Brain system segregation and pain catastrophizing in chronic pain progression.

Pain processing involves emotional and cognitive factors that can modify pain perception. Increasing evidence suggests that pain catastrophizing (PC) is implicated, through pain-related self-thoughts, in the maladaptive plastic changes related to the maintenance of chronic pain (CP). Functional magnetic resonance imaging (fMRI) studies have shown an association between CP and two main networks: default mode (DMN) and dorsoattentional (DAN). Brain system segregation degree (SyS), an fMRI framework used to quantify the extent to which functional networks are segregated from each other, is associated with cognitive abilities in both healthy individuals and neurological patients. We hypothesized that individuals suffering from CP would show worst health-related status compared to healthy individuals and that, within CP individuals, longitudinal changes in pain experience (pain intensity and affective interference), could be predicted by SyS and PC subdomains (rumination, magnification, and helplessness). To assess the longitudinal progression of CP, two pain surveys were taken before and after an in-person assessment (physical evaluation and fMRI). We first compared the sociodemographic, health-related, and SyS data in the whole sample (no pain and pain groups). Secondly, we ran linear regression and a moderation model only in the pain group, to see the predictive and moderator values of PC and SyS in pain progression. From our sample of 347 individuals (mean age = 53.84, 55.2% women), 133 responded to having CP, and 214 denied having CP. When comparing groups, results showed significant differences in health-related questionnaires, but no differences in SyS. Within the pain group, helplessness (ß = 0.325; p = 0.003), higher DMN (ß = 0.193; p = 0.037), and lower DAN segregation (ß = 0.215; p = 0.014) were strongly associated with a worsening in pain experience over time. Moreover, helplessness moderated the association between DMN segregation and pain experience progression (p = 0.003). Our findings indicate that the efficient functioning of these networks and catastrophizing could be used as predictors of pain progression, bringing new light to the influence of the interplay between psychological aspects and brain networks. Consequently, approaches focusing on these factors could minimize the impact on daily life activities.

The age-related contribution of cognitive function to dual-task gait in middle-aged adults in Spain: observations from a population-based study.

BACKGROUND: Poor dual-task gait performance is associated with a risk of falls and cognitive decline in adults aged 65 years or older. When and why dual-task gait performance begins to deteriorate is unknown. This study aimed to characterise the relationships between age, dual-task gait, and cognitive function in middle age (ie, aged 40-64 years). METHODS: We conducted a secondary analysis of data from community-dwelling adults aged 40-64 years that took part in the Barcelona Brain Health Initiative (BBHI) study, an ongoing longitudinal cohort study in Barcelona, Spain. Participants were eligible for inclusion if they were able to walk independently without assistance and had completed assessments of both gait and cognition at the time of analysis and ineligble if they could not understand the study protocol, had any clinically diagnosed neurological or psychiatric diseases, were cognitively impaired, or had lower-extremity pain, osteoarthritis, or rheumatoid arthritis that could cause abnormal gait. Stride time and stride time variability were measured under single-task (ie, walking only) and dual-task (ie, walking while performing serial subtractions) conditions. Dual-task cost (DTC; the percentage increase in the gait outcomes from single-task to dual-task conditions) to each gait outcome was calculated and used as the primary measure in analyses. Global cognitive function and composite scores of five cognitive domains were derived from neuropsychological testing. We used locally estimated scatterplot smoothing to characterise the relationship between age and dual-task gait, and structural equation modelling to establish whether cognitive function mediated the association between observed biological age and dual tasks. FINDINGS: 996 people were recruited to the BBHI study between May 5, 2018, and July 7, 2020, of which 640 participants completed gait and cognitive assessments during this time (mean 24 days [SD 34] between first and second visit) and were included in our analysis (342 men and 298 women). Non-linear associations were observed between age and dual-task performance. Starting at 54 years, the DTC to stride time (ß=0·27 [95% CI 0·11 to 0·36]; p<0·0001) and stride time variability (0·24 [0·08 to 0·32]; p=0·0006) increased with advancing age. In individuals aged 54 years or older, decreased global cognitive function correlated with increased DTC to stride time (ß=-0·27 [-0·38 to -0·11]; p=0·0006) and increased DTC to stride time variability (ß=-0·19 [-0·28 to -0·08]; p=0·0002). INTERPRETATION: Dual-task gait performance begins to deteriorate in the sixth decade of life and, after this point, interindividual variance in cognition explains a substantial portion of dual-task performance. FUNDING: La Caixa Foundation, Institut Guttmann, and Fundació Abertis.

Purpose in life promotes resilience to age-related brain burden in middle-aged adults.

BACKGROUND: Disease-modifying agents to counteract cognitive impairment in older age remain elusive. Hence, identifying modifiable factors promoting resilience, as the capacity of the brain to maintain cognition and function with aging and disease, is paramount. In Alzheimer's disease (AD), education and occupation are typical cognitive reserve proxies. However, the importance of psychological factors is being increasingly recognized, as their operating biological mechanisms are elucidated. Purpose in life (PiL), one of the pillars of psychological well-being, has previously been found to reduce the deleterious effects of AD-related pathological changes on cognition. However, whether PiL operates as a resilience factor in middle-aged individuals and what are the underlying neural mechanisms remain unknown. METHODS: Data was obtained from 624 middle-aged adults (mean age 53.71 ± 6.9; 303 women) from the Barcelona Brain Health Initiative cohort. Individuals with lower (LP; N = 146) and higher (HP; N = 100) PiL rates, according to the division of this variable into quintiles, were compared in terms of cognitive status, a measure reflecting brain burden (white matter lesions; WMLs), and resting-state functional connectivity, examining system segregation (SyS) parameters using 14 common brain circuits. RESULTS: Neuropsychological status and WMLs burden did not differ between the PiL groups. However, in the LP group, greater WMLs entailed a negative impact on executive functions. Subjects in the HP group showed lower SyS of the dorsal default-mode network (dDMN), indicating lesser segregation of this network from other brain circuits. Specifically, HP individuals had greater inter-network connectivity between specific dDMN nodes, including the frontal cortex, the hippocampal formation, the midcingulate region, and the rest of the brain. Greater functional connectivity in some of these nodes positively correlated with cognitive performance. CONCLUSION: Expanding previous findings on AD pathology and advanced age, the present results suggest that higher rates of PiL may promote resilience against brain changes already observable in middle age. Furthermore, having a purposeful life implies larger functional integration of the dDMN, which may potentially reflect greater brain reserve associated to better cognitive function.

Genome-wide QTL mapping across three tissues highlights several Alzheimer's and Parkinson's disease loci potentially acting via DNA methylation.

DNA methylation (DNAm) is an epigenetic mark with essential roles in disease development and predisposition. Here, we created genome-wide maps of methylation quantitative trait loci (meQTL) in three peripheral tissues and used Mendelian randomization (MR) analyses to assess the potential causal relationships between DNAm and risk for two common neurodegenerative disorders, i.e. Alzheimer's disease (AD) and Parkinson's disease (PD). Genome-wide single nucleotide polymorphism (SNP; ~5.5M sites) and DNAm (~850K CpG sites) data were generated from whole blood (n=1,058), buccal (n=1,527) and saliva (n=837) specimens. We identified between 11 and 15 million genome-wide significant (p<10-14) SNP-CpG associations in each tissue. Combining these meQTL GWAS results with recent AD/PD GWAS summary statistics by MR strongly suggests that the previously described associations between PSMC3, PICALM, and TSPAN14 and AD may be founded on differential DNAm in or near these genes. In addition, there is strong, albeit less unequivocal, support for causal links between DNAm at PRDM7 in AD as well as at KANSL1/MAPT in AD and PD. Our study adds valuable insights on AD/PD pathogenesis by combining two high-resolution "omics" domains, and the meQTL data shared along with this publication will allow like-minded analyses in other diseases.

Epigenome-Wide Association Study in Peripheral Tissues Highlights DNA Methylation Profiles Associated with Episodic Memory Performance in Humans.

The decline in episodic memory (EM) performance is a hallmark of cognitive aging and an early clinical sign in Alzheimer's disease (AD). In this study, we conducted an epigenome-wide association study (EWAS) using DNA methylation (DNAm) profiles from buccal and blood samples for cross-sectional (n = 1019) and longitudinal changes in EM performance (n = 626; average follow-up time 5.4 years) collected under the auspices of the Lifebrain consortium project. The mean age of participants with cross-sectional data was 69 ± 11 years (30−90 years), with 50% being females. We identified 21 loci showing suggestive evidence of association (p < 1 × 10−5) with either or both EM phenotypes. Among these were SNCA, SEPW1 (both cross-sectional EM), ITPK1 (longitudinal EM), and APBA2 (both EM traits), which have been linked to AD or Parkinson's disease (PD) in previous work. While the EM phenotypes were nominally significantly (p < 0.05) associated with poly-epigenetic scores (PESs) using EWASs on general cognitive function, none remained significant after correction for multiple testing. Likewise, estimating the degree of "epigenetic age acceleration" did not reveal significant associations with either of the two tested EM phenotypes. In summary, our study highlights several interesting candidate loci in which differential DNAm patterns in peripheral tissue are associated with EM performance in humans.

Validation and Normative Data of the Spanish Version of the Rey Auditory Verbal Learning Test and Associated Long-Term Forgetting Measures in Middle-Aged Adults.

Rey Auditory Verbal Learning Test (RAVLT) is an episodic memory helpful measure to detect changes associated with abnormal aging. There is a lack of RAVLT validation and normalization studies in Spain. The aim was to determine its psychometric properties and explore long-term forgetting (LTF) performance through 1-week delayed recall under three different modes of administration. The RAVLT was administered to 602 cognitively healthy volunteers, aged between 41 and 65 years, of whom 251 completed the LTF assessment. Findings reveal a factorial structure of four components, with satisfactory goodness of fit, and adequate convergent and divergent validity. We also demonstrated the differential effect of three methodologies used in LTF assessment, supporting that test expectancy positively influences long-term storage. Finally, normative data were generated according to age, sex, and education. The test, including the LTF measure, is a promising tool to estimate memory in middle-aged adults and develop predictive brain aging models.

Local Prefrontal Cortex TMS-Induced Reactivity Is Related to Working Memory and Reasoning in Middle-Aged Adults.

INTRODUCTION: The prefrontal cortex (PFC) plays a crucial role in cognition, particularly in executive functions. Cortical reactivity measured with Transcranial Magnetic Stimulation combined with Electroencephalography (TMS-EEG) is altered in pathological conditions, and it may also be a marker of cognitive status in middle-aged adults. In this study, we investigated the associations between cognitive measures and TMS evoked EEG reactivity and explored whether the effects of this relationship were related to neurofilament light chain levels (NfL), a marker of neuroaxonal damage. METHODS: Fifty two healthy middle-aged adults (41-65 years) from the Barcelona Brain Health Initiative cohort underwent TMS-EEG, a comprehensive neuropsychological assessment, and a blood test for NfL levels. Global and Local Mean-Field Power (GMFP/LMFP), two measures of cortical reactivity, were quantified after left prefrontal cortex (L-PFC) stimulation, and cognition was set as the outcome of the regression analysis. The left inferior parietal lobe (L-IPL) was used as a control stimulation condition. RESULTS: Local reactivity was significantly associated with working memory and reasoning only after L-PFC stimulation. No associations were found between NfL and cognition. These specific associations were independent of the status of neuroaxonal damage indexed by the NfL biomarker and remained after adjusting for age, biological sex, and education. CONCLUSION: Our results demonstrate that TMS evoked EEG reactivity at the L-PFC, but not the L-IPL, is related to the cognitive status of middle-aged individuals and independent of NfL levels, and may become a valuable biomarker of frontal lobe-associated cognitive function.

Associations between repetitive negative thinking and resting-state network segregation among healthy middle-aged adults.

Background: Repetitive Negative Thinking (RNT) includes negative thoughts about the future and past, and is a risk factor for depression and anxiety. Prefrontal and anterior cingulate cortices have been linked to RNT but several regions within large-scale networks are also involved, the efficiency of which depends on their ability to remain segregated. Methods: Associations between RNT and system segregation (SyS) of the Anterior Salience Network (ASN), Default Mode Network (DMN) and Executive Control Network (ECN) were explored in healthy middle-aged adults (N = 341), after undergoing resting-state functional magnetic resonance imaging. Regression analyses were conducted with RNT as outcome variable. Explanatory variables were: SyS, depression, emotional stability, cognitive complaints, age and sex. Results: Analyses indicated that RNT was associated with depression, emotional stability, cognitive complaints, age and segregation of the left ECN (LECN) and ASN. Further, the ventral DMN (vDMN) presented higher connectivity with the ASN and decreased connectivity with the LECN, as a function of RNT. Conclusion: Higher levels of perseverative thinking were related to increased segregation of the LECN and decreased segregation of the ASN. The dissociative connectivity of these networks with the vDMN may partially account for poorer cognitive control and increased self-referential processes characteristic of RNT.

Cognitive Reserve as a Protective Factor of Mental Health in Middle-Aged Adults Affected by Chronic Pain.

Chronic pain is associated with worse mental health and cognitive impairment, which can be a cause or a consequence of brain structure and function alterations, e.g., maladaptive plasticity, antinociceptive system dysregulation. Cognitive reserve reflects the effectiveness of the internal connections of the brain and it has been shown to be a protective factor in brain damage, slowing cognitive aging or reducing the risk of mental health disorders. The current study explored the impact of chronic pain on psychosocial factors, mental health, and cognition. Furthermore, we aimed to examine the role of cognitive reserve in the relationship between mental health and chronic pain clinical characteristics in middle-aged adults. The study group consisted of 477 volunteers from the Barcelona Brain Health Initiative who completed online surveys on pain, mental health, cognitive reserve, and psychosocial factors (sleep and quality of life). We described the differences in sociodemographic data, psychosocial factors, mental health, and self-perceived cognitive impairment, and neuropsychological assessment, between participants reporting pain compared with those without pain, as well as the main characteristics of the chronic pain group. Finally, to study the role of cognitive reserve in the modulation of the relationship between chronic pain and mental health, we compared variables between subgroups of participants with high/low pain intensity and cognitive reserve. The results showed that chronic pain was reported by 45.5% of middle-aged adults. Our results revealed that participants with chronic pain were older and had worse health status than people without pain. The presence of chronic pain affected working memory, mental health, and daily life activities. Moreover, cognitive reserve moderated the influence of pain intensity on mental health, resulting in less mental health affection in people suffering from high pain intensity with high cognitive reserve. In conclusion, the construct of the cognitive reserve could explain differential susceptibility between chronic pain and its mental health association and be a powerful tool in chronic pain assessment and treatment, principally due to its modifiable nature.

Associations Between Cardiorespiratory Fitness, Cardiovascular Risk, and Cognition Are Mediated by Structural Brain Health in Midlife.

Background Evidence in older adults suggests that higher cardiorespiratory fitness and lower cardiovascular risk are associated with greater cognition. However, given that changes in the brain that lead to cognitive decline begin decades before the onset of symptoms, understanding the mechanisms by which modifiable cardiovascular factors are associated with brain health in midlife is critical and can lead to the development of strategies to promote and maintain brain health as we age. Methods and Results In 501 middle-aged (aged 40-65 years) adult participants of the BBHI (Barcelona Brain Health Initiative), we found differential associations among cardiorespiratory fitness, cardiovascular risk, and cognition and cortical thickness. Higher cardiorespiratory fitness was significantly associated with better visuospatial abilities and frontal loading abstract problem solving (ß=3.16, P=0.049) in the older middle-aged group (aged 55-65 years). In contrast, cardiovascular risk was negatively associated with better visuospatial reasoning and problem-solving abilities (ß=-0.046, P=0.002), flexibility (ß=-0.054, P<0.001), processing speed (ß=-0.115, P<0.001), and memory (ß=-0.120, P<0.001). Cortical thickness in frontal regions mediated the relationship between cardiorespiratory fitness and cognition, whereas cortical thickness in a disperse network spanning multiple cortical regions across both hemispheres mediated the relationship between cardiovascular risk and cognition. Conclusions The relationships between modifiable cardiovascular factors, cardiorespiratory fitness, and cardiovascular risk, and cognition are present in healthy middle-aged adults. These relationships are also mediated by brain structure highlighting a potential mechanistic pathway through which higher cardiorespiratory fitness and lower cardiovascular risk can positively impact cognitive function in midlife.

The impact of Body Mass Index on functional rehabilitation outcomes of working-age inpatients with stroke.

BACKGROUND: Stroke is the most relevant cause of acquired persistent disability in adulthood. The relationship between patient's weight during rehabilitation and stroke functional outcome is controversial, previous research reported positive, negative and no effects, with scarce studies specifically addressing working-age patients. AIM: To evaluate the association between Body Mass Index (BMI) and the functional progress of adult (<65 years) patients with stroke admitted to a rehabilitation hospital. DESIGN: Retrospective observational cohort study. SETTING: Inpatient rehabilitation center. POPULATION: 178 stroke patients (ischemic or hemorrhagic). METHODS: Point-biserial and Spearman's correlations, multivariate linear regressions and analysis of covariance were used to describe differences in functional outcomes after adjusting for age, sex, severity, dysphagia, depression and BMI category. Functional Independence Measure (FIM), FIM gain, efficiency and effectiveness were assessed. RESULTS: Participants were separated in 3 BMI categories: normal weight (47%), overweight (33%) and obese (20%). There were no significant differences between BMI categories in any functional outcome (total FIM [T-FIM], cognitive [C-FIM]), motor [M-FIM]) at discharge, admission, gain, efficiency or effectiveness. In regression models BMI (as continuous variable) was not significant predictor of T-FIM at discharge after adjusting for age, sex, severity, dysphagia, depression and ataxia (R2=0.4813), significant predictors were T-FIM at admission (ß=0.528) and NIHSS (ß=-0.208). M-FIM efficiency did not significantly differ by BMI subgroups, neither did C-FIM efficiency. Length of stay (LOS) and T-FIM effectiveness were associated for normal (r=0.33) and overweight (r=0.43), but not for obese. LOS and T-FIM efficiency were strongly negatively associated only for obese (r=-0.50). CONCLUSIONS: FIM outcomes were not associated to BMI, nevertheless each BMI category when individually considered (normal weight, overweight or obese) was characterized by different associations involving FIM outcomes and clinical factors. CLINICAL REHABILITATION IMPACT: In subacute post-stroke working-age patients undergoing rehabilitation, BMI was not associated to FIM outcomes (no obesity paradox was reported in this sample). Distinctive significant associations emerged within each BMI category, (supporting their characterization) such as length of stay and T-FIM effectiveness were associated for normal weight and overweight, but not for obese. Length of stay and T-FIM efficiency were strongly negatively associated only for obese.

The Barcelona Brain Health Initiative: Cohort description and first follow-up.

The Barcelona Brain Health Initiative is a longitudinal cohort study that began in 2017 and aims to understand and characterize the determinants of brain health maintenance in middle aged adults. A cohort of 4686 individuals between the ages of 40 and 65 years free from any neurological or psychiatric diseases was established, and we collected extensive demographic, socio-economic information along with measures of self-perceived health and lifestyles (general health, physical activity, cognitive activity, socialization, sleep, nutrition and vital plan). Here we report on the baseline characteristics of the participants, and the results of the one-year follow-up evaluation. Participants were mainly women, highly educated, and with better lifestyles compared with the general population. After one year 60% of participants completed the one-year follow-up, and these were older, with higher educational level and with better lifestyles in some domains. In the absence of any specific interventions to-date, these participants showed small improvements in physical activity and sleep, but decreased adherence to a Mediterranean diet. These changes were negatively associated with baseline scores, and poorer habits at baseline were predictive of an improvement in lifestyle domains. Of the 2353 participants who completed the one-year follow-up, 73 had been diagnosed with new neurological and neuropsychiatric diseases. Changes in vital plan at follow-up, as well as gender, sleep quality and sense of coherence at baseline were shown to be significant risk factors for the onset of these diagnoses. Notably, gender risk factor decreased in importance as we adjusted by sleep habits, suggesting its potential mediator effects. These findings stress the importance of healthy lifestyles in sustaining brain health, and illustrate the individual benefit that can be derived from participation in longitudinal observational studies. Modifiable lifestyles, specifically quality of sleep, may partially mediate the effect of other risk factors in the development of some neuropsychiatric conditions.

Evidence of chronic stroke rehabilitation interventions in activities and participation outcomes: systematic review of meta-analyses of randomized controlled trials.

INTRODUCTION: Stroke is a leading cause of long-term disabilities worldwide. A great deal of meta-analyses of randomized controlled trials (RCTs) address rehabilitation in chronic stroke, several of them with focus on activities and participation, considered critical outcomes of successful rehabilitation. Nevertheless, substantial heterogeneity might exist between studies, the reported associations may be causal, but they might also be flawed, as inherent study biases such as residual confounding and selective reporting of positive results may exaggerate the effect of interventions in chronic phase. Furthermore, most RCTs might focus on specific rehabilitation domains, not paying the same attention to others. EVIDENCE ACQUSITION: Formal evaluation of published systematic reviews of meta-analyses (January 2008 to November 2018) of rehabilitation in chronic phase to 1) assess the strength of evidence: participants, publication biases, heterogeneity, prediction intervals (PIs) 2) grade the evidence to perform qualitative analysis on effects sizes and heterogeneity, 3) perform meta-regressions and sensitivity analysis on relevant covariates 4) map outcomes to activities and participation domain of the World Health Organization's International Classification of Functioning, Disability and Health (ICF). Systematic review on meta-analyses of RCTs addressing activities and participation will be performed in Medline, Web of Science, Scopus, Cochrane and Google Scholar. EVIDENCE SYNTHESIS: A total of 97 meta-analyses on 31 different rehabilitation interventions involving 25,275 participants were included. Thirty-nine meta-analyses (40.74%) reported statistically significant findings (P<0.05) in both fixed and random effects sizes. Their magnitude was small in 62.96% cases, moderate in 19.75% and large in 17.28%. Heterogeneity was low in 48,48%, moderate and high in 21.2%. The mean number of participants is 815, far away from the convincing, highly suggestive, or suggestive required evidence levels. All PIs include the null value. Mobility is addressed by 87% of the identified meta-analyses, with 75% of them focusing exclusively in mobility. CONCLUSIONS: The findings of this study show a clear need for high quality RCTs examining the effectiveness of rehabilitation interventions addressing activities and participation. The ICF framework may contribute to a holistic approach in chronic stroke rehabilitation, including not only motor functioning but also the ability to participate in everyday life activities.

The Barcelona Brain Health Initiative: A Cohort Study to Define and Promote Determinants of Brain Health.

The Barcelona Brain Health Initiative (BBHI) is an ongoing prospective longitudinal study focused on identifying determinants of brain health. The main objectives are: (i) to characterize lifestyle, cognitive, behavioral and environmental markers related to a given individual's cognitive and mental functions in middle to old age, (ii) to assess the biological determinants predictive of maintenance of brain health, and (iii) to evaluate the impact of a controlled multi-dimensional lifestyle intervention on improving and maintaining brain health. The BBHI cohort consists of >4500 healthy participants aged 40-65 years followed through online questionnaires (Phase I) assessing participants' self-perceived health and lifestyle factors in seven different domains: overall health, physical exercise, cognitive activity, sleep, nutrition, social interactions, and life purpose. In Phase II a sub-group of 1,000 individuals is undergoing detailed in-person evaluations repeated at two-yearly intervals. These evaluations will provide deep phenotyping of brain function, including medical, neurological and psychiatric examinations, assessment of physical fitness, neuropsychological assessments, structural and functional brain magnetic resonance imaging, electroencephalography and perturbation-based non-invasive brain stimulation evaluations of brain activity, as well as collection of biological samples. Finally, in Phase III a further sub-group of 500 participants will undergo a similar in-person assessment before and after a multi-dimensional intervention to optimize lifestyle habits and evaluate its effects on cognitive and brain structure and function. The intervention group will receive remote supervision through an ICT-based solution, with the support of an expert in health and lifestyle coaching strategies aimed at promoting adherence. On the other hand, the control group will not have this coaching support, and will only receive education and recommendations about healthy habits. Results of this three-part initiative shall critically contribute to a better understanding of the determinants to promote and maintain brain health over the lifespan.

Meaning in life: resilience beyond reserve.

BACKGROUND: The contribution of psychological factors to brain health and resilience remains poorly investigated. Furthermore, their possible interaction with 'classical' cognitive reserve (CR) estimates in predicting perceived mental health and cognitive status has not been specifically addressed. METHODS: We obtained data from 1081 adults responding to questionnaires on the three meaning in life (MiL) dimensions: purpose in life (PiL), sense of coherence (SoC), and engagement with life (EwL). A questionnaire on CR variables was also administered. The outcome measures were self-reported cognitive function and affective status (depression, stress, and anxiety). Multiple linear regression analyses were used to evaluate the association between sociodemographic variables, MiL dimensions, and CR with the two selected outcomes. Mediation analyses, adjusted for age and gender, were applied to determine whether the MiL dimensions mediated the putative effects of CR on self-reported mental and cognitive health. RESULTS: All three MiL components, but not CR estimates, correlated with the self-reported affective status of the participants. Higher CR, PiL, and SoC (but not EwL) scores significantly correlated with higher perceived cognitive function. Notably, the observed association between the CR measures and self-reported cognitive function was mediated by PiL and SoC. CONCLUSIONS: Psychological MiL dimensions mediate the association between classic CR estimates and self-perceived cognitive function. Further studies on CR could consider including formal measures of such psychological factors to better understand their unique or synergistic contributions, as well as investigate the associated mechanisms maintaining brain function at older ages.

Placebo-controlled study of rTMS combined with Lokomat® gait training for treatment in subjects with motor incomplete spinal cord injury.

High-frequency rTMS combined with gait training improves lower extremity motor score (LEMS) and gait velocity in SCI subjects who are able to walk over ground. The aim of this study was to optimize the functional outcome in early phases of gait rehabilitation in SCI using rTMS as an additional treatment to physical therapy. The present study included 31 motor incomplete SCI subjects randomized to receive real or sham rTMS, just before Lokomat gait training (15 subjects for real, 16 for sham rTMS). rTMS consisted of one daily session for 20 days over vertex (at 20 Hz). The subjects were evaluated using modified Ashworth scale (MAS) for spasticity, upper and lower extremity motor score (UEMS and LEMS, respectively), ten meters walking test (10MWT) and Walking Index for SCI (WISCI-II) for gait at baseline, after last rTMS session, and during follow-up. UEMS and LEMS improved significantly after last session in both groups and during follow-up period. The improvement was greater in real than in sham rTMS group. At follow-up, 71.4 % of the subjects after real rTMS and 40 % of the subjects after sham rTMS could perform 10MWT without significant differences in gait velocity, cadence, step length and WISCI-II between both groups. We conclude that 20 sessions of daily high-frequency rTMS combined with Lokomat gait training can lead to clinical improvement of gait in motor incomplete SCI. Such combined treatment improved motor strength in lower extremity in incomplete SCI subjects and in upper extremity in those with cervical SCI.

Artificial metaplasticity prediction model for cognitive rehabilitation outcome in acquired brain injury patients.

OBJECTIVE: The main purpose of this research is the novel use of artificial metaplasticity on multilayer perceptron (AMMLP) as a data mining tool for prediction the outcome of patients with acquired brain injury (ABI) after cognitive rehabilitation. The final goal aims at increasing knowledge in the field of rehabilitation theory based on cognitive affectation. METHODS AND MATERIALS: The data set used in this study contains records belonging to 123 ABI patients with moderate to severe cognitive affectation (according to Glasgow Coma Scale) that underwent rehabilitation at Institut Guttmann Neurorehabilitation Hospital (IG) using the tele-rehabilitation platform PREVIRNEC(©). The variables included in the analysis comprise the neuropsychological initial evaluation of the patient (cognitive affectation profile), the results of the rehabilitation tasks performed by the patient in PREVIRNEC(©) and the outcome of the patient after a 3-5 months treatment. To achieve the treatment outcome prediction, we apply and compare three different data mining techniques: the AMMLP model, a backpropagation neural network (BPNN) and a C4.5 decision tree. RESULTS: The prediction performance of the models was measured by ten-fold cross validation and several architectures were tested. The results obtained by the AMMLP model are clearly superior, with an average predictive performance of 91.56%. BPNN and C4.5 models have a prediction average accuracy of 80.18% and 89.91% respectively. The best single AMMLP model provided a specificity of 92.38%, a sensitivity of 91.76% and a prediction accuracy of 92.07%. CONCLUSIONS: The proposed prediction model presented in this study allows to increase the knowledge about the contributing factors of an ABI patient recovery and to estimate treatment efficacy in individual patients. The ability to predict treatment outcomes may provide new insights toward improving effectiveness and creating personalized therapeutic interventions based on clinical evidence.

Mechanical and thermal hyperalgesia in patients with poliomyelitis.

OBJECTIVE: Paralytic poliomyelitis (pPM) is clinically suspected in individuals experiencing a non-progressive syndrome of flaccid paralysis and atrophy as a sequel of an acute infection. Despite normal sensory perception, patients with pPM complain of pain more than matched siblings. Here, we studied the characteristics of evoked pain in a cohort of pPM patients using contact heat evoked potentials and psychophysical tests. METHODS: Fifteen patients with pPM and 15 controls were studied. Inclusion criteria were unilateral or asymmetric involvement of lower extremities. Mechanical, warm and heat pain perception thresholds and evoked pain were measured in both thighs. Contact heat evoked potentials were recorded from the vertex. RESULTS: Mechanical and heat pain thresholds were significantly lower in the affected than in the less-affected leg or in the legs of controls. Evoked pain ratings were significantly higher in the affected leg than in either the less-affected leg or in controls. Evoked potentials were significantly higher in the affected than in the less-affected leg. CONCLUSION: Patients with pPM have mechanical and thermal hyperalgesia, which suggests abnormalities in processing of somatosensory inputs in these patients. SIGNIFICANCE: This phenomenon should be taken into account in the routine clinical evaluation and management of pPM patients.

Effects of high-frequency repetitive transcranial magnetic stimulation on motor and gait improvement in incomplete spinal cord injury patients.

OBJECTIVE: Incomplete spinal cord injury (SCI) patients have the potential to regain some ambulatory function, and optimal reorganization of remaining circuits can contribute to this recovery. We hypothesized that repetitive transcranial magnetic stimulation (rTMS) may promote active recovery of motor function during gait rehabilitation. METHODS: A total of 17 incomplete SCI patients were randomized to receive active rTMS or sham stimulation coupled with rehabilitation therapy; 3 patients who began in the sham group crossed over to the active rTMS group after a washout period of more than 3 weeks. Active rTMS consisted of 15 daily sessions over the leg motor area (at 20 Hz). We compared lower-extremity motor score (LEMS), 10-m walking test for walking speed, timed up and go, Walking Index for SCI Scale, Modified Ashworth Scale, and Spinal Cord Injury Spasticity Evaluation Tool at baseline, after the last session, and 2 weeks later in the active rTMS and sham stimulation groups. RESULTS: A significant improvement was observed after the last rTMS session in the active group for LEMS, walking speed, and spasticity. Improvement in walking speed was maintained during the follow-up period. Sham stimulation did not induce any improvement in LEMS, gait assessment, and spasticity after the last session and neither during follow-up. CONCLUSION: In incomplete SCI, 15 daily sessions of high-frequency rTMS can improve motor score, walking speed, and spasticity in the lower limbs. The study provides evidence for the therapeutic potential of rTMS in the lower extremities in SCI rehabilitation.