Remote Brain Areas Research Articles

Association between Inhibitory-Excitatory Balance and Brain Activity Response during Cognitive Flexibility in Young and Older Individuals.

Cognitive flexibility represents the capacity to switch among different mental schemes, providing an adaptive advantage to a changing environment. The neural underpinnings of this executive function have been deeply studied in humans through fMRI, showing that the left inferior frontal cortex (IFC) and the left inferior parietal lobe (IPL) are crucial. Here, we investigated the inhibitory-excitatory balance in these regions by means of γ-aminobutyric acid (GABA+) and glutamate + glutamine (Glx), measured with magnetic resonance spectroscopy (MRS), during a cognitive flexibility task and its relationship with performance level and the local task-induced blood-oxygen level dependent (BOLD) response in 40 young (18-35 y.o.; 26 female) and 40 older (18-35 y.o.; 21 female) human adults. As the IFC and the IPL are richly connected regions, we also examined whole-brain effects associated with their local metabolic activity. Results did not show absolute metabolic modulations associated with flexibility performance, but performance level was related to the direction of metabolic modulation in the IPL with opposite patterns in young and older individuals. The individual inhibitory-excitatory balance modulation showed an inverse relationship with the local BOLD response in the IPL. Finally, the modulation of inhibitory-excitatory balance in IPL was related to whole-brain effects only in older individuals. These findings show disparities in the metabolic mechanisms underlying cognitive flexibility in young and older adults and their association with performance level and BOLD response. Such metabolic differences are likely to play a role in executive functioning during aging and specifically in cognitive flexibility.Significance Statement Cognitive flexibility provides an advantage in adapting to changing environments. We investigated the inhibitory-excitatory balance (GABA+/Glx) modulation in the frontal and parietal cortices during cognitive flexibility in young and older individuals through MRS. An increase in the excitatory tone during cognitive performance related to a better execution in younger adults. Interestingly, it was an increase in the inhibitory tone that was associated to a better performance in older adults. Furthermore, we revealed that an increased inhibitory tone in older adults related to a decreased oxygen consumption in remote brain areas (BOLD-fMRI). This may suggest that GABA modulation facilitates the segregation of neural networks, maximizing brain efficiency and cognitive performance. These findings underscore age-related disparities in the neurometabolic mechanisms underlying cognitive flexibility.

Visually or auditorily induced seizures involve the activation of nonhippocampal brain areas and hippocampal removal does not alleviate seizures in a mouse model of temporal lobe epilepsy.

Several studies have attributed epileptic activities in temporal lobe epilepsy (TLE) to the hippocampus; however, the participation of nonhippocampal neuronal networks in the development of TLE is often neglected. Here, we sought to understand how these nonhippocampal networks are involved in the pathology that is associated with TLE disease. A kainic acid (KA) model of temporal lobe epilepsy was induced by injecting KA into dorsal hippocampus of C57BL/6J mice. Network activation after spontaneous seizure was assessed using c-Fos expression. Protocols to induce seizure using visual or auditory stimulation were developed, and seizure onset zone (SOZ) and frequency of epileptic spikes were evaluated using electrophysiology. The hippocampus was removed to assess seizure recurrence in the absence of hippocampus. Our results showed that cortical and hippocampal epileptic networks are activated during spontaneous seizures. Perturbation of these networks using visual or auditory stimulation readily precipitates seizures in TLE mice; the frequency of the light-induced or noise-induced seizures depends on the induction modality adopted during the induction period. Localization of SOZ revealed the existence of cortical and hippocampal SOZ in light-induced and noise-induced seizures, and the development of local and remote epileptic spikes in TLE occurs during the early stage of the disease. Importantly, we further discovered that removal of the hippocampi does not stop seizure activities in TLE mice, revealing that seizures in TLE mice can occur independent of the hippocampus. This study has shown that the network pathology that evolves in TLE is not localized to the hippocampus; rather, remote brain areas are also recruited. The occurrence of light-induced or noise-induced seizures and epileptic discharges in epileptic mice is a consequence of the activation of nonhippocampal brain areas. This work therefore demonstrates the fundamental role of nonhippocampal epileptic networks in generating epileptic activities with or without the hippocampus in TLE disease.

Repetitive Transcranial Magnetic Stimulation of the Human Motor Cortex Modulates Processing of Heat Pain Sensation as Assessed by the Offset Analgesia Paradigm.

Offset analgesia (OA), which is defined as a disproportionately large reduction in pain perception following a small decrease in a heat stimulus, quantifies temporal aspects of endogenous pain modulation. In this study on healthy subjects, we aimed to (i) determine the Heat Pain Threshold (HPT) and the response to constant and dynamic heat stimuli assessing sensitization, adaptation and OA phenomena at the thenar eminence; (ii) evaluate the effects of high-frequency repetitive Transcranial Magnetic Stimulation (rTMS) of the primary motor cortex (M1) on these measures. Twenty-four healthy subjects underwent quantitative sensory testing before and after active or sham 10 Hz rTMS (1200 stimuli) of the left M1, during separate sessions. We did not observe any rTMS-related changes in the HPT or visual analogue scale (VAS) values recorded during the constant trial. Of note, at baseline, we did not find OA at the thenar eminence. Only after active rTMS did we detect significantly reduced VAS values during dynamic heat stimuli, indicating a delayed and attenuated OA phenomenon. rTMS of the left M1 may activate remote brain areas that belong to the descending pain modulatory and reward systems involved in the OA phenomenon. Our findings provide insights into the mechanisms by which rTMS of M1 could exert its analgesic effects.

Functional connectivity of sensorimotor network is enhanced in spastic diplegic cerebral palsy: A multimodal study using fMRI and MEG

ObjectiveTo assess the effects to functional connectivity (FC) caused by lesions related to spastic diplegic cerebral palsy (CP) in children and adolescents using multiple imaging modalities. MethodsWe used resting state magnetoencephalography (MEG) envelope signals in alpha, beta and gamma ranges and resting state functional magnetic resonance imaging (fMRI) signals to quantify FC between selected sensorimotor regions of interest (ROIs) in 11 adolescents with spastic diplegic cerebral palsy and 24 typically developing controls. Motor performance of the hands was quantified with gross motor, fine motor and kinesthesia tests. ResultsIn fMRI, participants with CP showed enhanced FC within posterior parietal regions; in MEG, they showed enhanced interhemispheric FC between sensorimotor regions and posterior parietal regions both in alpha and lower beta bands. There was a correlation between the kinesthesia score and fronto-parietal connectivity in the control population. ConclusionsCP is associated with enhanced FC in sensorimotor network. This difference is not correlated with hand coordination performance. The effect of the lesion is likely not fully captured by temporal correlation of ROI signals. SignificanceBrain lesions can show as increased temporal correlation of activity between remote brain areas. We suggest this effect is likely separate from typical physiological correlates of functional connectivity.

Mental flexibility depends on a largely distributed white matter network: Causal evidence from connectome-based lesion-symptom mapping

Mental flexibility (MF) refers to the capacity to dynamically switch from one task to another. Current neurocognitive models suggest that since this function requires interactions between multiple remote brain areas, the integrity of the anatomic tracts connecting these brain areas is necessary to maintain performance.We tested this hypothesis by assessing with a connectome-based lesion-symptom mapping approach the effects of white matter lesions on the brain’s structural connectome and their association with performance on the trail making test, a neuropsychological test of MF, in a sample of 167 first unilateral stroke patients.We found associations between MF deficits and damage of i) left lateralized fronto-temporo-parietal connections and interhemispheric connections between left temporo-parietal and right parietal areas; ii) left cortico-basal connections; and iii) left cortico-pontine connections. We further identified a relationship between MF and white matter disconnections within cortical areas composing the cognitive control, default mode and attention functional networks.These results for a central role of white matter integrity in MF extend current literature by providing causal evidence for a functional interdependence among the regional cortical and subcortical structures composing the MF network. Our results further emphasize the necessity to consider connectomics in lesion-symptom mapping analyses to establish comprehensive neurocognitive models of high-order cognitive functions.

Spinal cord injury induced exacerbation of Alzheimer's disease like pathophysiology is reduced by topical application of nanowired cerebrolysin with monoclonal antibodies to amyloid beta peptide, p-tau and tumor necrosis factor alpha.

Hallmark of Alzheimer's disease include amyloid beta peptide and phosphorylated tau deposition in brain that could be aggravated following traumatic of concussive head injury. However, amyloid beta peptide or p-tau in spinal cord following injury is not well known. In this investigation we measured amyloid beta peptide and p-tau together with tumor necrosis factor-alpha (TNF-α) in spinal cord and brain following 48h after spinal cord injury in relation to the blood-spinal cord and blood-brain barrier, edema formation, blood flow changes and cell injury in perifocal regions of the spinal cord and brain areas. A focal spinal cord injury was inflicted over the right dorsal horn of the T10-11 segment (4mm long and 2mm deep) and amyloid beta peptide and p-tau was measured in perifocal rostral (T9) and caudal (T12) spinal cord segments as well as in the brain areas. Our observations showed a significant increase in amyloid beta peptide in the T9 and T12 segments as well as in remote areas of brain and spinal cord after 24 and 48h injury. This is associated with breakdown of the blood-spinal cord (BSCB) and brain barriers (BBB), edema formation, reduction in blood flow and cell injury. After 48h of spinal cord injury elevation of amyloid beta peptide, phosphorylated tau (p-tau) and tumor necrosis factor-alpha (TNF-α) was seen in T9 and T12 segments of spinal cord in cerebral cortex, hippocampus and brain stem regions associated with microglial activation as seen by upregulation of Iba1 and CD86. Repeated nanowired delivery of cerebrolysin topically over the traumatized segment repeatedly together with monoclonal antibodies (mAb) to amyloid beta peptide (AβP), p-tau and TNF-α significantly attenuated amyloid beta peptide, p-tau deposition and reduces Iba1, CD68 and TNF-α levels in the brain and spinal cord along with blockade of BBB and BSCB, reduction in blood flow, edema formation and cell injury. These observations are the first to show that spinal cord injury induces Alzheimer's disease like symptoms in the CNS, not reported earlier.

Hippocampal gamma and sharp wave/ripples mediate bidirectional interactions with cortical networks during sleep

Hippocampus-neocortex interactions during sleep are critical for memory processes: Hippocampally initiated replay contributes to memory consolidation in the neocortex and hippocampal sharp wave/ripples modulate cortical activity. Yet, the spatial and temporal patterns of this interaction are unknown. With voltage imaging, electrocorticography, and laminarly resolved hippocampal potentials, we characterized cortico-hippocampal signaling during anesthesia and nonrapid eye movement sleep. We observed neocortical activation transients, with statistics suggesting a quasi-critical regime, may be helpful for communication across remote brain areas. From activity transients, we identified, in a data-driven fashion, three functional networks. A network overlapping with the default mode network and centered on retrosplenial cortex was the most associated with hippocampal activity. Hippocampal slow gamma rhythms were strongly associated to neocortical transients, even more than ripples. In fact, neocortical activity predicted hippocampal slow gamma and followed ripples, suggesting that consolidation processes rely on bidirectional signaling between hippocampus and neocortex.

Continuous theta-burst stimulation to the sensorimotor cortex affects contralateral gamma-aminobutyric acid level and resting-state networks.

Continuous theta-burst stimulation (cTBS) is a noninvasive repetitive brain stimulation protocol that suppresses the excitability of the primary motor cortex. It induces cerebral cortical inhibition by increasing inhibitory interneuronal excitability that is associated with increases in gamma-aminobutyric acid (GABA) concentration in the stimulated cortices. cTBS has been applied in the rehabilitation of stroke patients to modulate interhemispheric imbalance. However, the precise mechanisms of cTBS in remote brain areas remain uncertain. We evaluated cTBS-induced GABA level changes in bilateral sensorimotor cortices using GABA-edited magnetic resonance spectroscopy, alternations of motor evoked potentials (MEPs), and resting-state networks (RSNs) using resting-state functional magnetic resonance imaging in 24 healthy right-handed adults (mean age: 34.4 ± 5.0 years). GABA levels in the stimulated left hemisphere significantly increased from baseline (p = 0.013), which was comparable with those of previous reports. GABA levels in the unstimulated right hemisphere showed a trend decrease. cTBS induced a significant decrease in right hand-MEP amplitudes (22.06% ± 43.50%) from baseline (p = 0.026) in accordance with GABA concentrations. However, multiple RSNs, including the default mode and primary motor networks, did not show any obvious differences between pre- and post-stimulus comparisons in the sensorimotor network using the dual regression approach. These results suggest that cTBS simultaneously increases ipsilateral GABA in the stimulated left hemisphere and decreases contralateral GABA in the unstimulated right hemisphere. Neuromodulation following cTBS may be associated with the interhemispheric inhibition because of alterations in GABA levels between the stimulated and unstimulated cortices.

Neuromodulation Using Transcranial Focused Ultrasound on the Bilateral Medial Prefrontal Cortex.

Transcranial focused ultrasound (tFUS) is a promising technique of non-invasive brain stimulation for modulating neuronal activity with high spatial specificity. The medial prefrontal cortex (mPFC) has been proposed as a potential target for neuromodulation to prove emotional and sleep qualities. We aim to set up an appropriate clinical protocol for investigating the effects of tFUS stimulation of the bilateral mPFC for modulating the function of the brain-wide network using different sonication parameters. Seven participants received 20 min of 250 kHz tFUS to the bilateral mPFC with excitatory (70% duty cycle with sonication interval at 5 s) or suppressive (5% duty cycle with no interval) sonication protocols, which were compared to a sham condition. By placing the cigar-shaped sonication focus on the falx between both mPFCs, it was possible to simultaneously stimulate the bilateral mPFCs. Brain activity was analyzed using continuous electroencephalographic (EEG) recording during, before, and after tFUS. We investigated whether tFUS stimulation under the different conditions could lead to distinctive changes in brain activity in local brain regions where tFUS was directly delivered, and also in adjacent or remote brain areas that were not directly stimulated. This kind of study setting suggests that dynamic changes in brain cortical responses can occur within short periods of time, and that the distribution of these responses may differ depending on local brain states and functional brain architecture at the time of tFUS administration, or perhaps, at least temporarily, beyond the stimulation time. If so, tFUS could be useful for temporarily modifying regional brain activity, modulating functional connectivity, or reorganizing brain functions associated with various neuropsychiatric diseases, such as insomnia and depression.

Training-Specific Changes in Regional Spontaneous Neural Activity Among Professional Chinese Chess Players.

BackgroundOur previous reports reflected some aspects of neuroplastic changes from long-term Chinese chess training but were mainly based on large-scale intrinsic connectivity. In contrast to functional connectivity among remote brain areas, synchronization of local intrinsic activity demonstrates functional connectivity among regional areas. Until now, local connectivity changes in professional Chinese chess players (PCCPs) have been reported only at specific hubs; whole-brain-based local connectivity and its relation to training profiles has not been revealed.ObjectivesTo investigate whole-brain local connectivity changes and their relation to training profiles in PCCPs.MethodsRegional homogeneity (ReHo) analysis of rs-fMRI data from 22 PCCPs versus 21 novices was performed to determine local connectivity changes and their relation to training profiles.ResultsCompared to novices, PCCPs showed increased regional spontaneous activity in the posterior lobe of the left cerebellum, the left temporal pole, the right amygdala, and the brainstem but decreased ReHo in the right precentral gyrus. From a whole-brain perspective, local activity in areas such as the posterior lobe of the right cerebellum and the caudate correlated with training profiles.ConclusionRegional homogeneity changes in PCCPs were consistent with the classical view of automaticity in motor control and learning. Related areas in the pattern indicated an enhanced capacity for emotion regulation, supporting cool and focused attention during gameplay. The possible participation of the basal ganglia-cerebellar-cerebral networks, as suggested by these correlation results, expands our present knowledge of the neural substrates of professional chess players. Meanwhile, ReHo change occurred in an area responsible for the pronunciation and reading of Chinese characters. Additionally, professional Chinese chess training was associated with change in a region that is affected by Alzheimer’s disease (AD).

High-Frequency Transcranial Magnetic Stimulation Combined With Functional Magnetic Resonance Imaging Reveals Distinct Activation Patterns Associated With Different Dorsolateral Prefrontal Cortex Stimulation Sites

ObjectivesTranscranial magnetic stimulation (TMS) has been extensively used for the treatment of depression, obsessive-compulsive disorder, and certain neurologic disorders. Despite having promising treatment efficacy, the fundamental neural mechanisms of TMS remain understudied. Materials and MethodsIn this study, 15 healthy adult participants received simultaneous TMS and functional magnetic resonance imaging to map the modulatory effect of TMS when it was applied over three different sites in the dorsolateral prefrontal cortex. Independent component analysis (ICA) was used to identify the networks affected by TMS when applied over the different sites. The standard general linear model (GLM) analysis was used for comparison. ResultsICA showed that TMS affected the stimulation sites as well as remote brain areas, some areas/networks common across all TMS sites, and other areas/networks specific to each TMS site. In particular, TMS site and laterality differences were observed at the left executive control network. In addition, laterality differences also were observed at the dorsal anterior cingulate cortex and dorsolateral/dorsomedial prefrontal cortex. In contrast with the ICA findings, the GLM-based results mainly showed activation of auditory cortices regardless of the TMS sites. ConclusionsOur findings support the notion that TMS could act through a top-down mechanism, indirectly modulating deep subcortical nodes by directly stimulating cortical regions. Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT03394066.

Mapping Epileptic Networks Using Simultaneous Intracranial EEG-fMRI.

Background: Potentially curative epilepsy surgery can be offered if a single, discrete epileptogenic zone (EZ) can be identified. For individuals in whom there is no clear concordance between clinical localization, scalp EEG, and imaging data, intracranial EEG (icEEG) may be needed to confirm a predefined hypothesis regarding irritative zone (IZ), seizure onset zone (SOZ), and EZ prior to surgery. However, icEEG has limited spatial sampling and may fail to reveal the full extent of epileptogenic network if predefined hypothesis is not correct. Simultaneous icEEG-fMRI has been safely acquired in humans and allows exploration of neuronal activity at the whole-brain level related to interictal epileptiform discharges (IED) captured intracranially.Methods: We report icEEG-fMRI in eight patients with refractory focal epilepsy who had resective surgery and good postsurgical outcome. Surgical resection volume in seizure-free patients post-surgically reflects confirmed identification of the EZ. IEDs on icEEG were classified according to their topographic distribution and localization (Focal, Regional, Widespread, and Non-contiguous). We also divided IEDs by their location within the surgical resection volume [primary IZ (IZ1) IED] or outside [secondary IZ (IZ2) IED]. The distribution of fMRI blood oxygen level-dependent (BOLD) changes associated with individual IED classes were assessed over the whole brain using a general linear model. The concordance of resulting BOLD map was evaluated by comparing localization of BOLD clusters with surgical resection volume. Additionally, we compared the concordance of BOLD maps and presence of BOLD clusters in remote brain areas: precuneus, cuneus, cingulate, medial frontal, and thalamus for different IED classes.Results: A total of 38 different topographic IED classes were identified across the 8 patients: Focal (22) and non-focal (16, Regional = 9, Widespread = 2, Non-contiguous = 5). Twenty-nine IEDs originated from IZ1 and 9 from IZ2. All IED classes were associated with BOLD changes. BOLD maps were concordant with the surgical resection volume for 27/38 (71%) IED classes, showing statistical global maximum BOLD cluster or another cluster in the surgical resection volume. The concordance of BOLD maps with surgical resection volume was greater (p < 0.05) for non-focal (87.5%, 14/16) as compared to Focal (59%, 13/22) IED classes. Additionally, BOLD clusters in remote cortical and deep brain areas were present in 84% (32/38) of BOLD maps, more commonly (15/16; 93%) for non-focal IED-related BOLD maps.Conclusions: Simultaneous icEEG-fMRI can reveal BOLD changes at the whole-brain level for a wide range of IEDs on icEEG. BOLD clusters within surgical resection volume and remote brain areas were more commonly seen for non-focal IED classes, suggesting that a wider hemodynamic network is at play.

White matter degeneration in remote brain areas of stroke patients with motor impairment due to basal ganglia lesions.

Diffusion tensor imaging (DTI) studies have revealed distinct white matter (WM) characteristics of the brain following diseases. Beyond the lesion‐symptom maps, stroke is characterized by extensive structural and functional alterations of brain areas remote to local lesions. Here, we further investigated the structural changes over a global level by using DTI data of 10 ischemic stroke patients showing motor impairment due to basal ganglia lesions and 11 healthy controls. DTI data were processed to obtain fractional anisotropy (FA) maps, and multivariate pattern analysis was used to explore brain regions that play an important role in classification based on FA maps. The WM structural network was constructed by the deterministic fiber‐tracking approach. In comparison with the controls, the stroke patients showed FA reductions in the perilesional basal ganglia, brainstem, and bilateral frontal lobes. Using network‐based statistics, we found a significant reduction in the WM subnetwork in stroke patients. We identified the patterns of WM degeneration affecting brain areas remote to the lesions, revealing the abnormal organization of the structural network in stroke patients, which may be helpful in understanding of the neural mechanisms underlying hemiplegia.

Adenoviruses for better brain function

Using adenoviruses for therapy became well accepted due to some vaccines against COVID-19 pandemic. Actually, not the native viruses, but a recombinant form lacking fertility—a so called vector—is used with the aim to transfer genetic materials to adult cells. Decades of research preceded this development. Although the most important field of utilization is the vaccines, but neurological and even psychiatric disorders may also benefit from viral vectors. Neurons seem to be especially convenient target for viral vectors as they are considered as non-dividing cells. Extra genetic information provided by the viral vectors is not integrated into the genome rather remains in the cytoplasm as plasmid. During repeated cell divisions the cell loses this extra information, it is “diluted” and finally disappears. It is not the case in the slow dividing cells including neurons. For preclinical research purposes canine adenovirus 2 is widely used. It is a retrograde transporter therefore especially good in marking specific pathways between remote brain areas and providing a useful tool for functional brain mapping. Therapeutic usages include restoration of missing enzymes or parts of sensory systems and treatment of cancer. All in all, at present most of the studies on brain utilizing adenoviral vectors are still in preclinical phase and focus on studying mechanisms. However, we should be aware of this important topic, which may be an everyday therapy in the future.

Semi-automatic Extraction of Functional Dynamic Networks Describing Patient's Epileptic Seizures.

Intracranial electroencephalography (EEG) studies using stereotactic EEG (SEEG) have shown that during seizures, epileptic activity spreads across several anatomical regions from the seizure onset zone toward remote brain areas. A full and objective characterization of this patient-specific time-varying network is crucial for optimal surgical treatment. Functional connectivity (FC) analysis of SEEG signals recorded during seizures enables to describe the statistical relations between all pairs of recorded signals. However, extracting meaningful information from those large datasets is time consuming and requires high expertise. In the present study, we first propose a novel method named Brain-wide Time-varying Network Decomposition (BTND) to characterize the dynamic epileptogenic networks activated during seizures in individual patients recorded with SEEG electrodes. The method provides a number of pathological FC subgraphs with their temporal course of activation. The method can be applied to several seizures of the patient to extract reproducible subgraphs. Second, we compare the activated subgraphs obtained by the BTND method with visual interpretation of SEEG signals recorded in 27 seizures from nine different patients. As a whole, we found that activated subgraphs corresponded to brain regions involved during the course of the seizures and their time course was highly consistent with classical visual interpretation. We believe that the proposed method can complement the visual analysis of SEEG signals recorded during seizures by highlighting and characterizing the most significant parts of epileptic networks with their activation dynamics.

Sparse coupled logistic regression to estimate co-activation and modulatory influences of brain regions

Accurate mapping of the functional interactions between remote brain areas with resting-state functional magnetic resonance imaging requires the quantification of their underlying dynamics. In conventional methodological pipelines, a spatial scale of interest is first selected and dynamic analysis then proceeds at this hypothesised level of complexity. If large-scale functional networks or states are studied, more local regional rearrangements are then not described, potentially missing important neurobiological information. Here, we propose a novel mathematical framework that jointly estimates resting-state functional networks and spatially more localised cross-regional modulations. To do so, the changes in activity of each brain region are modelled by a logistic regression including co-activation coefficients (reflective of network assignment, as they highlight simultaneous activations across areas) and causal interplays (denoting finer regional cross-talks, when one region active at time t modulates the t to t + 1 transition likelihood of another area). A two-parameter regularisation scheme is used to make these two sets of coefficients sparse: one controls overall sparsity, while the other governs the trade-off between co-activations and causal interplays, enabling to properly fit the data despite the yet unknown balance between both types of couplings. Across a range of simulation settings, we show that the framework successfully retrieves the two types of cross-regional interactions at once. Performance across noise and sample size settings was globally on par with that of other existing methods, with the potential to reveal more precise information missed by alternative approaches. Preliminary application to experimental data revealed that in the resting brain, co-activations and causal modulations co-exist with a varying balance across regions. Our methodological pipeline offers a conceptually elegant alternative for the assessment of functional brain dynamics and can be downloaded at https://c4science.ch/source/Sparse_logistic_regression.git.

Cortical direct current stimulation improves signal transmission between the motor cortices of rats

Transcranial direct current (DC) stimulation is a noninvasive brain stimulation technique that is now widely used to improve motor and cognitive function. The neuromodulatory effects of DC is considered to extend to nearby as well as remote brain areas from the site of stimulation because of current flowing into the brain and/or signal transmission in neuronal networks. However, the effects of DC on cortico-cortical neuronal transmission are not well known. In the present study, we focused on signal transmission from the primary (M1) to secondary (M2) motor cortex of rats. Intra-cortical microstimulation (ICMS) was applied to the M1 under DC conditions, and changes in synaptic activity in the M2 were examined using current-source density analyses. The synaptic input to the M2 superficial layers was enhanced during DC stimulation, while the synaptic input to the M2 deeper layers was increased after DC stimulation. These results suggest that DC stimulation improves cortico-cortical neuronal transmission from M1 to M2, and that the effectiveness of DC may be different among different projection neuron types in the M1.

Cerebral microinfarcts disruption of remote cortical thickness

IntroductionCerebral microinfarcts (CMI) are common lesions, carrying an important contribution to small-vessel–related cognitive impairment. CMIs were previously found to cause local microstructural damage and disruption of white matter integrity. This study examines CMIs influence on cortical thickness in remote brain areas. MethodsSix small silent diffuse weighted imaging (DWI) lesions corresponding to subacute CMI were identified among five patients who underwent baseline and follow-up MRI scans from the Tel-Aviv Acute Brain Stroke Cohort (TABASCO). Regions of interest (ROIs) corresponding to the site of the DWI lesions and of the non-lesioned contralateral hemisphere (control ROI) were co-registered. DTI tractography was additionally performed to reconstruct the white matter tracts containing the ROIs. The normalized cortical thickness was calculated for the DWI lesional tract as well as for the contralateral non-lesional tract, and the lesion-to-control cortical thickness ratio (CTR) was calculated. ResultsPost-lesional scans, performed 25.1 ± 1.2 months after CMI detection, demonstrated reduced mean CTR within the ROI from 1.8 to 1.1 (p = 0.032). There was no difference between the CTR of the right hemisphere relative to those on the left hemisphere, or between the CTR change of the cortical and non-cortical CMI. DiscussionThis study demonstrated the prolonged influence of CMI on cortical thickness in remote ROI. The total number of CMIs is difficult to determine, however it has been shown that detecting even a single CMI suggests the existence of hundreds to thousands lesions. Therefore, the cumulative impact of these widely distributed lesions on cerebral cortex may have a significant contribution to the development of vascular cognitive impairment.

A Single-Neuron: Current Trends and Future Prospects.

The brain is an intricate network with complex organizational principles facilitating a concerted communication between single-neurons, distinct neuron populations, and remote brain areas. The communication, technically referred to as connectivity, between single-neurons, is the center of many investigations aimed at elucidating pathophysiology, anatomical differences, and structural and functional features. In comparison with bulk analysis, single-neuron analysis can provide precise information about neurons or even sub-neuron level electrophysiology, anatomical differences, pathophysiology, structural and functional features, in addition to their communications with other neurons, and can promote essential information to understand the brain and its activity. This review highlights various single-neuron models and their behaviors, followed by different analysis methods. Again, to elucidate cellular dynamics in terms of electrophysiology at the single-neuron level, we emphasize in detail the role of single-neuron mapping and electrophysiological recording. We also elaborate on the recent development of single-neuron isolation, manipulation, and therapeutic progress using advanced micro/nanofluidic devices, as well as microinjection, electroporation, microelectrode array, optical transfection, optogenetic techniques. Further, the development in the field of artificial intelligence in relation to single-neurons is highlighted. The review concludes with between limitations and future prospects of single-neuron analyses.

Altered activation in sensorimotor network after applying rTMS over the primary motor cortex at different frequencies.

IntroductionRepetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) can modulate brain activity both in the stimulated site and remote brain areas of the sensorimotor network. However, the modulatory effects of rTMS at different frequencies remain unclear. Here, we employed finger‐tapping task‐based fMRI to investigate alterations in activation of the sensorimotor network after the application of rTMS over the left M1 at different frequencies.Materials and MethodsForty‐five right‐handed healthy participants were randomly divided into three groups by rTMS frequency (HF, high‐frequency, 3 Hz; LF, low‐frequency, 1 Hz; and SHAM) and underwent two task‐fMRI sessions (RH, finger‐tapping with right index finger; LH, finger‐tapping with left index finger) before and after applying rTMS over the left M1. We defined regions of interest (ROIs) in the sensorimotor network based on group‐level activation maps (pre‐rTMS) from RH and LH tasks and calculated the percentage signal change (PSC) for each ROI. We then assessed the differences of PSC within HF or LF groups and between groups.ResultsApplication of rTMS at different frequencies resulted in a change in activation of several areas of the sensorimotor network. We observed the increased PSC in M1 after high‐frequency stimulation, while we detected the reduced PSC in the primary sensory cortex (S1), ventral premotor cortex (PMv), supplementary motor cortex (SMA), and putamen after low‐frequency stimulation. Moreover, the PSC in the SMA, dorsal premotor cortex (PMd), and putamen in the HF group was higher than in the LF group after stimulation.ConclusionOur findings suggested that activation alterations within sensorimotor network are dependent on the frequency of rTMS. Therefore, our findings contribute to understanding the effects of rTMS on brain activation in healthy individuals and ultimately may further help to suggest mechanisms of how rTMS could be employed as a therapeutic tool.