Non-invasive brain stimulation and plasticity changes in aging

Our conceptualization of brain changes across the lifespan is evolving (Pascual-Leone et al., 2011). There appears to be no period when the brain and its functions are static. Instead, changes are continuous throughout the lifespan, some resulting in benefits, others in functional loss and decline (Park and Reuter-Lorenz, 2009; Pascual-Leone and Taylor, 2011). Therefore, the most suitable framework appears to be that of life-long, continued “developmental” processes that influence each other, and there is a growing need for deeper understanding of brain changes (plasticity) from prenatal states and infancy through childhood into adult and old age..

Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability

Repetitive transcranial magnetic stimulation (rTMS) appears to have effects on cortical excitability that extend beyond the train of rTMS itself. These effects may be inhibitory or facilitatory and appear to depend on the frequency, intensity, duration and intertrain interval of the rTMS. Many studies assume facilitatory effects of high-frequency rTMS and inhibitory effects of low-frequency rTMS. Nevertheless, the interindividual variability of this modulation of cortical excitability by rTMS has not been systematically investigated. In this study, we applied 240 pulses of rTMS at 90% of the subjects' motor threshold to their motor cortex at different frequencies (1, 10, 15 and 20 Hz) and examined the effects on motor evoked potentials (frequency tuning curve). Although the averaged group data showed a frequency-dependent increase in cortical excitability, each subject had a different pattern of frequency tuning curve, i.e. a different modulatory effect on cortical excitability at different rTMS frequencies. The interindividual variability of these modulatory effects was still high, though less so, when the number of rTMS pulses was increased to 1600. These findings illustrate the degree of variability of the rTMS effects in the human brain.Supported in part by grants from the Cellular Science Research Foundation, Yoshida Science Foundation, Japan North America Medical Exchange Foundation, the Stanley Vada Foundation, the National Alliance for Research and Schizophrenia and Depression, and the National Institute of Mental Health (RO1MH57980)Medicin

Realistic modeling of mesoscopic ephaptic coupling in the human brain

Altres ajuts: The National Institutes of Health (R01HD069776, R01NS073601, R21MH099196, R21 NS082870, R21 NS085491, R21HD07616)Several decades of research suggest that weak electric fields may influence neural processing, including those induced by neuronal activity and proposed as a substrate for a potential new cellular communication system, i.e., ephaptic transmission. Here we aim to model mesoscopic ephaptic activity in the human brain and explore its trajectory during aging by characterizing the electric field generated by cortical dipoles using realistic finite element modeling. Extrapolating from electrophysiological measurements, we first observe that modeled endogenous field magnitudes are comparable to those in measurements of weak but functionally relevant self-generated fields and to those produced by noninvasive transcranial brain stimulation, and therefore possibly able to modulate neuronal activity. Then, to evaluate the role of these fields in the human cortex in large MRI databases, we adapt an interaction approximation that considers the relative orientation of neuron and field to estimate the membrane potential perturbation in pyramidal cells. We use this approximation to define a simplified metric (EMOD1) that weights dipole coupling as a function of distance and relative orientation between emitter and receiver and evaluate it in a sample of 401 realistic human brain models from healthy subjects aged 16-83. Results reveal that ephaptic coupling, in the simplified mesoscopic modeling approach used here, significantly decreases with age, with higher involvement of sensorimotor regions and medial brain structures. This study suggests that by providing the means for fast and direct interaction between neurons, ephaptic modulation may contribute to the complexity of human function for cognition and behavior, and its modification across the lifespan and in response to pathology

Antidepressant Effects of High and Low Frequency Repetitive Transcranial Magnetic Stimulation to the Dorsolateral Prefrontal Cortex

Repetitive transcranial magnetic stimulation(rTMS) has antidepressant effects in patients withmajor depressive disorder. The mechanisms of ac-tion and optimal stimulation parameters remainunclear. To test the hypothesis that rTMS exertsantidepressant effects either by enhancing left dor-solateral prefrontal cortex (DLPFC) excitability orby decreasing right DLPFC excitability, the au-thors studied 45 patients with unipolar recurrentmajor depressive disorder in a double-blind, ran-domized, parallel group, sham-controlled trial. Pa-tients were randomized to receive 1 Hz or 10 HzrTMS to the left DLPFC, 1 Hz to the rightDLPFC or sham TMS. Left 10 Hz and right 1 HzrTMS showed similar significant antidepressanteffects. Other parameters led to no significantantidepressant effectThis study was supported in part by grants from the Spanish Ministerio de Educacion y Cienca (DGICYT), the Milton Fund, the Stanley Vada NAMI Foundation, the National Alliance for Research in Schizophrenia and Depression, and NIMHMedicin

Face individual identity recognition: a potential endophenotype in autism

Funder: Autism Research TrustFunder: NIHR Biomedical Research CentreFunder: National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation TrustFunder: Sidney R. Baer, Jr. Foundation; doi: http://dx.doi.org/10.13039/100001479Funder: National Science Foundation; doi: http://dx.doi.org/10.13039/501100008982Funder: The Harvard Clinical and Translational Science CenterFunder: US-IT Fulbright CommissionAbstract: Background: Face individual identity recognition skill is heritable and independent of intellectual ability. Difficulties in face individual identity recognition are present in autistic individuals and their family members and are possibly linked to oxytocin polymorphisms in families with an autistic child. While it is reported that developmental prosopagnosia (i.e., impaired face identity recognition) occurs in 2–3% of the general population, no prosopagnosia prevalence estimate is available for autism. Furthermore, an autism within-group approach has not been reported towards characterizing impaired face memory and to investigate its possible links to social and communication difficulties. Methods: The present study estimated the prevalence of prosopagnosia in 80 autistic adults with no intellectual disability, investigated its cognitive characteristics and links to autism symptoms’ severity, personality traits, and mental state understanding from the eye region by using standardized tests and questionnaires. Results: More than one third of autistic participants showed prosopagnosia. Their face memory skill was not associated with their symptom’s severity, empathy, alexithymia, or general intelligence. Face identity recognition was instead linked to mental state recognition from the eye region only in autistic individuals who had prosopagnosia, and this relationship did not depend on participants’ basic face perception skills. Importantly, we found that autistic participants were not aware of their face memory skills. Limitations: We did not test an epidemiological sample, and additional work is necessary to establish whether these results generalize to the entire autism spectrum. Conclusions: Impaired face individual identity recognition meets the criteria to be a potential endophenotype in autism. In the future, testing for face memory could be used to stratify autistic individuals into genetically meaningful subgroups and be translatable to autism animal models

Time to reconcile research findings and clinical practice on upper limb neurorehabilitation

In the field of upper limb neurorehabilitation, the translation from research findings to clinical practice remains troublesome. Patients are not receiving treatments based on the best available evidence. There are certainly multiple reasons to account for this issue, including the power of habit over innovation, subjective beliefs over objective results. We need to take a step forward, by looking at most important results from randomized controlled trials, and then identify key active ingredients that determined the success of interventions. On the other hand, we need to recognize those specific categories of patients having the greatest benefit from each intervention, and why. The aim is to reach the ability to design a neurorehabilitation program based on motor learning principles with established clinical efficacy and tailored for specific patient's needs. The objective of the present manuscript is to facilitate the translation of research findings to clinical practice. Starting from a literature review of selected neurorehabilitation approaches, for each intervention the following elements were highlighted: definition of active ingredients; identification of underlying motor learning principles and neural mechanisms of recovery; inferences from research findings; and recommendations for clinical practice. Furthermore, we included a dedicated chapter on the importance of a comprehensive assessment (objective impairments and patient's perspective) to design personalized and effective neurorehabilitation interventions. It's time to reconcile research findings with clinical practice. Evidence from literature is consistently showing that neurological patients improve upper limb function, when core strategies based on motor learning principles are applied. To this end, practical take-home messages in the concluding section are provided, focusing on the importance of graded task practice, high number of repetitions, interventions tailored to patient's goals and expectations, solutions to increase and distribute therapy beyond the formal patient-therapist session, and how to integrate different interventions to maximize upper limb motor outcomes. We hope that this manuscript will serve as starting point to fill the gap between theory and practice in upper limb neurorehabilitation, and as a practical tool to leverage the positive impact of clinicians on patients' recovery

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

Mapping of the human visual cortex using image-guided transcranial magnetic stimulation

We describe a protocol using transcranial magnetic stimulation (TMS) to systematically map the visual sensations induced by focal and non-invasive stimulation of the human occipital cortex. TMS is applied with a figure of eight coil to 28 positions arranged in a 232-cm grid over the occipital area. A digitizing tablet connected to a PC computer running customized software, and audio and video recording are used for detailed and accurate data collection and analysis of evoked phosphenes. A frameless image-guided neuronavigational device is used to describe the position of the actual sites of the stimulation coils relative to the cortical surface. Our results show that TMS is able to elicit phosphenes in almost all sighted subjects and in a proportion of blind subjects. Evoked phosphenes are topographically organized. Despite minor inter-individual variations, the mapping results are reproducible and show good congruence among different subjects. This procedure has potential to improve our understanding of physiologic organization and plastic changes in the human visual system and to establish the degree of remaining functional visual cortex in blind subjects. Such a non-invasive method is critical for selection of suitable subjects for a cortical visual prosthesis.This research has been carried out with financial support from the Commission of the European Communities, specific RTD programme ‘Quality of Life and Management of Living Resources’, QLK6-CT-2001-00279 and by the Ministerio de Ciencia y Tecnologıa(MAT2000-1049)Fondo de Investigaciones de la Seguridad Social (FISS 01-0674)National Institute of Mental Health (MH60734, MH57980)National Eye Institute (EYEY12091)Harvard-Thorndike General Clinical Research Center at Beth Israel Deaconess Medical Center (NCRR MO1 RR01032).Medicin

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

Traumatic Brain Injury Modifies the Relationship Between Physical Activity and Global and Cognitive Health: Results From the Barcelona Brain Health Initiative

Physical activity has many health benefits for individuals with and without history of brain injury. Here, we evaluated in a large cohort study the impact of physical activity on global and cognitive health as measured by the PROMIS global health and NeuroQoL cognitive function questionnaires. A nested case control study assessed the influence of a history of traumatic brain injury (TBI) on the effects of physical activity since underlying pathophysiology and barriers to physical activity in individuals with TBI may mean the effects of physical activity on perceived health outcomes differ compared to the general population. Those with a history of TBI (n = 81) had significantly lower Global health (β = -1.66, p = 0.010) and NeuroQoL cognitive function (β = -2.65, p = 0.006) compared to healthy adults (n = 405). A similar proportion of individuals in both groups reported being active compared to being insufficiently active ( X2(1) = 0.519 p = 0.471). Furthermore, the effect of physical activity on global health (β = 0.061, p = 0.076) and particularly for NeuroQoL (β = 0.159, p = 0.002) was greater in those with a history of TBI. Individuals with a history of TBI can adhere to a physically active lifestyle, and if so, that is associated with higher global and cognitive health perceptions. Adhering to a physically active lifestyle is non-trivial, particularly for individuals with TBI, and therefore adapted strategies to increase participation in physical activity is critical for the promotion of public health