Changes In Cortical Activity Research Articles

Changes of functional response in sensorimotor cortex of preterm and full-term infants during the first year: An fNIRS study

BackgroundMotor impairments are frequently associated with preterm birth and interfere in acquisition of essential skills to global development. Using Near Infrared Spectroscopy (NIRS), the study of neural correlates of motor development in early stages of life are feasible in an ecological assessment. AimsTo evaluate changes in cortical activity in response to a sensorimotor stimulation in preterm and full-term infants at 6 and 12 months of age. Study designA longitudinal study was conducted with 22 infants (12 preterm and 10 full-term). Hemodynamic activity during sensorimotor task (8 blocks of 8 s of vibration applied to infant's right hand) was measured by Functional Near Infrared Spectroscopy (fNIRS). The optical probe consisted of 84 channels positioned according to the international 10–20 system coordinates, covering the frontal (38 channels), parietal (16 channels), temporal (22 channels) and occipital (8 channels) lobes of both hemispheres. ResultsPreterm and full-term infants exhibited differences of location of the activation as well on the hemodynamic response in both the evaluated age groups. ConclusionsGroup differences in activation of sensorimotor cortex observed in this study demonstrate the potential of fNIRS application for preterm evaluation of motor development in children. Overall, the present work contributes to our understanding of cortical activation of cerebral motor skills spanning early ages in preterm-born children.

Limb linkage rehabilitation training-related changes in cortical activation and effective connectivity after stroke: A functional near-infrared spectroscopy study

Stroke remains the leading cause of long-term disability worldwide. Rehabilitation training is essential for motor function recovery following stroke. Specifically, limb linkage rehabilitation training can stimulate motor function in the upper and lower limbs simultaneously. This study aimed to investigate limb linkage rehabilitation task-related changes in cortical activation and effective connectivity (EC) within a functional brain network after stroke by using functional near-infrared spectroscopy (fNIRS) imaging. Thirteen stroke patients with either left hemiparesis (L-H group, n = 6) and or right hemiparesis (R-H group, n = 7) and 16 healthy individuals (control group) participated in this study. A multichannel fNIRS system was used to measure changes in cerebral oxygenated hemoglobin (delta HbO2) and deoxygenated hemoglobin (delta HHb) in the bilateral prefrontal cortices (PFCs), motor cortices (MCs), and occipital lobes (OLs) during (1) the resting state and (2) a motor rehabilitation task with upper and lower limb linkage (first 10 min [task_S1], last 10 min [task_S2]). The frequency-specific EC among the brain regions was calculated based on coupling functions and dynamic Bayesian inference in frequency intervals: high-frequency I (0.6–2 Hz) and II (0.145–0.6 Hz), low-frequency III (0.052–0.145 Hz), and very-low-frequency IV (0.021–0.052 Hz). The results showed that the stroke patients exhibited an asymmetric (greater activation in the contralesional versus ipsilesional motor region) cortical activation pattern versus healthy controls. Compared with the healthy controls, the stroke patients showed significantly lower EC (p < 0.025) in intervals I and II in the resting and task states. The EC from the MC and OL to the right PFC in interval IV was significantly higher in the R-H group than in the control group during the resting and task states (p < 0.025). Furthermore, the L-H group showed significantly higher EC from the MC and OL to the left PFC in intervals III and IV during the task states compared with the control group (p < 0.025). The significantly increased influence of the MC and OL on the contralesional PFC in low- and very-low-frequency bands suggested that plastic reorganization of cognitive resources severed to compensate for impairment in stroke patients during the motor rehabilitation task. This study can serve as a basis for understanding task-related reorganization of functional brain networks and developing novel assessment techniques for stroke rehabilitation.

Waking qEEG to assess psychophysiological stress and alertness during simulated on-call conditions

IntroductionOn-call schedules are associated with stress and disrupted sleep. In a recent study, under non-sleep deprived conditions, low and high-stress on-call conditions did not significantly impact sleep quality but did impact next day performance. Our aim was to determine whether quantitative electroencephalography (qEEG) would reflect changes in cortical activity in on-call conditions, predicting that the high-stress condition would display faster qEEG frequencies compared with the control and low-stress condition. MethodsTwenty-four healthy male participants (age: 26.5 ± 4.0 yrs) spent four nights in a time-isolated sleep laboratory. The within-subjects, repeated measures experimental design assessed waking EEG, via the Karolinska Drowsiness Test (KDT) during four time-points across a control day and two experimental (on-call) days. Experimental days comprised a low-stress (LS – reading task) and high-stress (HS – speech task) condition and were counterbalanced. Mixed-models analysis was used to assess condition and time by EEG biomarkers: Alpha Attenuation Coefficient (AAC), Slowing Ratio (SR) and Scaling Exponent (SE). ResultsMain effects were found for all three biomarkers by condition, with pairwise analysis reported. There was a significant difference in AAC between the LS condition (M = 1.26 ± =1.24) and HS condition (M = 1.01 ± 0.76 p = .02) indicating decreased alertness between LS and HS. A significant increase in SR between control (M = 7.1 ± 4.3) and LS (M = 10.1 ± 8.5 p = .0001), and a significant increase between the LS and HS (M = 7.8 ± 6.8 p = .018) showing greatest EEG slowing in the LS condition, reflecting of a passive, sleepier brain state. The SE was significantly higher in the LS (M = 1.09, ±0.17) condition compared with control (M = 1.0, ±0.11 p = .001) indicating decreased alertness in the LS task. DiscussionUsing qEEG biomarkers, in contrast with our initial hypothesis, the current study found that compared with control, the LS condition resulted in greater EEG slowing. These findings have implications for on-call workers who engage in periods of passive attention and highlight a protective role task stress may play in maintaining alertness levels during on-call conditions.

Temporal evolution of quantitative EEG within 3 days of birth in early preterm infants

For the premature newborn, little is known about changes in brain activity during transition to extra-uterine life. We aim to quantify these changes in relation to the longer-term maturation of the developing brain. We analysed EEG for up to 72 hours after birth from 28 infants born <32 weeks of gestation. These infants had favourable neurodevelopment at 2 years of age and were without significant neurological compromise at time of EEG monitoring. Quantitative EEG was generated using features representing EEG power, discontinuity, spectral distribution, and inter-hemispheric connectivity. We found rapid changes in cortical activity over the 3 days distinct from slower changes associated with gestational age: for many features, evolution over 1 day after birth is equivalent to approximately 1 to 2.5 weeks of maturation. Considerable changes in the EEG immediately after birth implies that postnatal adaption significantly influences cerebral activity for early preterm infants. Postnatal age, in addition to gestational age, should be considered when analysing preterm EEG within the first few days after birth.

A Multimodal Training Modulates Short Afferent Inhibition and Improves Complex Walking in a Cohort of Faller Older Adults With an Increased Prevalence of Parkinson's Disease.

Falls are frequent in Parkinson's disease and aging. Impairments in the cholinergic-mediated attentional supervision of gait may contribute to increased fall risk, especially when obstacles challenge gait. Interventions combining motor-cognitive approaches have been shown to improve motor performance, cognitive skills, and falls number. Here, we hypothesized that an intervention simulating an attention-demanding walking condition could affect not only complex gait performance and fall risk but also short-latency afferent inhibition (SAI), as a marker of cholinergic activity. Thirty-nine participants at falls risk (24 Parkinson's disease participants and 15 older adults) were recruited in a randomized controlled trial. Participants were assigned to treadmill training or treadmill training with non-immersive virtual reality intervention and trained three times a week for 6 weeks. SAI, a transcranial magnetic stimulation paradigm, was used to assess cholinergic activity. Gait kinematics was measured during usual walking and while negotiating physical obstacles. Transcranial magnetic stimulation and gait assessments were performed pre, post, and 6 months post-intervention. Treadmill training combined with non-immersive virtual reality induced an increase in inhibition of the SAI protocol on cortical excitability, improved obstacle negotiation performance, and induced a reduction of the number of falls compared with treadmill training. Furthermore, the more SAI increased after training, the more the obstacle negotiation performance improved and fall rate decreased. We provide evidence that an innovative rehabilitation approach targeting cognitive components of complex motor actions can induce changes in cortical cholinergic activity, as indexed by SAI, thereby enabling functional gait improvements.

Pallidal thermolesion unleashes gamma oscillations in the motor cortex in Parkinson's disease.

In Parkinson's disease, the emergence of motor dysfunction is thought to be related to an imbalance between "antikinetic" and "prokinetic" patterns of oscillatory activity in the motor network. Invasive recordings from the basal ganglia and cortex in surgical patients have suggested that levodopa and therapeutic deep brain stimulation can suppress antikinetic beta band (13-30 Hz) rhythms while promoting prokinetic gamma band (60-90 Hz) rhythms. Surgical ablation of the globus pallidus internus is one of the oldest effective therapies for Parkinson's disease and produces remarkably immediate relief of rigidity and bradykinesia, but its effects on oscillatory activity in the motor network have not been studied. We characterize the effects of pallidotomy on cortical oscillatory activity in Parkinson's patients. Using a temporary 6-contact lead placed over the sensorimotor cortex in the subdural space, we recorded acute changes in cortical oscillatory activities in 3 Parkinson's disease patients undergoing pallidotomy and compared the results to that of 3 essential tremor patients undergoing thalamotomy. In all 3 Parkinson's disease patients, we observed the emergence of a ~70-80 Hz narrowband oscillation with effective thermolesion of the pallidum. This gamma oscillatory activity was spatially localized over the primary motor cortex, was minimally affected by voluntary movements, and was not found in the motor cortex of essential tremor patients undergoing thalamotomy. Our finding suggests that acute lesioning of the pallidum promotes cortical gamma band oscillations. This may represent an important mechanism for alleviating bradykinesia in Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.

Propagation of TMS pulses versus functional brain connectivity

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that is used to induce changes in cortical activity. Besides local TMS effects under the stimulation coil, overall effects of stimulation have been found in distributed areas throughout the brain. The aim of this study was to quantify the propagation of TMS effects in terms of the brain’s resting-state MR functional connectivity (FC).

Quantitative EEG and Verbal Fluency in DBS Patients: Comparison of Stimulator-On and -Off Conditions.

Introduction: Deep brain stimulation of the subthalamic nucleus (STN-DBS) ameliorates motor function in patients with Parkinson's disease and allows reducing dopaminergic therapy. Beside effects on motor function STN-DBS influences many non-motor symptoms, among which decline of verbal fluency test performance is most consistently reported. The surgical procedure itself is the likely cause of this decline, while the influence of the electrical stimulation is still controversial. STN-DBS also produces widespread changes of cortical activity as visualized by quantitative EEG. The present study aims to link an alteration in verbal fluency performance by electrical stimulation of the STN to alterations in quantitative EEG.Methods: Sixteen patients with STN-DBS were included. All patients had a high density EEG recording (256 channels) while testing verbal fluency in the stimulator on/off situation. The phonemic, semantic, alternating phonemic and semantic fluency was tested (Regensburger Wortflüssigkeits-Test).Results: On the group level, stimulation of STN did not alter verbal fluency performance. EEG frequency analysis showed an increase of relative alpha2 (10–13 Hz) and beta (13–30 Hz) power in the parieto-occipital region (p ≤ 0.01). On the individual level, changes of verbal fluency induced by stimulation of the STN were disparate and correlated inversely with delta power in the left temporal lobe (p < 0.05).Conclusion: STN stimulation does not alter verbal fluency performance in a systematic way at group level. However, when in individual patients an alteration of verbal fluency performance is produced by electrical stimulation of the STN, it correlates inversely with left temporal delta power.

The Cortical States of Wakefulness.

Cortical neurons process information on a background of spontaneous, ongoing activity with distinct spatiotemporal profiles defining different cortical states. During wakefulness, cortical states alter constantly in relation to behavioral context, attentional level or general motor activity. In this review article, we will discuss our current understanding of cortical states in awake rodents, how they are controlled, their impact on sensory processing, and highlight areas for future research. A common observation in awake rodents is the rapid change in spontaneous cortical activity from high-amplitude, low-frequency (LF) fluctuations, when animals are quiet, to faster and smaller fluctuations when animals are active. This transition is typically thought of as a change in global brain state but recent work has shown variation in cortical states across regions, indicating the presence of a fine spatial scale control system. In sensory areas, the cortical state change is mediated by at least two convergent inputs, one from the thalamus and the other from cholinergic inputs in the basal forebrain. Cortical states have a major impact on the balance of activity between specific subtypes of neurons, on the synchronization between nearby neurons, as well as the functional coupling between distant cortical areas. This reorganization of the activity of cortical networks strongly affects sensory processing. Thus cortical states provide a dynamic control system for the moment-by-moment regulation of cortical processing.

"Fast" versus "slow" word integration of visual and olfactory objects: EEG biomarkers of decision speed variability.

In psychological experiments, behavioral speed varies across trials, and this variation is often associated with corresponding fluctuations in cortical activity. Little is known about such cortical variations in semantic priming tasks where target words are matched with preceding sensory object cues. Here, two visually presented target words ("pear" and "lilac") were repeatedly cued by corresponding odors or pictures, and the participants were to indicate matching or nonmatching combinations. Data were split in behaviorally "fast" versus "slow" trials. We hypothesized that slow trials would be associated with higher prestimulus alpha activity and reduced ERP amplitudes, and that response-time differences between odor-cued and picture-cued trials would be especially large in slow behavioral trials. Results confirmed that slow trials showed increased alpha-band activity prior to word target onset, as well as amplitude decreases in the sensory P1 and semantic N400 components. However, no interactions between cue-modality and processing speed were observed. Instead, odor-cue integration responses were uniquely delayed on incongruent trials, a novel behavioral effect that was not observed in EEG measures. The results show that semantic integration speed is reflected in cortical activity before and during stimulus processing. Behavioral interactions with cue modality did not correspond to observed cortical activity changes, perhaps because olfactory circuits are not readily observed in scalp-recorded EEG. We conclude that combining behavioral speed variability and cortical EEG measures is useful in understanding the fluctuating nature of cognitive processing sequences. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Effects of a 12-Week Aerobic Spin Intervention on Resting State Networks in Previously Sedentary Older Adults.

Objective: We have previously demonstrated that aerobic exercise improves upper extremity motor function concurrent with changes in motor cortical activity using task-based functional magnetic resonance imaging (fMRI). However, it is currently unknown how a 12-week aerobic exercise intervention affects resting-state functional connectivity (rsFC) in motor networks. Previous work has shown that over a 6-month or 1-year exercise intervention, older individuals show increased resting state connectivity of the default mode network and the sensorimotor network (Voss et al., 2010b; Flodin et al., 2017). However, the effects of shorter-term 12-week exercise interventions on functional connectivity have received less attention.Method: Thirty-seven sedentary right-handed older adults were randomized to either a 12-week aerobic, spin cycling exercise group or a 12-week balance-toning exercise group. Resting state functional magnetic resonance images were acquired in sessions PRE/POST interventions. We applied seed-based correlation analysis to left and right primary motor cortices (L-M1 and R-M1) and anterior default mode network (aDMN) to test changes in rsFC between groups after the intervention. In addition, we performed a regression analysis predicting connectivity changes PRE/POST intervention across all participants as a function of time spent in aerobic training zone regardless of group assignment.Results: Seeding from L-M1, we found that participants in the cycling group had a greater PRE/POST change in rsFC in aDMN as compared to the balance group. When accounting for time in aerobic HR zone, we found increased heart rate workload was positively associated with increased change of rsFC between motor networks and aDMN. Interestingly, L-M1 to aDMN connectivity changes were also related to motor behavior changes in both groups. Respective of M1 laterality, comparisons of all participants from PRE to POST showed a reduction in the extent of bilateral M1 connectivity after the interventions with increased connectivity in dominant M1.Conclusion: A 12-week physical activity intervention can change rsFC between primary motor regions and default mode network areas, which may be associated with improved motor performance. The decrease in connectivity between L-M1 and R-M1 post-intervention may represent a functional consolidation to the dominant M1.Topic Areas: Neuroimaging, Aging.

Mice With Decreased Number of Interneurons Exhibit Aberrant Spontaneous and Oscillatory Activity in the Cortex.

GABAergic (γ-aminobutyric acid) neurons are inhibitory neurons and protect neural tissue from excessive excitation. Cortical GABAergic neurons play a pivotal role for the generation of synchronized cortical network oscillations. Imbalance between excitatory and inhibitory mechanisms underlies many neuropsychiatric disorders and is correlated with abnormalities in oscillatory activity, especially in the gamma frequency range (30–80 Hz). We investigated the functional changes in cortical network activity in response to developmentally reduced inhibition in the adult mouse barrel cortex (BC). We used a mouse model that displays ∼50% fewer cortical interneurons due to the loss of Rac1 protein from Nkx2.1/Cre-expressing cells [Rac1 conditional knockout (cKO) mice], to examine how this developmental loss of cortical interneurons may affect basal synaptic transmission, synaptic plasticity, spontaneous activity, and neuronal oscillations in the adult BC. The decrease in the number of interneurons increased basal synaptic transmission, as examined by recording field excitatory postsynaptic potentials (fEPSPs) from layer II networks in the Rac1 cKO mouse cortex, decreased long-term potentiation (LTP) in response to tetanic stimulation but did not alter the pair-pulse ratio (PPR). Furthermore, under spontaneous recording conditions, Rac1 cKO brain slices exhibit enhanced sensitivity and susceptibility to emergent spontaneous activity. We also find that this developmental decrease in the number of cortical interneurons results in local neuronal networks with alterations in neuronal oscillations, exhibiting decreased power in low frequencies (delta, theta, alpha) and gamma frequency range (30–80 Hz) with an extra aberrant peak in high gamma frequency range (80–150 Hz). Therefore, our data show that disruption in GABAergic inhibition alters synaptic properties and plasticity, while it additionally disrupts the cortical neuronal synchronization in the adult BC.

Motor Unit-Driven Identification of Pathological Tremor in Electroencephalograms

Background: Traditional studies on the neural mechanisms of tremor use coherence analysis to investigate the relationship between cortical and muscle activity, measured by electroencephalograms (EEG) and electromyograms (EMG). This methodology is limited by the need of relatively long signal recordings, and it is sensitive to EEG artifacts. Here, we analytically derive and experimentally validate a new method for automatic extraction of the tremor-related EEG component in pathological tremor patients that aims to overcome these limitations.Methods: We exploit the coupling between the tremor-related cortical activity and motor unit population firings to build a linear minimum mean square error estimator of the tremor component in EEG. We estimated the motor unit population activity by decomposing surface EMG signals into constituent motor unit spike trains, which we summed up into a cumulative spike train (CST). We used this CST to initialize our tremor-related EEG component estimate, which we optimized using a novel approach proposed here.Results: Tests on simulated signals demonstrate that our new method is robust to both noise and motor unit firing variability, and that it performs well across a wide range of spectral characteristics of the tremor. Results on 9 essential (ET) and 9 Parkinson's disease (PD) patients show a ~2-fold increase in amplitude of the coherence between the estimated EEG component and the CST, compared to the classical EEG-EMG coherence analysis.Conclusions: We have developed a novel method that allows for more precise and robust estimation of the tremor-related EEG component. This method does not require artifact removal, provides reliable results in relatively short datasets, and tracks changes in the tremor-related cortical activity over time.

Cortical reorganization after cochlear implantation for adults with single-sided deafness.

BackgroundAdults with single sided deafness (SSD) have lost binaural function, which limits sound source localization, speech understanding in noise, and quality of life. For SSD patients, restoration of bilateral auditory input is possible only with a cochlear implant (CI). In this study, cortical auditory evoked potentials (CAEPs) and behavioral performance were measured in left-implanted (SSD-CI-L) and right-implanted (SSD-CI-R) patients before and after cochlear implantation. We hypothesized that improvements in behavioral performance would be accompanied by changes in CAEPs after cochlear implantation.DesignProspective longitudinal study.SettingTertiary referral center.MethodNine right-handed adult SSD CI patients participated in the study. CAEPs were recorded before cochlear implantation and at 6 and 12 months post-implantation. CAEPs were elicited using speech stimuli (/ba/) delivered in sound field at 70 dBA. Global field power (GFP) latency and amplitude were calculated for P1, N1 and P2 peaks at each test session. CAEP were analyzed at frontocentral (Cz) and temporal (P7, P8, T7 and T8) and mastoid electrodes (M1 and M2) contralateral to the CI ear. Behavioral measures (sentence recognition in noise, with and without spatial cues) were collected at the same test sessions as for CAEPs. Speech performance and CAEPs were also measured in a control group of normal-hearing (NH) subjects.ResultsWhile increased N1 amplitude was observed in the scalp potential maps for GFP and Cz for SSD-CI-L patients after implantation, the changes were not statistically significant. Peak CAEP amplitude at electrodes to contralateral to the CI ear increased after cochlear implantation for all SSD-CI patients, but significant increases were observed only for mastoid sites. Peak latencies for some components at temporal and mastoid sites remained significantly longer than for the NH control group, even after cochlear implantation. For SSD-CI-R patients, P2 peak amplitude for baseline GFP and Cz was significantly lower than for the NH control group. A significant improvement for speech understanding in noise was observed at 12 months post-implantation when speech was presented to the CI ear and noise to the non-implanted ear.ConclusionAfter cochlear implantation, speech understanding significantly improved when speech and noise were spatially separated. The increased N1 amplitude for SSD-CI-L patients and the increased bilateral activation for all SSD-CI patients may reflect cortical reorganization and restoration of binaural function after one year of experience with the CI. However, because of the limited number of SSD patients, significant changes in cortical activity after cochlear implantation were often difficult to observe.

SMAD1/5 signaling in osteoclasts regulates bone formation via coupling factors.

Bone remodeling occurs via coupling between bone resorption by osteoclasts and bone formation by osteoblasts. The mechanisms that regulate osteoclast signals to osteoblasts are not well understood. Published studies have reported that BMP signaling in osteoclasts regulate osteoclast coupling targets. To investigate the necessity of canonical BMP signaling on osteoclast differentiation and coupling, we mated Smad1fl/fl; Smad5fl/fl mice to c-Fms-Cre mice. We analyzed male mice at 3 months of age to determine the skeletal phenotype of the Smad1fl/fl; Smad5fl/fl;c-Fms-Cre (SMAD1/5 cKO) mice. There was a 1.2-fold decrease in trabecular BV/TV in SMAD1/5 cKO. Analyses of osteoclast serum markers in SMAD1/5 cKO mice, showed a significant increase in CTX-1 (1.5 fold) and TRAP ELISA (3 fold) compared to control mice. In these same mice, there was a 1.3-fold increase in cortical thickness. Consistent with the increase in cortical thickness, we found a 3-fold increase in osteoblast activity as measured by P1NIP ELISA assay from SMAD1/5 cKO mice. To explain the changes in cortical thickness and P1NP activity, we determined conditioned media from SMAD1/5 cKO osteoclast cultures enhanced mineralization of an osteoblast cell line and coupling factors expressed by osteoclasts that regulate osteoblast activity Wnt1 (4.5-fold increase), Gja1 (3-fold increase) and Sphk1 (1.5-fold increase) were all upregulated in osteoclasts from SMAD1/5 cKO compared to control osteoclasts. Lastly osteoclasts treated with dorsomorphin, a chemical inhibitor of SMAD1/5 signaling, demonstrates an increase in Wnt1 and Gja1 expression similar to the SMAD1/5 cKO mice. Previous studies demonstrated that TGF-β signaling in osteoclasts leads to increases in WNT1 expression by osteoclasts. Therefore, our data suggest that TGF-β and BMP signaling pathways in osteoclasts could act in an antagonistic fashion to regulate osteoblast activity through WNT1 and other coupling factors.

P2. Spatial and temporal changes of electrical cortical activity induced by self-initiated finger tapping

Objective Sustained neuronal activity can be localized with functional magnetic resonance imaging (fMRI). Signal analysis of the time series within and across brain voxels reveal state specific characteristics enriching our understanding of, e.g., different states of consciousness ( Tagliazucchi et al., 2015 , Tagliazucchi et al., 2014 , Tagliazucchi et al., 2013a , Tagliazucchi et al., 2013b ). It should be possible to derive similar information from a more universally available and bed side tool, the electroencephalogram (EEG) ( Tagliazucchi et al., 2012a , Tagliazucchi et al., 2012b ). Because surface EEG is a blurred representation of multiple neuronal sources, source analysis is required to add spatial detail. Here, we validate a source reconstruction method facilitating the analysis of ongoing EEG in source space with methods comparable to those applied to fMRI time series: We test whether we can localize well described surface EEG changes induced by a finger tapping task to motor cortical brain regions. Method 30 subjects underwent a self-paced finger tapping task which induces desynchronization of the surface EEG ( Pfurtscheller et al., 1996 ). We recorded from 29 EEG channels and EMG electrodes over the right and left M. abductor pollicis brevis and created grand average maps for each tapping condition (left hand, right hand, both hands, no tapping) both in sensor and source (minimum variance distortionless response [‘minimum norm’] beamforming) space. Results In sensor space, we observed a drop in 8–12 Hz activity near C3 and C4 ( Fig. 1 ) with an onset a few seconds before the start of each tapping condition. In source space, the desynchronization localized to central regions ( Fig. 2 ). Discussion EEG desynchronization was in agreement with ( Pfurtscheller et al., 1996 , McFarland et al., 2000 ), the drop in power preceding the EMG-defined (self-paced) tapping might reflect motor planning. The minimum norm beamforming localized the EEG changes biologically plausible to central regions. In conclusion, we validated a technique, which transforms ongoing EEG into source space. This is an important prerequisite for further quantitative EEG signal analysis with spatial information similar those applied to fMRI time series.

Maternal Regulation of Pups' Cortical Activity: Role of Serotonergic Signaling.

A developing brain shows intense reorganization and heightened neuronal plasticity allowing for environmental modulation of its development. During early life, maternal care is a key factor of this environment and defects in this care can derail adaptive brain development and may result in susceptibility to neuropsychiatric disorders. Nevertheless, the mechanisms by which those maternal interactions immediately impact the offspring's brain activity to initiate the pathway to pathology are not well understood. We do know that multiple neurotransmitter systems are involved, including the serotonergic system, a key neuromodulator involved in brain development and emotional regulation. We tested the importance of the serotonergic system and pups' immediate neural response to maternal presence using wireless electrophysiological recordings, a novel approach allowing us to record neural activity during pups' interactions with their mother. We found that maternal contact modulates the P10-P12 rat pups' anterior cingulate cortex (ACC) activity by notably increasing local-field potential (LFP) power in low-frequency bands. We demonstrated, by blocking serotonergic receptors, that this increase is mediated through 5-HT2 receptors (5-HT2Rs). Finally, we showed in isolated pups that enhancing serotonergic transmission, using a selective-serotonin-reuptake-inhibitor, is sufficient to enhance LFP power in low-frequency bands in a pattern similar to that observed when the mother is in the nest. Our results highlight a significant contribution of the serotonergic system in mediating changes of cortical activity in pups related to maternal presence.

Nogo-A inactivation improves visual plasticity and recovery after retinal injury

Myelin-associated proteins such as Nogo-A are major inhibitors of neuronal plasticity that contribute to permanent neurological impairments in the injured CNS. In the present study, we investigated the influence of Nogo-A on visual recovery after retinal injuries in mice. Different doses of N-methyl-d-aspartate (NMDA) were injected in the vitreous of the left eye to induce retinal neuron death. The visual function was monitored using the optokinetic response (OKR) as a behavior test, and electroretinogram (ERG) and local field potential (LFP) recordings allowed to assess changes in retinal and cortical neuron activity, respectively. Longitudinal OKR follow-ups revealed reversible visual deficits after injection of NMDA ≤ 1 nmole in the left eye and concomitant functional improvement in the contralateral visual pathway of the right eye that was let intact. Irreversible OKR loss observed with NMDA ≥ 2 nmol was correlated with massive retinal cell death and important ERG response decline. Strikingly, the OKR mediated by injured and intact eye stimulation was markedly improved in Nogo-A KO mice compared with WT animals, suggesting that the inactivation of Nogo-A promotes visual recovery and plasticity. Moreover, OKR improvement was associated with shorter latency of the N2 wave of Nogo-A KO LFPs relative to WT animals. Strikingly, intravitreal injection of anti-Nogo-A antibody (11C7) in the injured eye exerted positive effects on cortical LFPs. This study presents the intrinsic ability of the visual system to recover from NMDA-induced retinal injury and its limitations. Nogo-A neutralization may promote visual recovery in retinal diseases such as glaucoma.

2190 Longitudinal changes in EEG power envelope connectivity are proportional to motor recovery in chronic stroke patients

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to determine the degree to which the use of a contralesionally-controlled brain-computer interface for stroke rehabilitation drives change in interhemispheric motor cortical activity. METHODS/STUDY POPULATION: Ten chronic stroke patients were trained in the use of a brain-computer interface device for stroke recovery. Patients perform motor imagery to control the opening and closing of a motorized hand orthosis. This device was sent home with patients for 12 weeks, and patients were asked to use the device 1 hour per day, 5 days per week. The Action Research Arm Test (ARAT) was performed at 2-week intervals to assess motor function improvement. Before the active motor imagery task, patients were asked to quietly rest for 90 seconds before the task to calibrate recording equipment. EEG signals were acquired from 2 electrodes—one each centered over left and right primary motor cortex. Signals were preprocessed with a 60 Hz notch filter for environmental noise and referenced to the common average. Power envelopes for 1 Hz frequency bands (1–30 Hz) were calculated through Gabor wavelet convolution. Correlations between electrodes were then calculated for each frequency envelope on the first and last 5 runs, thus generating one correlation value per subject, per run. The chosen runs approximately correspond to the first and last week of device usage. These correlations were Fisher Z-transformed for comparison. The first and last 5 run correlations were averaged separately to estimate baseline and final correlation values. A difference was then calculated between these averages to determine correlation change for each frequency. The relationship between beta-band correlation changes (13–30 Hz) and the change in ARAT score was determined by calculating a Pearson correlation. RESULTS/ANTICIPATED RESULTS: Beta-band inter-electrode correlations tended to decrease more in patients achieving greater motor recovery (Pearson’s r=−0.68, p=0.031). A similar but less dramatic effect was observed with alpha-band (8–12 Hz) correlation changes (Pearson’s r=−0.42, p=0.22). DISCUSSION/SIGNIFICANCE OF IMPACT: The negative correlation between inter-electrode power envelope correlations in the beta frequency band and motor recovery indicates that activity in the motor cortex on each hemisphere may become more independent during recovery. The role of the unaffected hemisphere in stroke recovery is currently under debate; there is conflicting evidence regarding whether it supports or inhibits the lesioned hemisphere. These findings may support the notion of interhemispheric inhibition, as we observe less in common between activity in the 2 hemispheres in patients successfully achieving recovery. Future neuroimaging studies with greater spatial resolution than available with EEG will shed further light on changes in interhemispheric communication that occur during stroke rehabilitation.

Efficacy of Yokukansankachimpihange on sleep disturbance in Parkinson's disease: A study protocol of a randomized, double blind, placebo-controlled pilot trial.

Introduction:Parkinson's disease (PD) is a progressive neurodegenerative disorder that includes motor and nonmotor symptoms. Sleep disturbance is known to decrease the quality of life in patients with PD, and there are limitations to the pharmacotherapy currently in use. Therefore, complementary treatment therapies are required to address these limitations. The traditional herbal medicines Yokukansan (YKS) and Yokukansankachimpihange (YKSCH) have been used to treat insomnia and night crying in children, suggesting their effectiveness against sleep disturbance in patients with PD. We will evaluate whether YKSCH improves sleep disturbance in PD and will identify YKS-related changes in hemodynamic parameters, and neurotransmitter and hormone levels in patients with PD experiencing sleep disturbance.Methods:We will conduct a randomized, double-blinded, placebo-controlled parallel trial in 34 patients with PD and sleep disturbance, randomly allocating the patients to either placebo-control (n = 17) or treatment groups (n = 17). The total study period will be 16 weeks; administration of YKSCH or placebo, as intervention, will be performed for a 12-week period, and follow-up will be performed over a 4-week period. All subjects will undergo conventional treatment, and be required to maintain a regular medication schedule throughout the study period. The primary outcome measure will be the Scales for Outcomes in PD-Sleep Scale score, and the secondary outcome measures will be polysomnography results, findings from instruments related to sleep disorders, neurotransmitter and hormone levels, and hemodynamic changes in the brain cortex.Discussion and conclusions:This trial will evaluate the effectiveness and safety of YKSCH for sleep improvement in PD with sleep disturbance, and investigate the underlying mechanism of action. We expect improvement in the scores for subjective and objective sleep scales, hemodynamic changes in prefrontal cortical activity, and changes in neurotransmitter and hormone levels. The findings will provide insight into the mechanism underlying the therapeutic effect of YKSCH in PD, and lay the foundation for further studies on whether YKSCH improves sleep disturbance in PD.Trial registration number:Clinical Research Information Service (KCT0002869).