Central visual pathways affected by degenerative retinal disease before and after gene therapy.

Genetic diseases affecting the retina can result in partial or complete loss of visual function. Leber's Congenital Amaurosis (LCA) is a rare blinding disease, usually inherited in an autosomally recessive manner, with no cure. Retinal gene therapy has been shown to improve vision in LCA patients caused by mutations in the RPE65 gene (LCA2). However, little is known about how activity in central visual pathways is affected by the disease or by subsequent gene therapy. Functional MRI was used to assess retinal signal transmission in cortical and subcortical visual structures before and one year after retinal intervention. The fMRI paradigm consisted of 15-second blocks of flickering (8-Hz) black and white checkerboards interleaved with 15 seconds of blank (black) screen. Visual activation in the brain was assessed using the general linear model, with multiple comparisons corrected using the false discovery rate method. Response to visual stimulation through untreated eyes of LCA2 patients showed heightened fMRI responses in the superior colliculus (SC) and diminished activities in the lateral geniculate nucleus (LGN) compared to controls, indicating a shift in the patients' visual processing towards the retinotectal pathway (RT). Following gene therapy, stimuli presented to the treated eye elicited significantly stronger fMRI responses in the LGN and primary visual cortex, indicating some reengagement of the geniculostriate pathway (GS) pathway. Across patients, the post-treatment LGN fMRI responses correlated significantly with performance on a clinical test measuring light sensitivity. Our results demonstrate that the low vision observed in LCA2 patients involves a shift in visual processing toward the retinotectal pathway, and that gene therapy partially reinstates visual transmission through the GS pathway. This selective boosting of retinal output through the GS pathway and its correlation to improved visual performance, following several years of degenerative retinal disease, is striking. However, while retinal gene therapy and other ocular interventions have given hope to RPE65 patients, it may take years before development of therapies tailored to treat the diseases in other low vision patients are available. Our demonstration of a shift toward the RT pathway in these patients may spur the development of new tools and rehabilitation strategies to help maximize the use of residual visual abilities and augment experience-dependent plasticity.

Remodeling of lateral geniculate nucleus projections to extrastriate area MT following long-term lesions of striate cortex.

Here, we report on a previously unknown form of thalamocortical plasticity observed following lesions of the primary visual area (V1) in marmoset monkeys. In primates, lateral geniculate nucleus (LGN) neurons form parallel pathways to the cortex, which are characterized by the expression of different calcium-binding proteins. LGN projections to the middle temporal (MT) area only originate in the koniocellular layers, where many neurons express calbindin. In contrast, projections to V1 also originate in the magnocellular and parvocellular layers, where neurons express parvalbumin but not calbindin. Our results demonstrate that this specificity is disrupted following long-term (1 to 3 y) unilateral V1 lesions, indicating active rearrangement of the geniculocortical circuit. In lesioned animals, retrograde tracing revealed MT-projecting neurons scattered throughout the lesion projection zone (LPZ, the sector of the LGN that underwent retrograde degeneration following a V1 lesion). Many of the MT-projecting neurons had large cell bodies and were located outside the koniocellular layers. Furthermore, we found that a large percentage of magno- and parvocellular neurons expressed calbindin in addition to the expected parvalbumin expression and that this coexpression was present in many of the MT-projecting neurons within the LPZ. These results demonstrate that V1 lesions trigger neurochemical and structural remodeling of the geniculo-extrastriate pathway, leading to the emergence of nonkoniocellular input to MT. This has potential implications for our understanding of the neurobiological bases of the residual visual abilities that survive V1 lesions, including motion perception and blindsight, and reveals targets for rehabilitation strategies to ameliorate the consequences of cortical blindness.

Long-term impact of maternal obesity on the gliovascular unit and ephrin signaling in the hippocampus of adult offspring.

BACKGROUND: Children born to obese mothers are at increased risk of developing mood disorders and cognitive impairment. Experimental studies have reported structural changes in the brain such as the gliovascular unit as well as activation of neuroinflammatory cells as a part of neuroinflammation processing in aged offspring of obese mothers. However, the molecular mechanisms linking maternal obesity to poor neurodevelopmental outcomes are not well established. The ephrin system plays a major role in a variety of cellular processes including cell-cell interaction, synaptic plasticity, and long-term potentiation. Therefore, in this study we determined the impact of maternal obesity in pregnancy on cortical, hippocampal development, vasculature and ephrin-A3/EphA4-signaling, in the adult offspring in mice. METHODS: Maternal obesity was induced in mice by a high fat/high sugar Western type of diet (HF/HS). We collected brain tissue (prefrontal cortex and hippocampus) from 6-month-old offspring of obese and lean (control) dams. Hippocampal volume, cortical thickness, myelination of white matter, density of astrocytes and microglia in relation to their activity were analyzed using 3-D stereological quantification. mRNA expression of ephrin-A3, EphA4 and synaptic markers were measured by qPCR in the brain tissue. Moreover, expression of gap junction protein connexin-43, lipocalin-2, and vascular CD31/Aquaporin 4 were determined in the hippocampus by immunohistochemistry. RESULTS: Volume of hippocampus and cortical thickness were significantly smaller, and myelination impaired, while mRNA levels of hippocampal EphA4 and post-synaptic density (PSD) 95 were significantly lower in the hippocampus in the offspring of obese dams as compared to offspring of controls. Further analysis of the hippocampal gliovascular unit indicated higher coverage of capillaries by astrocytic end-feet, expression of connexin-43 and lipocalin-2 in endothelial cells in the offspring of obese dams. In addition, offspring of obese dams demonstrated activation of microglia together with higher density of cells, while astrocyte cell density was lower. CONCLUSION: Maternal obesity affects brain size, impairs myelination, disrupts the hippocampal gliovascular unit and decreases the mRNA expression of EphA4 and PSD-95 in the hippocampus of adult offspring. These results indicate that the vasculature-glia cross-talk may be an important mediator of altered synaptic plasticity, which could be a link between maternal obesity and neurodevelopmental/neuropsychiatric disorders in the offspring.

Changes in brain functional connectivity and muscle strength independent of elbow flexor atrophy following upper limb immobilization in young females.

Muscle disuse induces a decline in muscle strength that exceeds the rate and magnitude of muscle atrophy, suggesting that factors beyond the muscle contribute to strength loss. The purpose of this study was to characterize changes in the brain and neuromuscular system in addition to muscle size following upper limb immobilization in young females. Using a within-participant, unilateral design, 12 females (age: 20.6 ± 2.1 years) underwent 14 days of upper arm immobilization using an elbow brace and sling. Bilateral measures of muscle strength (isometric and isokinetic dynamometry), muscle size (magnetic resonance imaging), voluntary muscle activation capacity, corticospinal excitability, cortical thickness and resting-state functional connectivity were collected before and after immobilization. Immobilization induced a significant decline in isometric elbow flexion (-21.3 ± 19.2%, interaction: P = 0.0440) and extension (-19.9 ± 15.7%, interaction: P = 0.0317) strength in the immobilized arm only. There was no significant effect of immobilization on elbow flexor cross-sectional area (CSA) (-1.2 ± 2.4%, interaction: P = 0.466), whereas elbow extensor CSA decreased (-2.9 ± 2.9%, interaction: P = 0.0177) in the immobilized arm. Immobilization did not differentially alter voluntary activation capacity, corticospinal excitability, or cortical thickness (P > 0.05); however, there were significant changes in the functional connectivity of brain regions related to movement planning and error detection (P < 0.05). This study reveals that elbow flexor strength loss can occur in the absence of significant elbow flexor muscle atrophy, and that the brain represents a site of functional adaptation in response to upper limb immobilization in young females.

Driving innovation in addiction treatment: role of transcranial magnetic stimulation.

Addictions comprises heterogenous psychiatric conditions caused by the complex interaction of genetic, neurobiological, psychological, and environmental factors with a chronic relapsing-remitting pattern. Despite the long-standing efforts of preclinical and clinical research studies, addiction field has seen relatively slow progress when it comes to the development of new therapeutic interventions, most of which failed to demonstrate a significant efficacy. This is likely due to the very complex interplay of many factors that contribute to both the development and expression of addictions. The imbalance between the salience and the reward brain network circuitry has been proposed as the neurobiological mechanisms explaining the pathognomonic symptoms of addictions.Non-invasive neuromodulation techniques have been proposed as a promising therapeutic intervention to restore these brain circuits dysfunctions. Here, we propose a multi-level strategy to innovate the diagnosis and the treatment of addictive disorders.

A single-center, assessor-blinded, randomized controlled clinical trial to test the safety and efficacy of a novel brain-computer interface controlled functional electrical stimulation (BCI-FES) intervention for gait rehabilitation in the chronic stroke population.

BACKGROUND: In the United States, there are over seven million stroke survivors, with many facing gait impairments due to foot drop. This restricts their community ambulation and hinders functional independence, leading to several long-term health complications. Despite the best available physical therapy, gait function is incompletely recovered, and this occurs mainly during the acute phase post-stroke. Therapeutic options are limited currently. Novel therapies based on neurobiological principles have the potential to lead to long-term functional improvements. The Brain-Computer Interface (BCI) controlled Functional Electrical Stimulation (FES) system is one such strategy. It is based on Hebbian principles and has shown promise in early feasibility studies. The current study describes the BCI-FES clinical trial, which examines the safety and efficacy of this system, compared to conventional physical therapy (PT), to improve gait velocity for those with chronic gait impairment post-stroke. The trial also aims to find other secondary factors that may impact or accompany these improvements and establish the potential of Hebbian-based rehabilitation therapies. METHODS: This Phase II clinical trial is a two-arm, randomized, controlled, longitudinal study with 66 stroke participants in the chronic (> 6 months) stage of gait impairment. The participants undergo either BCI-FES paired with PT or dose-matched PT sessions (three times weekly for four weeks). The primary outcome is gait velocity (10-meter walk test), and secondary outcomes include gait endurance, range of motion, strength, sensation, quality of life, and neurophysiological biomarkers. These measures are acquired longitudinally. DISCUSSION: BCI-FES holds promise for gait velocity improvements in stroke patients. This clinical trial will evaluate the safety and efficacy of BCI-FES therapy when compared to dose-matched conventional therapy. The success of this trial will inform the potential utility of a Phase III efficacy trial. TRIAL REGISTRATION: The trial was registered as "BCI-FES Therapy for Stroke Rehabilitation" on February 19, 2020, at clinicaltrials.gov with the identifier NCT04279067.

Auditory cortical plasticity after cochlear implantation in asymmetric hearing loss is related to spatial hearing: a PET H215O study.

In asymmetric hearing loss (AHL), the normal pattern of contralateral hemispheric dominance for monaural stimulation is modified, with a shift towards the hemisphere ipsilateral to the better ear. The extent of this shift has been shown to relate to sound localization deficits. In this study, we examined whether cochlear implantation to treat postlingual AHL can restore the normal functional pattern of auditory cortical activity and whether this relates to improved sound localization. The auditory cortical activity was found to be lower in the AHL cochlear implanted (AHL-CI) participants. A cortical asymmetry index was calculated and showed that a normal contralateral dominance was restored in the AHL-CI patients for the nonimplanted ear, but not for the ear with the cochlear implant. It was found that the contralateral dominance for the nonimplanted ear strongly correlated with sound localization performance (rho = 0.8, P < 0.05). We conclude that the reorganization of binaural mechanisms in AHL-CI subjects reverses the abnormal lateralization pattern induced by the deafness, and that this leads to improved spatial hearing. Our results suggest that cochlear implantation enables the reconstruction of the cortical mechanisms of spatial selectivity needed for sound localization.

First-time fathers show longitudinal gray matter cortical volume reductions: evidence from two international samples.

Emerging evidence points to the transition to parenthood as a critical window for adult neural plasticity. Studying fathers offers a unique opportunity to explore how parenting experience can shape the human brain when pregnancy is not directly experienced. Yet very few studies have examined the neuroanatomic adaptations of men transitioning into fatherhood. The present study reports on an international collaboration between two laboratories, one in Spain and the other in California (United States), that have prospectively collected structural neuroimaging data in 20 expectant fathers before and after the birth of their first child. The Spanish sample also included a control group of 17 childless men. We tested whether the transition into fatherhood entailed anatomical changes in brain cortical volume, thickness, and area, and subcortical volumes. We found overlapping trends of cortical volume reductions within the default mode network and visual networks and preservation of subcortical structures across both samples of first-time fathers, which persisted after controlling for fathers' and children's age at the postnatal scan. This study provides convergent evidence for cortical structural changes in fathers, supporting the possibility that the transition to fatherhood may represent a meaningful window of experience-induced structural neuroplasticity in males.

Virtual reality-based sensorimotor adaptation shapes subsequent spontaneous and naturalistic stimulus-driven brain activity.

Our everyday life summons numerous novel sensorimotor experiences, to which our brain needs to adapt in order to function properly. However, tracking plasticity of naturalistic behavior and associated brain modulations is challenging. Here, we tackled this question implementing a prism adaptation-like training in virtual reality (VRPA) in combination with functional neuroimaging. Three groups of healthy participants (N = 45) underwent VRPA (with a shift either to the left/right side, or with no shift), and performed functional magnetic resonance imaging (fMRI) sessions before and after training. To capture modulations in free-flowing, task-free brain activity, the fMRI sessions included resting-state and free-viewing of naturalistic videos. We found significant decreases in spontaneous functional connectivity between attentional and default mode (DMN)/fronto-parietal networks, only for the adaptation groups, more pronouncedly in the hemisphere contralateral to the induced shift. In addition, VRPA was found to bias visual responses to naturalistic videos: Following rightward adaptation, we found upregulation of visual response in an area in the parieto-occipital sulcus (POS) only in the right hemisphere. Notably, the extent of POS upregulation correlated with the size of the VRPA-induced after-effect measured in behavioral tests. This study demonstrates that a brief VRPA exposure can change large-scale cortical connectivity and correspondingly bias visual responses to naturalistic sensory inputs.

Brain plasticity in neonatal brachial plexus palsies: quantification and comparison with adults' brachial plexus injuries.

PURPOSE: To compare two populations of brachial plexus palsies, one neonatal (NBPP) and the other traumatic (NNBPP) who underwent different nerve transfers, using the plasticity grading scale (PGS) for detecting differences in brain plasticity between both groups. METHODS: To be included, all patients had to have undergone a nerve transfer as the unique procedure to recover one lost function. The primary outcome was the PGS score. We also assessed patient compliance to rehabilitation using the rehabilitation quality scale (RQS). Statistical analysis of all variables was performed. A p ≤ 0.050 set as criterion for statistical significance. RESULTS: A total of 153 NNBPP patients and 35 NBPP babies (with 38 nerve transfers) met the inclusion criteria. The mean age at surgery of the NBPP group was 9 months (SD 5.42, range 4 to 23 months). The mean age of NNBPP patients was 22 years (SD 12 years, range 3 to 69). They were operated around sixth months after the trauma. All transfers performed in NBPP patients had a maximum PGS score of 4. This was not the case for the NNBPP population that reached a PGS score of 4 in approximately 20% of the cases. This difference was statistically significant (p < 0.001). The RQS was not significantly different between groups. CONCLUSION: We found that babies with NBPP have a significantly greater capacity for plastic rewiring than adults with NNBPP. The brain in the very young patient can process the changes induced by the peripheral nerve transfer better than in adults.

Resting-state brain plasticity is associated with the severity in cervical spondylotic myelopathy.

OBJECTIVE: To investigate the brain mechanism of non-correspondence between imaging presentations and clinical symptoms in cervical spondylotic myelopathy (CSM) patients and to test the utility of brain imaging biomarkers for predicting prognosis of CSM. METHODS: Forty patients with CSM (22 mild-moderate CSM, 18 severe CSM) and 25 healthy controls (HCs) were recruited for rs-fMRI and cervical spinal cord diffusion tensor imaging (DTI) scans. DTI at the spinal cord (level C2/3) with fractional anisotropy (FA) and degree centrality (DC) were recorded. Then one-way analysis of covariance (ANCOVA) was conducted to detect the group differences in the DC and FA values across the three groups. Pearson correlation analysis was then separately performed between JOA with FA and DC. RESULTS: Among them, degree centrality value of left middle temporal gyrus exhibited a progressive increase in CSM groups compared with HCs, the DC value in severe CSM group was higher compared with mild-moderate CSM group. (P < 0.05), and the DC values of the right superior temporal gyrus and precuneus showed a decrease after increase. Among them, DC values in the area of precuneus in severe CSM group were significantly lower than those in mild-moderate CSM and HCs. (P < 0.05). The fractional anisotropy (FA) values of the level C2/3 showed a progressive decrease in different clinical stages, that severe CSM group was the lowest, significantly lower than those in mild-moderate CSM and HCs (P < 0.05). There was negative correlation between DC value of left middle temporal gyrus and JOA scores (P < 0.001), and the FA values of dorsal column in the level C2/3 positively correlated with the JOA scores (P < 0.001). CONCLUSION: Structural and functional changes have taken place in the cervical spinal cord and brain of CSM patients. The Brain reorganization plays an important role in maintaining the symptoms and signs of CSM, aberrant DC values in the left middle temporal gyrus may be the possible mechanism of inconsistency between imaging findings and clinical symptoms. Degree centrality is a potentially useful prognostic functional biomarker in cervical spondylotic myelopathy.

"Love looks not with the eyes": supranormal processing of emotional speech in individuals with late-blindness versus preserved processing in individuals with congenital-blindness.

Processing of emotional speech in the absence of visual information relies on two auditory channels: semantics and prosody. No study to date has investigated how blindness impacts this process. Two theories, Perceptual Deficit, and Sensory Compensation, yiled different expectations about the role of visual experience (or its lack thereof) in processing emotional speech. To test the effect of vision and early visual experience on processing of emotional speech, we compared individuals with congenital blindness (CB, n = 17), individuals with late blindness (LB, n = 15), and sighted controls (SC, n = 21) on identification and selective-attention of semantic and prosodic spoken-emotions. Results showed that individuals with blindness performed at least as well as SC, supporting Sensory Compensation and the role of cortical reorganisation. Individuals with LB outperformed individuals with CB, in accordance with Perceptual Deficit, supporting the role of early visual experience. The LB advantage was moderated by executive functions (working-memory). Namely, the advantage was erased for individuals with CB who showed higher levels of executive functions. Results suggest that vision is not necessary for processing of emotional speech, but early visual experience could improve it. The findings support a combination of the two aforementioned theories and reject a dichotomous view of deficiencies/enhancements of blindness.

Brain Plasticity in Patients with Spinal Cord Injuries: A Systematic Review.

A spinal cord injury (SCI) causes changes in brain structure and brain function due to the direct effects of nerve damage, secondary mechanisms, and long-term effects of the injury, such as paralysis and neuropathic pain (NP). Recovery takes place over weeks to months, which is a time frame well beyond the duration of spinal shock and is the phase in which the spinal cord remains unstimulated below the level of injury and is associated with adaptations occurring throughout the nervous system, often referred to as neuronal plasticity. Such changes occur at different anatomical sites and also at different physiological and molecular biological levels. This review aims to investigate brain plasticity in patients with SCIs and its influence on the rehabilitation process. Studies were identified from an online search of the PubMed, Web of Science, and Scopus databases. Studies published between 2013 and 2023 were selected. This review has been registered on OSF under (n) 9QP45. We found that neuroplasticity can affect the sensory-motor network, and different protocols or rehabilitation interventions can activate this process in different ways. Exercise rehabilitation training in humans with SCIs can elicit white matter plasticity in the form of increased myelin water content. This review has demonstrated that SCI patients may experience plastic changes either spontaneously or as a result of specific neurorehabilitation training, which may lead to positive outcomes in functional recovery. Clinical and experimental evidence convincingly displays that plasticity occurs in the adult CNS through a variety of events following traumatic or non-traumatic SCI. Furthermore, efficacy-based, pharmacological, and genetic approaches, alone or in combination, are increasingly effective in promoting plasticity.

Perineuronal Net Microscopy: From Brain Pathology to Artificial Intelligence.

Perineuronal nets (PNN) are a special highly structured type of extracellular matrix encapsulating synapses on large populations of CNS neurons. PNN undergo structural changes in schizophrenia, epilepsy, Alzheimer's disease, stroke, post-traumatic conditions, and some other brain disorders. The functional role of the PNN microstructure in brain pathologies has remained largely unstudied until recently. Here, we review recent research implicating PNN microstructural changes in schizophrenia and other disorders. We further concentrate on high-resolution studies of the PNN mesh units surrounding synaptic boutons to elucidate fine structural details behind the mutual functional regulation between the ECM and the synaptic terminal. We also review some updates regarding PNN as a potential pharmacological target. Artificial intelligence (AI)-based methods are now arriving as a new tool that may have the potential to grasp the brain's complexity through a wide range of organization levels-from synaptic molecular events to large scale tissue rearrangements and the whole-brain connectome function. This scope matches exactly the complex role of PNN in brain physiology and pathology processes, and the first AI-assisted PNN microscopy studies have been reported. To that end, we report here on a machine learning-assisted tool for PNN mesh contour tracing.

The Role of Visual Experience in Individual Differences of Brain Connectivity.

Visual cortex organization is highly consistent across individuals. But to what degree does this consistency depend on life experience, in particular sensory experience? In this study, we asked whether visual cortex reorganization in congenital blindness results in connectivity patterns that are particularly variable across individuals, focusing on resting-state functional connectivity (RSFC) patterns from the primary visual cortex. We show that the absence of shared visual experience results in more variable RSFC patterns across blind individuals than sighted controls. Increased variability is specifically found in areas that show a group difference between the blind and sighted in their RSFC. These findings reveal a relationship between brain plasticity and individual variability; reorganization manifests variably across individuals. We further investigated the different patterns of reorganization in the blind, showing that the connectivity to frontal regions, proposed to have a role in the reorganization of the visual cortex of the blind toward higher cognitive roles, is highly variable. Further, we link some of the variability in visual-to-frontal connectivity to another environmental factor-duration of formal education. Together, these findings show a role of postnatal sensory and socioeconomic experience in imposing consistency on brain organization. By revealing the idiosyncratic nature of neural reorganization, these findings highlight the importance of considering individual differences in fitting sensory aids and restoration approaches for vision loss.SIGNIFICANCE STATEMENT The typical visual system is highly consistent across individuals. What are the origins of this consistency? Comparing the consistency of visual cortex connectivity between people born blind and sighted people, we showed that blindness results in higher variability, suggesting a key impact of postnatal individual experience on brain organization. Further, connectivity patterns that changed following blindness were particularly variable, resulting in diverse patterns of brain reorganization. Individual differences in reorganization were also directly affected by nonvisual experiences in the blind (years of formal education). Together, these findings show a role of sensory and socioeconomic experiences in creating individual differences in brain organization and endorse the use of individual profiles for rehabilitation and restoration of vision loss.

Visuo-motor transformations in the intraparietal sulcus mediate the acquisition of endovascular medical skill.

Performing endovascular medical interventions safely and efficiently requires a diverse set of skills that need to be practised in dedicated training sessions. Here, we used multimodal magnetic resonance (MR) imaging to determine the structural and functional plasticity and core skills associated with skill acquisition. A training group learned to perform a simulator-based endovascular procedure, while a control group performed a simplified version of the task; multimodal MR images were acquired before and after training. Using a well-controlled interaction design, we found strong multimodal evidence for the role of the intraparietal sulcus (IPS) in endovascular skill acquisition that is in line with previous work implicating the structure in visuospatial transformations including simple visuo-motor and mental rotation tasks. Our results provide a unique window into the multimodal nature of rapid structural and functional plasticity of the human brain while learning a multifaceted and complex clinical skill. Further, our results provide a detailed description of the plasticity process associated with endovascular skill acquisition and highlight specific facets of skills that could enhance current medical pedagogy and be useful to explicitly target during clinical resident training.

Fine motor control improves in older adults after 1 year of piano lessons: Analysis of individual development and its coupling with cognition and brain structure.

Musical training can improve fine motor skills and cognitive abilities and induce macrostructural brain changes. However, it is not clear whether the changes in motor skills occur simultaneously with changes in cognitive and neurophysiological parameters. In this study, 156 healthy, musically naïve and right-handed older adults were recruited and randomly assigned to a piano training or a music listening group. Before, after 6 and 12 months, participants were scanned using MRI and assessed for fine motor skills, auditory working memory and processing speed. A Bayesian multilevel modelling approach was used to examine behavioural and neurophysiological group differences. The relationships between motor and cognitive and between motor and neurophysiological parameters were determined using latent change score models. Compared with music listening, practicing piano resulted in greater improvement in fine motor skills and probably working memory. Only in the piano group, unimanual fine motor skills and grey matter volume of the contralateral M1 changed together during the 6-12-month period. Additionally, M1 co-developed with ipsilateral putamen and thalamus. Playing piano induced more prevalent coupling between the motor and cognitive domains. However, there is little evidence that fine motor control develops concurrently with cognitive functions. Playing an instrument promotes motor, cognitive and neural development into older age. During the learning process, the consolidation of piano skills appears to take place in sensorimotor networks, enabling musicians to perform untrained motor tasks with higher acuity. Relationships between the development of motor acuity and cognition were bidirectional and can be explained by a common cause as well as by shared resources with compensatory mechanisms.

Role of resting-state functional MRI in detecting brain functional changes following radiotherapy for head and neck cancer: a systematic review and meta-analysis.

PURPOSE: Increasing evidence implicates changes in brain function following radiotherapy for head and neck cancer as precursors for brain dysfunction. These changes may thus be used as biomarkers for early detection. This review aimed to determine the role of resting-state functional magnetic resonance imaging (rs-fMRI) in detecting brain functional changes. METHODS: A systematic search was performed in the PubMed, Scopus, and Web of Science (WoS) databases in June 2022. Patients with head and neck cancer treated with radiotherapy and periodic rs-fMRI assessments were included. A meta-analysis was performed to determine the potential of rs-fMRI for detecting brain changes. RESULTS: Ten studies with a total of 513 subjects (head and neck cancer patients, n = 437; healthy controls, n = 76) were included. A significance of rs-fMRI for detecting brain changes in the temporal and frontal lobes, cingulate cortex, and cuneus was demonstrated in most studies. These changes were reported to be associated with dose (6/10 studies) and latency (4/10 studies). A strong effect size (r = 0.71, p < 0.001) between rs-fMRI and brain changes was also reported, suggesting rs-fMRI's capability for monitoring brain alterations. CONCLUSION: Resting-state functional MRI is a promising tool for detecting brain functional changes following head and neck radiotherapy. These changes are correlated with latency and prescription dose.

DiSCIoser: unlocking recovery potential of arm sensorimotor functions after spinal cord injury by promoting activity-dependent brain plasticity by means of brain-computer interface technology: a randomized controlled trial to test efficacy.

BACKGROUND: Traumatic cervical spinal cord injury (SCI) results in reduced sensorimotor abilities that strongly impact on the achievement of daily living activities involving hand/arm function. Among several technology-based rehabilitative approaches, Brain-Computer Interfaces (BCIs) which enable the modulation of electroencephalographic sensorimotor rhythms, are promising tools to promote the recovery of hand function after SCI. The "DiSCIoser" study proposes a BCI-supported motor imagery (MI) training to engage the sensorimotor system and thus facilitate the neuroplasticity to eventually optimize upper limb sensorimotor functional recovery in patients with SCI during the subacute phase, at the peak of brain and spinal plasticity. To this purpose, we have designed a BCI system fully compatible with a clinical setting whose efficacy in improving hand sensorimotor function outcomes in patients with traumatic cervical SCI will be assessed and compared to the hand MI training not supported by BCI. METHODS: This randomized controlled trial will include 30 participants with traumatic cervical SCI in the subacute phase randomly assigned to 2 intervention groups: the BCI-assisted hand MI training and the hand MI training not supported by BCI. Both interventions are delivered (3 weekly sessions; 12 weeks) as add-on to standard rehabilitation care. A multidimensional assessment will be performed at: randomization/pre-intervention and post-intervention. Primary outcome measure is the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) somatosensory sub-score. Secondary outcome measures include the motor and functional scores of the GRASSP and other clinical, neuropsychological, neurophysiological and neuroimaging measures. DISCUSSION: We expect the BCI-based intervention to promote meaningful cortical sensorimotor plasticity and eventually maximize recovery of arm functions in traumatic cervical subacute SCI. This study will generate a body of knowledge that is fundamental to drive optimization of BCI application in SCI as a top-down therapeutic intervention, thus beyond the canonical use of BCI as assistive tool. TRIAL REGISTRATION: Name of registry: DiSCIoser: improving arm sensorimotor functions after spinal cord injury via brain-computer interface training (DiSCIoser). TRIAL REGISTRATION NUMBER: NCT05637775; registration date on the ClinicalTrial.gov platform: 05-12-2022.

Functional brain plasticity following childhood maltreatment: A longitudinal fMRI investigation of autobiographical memory processing.

Altered autobiographical memory (ABM) processing characterizes some individuals with experiences of childhood maltreatment. This fMRI study of ABM processing evaluated potential developmental plasticity in neural functioning following maltreatment. Adolescents with (N = 19; MT group) and without (N = 18; Non-MT group) documented childhood maltreatment recalled specific ABMs in response to emotionally valenced cue words during fMRI at baseline (age 12.71 ± 1.48) and follow-up (14.88 ± 1.53 years). Psychological assessments were collected at both timepoints. Longitudinal analyses were carried out with BOLD signal changes during ABM recall and psychopathology to investigate change over time. In both groups there was relative stability of the ABM brain network, with some developmental maturational changes observed in cortical midline structures (ventromedial PFC (vmPFC), posterior cingulate cortex (pCC), and retrosplenial cortex (rSC). Significantly increased activation of the right rSC was observed only in the MT group, which was associated with improved psychological functioning. Baseline group differences in relation to hippocampal functioning, were not detected at follow-up. This study provides preliminary empirical evidence of functional developmental plasticity in children with documented maltreatment experience using fMRI. This suggests that altered patterns of brain function, associated with maltreatment experience, are not fixed and may reflect the potential to track a neural basis of resilience.