What Else Can Be Done by the Spinal Cord? A Review on the Effectiveness of Transpinal Direct Current Stimulation (tsDCS) in Stroke Recovery.

Since the spinal cord has traditionally been considered a bundle of long fibers connecting the brain to all parts of the body, the study of its role has long been limited to peripheral sensory and motor control. However, in recent years, new studies have challenged this view pointing to the spinal cord's involvement not only in the acquisition and maintenance of new motor skills but also in the modulation of motor and cognitive functions dependent on cortical motor regions. Indeed, several reports to date, which have combined neurophysiological techniques with transpinal direct current stimulation (tsDCS), have shown that tsDCS is effective in promoting local and cortical neuroplasticity changes in animals and humans through the activation of ascending corticospinal pathways that modulate the sensorimotor cortical networks. The aim of this paper is first to report the most prominent tsDCS studies on neuroplasticity and its influence at the cortical level. Then, a comprehensive review of tsDCS literature on motor improvement in animals and healthy subjects and on motor and cognitive recovery in post-stroke populations is presented. We believe that these findings might have an important impact in the future making tsDCS a potential suitable adjunctive approach for post-stroke recovery.

The Impact of COVID-19 Lockdown Measures and COVID-19 Infection on Cognitive Functions: A Review in Healthy and Neurological Populations.

The COVID-19 pandemic severely affected people's mental health all over the world. This review aims to present a comprehensive overview of the literature related to the effects of COVID-19 lockdown measures and COVID-19 infection on cognitive functioning in both healthy people and people with neurological conditions by considering only standardized tests. We performed a narrative review of the literature via two databases, PUBMED and SCOPUS, from December 2019 to December 2022. In total, 62 out of 1356 articles were selected and organized into three time periods: short-term (1-4 months), medium-term (5-8 months), and long-term (9-12 months), according to the time in which the tests were performed. Regardless of the time period, most studies showed a general worsening in cognitive performance in people with neurological conditions due to COVID-19 lockdown measures and in healthy individuals recovered from COVID-19 infection. Our review is the first to highlight the importance of considering standardized tests as reliable measures to quantify the presence of cognitive deficits due to COVID-19. Indeed, we believe that they provide an objective measure of the cognitive difficulties encountered in the different populations, while allowing clinicians to plan rehabilitation treatments that can be of great help to many patients who still, nowadays, experience post-COVID-19 symptoms.

How Has COVID-19 Impacted Our Language Use?

The COVID-19 pandemic has led to severe consequences for people's mental health. The pandemic has also influenced our language use, shaping our word formation habits. The overuse of new metaphorical meanings has received particular attention from the media. Here, we wanted to investigate whether these metaphors have led to the formation of new semantic associations in memory. A sample of 120 university students was asked to decide whether a target word was or was not related to a prime stimulus. Responses for pandemic pairs in which the target referred to the newly acquired metaphorical meaning of the prime (i.e., "trench"-"hospital") were compared to pre-existing semantically related pairs (i.e., "trench"-"soldier") and neutral pairs (i.e., "trench"-"response"). Results revealed greater accuracy and faster response times for pandemic pairs than for semantic pairs and for semantic pairs compared to neutral ones. These findings suggest that the newly learned pandemic associations have created stronger semantic links in our memory compared to the pre-existing ones. Thus, this work confirms the adaptive nature of human language, and it underlines how the overuse of metaphors evoking dramatic images has been, in part, responsible for many psychological disorders still reported among people nowadays.

Does Executive Function Training Impact on Communication? A Randomized Controlled tDCS Study on Post-Stroke Aphasia.

New approaches in aphasia rehabilitation have recently identified the crucial role of executive functions (EFs) in language recovery, especially for people with severe aphasia (PWSA). Indeed, EFs include high-order cognitive abilities such as planning and problem solving, which enable humans to adapt to novel situations and are essential for everyday functional communication. In a randomized double-blind crossover design, twenty chronic Italian PWSA underwent ten days of transcranial direct current stimulation (tDCS) (20 min, 2 mA) over the right dorsolateral prefrontal cortex (DLPFC). Two conditions were considered, i.e., anodal and sham, while performing four types of cognitive training (alertness, selective attention, visuo-spatial working memory, and planning), all of which were related to executive functions. After anodal tDCS, a greater improvement in selective attention, visuospatial working memory and planning abilities was found compared to the sham condition; this improvement persisted one month after the intervention. Importantly, a significant improvement was also observed in functional communication, as measured through the Communication Activities of Daily Living Scale, in noun and verb naming, in auditory and written language comprehension tasks and in executive function abilities. This evidence emphasizes, for the first time, that tDCS over the right DLPFC combined with executive training enhances functional communication in severe aphasia.

A checklist for assessing the methodological quality of concurrent tES-fMRI studies (ContES checklist): a consensus study and statement.

Low-intensity transcranial electrical stimulation (tES), including alternating or direct current stimulation, applies weak electrical stimulation to modulate the activity of brain circuits. Integration of tES with concurrent functional MRI (fMRI) allows for the mapping of neural activity during neuromodulation, supporting causal studies of both brain function and tES effects. Methodological aspects of tES-fMRI studies underpin the results, and reporting them in appropriate detail is required for reproducibility and interpretability. Despite the growing number of published reports, there are no consensus-based checklists for disclosing methodological details of concurrent tES-fMRI studies. The objective of this work was to develop a consensus-based checklist of reporting standards for concurrent tES-fMRI studies to support methodological rigor, transparency and reproducibility (ContES checklist). A two-phase Delphi consensus process was conducted by a steering committee (SC) of 13 members and 49 expert panelists through the International Network of the tES-fMRI Consortium. The process began with a circulation of a preliminary checklist of essential items and additional recommendations, developed by the SC on the basis of a systematic review of 57 concurrent tES-fMRI studies. Contributors were then invited to suggest revisions or additions to the initial checklist. After the revision phase, contributors rated the importance of the 17 essential items and 42 additional recommendations in the final checklist. The state of methodological transparency within the 57 reviewed concurrent tES-fMRI studies was then assessed by using the checklist. Experts refined the checklist through the revision and rating phases, leading to a checklist with three categories of essential items and additional recommendations: (i) technological factors, (ii) safety and noise tests and (iii) methodological factors. The level of reporting of checklist items varied among the 57 concurrent tES-fMRI papers, ranging from 24% to 76%. On average, 53% of checklist items were reported in a given article. In conclusion, use of the ContES checklist is expected to enhance the methodological reporting quality of future concurrent tES-fMRI studies and increase methodological transparency and reproducibility.

Editorial: New Perspectives and Methodologies in the Diagnosis and Rehabilitation of Aphasia.

Aphasia is a highly disabling acquired language disorder, usually caused by left-lateralized brain damage [...].

A Standardized Prospective Memory Evaluation of the Effects of COVID-19 Confinement on Young Students.

The restriction imposed worldwide for limiting the spread of coronavirus disease 2019 (COVID-19) globally impacted our lives, decreasing people's wellbeing, causing increased anxiety, depression, and stress and affecting cognitive functions, such as memory. Recent studies reported decreased working memory (WM) and prospective memory (PM), which are pivotal for the ability to plan and perform future activities. Although the number of studies documenting the COVID-19 effects has recently blossomed, most of them employed self-reported questionnaires as the assessment method. The main aim of our study was to use standardized tests to evaluate WM and PM in a population of young students. A sample of 150 female psychology students was recruited online for the administration of two self-reported questionnaires that investigated psychological wellbeing (DASS-21), prospective, and retrospective memory (PRMQ). Subjects were also administered two standardized tests for WM (PASAT) and PM (MIST). We found increased anxiety, depression, and stress and decreased PM as measured by self-reports. The perceived memory failures agreed with the results from the standardized tests, which demonstrated a decrease in both WM and PM. Thus, COVID-19 restriction has strongly impacted on students' mental health and memory abilities, leaving an urgent need for psychological and cognitive recovery plans.

Procedural Learning through Action Observation: Preliminary Evidence from Virtual Gardening Activity in Intellectual Disability.

Intellectual disability (ID) compromises intellectual and adaptive functioning. People with an ID show difficulty with procedural skills, with loss of autonomy in daily life. From an embodiment perspective, observation of action promotes motor skill learning. Among promising technologies, virtual reality (VR) offers the possibility of engaging the sensorimotor system, thus, improving cognitive functions and adaptive capacities. Indeed, VR can be used as sensorimotor feedback, which enhances procedural learning. In the present study, fourteen subjects with an ID underwent progressive steps training combined with VR aimed at learning gardening procedures. All participants were trained twice a week for fourteen weeks (total 28 sessions). Participants were first recorded while sowing zucchini, then they were asked to observe a virtual video which showed the correct procedure. Next, they were presented with their previous recordings, and they were asked to pay attention and to comment on the errors made. At the end of the treatment, the results showed that all participants were able to correctly garden in a real environment. Interestingly, action observation facilitated, not only procedural skills, but also specific cognitive abilities. This evidence emphasizes, for the first time, that action observation combined with VR improves procedural learning in ID.

DUAL-tDCS Treatment over the Temporo-Parietal Cortex Enhances Writing Skills: First Evidence from Chronic Post-Stroke Aphasia.

The learning of writing skills involves the re-engagement of previously established independent procedures. Indeed, the writing deficit an adult may acquire after left hemispheric brain injury is caused by either an impairment to the lexical route, which processes words as a whole, to the sublexical procedure based on phoneme-to-grapheme conversion rules, or to both procedures. To date, several approaches have been proposed for writing disorders, among which, interventions aimed at restoring the sub-lexical procedure were successful in cases of severe agraphia. In a randomized double-blind crossover design, fourteen chronic Italian post-stroke aphasics underwent dual transcranial direct current stimulation (tDCS) (20 min, 2 mA) with anodal and cathodal current simultaneously placed over the left and right temporo-parietal cortex, respectively. Two different conditions were considered: (1) real, and (2) sham, while performing a writing task. Each experimental condition was performed for ten workdays over two weeks. After real stimulation, a greater amelioration in writing with respect to the sham was found. Relevantly, these effects generalized to different language tasks not directly treated. This evidence suggests, for the first time, that dual tDCS associated with training is efficacious for severe agraphia. Our results confirm the critical role of the temporo-parietal cortex in writing skills.

Adjunctive Approaches to Aphasia Rehabilitation: A Review on Efficacy and Safety.

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, unconventional rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the principal approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proven to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review reveals an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders.

BACKGROUND: Transcranial direct current stimulation has shown promising clinical results, leading to increased demand for an evidence-based review on its clinical effects. OBJECTIVE: We convened a team of transcranial direct current stimulation experts to conduct a systematic review of clinical trials with more than 1 session of stimulation testing: pain, Parkinson's disease motor function and cognition, stroke motor function and language, epilepsy, major depressive disorder, obsessive compulsive disorder, Tourette syndrome, schizophrenia, and drug addiction. METHODS: Experts were asked to conduct this systematic review according to the search methodology from PRISMA guidelines. Recommendations on efficacy were categorized into Levels A (definitely effective), B (probably effective), C (possibly effective), or no recommendation. We assessed risk of bias for all included studies to confirm whether results were driven by potentially biased studies. RESULTS: Although most of the clinical trials have been designed as proof-of-concept trials, some of the indications analyzed in this review can be considered as definitely effective (Level A), such as depression, and probably effective (Level B), such as neuropathic pain, fibromyalgia, migraine, post-operative patient-controlled analgesia and pain, Parkinson's disease (motor and cognition), stroke (motor), epilepsy, schizophrenia, and alcohol addiction. Assessment of bias showed that most of the studies had low risk of biases, and sensitivity analysis for bias did not change these results. Effect sizes vary from 0.01 to 0.70 and were significant in about 8 conditions, with the largest effect size being in postoperative acute pain and smaller in stroke motor recovery (nonsignificant when combined with robotic therapy). CONCLUSION: All recommendations listed here are based on current published PubMed-indexed data. Despite high levels of evidence in some conditions, it must be underscored that effect sizes and duration of effects are often limited; thus, real clinical impact needs to be further determined with different study designs.

Spinal or cortical direct current stimulation: Which is the best? Evidence from apraxia of speech in post-stroke aphasia.

To date, new advances in technology have already shown the effectiveness of non-invasive brain stimulation and, in particular, of transcranial direct current stimulation (tDCS), in enhancing language recovery in post-stroke aphasia. More recently, it has been suggested that the stimulation over the spinal cord improves the production of words associated to sensorimotor schemata, such as action verbs. Here, for the first time, we present evidence that transpinal direct current stimulation (tsDCS) combined with a language training is efficacious for the recovery from speech apraxia, a motor speech disorder which might co-occur with aphasia. In a randomized-double blind experiment, ten aphasics underwent five days of tsDCS with concomitant treatment for their articulatory deficits in two different conditions: anodal and sham. In all patients, language measures were collected before (T0), at the end (T5) and one week after the end of treatment (F/U). Results showed that only after anodal tsDCS patients exhibited a better accuracy in repeating the treated items. Moreover, these effects persisted at F/U and generalized to other oral language tasks (i.e. picture description, noun and verb naming, word repetition and reading). A further analysis, which compared the tsDCS results with those collected in a matched group of patients who underwent the same language treatment but combined with tDCS, revealed no differences between the two groups. Given the persistency and severity of articulatory deficits in aphasia and the ease of use of tsDCS, we believe that spinal stimulation might result a new innovative approach for language rehabilitation.

Does COVID-19 Impact Less on Post-stroke Aphasia? This Is Not the Case.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has greatly affected people's mental health resulting in severe psychological consequences. One of the leading causes of long-term disability worldwide is aphasia. The language changes experienced by a person with aphasia (PWA) often have a sudden and long-lasting negative impact on social interaction, quality of life, and emotional wellbeing. The main aim of this study was to investigate the impact of COVID-19 on the different psychosocial dimensions which affect PWA. METHODS: This retrospective study included 73 PWA and 81 elderly matched controls. All patients were in the chronic phase. They were all discharged from rehabilitation services, which left them with different degrees of language deficits (i.e., severe vs. mild vs. moderate). All participants were administered the hospital anxiety and depression scale (HADS) through an online survey. PWA also took part in the stroke and aphasia quality of life scale questionnaire (SAQOL-39). RESULTS: Although the comparison between two different time points [one month before (T0) and one month after the lockdown (T1)] led to a significant increase in depression and anxiety symptoms in both groups (PWA vs. control), lower rates of depression and anxiety were found in PWA compared to the healthy group. Significant deterioration was also present in PWA in the communication and psychosocial scales of the SAQOL-39 test, which correlated with the observed changes in the psychological domains. Interestingly, the results were not significantly influenced by the degree of aphasia severity. Similarly, in both groups, none of the demographic variables (gender, age, and educational level) significantly affected the scores in the different subscales. CONCLUSIONS: This evidence which, at first glance, seems to suggest that PWA have been partially spared from the impact of COVID-19, actually masks a dramatic situation that has always characterized this population. Indeed, given that PWA already live in a state of social isolation and emotional instability, these conditions might have, paradoxically, limited the effects of the coronavirus. However, as our results showed a deterioration in the emotional state and communication skills of our patients, possible solutions are discussed in order to prevent further decline of their cognitive abilities.

Can Alzheimer's Disease Be Prevented? First Evidence from Spinal Stimulation Efficacy on Executive Functions.

BACKGROUND: Recently, a growing body of evidence has shown that, from the early stage of impairment, Alzheimer's patients (AD) present difficulties on a variety of tasks mostly relying on executive functions. These strongly impact their daily life activities causing a severe loss of independency and autonomy. OBJECTIVE: To evaluate the efficacy of transpinal direct current stimulation (tsDCS) combined with cognitive trainings for improving attentional and executive function abilities in a group of AD patients. METHODS: In a randomized-double blind design, sixteen AD patients underwent different cognitive trainings combined with tsDCS. During the treatment, each subject received tsDCS (20 min, 2 mA) over the thoracic vertebrae (IX-X vertebrae) in two different conditions: 1) anodal, and 2) sham while performing three computerized tasks: alertness, selective attention, and executive functions. Each experimental condition was run in ten consecutive daily sessions over two weeks. RESULTS: After anodal tsDCS, a greater improvement in executive functions compared to sham condition was found. More importantly, the follow-up testing revealed that these effects lasted over 1 month after the intervention and generalized to the different neuropsychological tests administered before, after the treatment and at one month after the end of the intervention. This generalization was present also in the attentional domain. CONCLUSION: This evidence emphasizes, for the first time, that tsDCS combined with cognitive training results efficacious for AD patients. We hypothesize that enhancing activity into the spinal sensorimotor pathways through stimulation improved cognitive abilities which rely on premotor activity, such as attention and executive functions.

Guidelines for TMS/tES clinical services and research through the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. OBJECTIVE: To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). METHODS: The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain-relevant expertise spanning NIBS technology, clinical services, and basic and clinical research - with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. RESULTS: A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. CONCLUSION: There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.

The potential effects of transcranial direct current stimulation (tDCS) on language functioning: Combining neuromodulation and behavioral intervention in aphasia.

Aphasia is a highly disabling language disorder usually caused by a left stroke brain damage. Even if traditional language therapies have been proved to induce an adequate clinical recovery, a large percentage of patients are left with chronic deficits at 6 months post-stroke. Therefore, new strategies to common speech therapies are urgently needed in order to maximize the recovery from aphasia. The recent application of transcranial direct current stimulation (tDCS) to language rehabilitation has already provided promising results. This brief review gives an overview of the most important results achieved using this approach and discusses how the application of this treatment might potentiate aphasia recovery.

Stairways to the brain: Transcutaneous spinal direct current stimulation (tsDCS) modulates a cerebellar-cortical network enhancing verb recovery.

It has long been assumed that the language function is hierarchically organized into specific cortical areas. Here, for the first time, we present direct evidence that the spinal cord takes part in language processing. In a randomized-double blind design, sixteen aphasics underwent a language treatment combined with transcutaneous spinal direct current stimulation (tsDCS). During the treatment, each subject received tsDCS (20 min, 2 mA) over the thoracic vertebrae (IX-X vertebrae) in two different conditions: (1) anodal, and (2) sham while performing a verb naming task. Each experimental condition was run in five consecutive daily sessions over two weeks. Before and after each condition, all patients underwent a resting state functional magnetic resonance imaging (rs-fMRI). After anodal tsDCS, significant functional connectivity changes were found in a cerebellar-cortical network recruiting regions such as the left cerebellum, the right parietal and premotor cortex known to be also involved in action-related verb processing. Indeed, this increase of connectivity significantly correlated with the greatest amount of improvement found in verb naming. In line with our experimental data, we also found a greater improvement after anodal tsDCS also on untreated items of the language test but only on tasks which required the use of verbs, such as verb naming and picture description. No significant changes were found in noun naming. Thus, this evidence emphasizes, for the first time, that the neural response due to tsDCS combined with language treatment changes during the course of recovery by enhancing activity into cortical regions which influence verb processing.

Conversational Therapy in Aphasia: From Behavioral Intervention to Neuromodulation.

This article describes the conversational therapy approach for the treatment of persons with aphasia (PWAs). Around 1970s, this approach was inspired by a series of pragmatic principles and techniques to aphasia rehabilitation whose main objective was to set up a condition of communicative exchange with the PWA using his/her own available communicative resources. Indeed, although language represents the most powerful behavior that humans use for communicating, within the conversational approach any intentional action (i.e., gestures, body movements, facial expression, drawing) can be used to communicate. For this reason, its application is particularly suitable for severe PWAs whose damage has compromised all the modalities of language (i.e., production, comprehension, reading, and writing). In this perspective, the speech-language pathologist's (SLP's) goal is not necessarily focused on restoring the damaged linguistic functions, still today pursued by the cognitive approach, but to ameliorate the use of language by teaching the PWA compensatory, productive strategies, and strengthening his/her residual communicative abilities. In this review, the fundamental principles of the conversational approach together with its modalities of treatment, which emphasize the importance of an active interaction between the SLP and the PWA, are reported. A brief summary of recent experimental evidence which combines conversational therapy with a noninvasive brain stimulation technique, transcranial direct current stimulation, is also included.

High-Definition Transcranial Direct Current Stimulation Improves Verb Recovery in Aphasic Patients Depending on Current Intensity.

High-definition transcranial direct current stimulation (HD-tDCS) is a variant of tDCS, which produces more focal stimulation, delimiting brain current flow to a defined region compared to conventional tDCS. To date, only one study has been conducted to investigate HD-tDCS effects on language recovery in aphasia. Here, we aimed to assess the effects of cathodal HD-tDCS on verb naming by comparing two current intensities: 1 vs 2 mA. In a double-blinded cross over study, two groups of 10 aphasic individuals were submitted to active cathodal HD-tDCS and sham stimulation over the right homolog of Broca's area, while performing a verb naming task. Indeed, we reasoned that, by applying inhibitory current over the right Broca's area, we would decrease the inhibitory impact from the right hemisphere to the left perilesional cortex, thus boosting language recovery. The groups differed in the intensity of the active stimulation (1 mA or 2 mA). In both groups, each condition was carried out in five consecutive daily sessions with one week of interval between the two experimental conditions. A significant improvement in verb naming was found only after cathodal HD-tDCS at 2 mA, which endured one week after the end of treatment. The improvement was not observed on the group receiving cathodal HD-tDCS at 1 mA. Our findings showed that HD-tDCS applied to the right intact hemisphere are efficacious for language recovery. These results indicate that HD-tDCS represents a promising new technique for language rehabilitation. However, systematic determination of stimulation intensity appears to be crucial for obtaining relevant effects.