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.

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.

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.

Transcranial Cerebellar Direct Current Stimulation Enhances Verb Generation but Not Verb Naming in Poststroke Aphasia.

Although the role of the cerebellum in motor function is well recognized, its involvement in the lexical domain remains to be further elucidated. Indeed, it has not yet been clarified whether the cerebellum is a language structure per se or whether it contributes to language processing when other cognitive components (e.g., cognitive effort, working memory) are required by the language task. Neuromodulation studies on healthy participants have suggested that cerebellar transcranial direct current stimulation (tDCS) is a valuable tool to modulate cognitive functions. However, so far, only a single case study has investigated whether cerebellar stimulation enhances language recovery in aphasic individuals. In a randomized, crossover, double-blind design, we explored the effect of cerebellar tDCS coupled with language treatment for verb improvement in 12 aphasic individuals. Each participant received cerebellar tDCS (20 min, 2 mA) in four experimental conditions: (1) right cathodal and (2) sham stimulation during a verb generation task and (3) right cathodal and (4) sham stimulation during a verb naming task. Each experimental condition was run in five consecutive daily sessions over 4 weeks. At the end of treatment, a significant improvement was found after cathodal stimulation only in the verb generation task. No significant differences were present for verb naming among the two conditions. We hypothesize that cerebellar tDCS is a viable tool for recovery from aphasia but only when the language task, such as verb generation, also demands the activation of nonlinguistic strategies.

Transcranial direct current stimulation (tDCS) facilitates verb learning by altering effective connectivity in the healthy brain.

Recent studies have shown that the left inferior frontal gyrus (IFG) plays a key role in language learning. Facilitatory stimulation over this region by means of anodal transcranial direct current stimulation (tDCS) can modulate linguistic abilities in healthy individuals and improve language performance in patients with post-stroke aphasia. Neuroimaging studies in healthy participants have suggested that anodal tDCS decreases task-related activity at the stimulated site when applied during different language tasks, and changes resting-state connectivity in a larger network of areas associated with language processing. However, to date, the neural correlates of the potential beneficial effects of tDCS on verb learning remain unclear. The current study investigated how anodal tDCS during verb learning modulates task-related activity and effective connectivity in the healthy language network. To this end, we combined a verb learning paradigm during functional neuroimaging with simultaneous tDCS over the left IFG in healthy human volunteers. We found that, relative to sham stimulation, anodal tDCS significantly decreased task-related activity at the stimulated left IFG and in the right homologue. Effective connectivity analysis showed that anodal tDCS significantly decreased task-related functional coupling between the left IFG and the right insula. Importantly, the individual decrease in connectivity was significantly correlated with the individual behavioural improvement during anodal tDCS. These results demonstrate, for the first time, that the behavioural improvements induced by anodal tDCS might be related to an overall decrease in processing effort both with respect to task-related activity and effective connectivity within a large language network.

Bilateral Transcranial Direct Current Stimulation Language Treatment Enhances Functional Connectivity in the Left Hemisphere: Preliminary Data from Aphasia.

Several studies have already shown that transcranial direct current stimulation (tDCS) is a useful tool for enhancing recovery in aphasia. However, no reports to date have investigated functional connectivity changes on cortical activity because of tDCS language treatment. Here, nine aphasic persons with articulatory disorders underwent an intensive language therapy in two different conditions: bilateral anodic stimulation over the left Broca's area and cathodic contralesional stimulation over the right homologue of Broca's area and a sham condition. The language treatment lasted 3 weeks (Monday to Friday, 15 sessions). In all patients, language measures were collected before (T0) and at the end of treatment (T15). Before and after each treatment condition (real vs. sham), each participant underwent a resting-state fMRI study. Results showed that, after real stimulation, patients exhibited the greatest recovery not only in terms of better accuracy in articulating the treated stimuli but also for untreated items on different tasks of the language test. Moreover, although after the sham condition connectivity changes were confined to the right brain hemisphere, real stimulation yielded to stronger functional connectivity increase in the left hemisphere. In conclusion, our data provide converging evidence from behavioral and functional imaging data that bilateral tDCS determines functional connectivity changes within the lesioned hemisphere, enhancing the language recovery process in stroke patients.

Neurobiological Effects of Transcranial Direct Current Stimulation over the Inferior Frontal Gyrus: A Systematic Review on Cognitive Enhancement in Healthy and Neurological Adults.

The neurobiological effects of transcranial direct current stimulation (tDCS) have still not been unequivocally clarified. Some studies have suggested that the application of tDCS over the inferior frontal gyrus (IFG) enhances different aspects of cognition in healthy and neurological individuals, exerting neural changes over the target area and its neural surroundings. In this systematic review, randomized sham-controlled trials in healthy and neurological adults were selected through a database search to explore whether tDCS over the IFG combined with cognitive training modulates functional connectivity or neural changes. Twenty studies were finally included, among which twelve measured tDCS effects through functional magnetic resonance (fMRI), two through functional near-infrared spectroscopy (fNIRS), and six through electroencephalography (EEG). Due to the high heterogeneity observed across studies, data were qualitatively described and compared to assess reliability. Overall, studies that combined fMRI and tDCS showed widespread changes in functional connectivity at both local and distant brain regions. The findings also suggested that tDCS may also modulate electrophysiological changes underlying the targeted area. However, these outcomes were not always accompanied by corresponding significant behavioral results. This work raises the question concerning the general efficacy of tDCS, the implications of which extend to the steadily increasing tDCS literature.

Bihemispheric stimulation over left and right inferior frontal region enhances recovery from apraxia of speech in chronic aphasia.

Several studies have already shown that transcranial direct current stimulation (tDCS) is a useful tool for enhancing recovery in aphasia. However, all tDCS studies have previously investigated the effects using unihemisperic stimulation. No reports to date have examined the role of bihemispheric tDCS on aphasia recovery. Here, eight aphasic persons with apraxia of speech underwent intensive language therapy in two different conditions: real bihemispheric anodic ipsilesional stimulation over the left Broca's area and cathodic contralesional stimulation over the right homologue of Broca's area, and a sham condition. In both conditions, patients underwent concurrent language therapy for their apraxia of speech. The language treatment lasted 10 days (Monday to Friday, then weekend off, then Monday to Friday). There was a 14-day intersession interval between the real and the sham conditions. In all patients, language measures were collected before (T0), at the end of (T10) and 1 week after the end of (F/U) treatment. Results showed that after simultaneous excitatory stimulation to the left frontal hemisphere and inhibitory stimulation to the right frontal hemisphere regions, patients exhibited a significant recovery not only in terms of better accuracy and speed in articulating the treated stimuli but also in other language tasks (picture description, noun and verb naming, word repetition, word reading) which persisted in the follow-up session. Taken together, these data suggest that bihemispheric anodic ipsilesional and cathodic contralesional stimulation in chronic aphasia patients may affect the treated function, resulting in a positive influence on different language tasks.

When solving 22-7 is much more difficult than 99-12.

We describe the case of a 69-year-old professor of mathematics (GV) who was examined 2 years after left-hemispheric capsular-thalamic haemorrhage. GV showed disproportionate impairment in subtractions requiring borrowing (22 - 7). For large subtraction problems without borrowing (99 - 12) performance was almost flawless. Subtractions with borrowing mostly relied on inadequate attempts to invert subtractions into the corresponding additions (22 - 7 = x as 7 + x = 22). The hypothesis is advanced that difficulty in the inhibitory components of attention tasks (Stroop test, go-no-go task) might be the responsible factor of his calculation impairment. A deficit in subtractions with borrowing might be related to left-hemispheric damage involving thalamo-cortical connections.

How Conversational Therapy influences language recovery in chronic non-fluent aphasia.

The study aimed to determine the efficacy of a Conversational Therapy approach in the treatment of chronic patients with moderately severe non-fluent aphasia. Eight patients completed a six week intensive language training. Every two weeks, each patient received rehabilitation using a different videoclip depicting everyday life. To elicit verbal communication, patients were required to observe each videoclip and to converse about it with the help of an experienced clinician. To measure any significant improvement in speech production all patients were tested before and after treatment. A significant increase in their ability to produce correct informative words (C-Units), verbs, nouns, adjectives, adverbs, as well as closed-class words (pronouns, articles and conjunctions) and well-formed sentences was found after therapy. Such improvement persisted at one week and one month after the end of the treatment. These results suggest that conversational therapy, applied through intensive language training, has a significant efficacy in the recovery of verbal communication in chronic non-fluent aphasic individuals. This approach should be considered for patients with moderately severe non-fluent aphasia, as it enhances not only the ability to use informative language but also its correct use in daily living.

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.

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.

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.

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.

Transcranial direct current stimulation improves word retrieval in healthy and nonfluent aphasic subjects.

A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects performances of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS to enhance associative verbal learning in 10 healthy individuals and to improve word retrieval deficits in three patients with stroke-induced aphasia. In healthy individuals, tDCS (20 min, 1 mA) was applied over Wernicke's area (position CP5 of the International 10-20 EEG System) while they learned 20 new "words" (legal nonwords arbitrarily assigned to 20 different pictures). The healthy subjects participated in a randomized counterbalanced double-blind procedure in which they were subjected to one session of anodic tDCS over left Wernicke's area, one sham session over this location and one session of anodic tDCS stimulating the right occipito-parietal area. Each experimental session was performed during a different week (over three consecutive weeks) with 6 days of intersession interval. Over 2 weeks, three aphasic subjects participated in a randomized double-blind experiment involving intensive language training for their anomic difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation over Wernicke's area while they performed a picture-naming task. By the end of each week, anodic tDCS had significantly improved their accuracy on the picture-naming task. Both normal subjects and aphasic patients also had shorter naming latencies during anodic tDCS than during sham condition. At two follow-ups (1 and 3 weeks after the end of treatment), performed only in two aphasic subjects, response accuracy and reaction times were still significantly better in the anodic than in the sham condition, suggesting a long-term effect on recovery of their anomic disturbances.

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 [...].

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.

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.

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.

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.