural function (M1 i -M1 c Delta coherence) nor neural injury (CC integrity) alone significantly predicted FIM-m score change. However, when combined into a single model, these measures did significantly predicted FIM-m score change (R 2 = 0.85, p=0.024); note that baseline behavior was not a significant predictor. An identical neural injury+function model approached significance at predicting FM score change (R 2 = 0.72 p=0.08). These models failed, however, when applied to all 15 patients (R 2 = 0.06, p=0.81). Conclusions: Results thus far in this ongoing study suggest that recovery during inpatient rehabilitation is best predicted by combining neural function and injury measures, and not by behavioral assessments. Performance of recovery predictors varies according to severity of baseline deficits, as adding mild strokes to moderate/severe strokes increased the sample size but diluted the model. These findings could potentially inform patient selection, treatment decisions, and discharge planning in an IRF setting.

Subthalamic oscillatory activity and connectivity during gait in Parkinson's disease.

Local field potentials (LFP) of the subthalamic nucleus (STN) recorded during walking may provide clues for determining the function of the STN during gait and also, may be used as biomarker to steer adaptive brain stimulation devices. Here, we present LFP recordings from an implanted sensing neurostimulator (Medtronic Activa PC + S) during walking and rest with and without stimulation in 10 patients with Parkinson's disease and electrodes placed bilaterally in the STN. We also present recordings from two of these patients recorded with externalized leads. We analyzed changes in overall frequency power, bilateral connectivity, high beta frequency oscillatory characteristics and gait-cycle related oscillatory activity. We report that deep brain stimulation improves gait parameters. High beta frequency power (20-30 Hz) and bilateral oscillatory connectivity are reduced during gait, while the attenuation of high beta power is absent during stimulation. Oscillatory characteristics are affected in a similar way. We describe a reduction in overall high beta burst amplitude and burst lifetimes during gait as compared to rest off stimulation. Investigating gait cycle related oscillatory dynamics, we found that alpha, beta and gamma frequency power is modulated in time during gait, locked to the gait cycle. We argue that these changes are related to movement induced artifacts and that these issues have important implications for similar research.

In search of beta

Despite its limitations, the CAPM is a popular asset pricing model. However, the estimation of beta in the CAPM is affected by the choice of the returns frequency and firm characteristics. This study undertakes a detailed examination of the evidence for the UK and we find that the differences in beta computed from returns of various frequencies are related to size, liquidity, book-to-market and to some degree, opacity factors. One area where our conclusions might have important implications is in the regulatory use of the CAPM. Our results imply that low frequency beta estimates should, in most cases, be preferred to high frequency beta estimates.