Functional Brain Connectivity Prior to the COVID-19 Outbreak Moderates the Effects of Coping and Perceived Stress on Mental Health Changes: A First Year of COVID-19 Pandemic Follow-up Study.

BACKGROUND: The COVID-19 pandemic provides a unique opportunity to investigate the psychological impact of a global major adverse situation. Our aim was to examine, in a longitudinal prospective study, the demographic, psychological, and neurobiological factors associated with interindividual differences in resilience to the mental health impact of the pandemic. METHODS: We included 2023 healthy participants (age: 54.32 ± 7.18 years, 65.69% female) from the Barcelona Brain Health Initiative cohort. A linear mixed model was used to characterize the change in anxiety and depression symptoms based on data collected both pre-pandemic and during the pandemic. During the pandemic, psychological variables assessing individual differences in perceived stress and coping strategies were obtained. In addition, in a subsample (n = 433, age 53.02 ± 7.04 years, 46.88% female) with pre-pandemic resting-state functional magnetic resonance imaging available, the system segregation of networks was calculated. Multivariate linear models were fitted to test associations between COVID-19-related changes in mental health and demographics, psychological features, and brain network status. RESULTS: The whole sample showed a general increase in anxiety and depressive symptoms after the pandemic onset, and both age and sex were independent predictors. Coping strategies attenuated the impact of perceived stress on mental health. The system segregation of the frontoparietal control and default mode networks were found to modulate the impact of perceived stress on mental health. CONCLUSIONS: Preventive strategies targeting the promotion of mental health at the individual level during similar adverse events in the future should consider intervening on sociodemographic and psychological factors as well as their interplay with neurobiological substrates.

Functional improvement in chronic stroke patients when following a supervised home-based computerized cognitive training.

BACKGROUND: Computerized Cognitive Training (CCT) is an effective treatment for cognitive impairment in the post-acute stage of stroke. However, it is still not clear if it is suitable for chronic stage. OBJECTIVES: To explore if patients with cognitive deficit following stroke may benefit from CCT. METHODS: Thirty patients post-stroke between 24 and 62 years old were randomized into two groups (A and B) to receive two different types of CCT. All patients were tested with a neuropsychological battery and functional questionnaires, before and after each CCT and also 6 months after the end of the study. In phase I, Group A received a customized CCT and Group B received a non-customized CCT, over 6 weeks. Three months after, each group received the other intervention (phase II). RESULTS: After phase I, between-group analyses revealed that Group A showed a relative decrease in subjective complaints. In contrast, Group B showed improvement in performance-based measures. After phase II, the decrease in subjective complaints continued in Group A, and both groups showed improvement in performance-based measures. CONCLUSIONS: Patients with chronic stroke improved cognitive functioning after performing supervised home-based multi-domain computerized cognitive training.

Corrigendum to "Prefrontal reactivity to TMS perturbation as a toy model of mental health outcomes during the COVID-19 pandemic"[Heliyon 8 (8), (August 2022) Article e10208].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e10208.].

Long-interval intracortical inhibition in primary motor cortex related to working memory in middle-aged adults.

Introduction: Excitability of the primary motor cortex measured with TMS has been associated with cognitive dysfunctions in patient populations. However, only a few studies have explored this relationship in healthy adults, and even fewer have considered the role of biological sex. Methods: Ninety-seven healthy middle-aged adults (53 male) completed a TMS protocol and a neuropsychological assessment. Resting Motor Threshold (RMT) and Long-Interval Intracortical Inhibition (LICI) were assessed in the left motor cortex and related to attention, episodic memory, working memory, reasoning, and global cognition composite scores to evaluate the relationship between cortical excitability and cognitive functioning. Results: In the whole sample, there was a significant association between LICI and cognition; specifically, higher motor inhibition was related to better working memory performance. When the sample was broken down by biological sex, LICI was only associated with working memory, reasoning, and global cognition in men. No associations were found between RMT and cognitive functions. Conclusion: Greater intracortical inhibition, measured by LICI, could be a possible marker of working memory in healthy middle-aged adults, and biological sex plays a critical role in this association.

Prefrontal reactivity to TMS perturbation as a toy model of mental health outcomes during the COVID-19 pandemic.

Psychosocial hardships associated with the COVID-19 pandemic led many individuals to suffer adverse mental health consequences, however, others show no negative effects. We hypothesized that the electroencephalographic (EEG) response to transcranial magnetic stimulation (TMS) could serve as a toy-model of an individual's capacity to resist psychological stress, in this case linked to the COVID-19 pandemic. We analyzed data from 74 participants who underwent mental health monitoring and concurrent electroencephalography with transcranial magnetic stimulation of the left dorsolateral prefrontal cortex (L-DLPFC) and left inferior parietal lobule (L-IPL). Within the following 19 months, mental health was reassessed at three timepoints during lock-down confinement and different phases of de-escalation in Spain. Compared with participants who remained stable, those who experienced increased mental distress showed, months earlier, significantly larger late EEG responses locally after L-DLPFC stimulation (but not globally nor after L-IPL stimulation). This response, together with years of formal education, was significantly predictive of mental health status during the pandemic. These findings reveal that the effect of TMS perturbation offers a predictive toy model of psychosocial stress response, as exemplified by the COVID-19 pandemic.

Associations of circulating C-reactive proteins, APOE ε4, and brain markers for Alzheimer's disease in healthy samples across the lifespan.

The apolipoprotein E gene ε4 allele (APOE ε4) and higher circulating level of C-reactive protein (CRP) have been extensively investigated as risk factors for Alzheimer's disease (AD). Paradoxically, APOE ε4 has been associated with lower levels of blood CRP in middle-aged and older populations. However, few studies have investigated this intriguing relation and its impact on neurological markers for AD in younger ages, nor across the whole lifespan. Here, we examine associations of blood CRP levels, APOE ε4, and biomarkers for AD in a cognitively healthy lifespan cohort (N up to 749; 20-81 years of age) and replicate the findings in UK Biobank (N = 304 322; 37-72 years of age), the developmental ABCD study (N = 10 283; 9-11 years of age), and a middle-aged sample (N = 339; 40-65 years of age). Hippocampal volume, brain amyloid-ß (Aß) plaque levels, cerebrospinal fluid (CSF) levels of Aß and tau species, and neurofilament protein light protein (NFL) were used as AD biomarkers in subsamples. In addition, we examined the genetic contribution to the variation of CRP levels over different CRP ranges using polygenic scores for CRP (PGS-CRP). Our results show APOE ε4 consistently associates with low blood CRP levels across all age groups (p < 0.05). Strikingly, both ε4 and PGS-CRP associated mainly with blood CRP levels within the low range (<5mg/L). We then show both APOE ε4 and high CRP levels associate with smaller hippocampus volumes across the lifespan (p < 0.025). APOE ε4 was associated with high Aß plaque levels in the brain (FDR-corrected p = 8.69x10-4), low levels of CSF Aß42 (FDR-corrected p = 6.9x10-2), and lower ratios of Aß42 to Aß40 (FDR-corrected p = 5.08x10-5). Blood CRP levels were weakly correlated with higher ratio of CSF Aß42 to Aß40 (p = 0.03, FDR-corrected p = 0.4). APOE ε4 did not correlate with blood concentrations of another 9 inflammatory cytokines, and none of these cytokines correlated with AD biomarkers. CONCLUSION: The inverse correlation between APOEε 4 and blood CRP levels existed before any pathological AD biomarker was observed, and only in the low CRP level range. Thus, we suggest to investigate whether APOEε 4 can confer risk by being associated with a lower inflammatory response to daily exposures, possibly leading to greater accumulation of low-grade inflammatory stress throughout life. A lifespan perspective is needed to understand this relationship concerning risk of developing AD.

Toward Personalized Web-Based Cognitive Rehabilitation for Patients With Ischemic Stroke: Elo Rating Approach.

BACKGROUND: Stroke is a worldwide cause of disability; 40% of stroke survivors sustain cognitive impairments, most of them following inpatient rehabilitation at specialized clinical centers. Web-based cognitive rehabilitation tasks are extensively used in clinical settings. The impact of task execution depends on the ratio between the skills of the treated patient and the challenges imposed by the task itself. Thus, treatment personalization requires a trade-off between patients' skills and task difficulties, which is still an open issue. In this study, we propose Elo ratings to support clinicians in tasks assignations and representing patients' skills to optimize rehabilitation outcomes. OBJECTIVE: This study aims to stratify patients with ischemic stroke at an early stage of rehabilitation into three levels according to their Elo rating; to show the relationships between the Elo rating levels, task difficulty levels, and rehabilitation outcomes; and to determine if the Elo rating obtained at early stages of rehabilitation is a significant predictor of rehabilitation outcomes. METHODS: The PlayerRatings R library was used to obtain the Elo rating for each patient. Working memory was assessed using the DIGITS subtest of the Barcelona test, and the Rey Auditory Verbal Memory Test (RAVLT) was used to assess verbal memory. Three subtests of RAVLT were used: RAVLT learning (RAVLT075), free-recall memory (RAVLT015), and recognition (RAVLT015R). Memory predictors were identified using forward stepwise selection to add covariates to the models, which were evaluated by assessing discrimination using the area under the receiver operating characteristic curve (AUC) for logistic regressions and adjusted R2 for linear regressions. RESULTS: Three Elo levels (low, middle, and high) with the same number of patients (n=96) in each Elo group were obtained using the 50 initial task executions (from a total of 38,177) for N=288 adult patients consecutively admitted for inpatient rehabilitation in a clinical setting. The mid-Elo level showed the highest proportions of patients that improved in all four memory items: 56% (54/96) of them improved in DIGITS, 67% (64/96) in RAVLT075, 58% (56/96) in RAVLT015, and 53% (51/96) in RAVLT015R (P<.001). The proportions of patients from the mid-Elo level that performed tasks at difficulty levels 1, 2, and 3 were 32.1% (3997/12,449), 31.% (3997/12,449), and 36.9% (4595/12,449), respectively (P<.001), showing the highest match between skills (represented by Elo level) and task difficulties, considering the set of 38,177 task executions. Elo ratings were significant predictors in three of the four models and quasi-significant in the fourth. When predicting RAVLT075 and DIGITS at discharge, we obtained R2=0.54 and 0.43, respectively; meanwhile, we obtained AUC=0.73 (95% CI 0.64-0.82) and AUC=0.81 (95% CI 0.72-0.89) in RAVLT075 and DIGITS improvement predictions, respectively. CONCLUSIONS: Elo ratings can support clinicians in early rehabilitation stages in identifying cognitive profiles to be used for assigning task difficulty levels.

tDCS-Induced Memory Reconsolidation Effects and Its Associations With Structural and Functional MRI Substrates in Subjective Cognitive Decline.

Previous evidence suggests that transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (l-DLPFC) can enhance episodic memory in subjects with subjective cognitive decline (SCD), known to be at risk of dementia. Our main goal was to replicate such findings in an independent sample and elucidate if baseline magnetic resonance imaging (MRI) characteristics predicted putative memory improvement. Thirty-eight participants with SCD (aged: 60-65 years) were randomly assigned to receive active (N = 19) or sham (N = 19) tDCS in a double-blind design. They underwent a verbal learning task with 15 words (DAY-1), and 24 h later (DAY-2) stimulation was applied for 15 min at 1.5 mA targeting the l-DLPFC after offering a contextual reminder. Delayed recall and recognition were measured 1 day after the stimulation session (DAY-3), and at 1-month follow-up (DAY-30). Before the experimental session, structural and functional MRI were acquired. We identified a group∗time interaction in recognition memory, being the active tDCS group able to maintain stable memory performance between DAY-3 and DAY-30. MRI results revealed that individuals with superior tDCS-induced effects on memory reconsolidation exhibited higher left temporal lobe thickness and greater intrinsic FC within the default-mode network. Present findings confirm that tDCS, through the modulation of memory reconsolidation, is capable of enhancing performance in people with self-perceived cognitive complaints. Results suggest that SCD subjects with more preserved structural and functional integrity might benefit from these interventions, promoting maintenance of cognitive function in a population at risk to develop dementia.

Meaning in Life: A Major Predictive Factor for Loneliness Comparable to Health Status and Social Connectedness.

Objective: Loneliness is the subjective distress of feeling alone and has a strong impact on wellbeing and health. In addition to well-known predictors like isolation and poor health, a better understanding of the psychological determinants of loneliness would offer effective targets for future complementary interventions. Methods: In this cross-sectional observational study (N = 2,240), we compared the explanatory power of several important risk factors of loneliness with the affective, motivational, and cognitive aspects of the Meaning in Life (MiL) construct. Different nested linear models were compared including socio-demographic, lifestyles, social-connectedness, and self-rated health variables, to assess the overlapping and non-overlapping explanatory power of each of them. Results: Health status and MiL were found to be the most important predictors of loneliness, followed by social connectedness and, with a much lower weight, lifestyles, and socio-demographic factors. Within the MiL factor, the most cognitive component, sense of coherence, had a greater explanatory power than the more affective and motivational ones. Conclusion: Reduced MiL, the capacity of an individual to attach "value and significance" to life, is a crucial predictor to the feeling of loneliness. These results suggest that programs aiming to combat loneliness should go well beyond situational interventions and include more cognitive, value-centered interventions that enable individuals to define and pursue a meaningful vital plan.

The paradoxical effect of COVID-19 outbreak on loneliness.

As in previous periods of quarantine, lockdown confinement measures dictated to control SARS-CoV-2 would be expected to negatively affect mental health. We investigated the immediate effects (over a 10 day period) of a strict nationwide stay-at-home order imposed in Spain, one of the countries most affected by the COVID-19 pandemic. Focusing our analysis on the feelings of loneliness, we obtained our measures within a social context characterised by strong and continuous public and governmental support for increasing social bonds and cooperation in order to face the common public threat. Leveraging data from the Barcelona Brain Health Initiative, a prospective population-based study cohort, the short UCLA Loneliness Scale was administered to 1604 participants 2 years and 1 year before the stay-at-home lockdown and repeated, on average, 10 days after the official confinement order issued by the Spanish government. Ratings of loneliness remained stable during the 2 years before lockdown; however, they decreased significantly during the early stages of home confinement. This effect was particularly significant for the item 'feeling excluded from others' and was also observed among individuals who were confined alone. Overall, the results suggest that gestures and manifestations of appreciation by people for the labour and efforts of certain individuals, along with official campaigns designed to promote feelings of inclusion and belonging, may have beneficial effects on feelings of loneliness, a negative emotional state strongly regarded as a risk factor for impaired mental and general health status. Further assessments during the later stages of home confinement are now warranted.

A Positive Relationship between Cognitive Reserve and Cognitive Function after Stroke: Dynamic Proxies Correlate Better than Static Proxies.

OBJECTIVES: How brain damage after stroke is related to specific clinical manifestation and recovery is incompletely understood. We studied cognitive reserve (CR) in stroke patients by two types of measurements: (i) objectively verifiable static proxies (i.e., education, occupational attainment), and (ii) subjective, dynamic proxies based on patient testimony in response to a questionnaire. We hypothesized that one or both of these types of CR measurements might correlate positively with patient cognitive performance during the post-acute and chronic phases of recovery. METHOD: Thirty-four stroke patients underwent neuropsychological assessment at 2, 6 and 24 months after stroke onset. In chronic stage at 24+ months, self-rating assessments of cognitive performance in daily life and social integration were obtained. CR before and after stroke was estimated using static proxies and dynamic proxies were obtained using the Cognitive Reserve Scale (CRS-Pre-stroke, CRS-Post-stroke). RESULTS: CRS-Pre-stroke and CRS-Post-stroke showed significant mean differences. Dynamic proxies showed positive correlation with self-assessment of attention, metacognition, and functional ability in chronic stage. In contrast, significant correlations between static proxies and cognitive recovery were not found. CONCLUSIONS: Dynamic proxies of CR were positively correlated with patients' perception of their functional abilities in daily life. To best guide cognitive prognosis and treatment, we propose that dynamic proxies of CR should be included in neuropsychological assessments of patients with brain damage.

A customized home-based computerized cognitive rehabilitation platform for patients with chronic-stage stroke: study protocol for a randomized controlled trial.

BACKGROUND: Stroke patients usually suffer primary cognitive impairment related to attention, memory, and executive functions. This impairment causes a negative impact on the quality of life of patients and their families, and may be long term. Cognitive rehabilitation has been shown to be an effective way to treat cognitive impairment and should be continued after hospital discharge. Computerized cognitive rehabilitation can be performed at home using exercise programs that advance with predetermined course content, interval, and pace. We hypothesize that computerized rehabilitation might be improved if a program could customize course content and pace in response to patient-specific progress. The present pilot study is a randomized controlled double-blind crossover clinical trial aiming to study if chronic stroke patients with cognitive impairment could benefit from cognitive training through a customized tele-rehabilitation platform ("Guttmann, NeuroPersonalTrainer"®, GNPT®). METHODS/DESIGN: Individuals with chronic-stage stroke will be recruited. Participants will be randomized to receive experimental intervention (customized tele-rehabilitation platform, GNPT®) or sham intervention (ictus.online), both with the same frequency and duration (five sessions per week over 6 weeks). After a washout period of 3 months, crossover will occur and participants from the GNPT® condition will receive sham intervention, while participants originally from the sham intervention will receive GNPT®. Patients will be assessed before and after receiving each treatment regimen with an exhaustive neuropsychological battery. Primary outcomes will include rating measures that assess attention difficulties, memory failures, and executive dysfunction for daily activities, as well as performance-based measures of attention, memory, and executive functions. DISCUSSION: Customized cognitive training could lead to better cognitive function in patients with chronic-stage stroke and improve their quality of life. TRIAL REGISTRATION: NCT03326349 . Registered 31 October 2017.

Transcranial direct current stimulation is not effective in the motor strength and gait recovery following motor incomplete spinal cord injury during Lokomat(®) gait training.

OBJECTIVE/HYPOTHESIS: Transcranial direct current stimulation (tDCS) is a potential tool to improve motor recovery in patients with neurological disorders. Safety and efficacy of this procedure for lower extremity motor strengthe and gait function in motor incomplete spinal cord injury (SCI) have not yet been addressed. The aim of this study is to optimize the functional outcome in early phases of gait rehabilitation assisted by Lokomat(®) in motor incomplete SCI patients using tDCS as an additional treatment to physical therapy. METHODS: We performed in a SCI unit a single-centre randomized, double-blind, sham-controlled study to investigate safety and efficacy of anodal tDCS of over leg motor cortex in motor incomplete SCI patients. Twenty-four SCI patients received either daily sessions of anodal tDCS (n=12) at 2mA for 20min to the vertex (leg motor cortex) during twenty days or sham tDCS (n=12). Motor deficit was assessed by the lower extremity motor score (LEMS) and for gait function: ten meter walking test (10MWT) and Walking Index for SCI (WISCI II) at baseline, after last tDCS session (after 4 weeks of stimulation), and after 8 weeks (from baseline) for follow-up. RESULTS: No side effects were detected during either tDCS or sham. In both groups, there was a significant improvement in LEMS (p<0.03), which did not significantly differ when comparing anodal and sham tDCS groups. During follow-up, in both group 5 of 12 patients could perform gait, without significant differences in gait velocity, cadence, step length and WISCI-II between both groups. CONCLUSION: Combination twenty sessions of daily tDCS to the leg motor cortex and Lokomat(®) gait training appear to be safe in motor incomplete SCI patients. There was an expected improvement in both LEMS and gait scales however, did not differ between patients treated with anodal or sham tDCS.

Combination treatment in the rehabilitation of visuo-spatial neglect.

BACKGROUND: Visuo-spatial neglect predicts longer hospitalization, poorer recovery of motor skills and greater functional limitation. The aim of the present study was to analyze whether the combined administration of computerized cognitive rehabilitation with right hemifield eye-patching in patients with left spatial neglect following a right hemisphere stroke is more effective than computerized cognitive rehabilitation applied in isolation. METHOD: Randomized clinical trial conducted in 28 patients. These were grouped into two experimental groups: single treatment group (ST) (n= 15) and combined treatment group (CT) (n= 13). All received an average of 15 one-hour sessions of computerized cognitive rehabilitation using the Guttmann, NeuroPersonalTrainer® telerehabilitation platform. Those patients in the TC group performed the sessions wearing a visual device with which the right hemifield of each eye was occluded. RESULTS: Following treatment, both the ST and the TC group showed improvements in neuropsychological examination protocol although there were no differences pre- and post-treatment on the functional scale in either group. Likewise, no statistically significant differences were observed in intergroup comparison. CONCLUSIONS: The results from this study indicate that combination treatment is not more effective than rehabilitation applied in isolation.

Improving brain injury cognitive rehabilitation by personalized telerehabilitation services: Guttmann neuropersonal trainer.

Cognitive rehabilitation aims to remediate or alleviate the cognitive deficits appearing after an episode of acquired brain injury (ABI). The purpose of this work is to describe the telerehabilitation platform called Guttmann Neuropersonal Trainer (GNPT) which provides new strategies for cognitive rehabilitation, improving efficiency and access to treatments, and to increase knowledge generation from the process. A cognitive rehabilitation process has been modeled to design and develop the system, which allows neuropsychologists to configure and schedule rehabilitation sessions, consisting of set of personalized computerized cognitive exercises grounded on neuroscience and plasticity principles. It provides remote continuous monitoring of patient's performance, by an asynchronous communication strategy. An automatic knowledge extraction method has been used to implement a decision support system, improving treatment customization. GNPT has been implemented in 27 rehabilitation centers and in 83 patients' homes, facilitating the access to the treatment. In total, 1660 patients have been treated. Usability and cost analysis methodologies have been applied to measure the efficiency in real clinical environments. The usability evaluation reveals a system usability score higher than 70 for all target users. The cost efficiency study results show a relation of 1-20 compared to face-to-face rehabilitation. GNPT enables brain-damaged patients to continue and further extend rehabilitation beyond the hospital, improving the efficiency of the rehabilitation process. It allows customized therapeutic plans, providing information to further development of clinical practice guidelines.

Circles of Health: towards an advanced social network about disabilities of neurological origin.

OBJECTIVES: This research is concerned with the study of a new social-network platform, which (1) provides people with disabilities of neurological origin, their relatives, health professionals, therapists, carers and institutions with an interoperable platform that supports standard indicators, (2) promotes knowledge democratization and user empowerment, and (3) allows making decisions with a more informed opinion. METHODS: A new social network, Circles of Health, has been designed, developed and tested by end-users. To allow monitoring the evolution of people's health status and comparing it with other users and with their cohort, anonymized data of 2675 people from comprehensive and multidimensional medical evaluations, carried out yearly from 2006 to 2010, have been standardized to the International Classification of Functioning, Disability and Health, integrated into the corresponding medical health records and then used to automatically generate and graphically represent multidimensional indicators. These indicators have been integrated into Circles of Health's social environment, which has been then evaluated via expert and user-experience analyses. RESULTS: Patients used Circles of Health to exchange bio-psycho-social information (medical and otherwise) about their everyday lives. Health professionals remarked that the use of color-coding in graphical representations is useful to quickly diagnose deficiencies, difficulties or barriers in rehabilitation. Most people with disabilities complained about the excessive amount of information and the difficulty in interpreting graphical representations. CONCLUSIONS: Health professionals found Circles of Health useful to generate a more integrative understanding of health based on a comprehensive profile of individuals instead of being focused on patient's diseases and injuries. People with disabilities found enriching personal knowledge with the experiences of other users helpful. The number of descriptors used at the same time in the graphical interface should be reduced in future versions of the social-network platform.

White matter/gray matter contrast changes in chronic and diffuse traumatic brain injury.

Signal-intensity contrast of T1-weighted magnetic resonance imaging scans has been associated with tissue integrity and reported as a sign of neurodegenerative changes in diseases such as Alzheimer's disease. After severe traumatic brain injury (TBI), progressive structural changes occur in white (WM) and gray matter (GM). In the current study, we assessed the signal-intensity contrast of GM and WM in patients with diffuse TBI in the chronic stage to (1) characterize the regional pattern of WM/GM changes in intensity contrast associated with traumatic axonal injury, (2) evaluate possible associations between this measure and diffusion tensor image (DTI)/fractional anisotropy (FA) for detecting WM damage, and (3) investigate the correlates of both measures with cognitive outcomes. Structural T1 scans were processed with FreeSurfer software to identify the boundary and calculate the WM/GM contrast maps. DTIs were processed with the FMRIB software library to obtain FA maps. The WM/GM contrast in TBI patients showed a pattern of reduction in almost all of the brain, except the visual and motor primary regions. Global FA values obtained from DTI correlated with the intensity contrast of all associative cerebral regions. WM/GM contrast correlated with memory functions, whereas FA global values correlated with tests measuring memory and mental processing speed. In conclusion, tissue-contrast intensity is a very sensitive measure for detecting structural brain damage in chronic, severe and diffuse TBI, but is less sensitive than FA for reflecting neuropsychological sequelae, such as impaired mental processing speed.

Resting-state functional magnetic resonance imaging activity and connectivity and cognitive outcome in traumatic brain injury.

IMPORTANCE: The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of the brain substrates of cognitive outcome after traumatic axonal injury. This knowledge may contribute to improve clinical management and rehabilitation programs. OBJECTIVE: To study functional magnetic resonance imaging abnormalities in signal amplitude and brain connectivity at rest and their relationship to cognitive outcome in patients with chronic and severe traumatic axonal injury. DESIGN: Observational study. SETTING: University of Barcelona and Hospital Clinic de Barcelona, Barcelona, and Institut Guttmann-Neurorehabilitation Hospital, Badalona, Spain. PARTICIPANTS: Twenty patients with traumatic brain injury (TBI) were studied, along with 17 matched healthy volunteers. INTERVENTIONS: Resting-state functional magnetic resonance imaging and diffusion tensor imaging data were acquired. After exploring group differences in amplitude of low-frequency fluctuations (ALFF), we studied functional connectivity within the default mode network (DMN) by means of independent component analysis, followed by a dual regression approach and seed-based connectivity analyses. Finally, we performed probabilistic tractography between the frontal and posterior nodes of the DMN. MAIN OUTCOMES AND MEASURES: Signal amplitude and functional connectivity during the resting state, tractography related to DMN, and the association between signal amplitudes and cognitive outcome. RESULTS: Patients had greater ALFF in frontal regions, which was correlated with cognitive performance. Within the DMN, patients showed increased connectivity in the frontal lobes. Seed-based connectivity analyses revealed augmented connectivity within surrounding areas of the frontal and left parietal nodes of the DMN. Fractional anisotropy of the cingulate tract was correlated with increased connectivity of the frontal node of the DMN in patients with TBI. CONCLUSIONS AND RELEVANCE: Increased ALFF is related to better cognitive performance in chronic TBI. The loss of structural connectivity produced by damage to the cingulum tract explained the compensatory increases in functional connectivity within the frontal node of the DMN.

Somatosensory cortectomy induces motor cortical hyperexcitability and scoliosis: an experimental study in developing rats.

BACKGROUND CONTEXT: Dysfunctions in sensorimotor integration, reminiscent to those described in idiopathic dystonia, have been found in idiopathic scoliosis (IS) and might be involved in its pathogenesis. Studying the effects of experimental disruption of sensory cortex may shed further insight into the etiopathology of IS. PURPOSE: To evaluate whether disruption of central sensorimotor integration through partial ablation of the somatosensory cortex leads to scoliosis in developing rats and to describe the effects of such an intervention on motor cortico-cortical inhibition and facilitation. METHODS: Fifty Wistar rats aged 3 weeks were used in the study. Twenty-four rats underwent craniotomy and electrocoagulation of the sensory cortex (PAR1) in the right hemisphere. A second group of 16 rats underwent a sham operation with craniotomy but no electrocoagulation. A third group of 10 rats was used as intact controls. Four weeks after surgery, motor cortical excitability was assessed with paired-pulse electrical cortical stimulation. Neurologic and behavioral examinations were completed serially, and 10 weeks after surgery, X-ray examinations were performed in anesthetized rats to assess spinal curvature. Electromyographic recordings of paravertebral muscle activity were performed in waking rats. At the end of the study, rats were sacrificed, and histologic examinations of brain tissue were performed to confirm the extent of the lesion. A grant from a Government Health Research Fund without salaries assignment financed the study. RESULTS: Almost half of the animals with somatosensory cortectomy (46%) developed scoliosis, with an average Cobb angle of 23 ± 8°. None of the animals in the sham or control groups developed scoliosis. Despite cortical lesions, no motor or behavioral deficits were apparent in the experimental group, and cortectomized rats were neurologically indistinguishable from sham or control animals, except for the presence of scoliosis. Cortico-cortical inhibition was significantly reduced in the hemisphere of scoliotic concavity in the cortectomized group but was normal in the other groups. CONCLUSIONS: These findings indicate that altered sensorimotor integration may cause scoliosis without noticeable motor impairment. Reduced cortico-cortical inhibition was observed in cortectomized rats. This finding is consistent with results in adolescents with IS and suggests that alteration of cortical hemispheric balance of sensorimotor integration may play an important role in the pathogenesis of IS.