Stroke Recovery-Related Changes in Cortical Reactivity Based on Modulation of Intracortical Inhibition.

BACKGROUND: Cortical excitation/inhibition dynamics have been suggested as a key mechanism occurring after stroke. Their supportive or maladaptive role in the course of recovery is still not completely understood. Here, we used transcranial magnetic stimulation (TMS)-electroencephalography coupling to study cortical reactivity and intracortical GABAergic inhibition, as well as their relationship to residual motor function and recovery longitudinally in patients with stroke. METHODS: Electroencephalography responses evoked by TMS applied to the ipsilesional motor cortex were acquired in patients with stroke with upper limb motor deficit in the acute (1 week), early (3 weeks), and late subacute (3 months) stages. Readouts of cortical reactivity, intracortical inhibition, and complexity of the evoked dynamics were drawn from TMS-evoked potentials induced by single-pulse and paired-pulse TMS (short-interval intracortical inhibition). Residual motor function was quantified through a detailed motor evaluation. RESULTS: From 76 patients enrolled, 66 were included (68.2±13.2 years old, 18 females), with a Fugl-Meyer score of the upper extremity of 46.8±19. The comparison with TMS-evoked potentials of healthy older revealed that most affected patients exhibited larger and simpler brain reactivity patterns (Pcluster<0.05). Bayesian ANCOVA statistical evidence for a link between abnormally high motor cortical excitability and impairment level. A decrease in excitability in the following months was significantly correlated with better motor recovery in the whole cohort and the subgroup of recovering patients. Investigation of the intracortical GABAergic inhibitory system revealed the presence of beneficial disinhibition in the acute stage, followed by a normalization of inhibitory activity. This was supported by significant correlations between motor scores and the contrast of local mean field power and readouts of signal dynamics. CONCLUSIONS: The present results revealed an abnormal motor cortical reactivity in patients with stroke, which was driven by perturbations and longitudinal changes within the intracortical inhibition system. They support the view that disinhibition in the ipsilesional motor cortex during the first-week poststroke is beneficial and promotes neuronal plasticity and recovery.

Differential Impact of Brain Network Efficiency on Poststroke Motor and Attentional Deficits.

BACKGROUND: Most studies on stroke have been designed to examine one deficit in isolation; yet, survivors often have multiple deficits in different domains. While the mechanisms underlying multiple-domain deficits remain poorly understood, network-theoretical methods may open new avenues of understanding. METHODS: Fifty subacute stroke patients (7±3days poststroke) underwent diffusion-weighted magnetic resonance imaging and a battery of clinical tests of motor and cognitive functions. We defined indices of impairment in strength, dexterity, and attention. We also computed imaging-based probabilistic tractography and whole-brain connectomes. To efficiently integrate inputs from different sources, brain networks rely on a rich-club of a few hub nodes. Lesions harm efficiency, particularly when they target the rich-club. Overlaying individual lesion masks onto the tractograms enabled us to split the connectomes into their affected and unaffected parts and associate them to impairment. RESULTS: We computed efficiency of the unaffected connectome and found it was more strongly correlated to impairment in strength, dexterity, and attention than efficiency of the total connectome. The magnitude of the correlation between efficiency and impairment followed the order attention>dexterity ≈ strength (strength: |r|=.03, P=0.02, dexterity: |r|=.30, P=0.05, attention: |r|=.55, P<0.001). Network weights associated with the rich-club were more strongly correlated to efficiency than non-rich-club weights. CONCLUSIONS: Attentional impairment is more sensitive to disruption of coordinated networks between brain regions than motor impairment, which is sensitive to disruption of localized networks. Providing more accurate reflections of actually functioning parts of the network enables the incorporation of information about the impact of brain lesions on connectomics contributing to a better understanding of underlying stroke mechanisms.

Transcranial Magnetic Stimulation Improves Executive Functioning through Modulation of Social Cognitive Networks in Patients with Mild Cognitive Impairment: Preliminary Results.

(1) Background: Patients with mild cognitive impairment (MCI) often present impairment in executive functions (EFs). This study aimed to investigate the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on EFs in patients with MCI. (2) Methods: A prospective trial was conducted on 11 patients with MCI. Participants underwent 25 min of 20 Hz rTMS for ten days on the right temporo-parietal junction (RTPJ) and medial prefrontal cortex (MPFC). Before (T0) and after rTMS treatment (T1), global cognitive profile and EFs were investigated using the Montreal cognitive assessment (MoCA), trial making test (TMT) A and B, and frontal assessment battery (FAB). Depression symptoms were assessed using the geriatric depression scale (GDS). Statistical analysis included Wilcoxon signed-rank test. (3) Results: After treatment, patients showed a significant improvement in the MoCA EFs subtask (T0 vs. T1, p = 0.015) and TMT-B (T0 vs. T1, p = 0.028). Five MCI patients with EF impairment showed full recovery of these deficits. No significant changes in the GDS were observed. (4) Conclusions: rTMS stimulation over the TPJ and MPFC induced significant short-term improvements in EFs in MCI patients. These findings suggest that the TPJ and MPFC may be involved in the attention-executive skills to redirect attention toward behaviorally relevant stimuli.

Attentive-executive functioning and compensatory strategies in adult ADHD: A retrospective case series study.

Background: Adults with ADHD exhibit a neuropsychological profile that may present deficits in many cognitive domains, particularly attention and executive functions (EFs). However, some authors do not consider executive disfunction as an important part of the clinical profile of the syndrome; this could be related to the use of inappropriate neuropsychological tests, probably not adapted and not sufficiently ecological. Moreover, new data are required on specific correlation of attentive-executive symptoms with socio-demographic factors. Therefore, the aim of this study is to analyze the neuropsychological performance of a group of adults with ADHD, also evaluating the influence of gender, age and education level. Methods: We retrospectively collected health-related personal data of 40 adult ADHD patients, clinically diagnosed and evaluated via a battery of 4 neuropsychological tests and 1 self-administered questionnaire. Gender, age and years of education differences were assessed. Results: Attention and EFs deficits have been highlighted mainly on the d2-R and 5-point neuropsychological tests, which therefore seem to be more sensitive in measuring the attention-executive dysfunction in an adult ADHD population, than TAP Go/No-go and ROCFT. ADHD patients also manifested subjective behavioral impulsivity disorders on BIS-11. There were no statistically significant gender differences in cognitive performance. On the contrary, younger patients performed worse on subscales TAP Go/No-go errors and 5-points number of drawings, while participants with a higher education level performed better on subscales d2-R speed of execution and d2-R errors. This supports a reduction in the number of errors and the execution time as a function of older age and a higher level of education. Finally, patients with higher education also self-reported greater impulsivity in planning. Conclusion: Our preliminary findings suggest that adult ADHD is not a lifelong stable disorder, but it may change over time. Moreover, attention-executive deficits may be influenced and partially counterbalanced by experience (i.e., advancing age) and a higher level of education. This could underlie the development of specific psycho-behavioral and cognitive compensatory strategies. The use of self-administered questionnaires is therefore recommended to highlight attentional and executive difficulties that may not result in neuropsychological tests.

Social Cognition in Adult ADHD: A Systematic Review.

The aim of this systematic review was to collect and align the research on social cognition impairments in adults with Attention-deficit/hyperactivity disorder (ADHD). In particular, we selected and analyzed papers on emotion recognition and processing, Theory of Mind (TOM), empathy, and other facets of social cognition as decision making. We identified 16 papers published between 2012 and 2022 which meet inclusion criteria. Papers search, selection, and extraction followed the PRISMA guidelines. In order to summarize data from papers, we used a narrative synthesis approach. Results show different evidence of impairment in social cognition domains in adults with ADHD. Our systematic review suggests the importance of promoting more research on this topic because it is essential to keep in mind that social cognition plays a central role in socialization and social relationships.

Theory of mind in patients with mild cognitive impairment: A systematic review.

The focus of this systematic review was to collect and align studies which analyze the functionality of theory of mind (TOM) in patients with mild cognitive impairments (MCI). Specifically, we identified 20 papers published between 2012 and 2022 which met inclusion criteria. Papers search, selection, and extraction followed the PRISMA guidelines. In order to summarize data from the papers, we used a narrative synthesis approach. Results in 18 of these 20 papers show that theory of mind (TOM) is impaired in all types of MCI patients-regardless of different etiology and diagnostic criteria. Only 2 out of 20 reported no significant differences in TOM performance between MCI patients and healthy control subjects. The review additionally aimed to bundle the variety of the type of tasks used by the author to assess multiple domains of TOM. This heterogeneity does not allow us to make a comprehensive comparison between the results, so we suggest the need to align the results using the same type of tests and TOM assessment. In the end, our work highlights the 2 neuropsychological studies which confirm more of our results; due to the objective approach adopted to investigate this topic, we suggest exploring this point of view more in future research.

Emotion recognition and processing in patients with mild cognitive impairment: A systematic review.

The purpose of this study was to investigate emotion recognition and processing in patients with mild cognitive impairment (MCI) in order to update the state of current literature on this important but undervalued topic. We identified 15 papers published between 2012 and 2022 that meet the inclusion criteria. Paper search, selection, and extraction followed the PRISMA guidelines. We used a narrative synthesis approach in order to report a summary of the main findings taken from all papers. The results collected are still ambiguous: some studies did not find any differences between MCI and healthy controls (HC) groups in emotion recognition and processing, and other results reported emotion-specific deficits in emotion recognition regarding MCI patients (both regarding negative and neutral emotions). It is essential to underline that these findings could not be generalized to the whole MCI population due to the heterogeneous use of measures and composition of the sample. This does not allow us to make a comprehensive comparison between the results. Our suggestion for future research is to align the results using the same type of tests and emotion recognition assessment.

Toward individualized medicine in stroke-The TiMeS project: Protocol of longitudinal, multi-modal, multi-domain study in stroke.

Despite recent improvements, complete motor recovery occurs in <15% of stroke patients. To improve the therapeutic outcomes, there is a strong need to tailor treatments to each individual patient. However, there is a lack of knowledge concerning the precise neuronal mechanisms underlying the degree and course of motor recovery and its individual differences, especially in the view of brain network properties despite the fact that it became more and more clear that stroke is a network disorder. The TiMeS project is a longitudinal exploratory study aiming at characterizing stroke phenotypes of a large, representative stroke cohort through an extensive, multi-modal and multi-domain evaluation. The ultimate goal of the study is to identify prognostic biomarkers allowing to predict the individual degree and course of motor recovery and its underlying neuronal mechanisms paving the way for novel interventions and treatment stratification for the individual patients. A total of up to 100 patients will be assessed at 4 timepoints over the first year after the stroke: during the first (T1) and third (T2) week, then three (T3) and twelve (T4) months after stroke onset. To assess underlying mechanisms of recovery with a focus on network analyses and brain connectivity, we will apply synergistic state-of-the-art systems neuroscience methods including functional, diffusion, and structural magnetic resonance imaging (MRI), and electrophysiological evaluation based on transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG) and electromyography (EMG). In addition, an extensive, multi-domain neuropsychological evaluation will be performed at each timepoint, covering all sensorimotor and cognitive domains. This project will significantly add to the understanding of underlying mechanisms of motor recovery with a strong focus on the interactions between the motor and other cognitive domains and multimodal network analyses. The population-based, multi-dimensional dataset will serve as a basis to develop biomarkers to predict outcome and promote personalized stratification toward individually tailored treatment concepts using neuro-technologies, thus paving the way toward personalized precision medicine approaches in stroke rehabilitation.