Regions Of Sensorimotor Cortex Research Articles

Vestibular Function is Associated with Prefrontal and Sensorimotor Cortical Gray Matter Volumes in a Cross-Sectional Study of Healthy, Older Adults

Background The vestibular system is associated with alterations in the structure and function of the central nervous system. Yet, whether age-related vestibular loss is related to volume loss in the cerebral cortical areas that have been reported to receive vestibular input remains unknown. In this cross-sectional study of 117 healthy, older adults from the Baltimore Longitudinal Study of Aging, we examine the relationships between age-related vestibular functions and the gray matter volumes of the prefrontal cortex and its subregions and of the sensorimotor cortex—regions known to process vestibular information. Methods T1-weighted MRI scans were automatically segmented using MRICloud. Log-linear multiple regression was used to investigate the relationships between average regional volume and vestibular function, adjusting for age, sex, and intracranial volume. Permutation testing was used for hypothesis testing, and bootstrapping was used to estimate confidence intervals. Results We found that age-related changes in vestibular end-organ function are associated with differentially altered gray matter volumes in the prefrontal and sensorimotor cortices, with many findings persisting when considering left (or right) side only. Concomitant with age-related, global brain atrophy, lower canal and utricular function were associated with additional volume atrophy of the prefrontal cortex and middle frontal gyrus, respectively. Lower saccular and utricular function were associated with the preservation of the volumes of the sensorimotor cortex and the pole of the superior frontal gyrus, respectively, against age-related, global brain atrophy. Canal and utricular function were not associated with the volumes of the sensorimotor cortex, and saccular function was not associated with the relative volumes of the prefrontal cortex. Conclusion Together, these findings of relative volume preservation or additional atrophy suggest that vestibular function may play a role in the resilience to or magnification of global age effects on cerebral cortical structure.

Differential impact of unilateral stroke on the bihemispheric motor cortex representation of the jaw and tongue muscles in young and aged rats.

Dysphagia commonly occurs after stroke, yet the mechanisms of post-stroke corticobulbar plasticity are not well understood. While cortical activity associated with swallowing actions is bihemispheric, prior research has suggested that plasticity of the intact cortex may drive recovery of swallowing after unilateral stroke. Age may be an important factor as it is an independent predictor of dysphagia after stroke and neuroplasticity may be reduced with age. Based on previous clinical studies, we hypothesized that cranial muscle activating volumes may be expanded in the intact hemisphere and would contribute to swallowing function. We also hypothesized that older age would be associated with limited map expansion and reduced function. As such, our goal was to determine the impact of stroke and age on corticobulbar plasticity by examining the jaw and tongue muscle activating volumes within the bilateral sensorimotor cortices. Using the middle cerebral artery occlusion rat stroke model, intracortical microstimulation (ICMS) was used to map regions of sensorimotor cortex that activate tongue and jaw muscles in both hemispheres. Young adult (7 months) and aged (30 months) male F344 × BN rats underwent a stroke or sham-control surgery, followed by ICMS mapping 8 weeks later. Videofluoroscopy was used to assess oral-motor functions. Increased activating volume of the sensorimotor cortex within the intact hemisphere was found only for jaw muscles, whereas significant stroke-related differences in tongue activating cortical volume were limited to the infarcted hemisphere. These stroke-related differences were correlated with infarct size, such that larger infarcts were associated with increased jaw representation in the intact hemisphere and decreased tongue representation in the infarcted hemisphere. We found that both age and stroke were independently associated with swallowing differences, weight loss, and increased corticomotor thresholds. Laterality of tongue and jaw representations in the sham-control group revealed variability between individuals and between muscles within individuals. Our findings suggest the role of the intact and infarcted hemispheres in the recovery of oral motor function may differ between the tongue and jaw muscles, which may have important implications for rehabilitation, especially hemisphere-specific neuromodulatory approaches. This study addressed the natural course of recovery after stroke; future work should expand to focus on rehabilitation.

Epilepsy-related functional brain network alterations are already present at an early age in the GAERS rat model of genetic absence epilepsy.

Genetic Absence Epilepsy Rats from Strasbourg (GAERS) represent a model of genetic generalized epilepsy. The present longitudinal study in GAERS and age-matched non-epileptic controls (NEC) aimed to characterize the epileptic brain network using two functional measures, resting state-functional magnetic resonance imaging (rs-fMRI) and manganese-enhanced MRI (MEMRI) combined with morphometry, and to investigate potential brain network alterations, following long-term seizure activity. Repeated rs-fMRI measurements at 9.4 T between 3 and 8 months of age were combined with MEMRI at the final time point of the study. We used graph theory analysis to infer community structure and global and local network parameters from rs-fMRI data and compared them to brain region-wise manganese accumulation patterns and deformation-based morphometry (DBM). Functional connectivity (FC) was generally higher in GAERS when compared to NEC. Global network parameters and community structure were similar in NEC and GAERS, suggesting efficiently functioning networks in both strains. No progressive FC changes were observed in epileptic animals. Network-based statistics (NBS) revealed stronger FC within the cortical community, including regions of association and sensorimotor cortex, and with basal ganglia and limbic regions in GAERS, irrespective of age. Higher manganese accumulation in GAERS than in NEC was observed at 8 months of age, consistent with higher overall rs-FC, particularly in sensorimotor cortex and association cortex regions. Functional measures showed less similarity in subcortical regions. Whole brain volumes of 8 months-old GAERS were higher when compared to age-matched NEC, and DBM revealed increased volumes of several association and sensorimotor cortex regions and of the thalamus. rs-fMRI, MEMRI, and volumetric data collectively suggest the significance of cortical networks in GAERS, which correlates with an increased fronto-central connectivity in childhood absence epilepsy (CAE). Our findings also verify involvement of basal ganglia and limbic regions. Epilepsy-related network alterations are already present in juvenile animals. Consequently, this early condition seems to play a greater role in dynamic brain function than chronic absence seizures.

Timing and location of speech errors induced by direct cortical stimulation.

Cortical regions supporting speech production are commonly established using neuroimaging techniques in both research and clinical settings. However, for neurosurgical purposes, structural function is routinely mapped peri-operatively using direct electrocortical stimulation. While this method is the gold standard for identification of eloquent cortical regions to preserve in neurosurgical patients, there is lack of specificity of the actual underlying cognitive processes being interrupted. To address this, we propose mapping the temporal dynamics of speech arrest across peri-sylvian cortices by quantifying the latency between stimulation and speech deficits. In doing so, we are able to substantiate hypotheses about distinct region-specific functional roles (e.g. planning versus motor execution). In this retrospective observational study, we analysed 20 patients (12 female; age range 14-43) with refractory epilepsy who underwent continuous extra-operative intracranial EEG monitoring of an automatic speech task during clinical bedside language mapping. Latency to speech arrest was calculated as time from stimulation onset to speech arrest onset, controlling for individual speech rate. Most instances of motor-based arrest (87.5% of 96 instances) were in sensorimotor cortex with mid-range latencies to speech arrest with a distributional peak at 0.47 s. Speech arrest occurred in numerous regions, with relatively short latencies in supramarginal gyrus (0.46 s), superior temporal gyrus (0.51 s) and middle temporal gyrus (0.54 s), followed by relatively long latencies in sensorimotor cortex (0.72 s) and especially long latencies in inferior frontal gyrus (0.95 s). Non-parametric testing for speech arrest revealed that region predicted latency; latencies in supramarginal gyrus and in superior temporal gyrus were shorter than in sensorimotor cortex and in inferior frontal gyrus. Sensorimotor cortex is primarily responsible for motor-based arrest. Latencies to speech arrest in supramarginal gyrus and superior temporal gyrus (and to a lesser extent middle temporal gyrus) align with latencies to motor-based arrest in sensorimotor cortex. This pattern of relatively quick cessation of speech suggests that stimulating these regions interferes with the outgoing motor execution. In contrast, the latencies to speech arrest in inferior frontal gyrus and in ventral regions of sensorimotor cortex were significantly longer than those in temporoparietal regions. Longer latencies in the more frontal areas (including inferior frontal gyrus and ventral areas of precentral gyrus and postcentral gyrus) suggest that stimulating these areas interrupts a higher-level speech production process involved in planning. These results implicate the ventral specialization of sensorimotor cortex (including both precentral and postcentral gyri) for speech planning above and beyond motor execution.

Multiple regions of sensorimotor cortex encode bite force and gape.

The precise control of bite force and gape is vital for safe and effective breakdown and manipulation of food inside the oral cavity during feeding. Yet, the role of the orofacial sensorimotor cortex (OSMcx) in the control of bite force and gape is still largely unknown. The aim of this study was to elucidate how individual neurons and populations of neurons in multiple regions of OSMcx differentially encode bite force and static gape when subjects (Macaca mulatta) generated different levels of bite force at varying gapes. We examined neuronal activity recorded simultaneously from three microelectrode arrays implanted chronically in the primary motor (MIo), primary somatosensory (SIo), and cortical masticatory (CMA) areas of OSMcx. We used generalized linear models to evaluate encoding properties of individual neurons and utilized dimensionality reduction techniques to decompose population activity into components related to specific task parameters. Individual neurons encoded bite force more strongly than gape in all three OSMCx areas although bite force was a better predictor of spiking activity in MIo vs. SIo. Population activity differentiated between levels of bite force and gape while preserving task-independent temporal modulation across the behavioral trial. While activation patterns of neuronal populations were comparable across OSMCx areas, the total variance explained by task parameters was context-dependent and differed across areas. These findings suggest that the cortical control of static gape during biting may rely on computations at the population level whereas the strong encoding of bite force at the individual neuron level allows for the precise and rapid control of bite force.

Differentiation of claustrum resting-state functional connectivity in healthy aging, Alzheimer's disease, and Parkinson's disease.

The claustrum is a sheet-like of telencephalic gray matter structure whose function is poorly understood. The claustrum is considered a multimodal computing network due to its reciprocal connections with almost all cortical areas as well as subcortical structures. Although the claustrum has been involved in several neurodegenerative diseases, specific changes in connections of the claustrum remain unclear in Alzheimer's disease (AD), and Parkinson's disease (PD). Resting-state fMRI and T1-weighted structural 3D images from healthy elderly (n=15), AD (n=16), and PD (n=12) subjects were analyzed. Seed-based FC analysis was performed using CONN FC toolbox and T1-weighted images were analyzed with the Computational Anatomy Toolbox for voxel-based morphometry analysis. While we observed a decreased FC between the left claustrum and sensorimotor cortex, auditory association cortex, and cortical regions associated with social cognition in PD compared with the healthy control group (HC), no significant difference was found in alterations in the FC of both claustrum comparing the HC and AD groups. In the AD group, high FC of claustrum with regions of sensorimotor cortex and cortical regions related to cognitive control, including cingulate gyrus, supramarginal gyrus, and insular cortex were demonstrated. In addition, the structural results show significantly decreased volume in bilateral claustrum in AD and PD compared with HC. There were no significant differences in the claustrum volumes between PD and AD groups so the FC may offer more precise findings in distinguishing changes for claustrum in AD and PD.

EEG-Based Brain Network Analysis of Chronic Stroke Patients After BCI Rehabilitation Training.

Traditional rehabilitation strategies become difficult in the chronic phase stage of stroke prognosis. Brain–computer interface (BCI) combined with external devices may improve motor function in chronic stroke patients, but it lacks comprehensive assessments of neurological changes regarding functional rehabilitation. This study aimed to comprehensively and quantitatively investigate the changes in brain activity induced by BCI–FES training in patients with chronic stroke. We analyzed the EEG of two groups of patients with chronic stroke, one group received functional electrical stimulation (FES) rehabilitation training (FES group) and the other group received BCI combined with FES training (BCI–FES group). We constructed functional networks in both groups of patients based on direct directed transfer function (dDTF) and assessed the changes in brain activity using graph theory analysis. The results of this study can be summarized as follows: (i) after rehabilitation training, the Fugl–Meyer assessment scale (FMA) score was significantly improved in the BCI–FES group (p < 0.05), and there was no significant difference in the FES group. (ii) Both the global and local graph theory measures of the brain network of patients with chronic stroke in the BCI–FES group were improved after rehabilitation training. (iii) The node strength in the contralesional hemisphere and central region of patients in the BCI–FES group was significantly higher than that in the FES group after the intervention (p < 0.05), and a significant increase in the node strength of C4 in the contralesional sensorimotor cortex region could be observed in the BCI–FES group (p < 0.05). These results suggest that BCI–FES rehabilitation training can induce clinically significant improvements in motor function of patients with chronic stroke. It can improve the functional integration and functional separation of brain networks and boost compensatory activity in the contralesional hemisphere to a certain extent. The findings of our study may provide new insights into understanding the plastic changes of brain activity in patients with chronic stroke induced by BCI–FES rehabilitation training.

Effect of Xenon Treatment on Gene Expression in Brain Tissue after Traumatic Brain Injury in Rats.

The overactivation of inflammatory pathways and/or a deficiency of neuroplasticity may result in the delayed recovery of neural function in traumatic brain injury (TBI). A promising approach to protecting the brain tissue in TBI is xenon (Xe) treatment. However, xenon’s mechanisms of action remain poorly clarified. In this study, the early-onset expression of 91 target genes was investigated in the damaged and in the contralateral brain areas (sensorimotor cortex region) 6 and 24 h after injury in a TBI rat model. The expression of genes involved in inflammation, oxidation, antioxidation, neurogenesis and neuroplasticity, apoptosis, DNA repair, autophagy, and mitophagy was assessed. The animals inhaled a gas mixture containing xenon and oxygen (ϕXe = 70%; ϕO2 25–30% 60 min) 15–30 min after TBI. The data showed that, in the contralateral area, xenon treatment induced the expression of stress genes (Irf1, Hmox1, S100A8, and S100A9). In the damaged area, a trend towards lower expression of the inflammatory gene Irf1 was observed. Thus, our results suggest that xenon exerts a mild stressor effect in healthy brain tissue and has a tendency to decrease the inflammation following damage, which might contribute to reducing the damage and activating the early compensatory processes in the brain post-TBI.

Cortical representations of phantom movements in lower limb amputees.

Understanding how sensorimotor cortex (SMC) organization relates to limb loss has major clinical implications, as cortical activity associated with phantom hand movements has been shown to predict phantom pain reports. Critically, earlier studies have largely focused on upper limb amputees; far less is known regarding SMC activity in lower limb amputees, despite the fact that this population comprises the majority of major limb loss cases. We aimed to characterize BOLD fMRI responses associated with phantom and sound limb movements to test the hypothesis that SMC organization is preserved in individuals with lower limb loss. Individuals with unilateral or bilateral lower limb loss underwent fMRI scans as they performed simple movements of their sound or phantom limbs. We observed that voluntary movements of the sound and phantom ankles were associated with BOLD signal changes in medial and superior portions of the precentral and postcentral gyri. In both hemispheres, contralateral limb movements were associated with greater signal changes compared to ipsilateral limb movements. Hand and mouth movements were associated with distinct activation patterns localized to more lateral SMC regions. We additionally tested whether activations associated with phantom movements related to self-report assessments indexing phantom pain experiences, nonpainful phantom sensations and phantom movement capabilities. We found that responses during phantom ankle movements did not correlate with any of the composite phantom limb indices in our sample. Our collective results reveal that SMC representations of the amputated limb persist and that traditional somatotopic organization is generally preserved in individuals suffering from lower limb loss.

A gradient from long-term memory to novel cognition: Transitions through default mode and executive cortex

Human cognition flexibly guides decision-making in familiar and novel situations. Although these decisions are often treated as dichotomous, in reality, situations are neither completely familiar, nor entirely new. Contemporary accounts of brain organization suggest that neural function is organized along a connectivity gradient from unimodal regions of sensorimotor cortex, through executive regions to transmodal default mode network. We examined whether this graded view of neural organization helps to explain how decision-making changes across situations that vary in their alignment with long-term knowledge. We used a semantic judgment task, which parametrically varied the global semantic similarity of items within a feature matching task to create a ‘task gradient’, from conceptual combinations that were highly overlapping in long-term memory to trials that only shared the goal-relevant feature. We found the brain’s response to the task gradient varied systematically along the connectivity gradient, with the strongest response in default mode network when the probe and target items were highly overlapping conceptually. This graded functional change was seen in multiple brain regions and within individual brains, and was not readily explained by task difficulty. Moreover, the gradient captured the spatial layout of networks involved in semantic processing, providing an organizational principle for controlled semantic cognition across the cortex. In this way, the cortex is organized to support semantic decision-making in both highly familiar and less familiar situations.

Functionally matched domains in parietal-frontal cortex of monkeys project to overlapping regions of the striatum.

Projections of small regions (domains) of primary motor cortex (M1), premotor cortex (PMC) and posterior parietal cortex (PPC) to the striatum of squirrel monkeys were revealed by restricted injections of anterograde tracers. As many as 8 classes of action-specific domains can be identified in PPC, as well as in PMC and M1, and some have been identified for injections by the action evoked by 0.5 s trains of electrical microstimulation. Injections of domains in all three cortical regions labeled dense patches of terminations in the matrix of the ipsilateral putamen, while providing sparse or no projections to corresponding regions of the contralateral putamen. When two or three of these domains were injected with different tracers, projection fields in the putamen were highly overlapped for injections in functionally matched domains across cortical areas, but were highly segregated for injections placed in functionally mismatched domains. While not all classes of domains were studied, the results suggest that the striatum potentially has separate representations of eight or more classes of actions that receive inputs from domains in three or more cortical regions in sensorimotor cortex. The overlap/segregation of cortico-striatal projections correlates with the strength of cortico-cortical connections between injected motor areas.

Assessing sensorimotor control of the lumbopelvic-hip region using task-based functional MRI.

Recent brain imaging studies have suggested that cortical remodeling within sensorimotor regions are associated with persistent low back pain and may be a driving mechanism for the impaired neuromuscular control associated with this condition. This paper outlines a new approach for investigating cortical sensorimotor integration during the performance of small-amplitude lumbopelvic movements with functional MRI. Fourteen healthy right-handed participants were instructed in the lumbopelvic movement tasks performed during fMRI acquisition. Surface electromyography (EMG) collected on 8 lumbopelvic and thigh muscles captured organized patterns of muscle activation during the movement tasks. fMRI data were collected on 10 of 14 participants. Sensorimotor cortical activation across the tasks was identified using a whole brain analysis and further explored with regional analyses of key components of the cortical sensorimotor network. Head motion had low correlation to the tasks (r = -0.101 to 0.004) and head translation averaged 0.98 (0.59 mm) before motion correction. Patterns of activation of the key lumbopelvic and thigh musculature (average amplitude normalized 2-17%) were significantly different across tasks (P > 0.001). Neuroimaging demonstrated activation in key sensorimotor cortical regions that were consistent with motor planning and sensory feedback needed for performing the different tasks. This approach captures the specificity of lumbopelvic sensorimotor control using goal-based tasks (e.g., "lift your hip" vs. "contract your lumbar multifidus to 20% of maximum") performed within the confines of the scanner. Specific patterns of sensorimotor cortex activation appear to capture differences between bilateral and unilateral tasks during voluntary control of multisegmental movement in the lumbopelvic region.NEW & NOTEWORTHY We demonstrated the feasibility of using task-based functional magnetic resonance imaging (fMRI) protocols for acquiring the blood oxygen level-dependent (BOLD) response of key sensorimotor cortex regions during voluntary lumbopelvic movements. Our approach activated lumbopelvic muscles during small-amplitude movements while participants were lying supine in the scanner. Our data supports these tasks can be done with limited head motion and low correlation of head motion to the task. The approach provides opportunities for assessing the role of brain changes in persistent low back pain.

The single intravenous administration of methylene blue after traumatic brain injury diminishes neurological deficit, blood-brain barrier disruption and decrease in the expression of S100 protein in rats

The protective effect of methylene blue (MB) was investigated on the model of focal one-sided traumatic brain injury (TBI) of the sensorimotor cortex region from 1 to 7 days after the injury. TBI caused a reliable disruption of the functions of the limbs contralateral to injury focus, an increase in the expression of S100 protein and blood-brain barrier (BBB) permeability in the ipsilateral hemisphere. The single intravenous injection of MB (1 mg/kg body weight) 30 min after TBI significantly reduced the limb function impairment as well as a TBI-induced increase in the expression of inflammatory marker S100 protein, and BBB permeability. When modeling inflammation in vitro, MB was found to protect cultured neurons from the toxic effects of lipopolysaccharide.In conclusion, the preservation of blood-brain barrier and a decrease in the expression of S100 protein may be an important mechanism by means of which MB improves neurological outcome.Our data demonstrate that MB can be a very promising pharmacological compound with neuroprotective properties for TBI treatment.

No effect of triple-pulse TMS medial to intraparietal sulcus on online correction for target perturbations during goal-directed hand and foot reaches.

Posterior parietal cortex (PPC) is central to sensorimotor processing for goal-directed hand and foot movements. Yet, the specific role of PPC subregions in these functions is not clear. Previous human neuroimaging and transcranial magnetic stimulation (TMS) work has suggested that PPC lateral to the intraparietal sulcus (IPS) is involved in directing the arm, shaping the hand, and correcting both finger-shaping and hand trajectory during movement. The lateral localization of these functions agrees with the comparably lateral position of the hand and fingers within the motor and somatosensory homunculi along the central sulcus; this might suggest that, in analogy, (goal-directed) foot movements would be mediated by medial portions of PPC. However, foot movement planning activates similar regions for both hand and foot movement along the caudal-to-rostral axis of PPC, with some effector-specificity evident only rostrally, near the central regions of sensorimotor cortex. Here, we attempted to test the causal involvement of PPC regions medial to IPS in hand and foot reaching as well as online correction evoked by target displacement. Participants made hand and foot reaches towards identical visual targets. Sometimes, the target changed position 100–117 ms into the movement. We disturbed cortical processing over four positions medial to IPS with three pulses of TMS separated by 40 ms, both during trials with and without target displacement. We timed TMS to disrupt reach execution and online correction. TMS did not affect endpoint error, endpoint variability, or reach trajectories for hand or foot. While these negative results await replication with different TMS timing and parameters, we conclude that regions medial to IPS are involved in planning, rather than execution and online control, of goal-directed limb movements.

The single intravenous administration of mitochondria-targeted antioxidant SkQR1 after traumatic brain injury attenuates neurological deficit in rats

The protective effect of SkQR1, a mitochondria-targeted antioxidant, was investigated on the model of focal one-sided traumatic brain injury (TBI) of the sensorimotor cortex region from 1 to 7 days after the injury. TBI caused a reliable disruption of the functions of the limbs contralateral to injury focus. The intravenous single injection of SkQR1 (250 nmol/kg) but not C12R1 (a SkQR1 homologue devoid of the antioxidant group) 30 min after TBI reduced the impairment of the motor functions of the limbs. A statistically significant improvement in limb function in animals was shown using 3 different tests: limb-placing test, beam-walking test and grip strength test. A pronounced therapeutic effect appeared on the 1th day and lasted until the end of the experiment - the 7th day after TBI. Histopathological examination showed that in the group of animals that did not receive SkQR1 in the marginal layer of the lesion there was a marked increase in astroglial expression, infiltration with segmented neutrophils, and poor survivability of neurons compared with animals treated with SkQR1.The obtained results demonstrate that the single use of plastoquinone-containing mitochondria-targeted antioxidant SkQR1 at the early stages of development of traumatic brain damage can reduce TBI-related disruptions of limb functions, and that mechanisms of the brain damage after trauma are dependent on the production of mitochondrial reactive oxygen species.

Visual responsiveness in sensorimotor cortex is increased following amputation and reduced after mirror therapy.

Phantom limb pain (PLP) following amputation, which is experienced by the vast majority of amputees, has been reported to be relieved with daily sessions of mirror therapy. During each session, a mirror is used to view the reflected image of the intact limb moving, providing visual feedback consistent with the movement of the missing/phantom limb. To investigate potential neural correlates of the treatment effect, we measured brain responses in volunteers with unilateral leg amputation using functional magnetic resonance imaging (fMRI) during a four-week course of mirror therapy. Mirror therapy commenced immediately following baseline scans, which were repeated after approximately two and four week intervals. We focused on responses in the region of sensorimotor cortex corresponding to primary somatosensory and motor representations of the missing leg. At baseline, prior to starting therapy, we found a strong and unexpected response in sensorimotor cortex of amputees to visually presented images of limbs. This response was stronger for images of feet compared to hands and there was no such response in matched controls. Further, this response to visually presented limbs was no longer present at the end of the four week mirror therapy treatment, when perceived phantom limb pain was also reduced. A similar pattern of results was also observed in extrastriate and parietal regions typically responsive to viewing hand actions, but not in regions corresponding to secondary somatosensory cortex. Finally, there was a significant correlation between initial visual responsiveness in sensorimotor cortex and reduction in PLP suggesting a potential marker for predicting efficacy of mirror therapy. Thus, enhanced visual responsiveness in sensorimotor cortex is associated with PLP and modulated over the course of mirror therapy.

Classification and characterisation of brain network changes in chronic back pain: A multicenter study.

Background. Chronic pain is a common, often disabling condition thought to involve a combination of peripheral and central neurobiological factors. However, the extent and nature of changes in the brain is poorly understood. Methods. We investigated brain network architecture using resting-state fMRI data in chronic back pain patients in the UK and Japan (41 patients, 56 controls), as well as open data from USA. We applied machine learning and deep learning (conditional variational autoencoder architecture) methods to explore classification of patients/controls based on network connectivity. We then studied the network topology of the data, and developed a multislice modularity method to look for consensus evidence of modular reorganisation in chronic back pain. Results. Machine learning and deep learning allowed reliable classification of patients in a third, independent open data set with an accuracy of 63%, with 68% in cross validation of all data. We identified robust evidence of network hub disruption in chronic pain, most consistently with respect to clustering coefficientand betweenness centrality. We found a consensus pattern of modular reorganisation involving extensive, bilateral regions of sensorimotor cortex, and characterised primarily by negative reorganisation - a tendency for sensorimotor cortex nodes to be less inclined to form pairwise modular links with other brain nodes. Furthermore, these regions were found to display increased connectivity with the pregenual anterior cingulate cortex, a region known to be involved in endogenous pain control. In contrast, intraparietal sulcus displayed a propensity towards positive modular reorganisation, suggesting that it might have a role in forming modules associated with the chronic pain state. Conclusion. The results provide evidence of consistent and characteristic brain network changes in chronic pain, characterised primarily by extensive reorganisation of the network architecture of the sensorimotor cortex.

Classification and characterisation of brain network changes in chronic back pain: A multicenter study

Background. Chronic pain is a common, often disabling condition thought to involve a combination of peripheral and central neurobiological factors. However, the extent and nature of changes in the brain is poorly understood. Methods. We investigated brain network architecture using resting-state fMRI data in chronic back pain patients in the UK and Japan (41 patients, 56 controls), as well as open data from USA. We applied machine learning and deep learning (conditional variational autoencoder architecture) methods to explore classification of patients/controls based on network connectivity. We then studied the network topology of the data, and developed a multislice modularity method to look for consensus evidence of modular reorganisation in chronic back pain. Results. Machine learning and deep learning allowed reliable classification of patients in a third, independent open data set with an accuracy of 63%, with 68% in cross validation of all data. We identified robust evidence of network hub disruption in chronic pain, most consistently with respect to clustering coefficient and betweenness centrality. We found a consensus pattern of modular reorganisation involving extensive, bilateral regions of sensorimotor cortex, and characterised primarily by negative reorganisation - a tendency for sensorimotor cortex nodes to be less inclined to form pairwise modular links with other brain nodes. Furthermore, these regions were found to display increased connectivity with the pregenual anterior cingulate cortex, a region known to be involved in endogenous pain control. In contrast, intraparietal sulcus displayed a propensity towards positive modular reorganisation, suggesting that it might have a role in forming modules associated with the chronic pain state. Conclusion. The results provide evidence of consistent and characteristic brain network changes in chronic pain, characterised primarily by extensive reorganisation of the network architecture of the sensorimotor cortex.

TPP903, a novel anti-rat C5 IgG1, potently inhibits C5 activation in vitro and in vivo

The protective effect of SkQR1, a mitochondria-targeted antioxidant, was investigated on the model of focal one-sided traumatic brain injury (TBI) of the sensorimotor cortex region from 1 to 7 days after the injury. TBI caused a reliable disruption of the functions of the limbs contralateral to injury focus. The intravenous single injection of SkQR1 (250 nmol/kg) but not C12R1 (a SkQR1 homologue devoid of the antioxidant group) 30 min after TBI reduced the impairment of the motor functions of the limbs. A statistically significant improvement in limb function in animals was shown using 3 different tests: limb-placing test, beam-walking test and grip strength test. A pronounced therapeutic effect appeared on the 1th day and lasted until the end of the experiment - the 7th day after TBI. Histopathological examination showed that in the group of animals that did not receive SkQR1 in the marginal layer of the lesion there was a marked increase in astroglial expression, infiltration with segmented neutrophils, and poor survivability of neurons compared with animals treated with SkQR1.The obtained results demonstrate that the single use of plastoquinone-containing mitochondria-targeted antioxidant SkQR1 at the early stages of development of traumatic brain damage can reduce TBI-related disruptions of limb functions, and that mechanisms of the brain damage after trauma are dependent on the production of mitochondrial reactive oxygen species.

Mapping of fine-scale rat prefrontal cortex connections: Evidence for detailed ordering of inputs and outputs connecting the temporal cortex and sensory-motor regions.

Cerebral cortex structure is crucially important for cortical organization and function. The organization of prefrontal cortex (PFC) is controversial and here we seek to understand it more clearly through the study of fine-scale cortical connections. To determine the ordering of microscale input and output connections in the rat PFC, we injected small volumes (20-30nl) of anterograde (Fluro-Ruby) and retrograde (Fluoro-Gold) neuroanatomical tracers into PFC. These injections revealed several connected regions of the brain but here we report findings restricted to PFC to temporal cortex and sensory-motor cortex pathways. In agreement with previous studies incorporating larger injection volumes we found that smaller injection volumes revealed a more detailed, fine-scale ordering of both prefrontal inputs and output connections to the temporal cortex and sensory-motor cortex regions. These findings are also supported by labelling observed from additional tracer injections made into corresponding regions of temporal cortex. The topography observed reflected the ordering seen at a larger level (i.e., with larger injection volumes) but there were some differences in the topography, such as in relation to the direction of ordering. In agreement with earlier work, we found that fine-scale input and output connections were not always aligned with respect to one another. These results provide evidence for topographically arranged inputs and outputs in two distinct PFC pathways, along with evidence for different connectional patterns within the same pathways. Based on theories of functional connectivity, these findings provide evidence for prefrontal cortical regions residing within networks that contribute to different cognitive functions.