Virtual reality-based sensorimotor adaptation shapes subsequent spontaneous and naturalistic stimulus-driven brain activity.

Our everyday life summons numerous novel sensorimotor experiences, to which our brain needs to adapt in order to function properly. However, tracking plasticity of naturalistic behavior and associated brain modulations is challenging. Here, we tackled this question implementing a prism adaptation-like training in virtual reality (VRPA) in combination with functional neuroimaging. Three groups of healthy participants (N = 45) underwent VRPA (with a shift either to the left/right side, or with no shift), and performed functional magnetic resonance imaging (fMRI) sessions before and after training. To capture modulations in free-flowing, task-free brain activity, the fMRI sessions included resting-state and free-viewing of naturalistic videos. We found significant decreases in spontaneous functional connectivity between attentional and default mode (DMN)/fronto-parietal networks, only for the adaptation groups, more pronouncedly in the hemisphere contralateral to the induced shift. In addition, VRPA was found to bias visual responses to naturalistic videos: Following rightward adaptation, we found upregulation of visual response in an area in the parieto-occipital sulcus (POS) only in the right hemisphere. Notably, the extent of POS upregulation correlated with the size of the VRPA-induced after-effect measured in behavioral tests. This study demonstrates that a brief VRPA exposure can change large-scale cortical connectivity and correspondingly bias visual responses to naturalistic sensory inputs.

Everything you ever wanted to know about the Think/No-Think task, but forgot to ask.

The Think/No-Think (TNT) task has just celebrated 20 years since its inception, and its use has been growing as a tool to investigate the mechanisms underlying memory control and its neural underpinnings. Here, we present a theoretical and practical guide for designing, implementing, and running TNT studies. For this purpose, we provide a step-by-step description of the structure of the TNT task, methodological choices that can be made, parameters that can be chosen, instruments available, aspects to be aware of, systematic information about how to run a study and analyze the data. Importantly, we provide a TNT training package (as Supplementary Material), that is, a series of multimedia materials (e.g., tutorial videos, informative HTML pages, MATLAB code to run experiments, questionnaires, scoring sheets, etc.) to complement this method paper and facilitate a deeper understanding of the TNT task, its rationale, and how to set it up in practice. Given the recent discussion about the replication crisis in the behavioral sciences, we hope that this contribution will increase standardization, reliability, and replicability across laboratories.

Immersion Ultrasound Therapy in Combination with Manual Therapy in the Treatment of Ischemic Digital Ulcers in Systemic Sclerosis.

Background and Objectives: Digital ulcers (DUs) are the most common complication in patients with Systemic Sclerosis (SSc). They cause pain with hand dysfunction and negatively impact activities of daily and working life. Our study aims to evaluate the efficacy of a combined treatment of manual therapy and ultrasound therapy in SSc patients with ischemic DU (IDU) compared to manual therapy alone. Materials and Methods: We conducted a before-and-after study (non-randomized study). We enrolled a consecutive series of IDU patients undergoing rehabilitation treatment and divided them into two groups: a treatment group consisting of patients undergoing a combination of manual therapy and US water immersion and a standard care group consisting of patients subjected to manual therapy alone. At the time of the first visit (T0) and at the end of the 4-week rehabilitation period (T1), we evaluated functional capacity, pain intensity, ulcer evolution, and quality of life. Results: In the treatment group, we observed a statistically significant improvement in the functional capacity of the hand (DHI: 28.15 ± 11.0 vs. 19.05 ± 8.83; p < 0.05), pain (NRS: 5.55 ± 1.2 vs. 2.9 ± 1.09; p < 0.05), and PSST score (24.4 ± 4.0 vs. 16.2 ± 2.36; p < 0.05). In the standard care group, we observed a statistically significant improvement only for the functional capacity of the hand (DHI: 28.85 ± 9.72 vs. 22.7 ± 7.68; p < 0.05). Finally, from the comparison between the treatment group and the standard care group, we observed statistically significant improvements in pain (2.9 ± 1.09 vs. 4.5 ± 1.07; p < 0.05) and in the PSST scale (16.2 ± 2.36 vs. 20.4 ± 4.02; p < 0.05). Furthermore, at the end of treatment in the treatment group, 15 ulcers (62.5%) were completely healed, while in the standard care group, only 3 ulcers were completely healed (14.3%). Conclusions: Combined treatment with manual therapy and ultrasound therapy appears to be useful in the management of IDU in patients with scleroderma.

Brain metabolic changes across King's stages in amyotrophic lateral sclerosis: a 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography study.

PURPOSE: To assess the brain metabolic correlates of the different regional extent of ALS, evaluated with the King's staging system, using brain 18F-2-fluoro-2-deoxy-D-glucose-PET (18F-FDG-PET). METHODS: Three hundred ninety ALS cases with King's stages 1, 2, and 3 (n = 390), i.e., involvement of 1, 2, and 3 body regions respectively, underwent brain 18F-FDG-PET at diagnosis. King's stage at PET was derived from ALSFRS-R and was regressed out against whole-brain metabolism in the whole sample. The full factorial design confirmed the hypothesis that differences among groups (King's 1, King's 2, King's 3, and 40 healthy controls (HC)) existed overall. Comparisons among stages and between each group and HC were performed. We included age at PET and sex as covariates. RESULTS: Brain metabolism was inversely correlated with stage in medial frontal gyrus bilaterally, and right precentral and postcentral gyri. The full factorial design resulted in a significant main effect of groups. There was no significant difference between stages 1 and 2. Comparing stage 3 to stage 1+2, a significant relative hypometabolism was highlighted in the former in the left precentral and medial frontal gyri, and in the right medial frontal, postcentral, precentral, and middle frontal gyri. The comparisons between each group and HC showed the extension of frontal metabolic changes from stage 1 to stage 3, with the larger metabolic gap between stages 2 and 3. CONCLUSIONS: Our findings support the hypothesis that in ALS, the propagation of neurodegeneration follows a corticofugal, regional ordered pattern, extending from the motor cortex to posterior and anterior regions.

Efficacy of spoken word comprehension therapy in patients with chronic aphasia: a cross-over randomised controlled trial with structural imaging.

OBJECTIVE: The efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, 'Listen-In', and examined the relation between brain structure and therapy response. METHODS: A cross-over randomised repeated measures trial with five testing time points (12-week intervals), conducted at the university or participants' homes, captured baseline (T1), therapy (T2-T4) and maintenance (T5) effects. Participants with chronic poststroke aphasia and spoken language comprehension impairments completed consecutive Listen-In and standard care blocks (both 12 weeks with order randomised). Repeated measures analyses of variance compared change in spoken language comprehension on two co-primary outcomes over therapy versus standard care. Three structural MRI scans (T2-T4) for each participant (subgroup, n=25) were analysed using cross-sectional and longitudinal voxel-based morphometry. RESULTS: Thirty-five participants completed, on average, 85 hours (IQR=70-100) of Listen-In (therapy first, n=18). The first study-specific co-primary outcome (Auditory Comprehension Test (ACT)) showed large and significant improvements for trained spoken words over therapy versus standard care (11%, Cohen's d=1.12). Gains were largely maintained at 12 and 24 weeks. There were no therapy effects on the second standardised co-primary outcome (Comprehensive Aphasia Test: Spoken Words and Sentences). Change on ACT trained words was associated with volume of pretherapy right hemisphere white matter and post-therapy grey matter tissue density changes in bilateral temporal lobes. CONCLUSIONS: Individuals with chronic aphasia can improve their spoken word comprehension many years after stroke. Results contribute to hemispheric debates implicating the right hemisphere in therapy-driven language recovery. Listen-In will soon be available on GooglePlay. TRIAL REGISTRATION NUMBER: NCT02540889.

Use of autobilevel ventilation in patients with obstructive sleep apnea: An observational study.

Continuous positive airway pressure (CPAP) is the first-choice treatment for obstructive sleep-disordered breathing. Automatic bilevel ventilation can be used to treat obstructive sleep-disordered breathing when CPAP is ineffective, but clinical experience is still limited. To assess the outcome of titration with CPAP and automatic bilevel ventilation, the charts of 356 outpatients (obstructive sleep apnea, n = 242; chronic obstructive pulmonary disease + obstructive sleep apnea overlap, n = 80; obesity hypoventilation syndrome [OHS], n = 34; 103 females) treated for obstructive sleep-disordered breathing from January 2014 to April 2017 were reviewed. Positive airway pressure titration was considered successful in the case of sleep-disordered breathing resolution (apnea-hypopnea index <10/hr) with cumulative time at SaO2  < 90% (CT90%) <10% and/or improved daytime arterial blood gases at the end of titration. CPAP was effective in 268 patients (75.0%). CPAP treatment failure (n = 88) occurred in 13.6% of obstructive sleep apnea, 32.5% of overlap, and 85.3% of OHS patients. Compared with successful CPAP cases, patients undergoing the automatic bilevel ventilation trial showed higher body mass index (39.3 ± 10.5 kg/m2 versus 34.8 ± 6.9 kg/m2 , p < 0.0001), worse mean nocturnal SaO2 (89.2 ± 4.0% versus 91.3 ± 4.0%, p < 0.003) and CT90% (40.6 ± 28.6% versus 24.0 ± 23.3%), but similar age (62.8 ± 11.9 years versus 60.5 ± 12.0 years, p = 0.11), apnea-hypopnea index (39.4 ± 23.2/hr versus 41.0 ± 21.2/hr, p = 0.55) and oxygen desaturation index (37.8 ± 23.5/hr versus 39.2 ± 21.1/hr, p = 0.61) at diagnosis. Automatic bilevel ventilation was successful in 79.5% of CPAP treatment failures (n = 70). Automatic bilevel ventilation failure was independently associated with baseline body mass index >40 kg/m2 (odds ratio 6.16, confidence interval 1.50-25.17, p = 0.011) and CT90% >42% (odds ratio 5.87, confidence interval 1.39-24.83, p = 0.016). During follow-up, automatic bilevel ventilation treatment failed in seven patients (10%), and compliance was similar in CPAP (4.5 ± 2.2 hr) and automatic bilevel ventilation (5.2 ± 2.3 hr, p = 0.09) groups. Automatic bilevel ventilation was useful to treat sleep-disordered breathing, but failed in patients with severe OHS.

Less is more: neural mechanisms underlying anomia treatment in chronic aphasic patients.

See Thompson and Woollams (doi:10.1093/brain/awx264) for a scientific commentary on this article. Previous research with aphasic patients has shown that picture naming can be facilitated by concurrent phonemic cueing [e.g. initial phoneme(s) of the word that the patient is trying to retrieve], both as an immediate word retrieval technique, and when practiced repeatedly over time as a long-term anomia treatment. Here, to investigate the neural mechanisms supporting word retrieval, we adopted­for the first time­a functional magnetic resonance imaging task using the same naming procedure as it occurs during the anomia treatment process. Before and directly after a 6-week anomia treatment programme, 18 chronic aphasic stroke patients completed our functional magnetic resonance imaging protocol­a picture naming task aided by three different types of phonemic cues (whole words, initial phonemes, final phonemes) and a noise-control condition. Patients completed a naming task based on the training materials, and a more general comprehensive battery of language tests both before and after the anomia treatment, to determine the effectiveness and specificity of the therapy. Our results demonstrate that the anomia treatment was effective and specific to speech production, significantly improving both patients' naming accuracy and reaction time immediately post-treatment (unstandardized effect size: 29% and 17%, respectively; Cohen's d: 3.45 and 1.83). Longer term gains in naming were maintained 3 months later. Functional imaging results showed that both immediate and long-term facilitation of naming involved a largely overlapping bilateral frontal network including the right anterior insula, inferior frontal and dorsal anterior cingulate cortices, and the left premotor cortex. These areas were associated with a neural priming effect (i.e. reduced blood oxygen level-dependent signal) during both immediate (phonemically-cued versus control-cue conditions), and long-term facilitation of naming (i.e. treated versus untreated items). Of note is that different brain regions were sensitive to different phonemic cue types. Processing of whole word cues was associated with increased activity in the right angular gyrus; whereas partial word cues (initial and final phonemes) recruited the left supplementary motor area, and right anterior insula, inferior frontal cortex, and basal ganglia. The recruitment of multiple and bilateral areas may help explain why phonemic cueing is such a successful behavioural facilitation tool for anomia treatment. Our results have important implications for optimizing current anomia treatment approaches, developing new treatments, and improving speech outcome for aphasic patients.

Spatial orienting in complex audiovisual environments.

Previous studies on crossmodal spatial orienting typically used simple and stereotyped stimuli in the absence of any meaningful context. This study combined computational models, behavioural measures and functional magnetic resonance imaging to investigate audiovisual spatial interactions in naturalistic settings. We created short videos portraying everyday life situations that included a lateralised visual event and a co-occurring sound, either on the same or on the opposite side of space. Subjects viewed the videos with or without eye-movements allowed (overt or covert orienting). For each video, visual and auditory saliency maps were used to index the strength of stimulus-driven signals, and eye-movements were used as a measure of the efficacy of the audiovisual events for spatial orienting. Results showed that visual salience modulated activity in higher-order visual areas, whereas auditory salience modulated activity in the superior temporal cortex. Auditory salience modulated activity also in the posterior parietal cortex, but only when audiovisual stimuli occurred on the same side of space (multisensory spatial congruence). Orienting efficacy affected activity in the visual cortex, within the same regions modulated by visual salience. These patterns of activation were comparable in overt and covert orienting conditions. Our results demonstrate that, during viewing of complex multisensory stimuli, activity in sensory areas reflects both stimulus-driven signals and their efficacy for spatial orienting; and that the posterior parietal cortex combines spatial information about the visual and the auditory modality.

Effectiveness of cryo plus ultrasound therapy versus diathermy in combination with high-intensity laser therapy for pain relief in footballers with muscle injuries: A prospective study.

BACKGROUND: Muscle injuries are common traumatic events in the clinical practice of the rehabilitation field. There is still a gap in the scientific literature on the effectiveness of physical agent modalities in the management of muscle injuries in athletes. OBJECTIVE: The aim of this study was to assess the effectiveness of cryo plus ultrasound therapy com-pared to diathermy in combination with high-intensity laser therapy (HILT) for pain relief in professional footballers with muscle injuries. METHODS: A case-control study was conducted on 31 professional footballers with a muscle injury of the lower limbs. Of these, 17 patients, assigned to a Group A (AG), were treated with HILT and cryoultrasound therapy; the remaining 14 patients, assigned to a Group B (BG), underwent HILT and diathermy. We assessed the extent of the pain, the size of the muscle injury, frequency of recurrence and number of days to recovery, at the time of recruitment, at the end of the rehabilitation and 3 months after the injury. RESULTS: Group A athletes had a greater benefit on pain (4.65 ± 0.61 vs 3.24 ± 0.63; p< 0.05) and muscle injury recurrence. The return to play in the athletes of group A took place 4.73 days earlier. CONCLUSION: HILT and cryo plus ultrasound therapy, in combination with therapeutic exercise, rep-resent a valid strategy in the treatment of muscle injuries in professional footballers.

Predicting Online Behavioural Responses to Transcranial Direct Current Stimulation in Stroke Patients with Anomia.

Anomia, or difficulty naming common objects, is the most common, acquired impairment of language. Effective therapeutic interventions for anomia typically involve massed practice at high doses. This requires significant investment from patients and therapists. Aphasia researchers have increasingly looked to neurostimulation to accelerate these treatment effects, but the evidence behind this intervention is sparse and inconsistent. Here, we hypothesised that group-level neurostimulation effects might belie a more systematic structure at the individual level. We sought to test the hypothesis by attempting to predict the immediate (online), individual-level behavioural effects of anodal and sham neurostimulation in 36 chronic patients with anomia, performing naming and size judgement tasks. Using clinical, (pre-stimulation) behavioural and MRI data, as well as Partial Least Squares regression, we attempted to predict neurostimulation effects on accuracies and reaction times of both tasks. Model performance was assessed via cross-validation. Predictive performances were compared to that of a null model, which predicted the mean neurostimulation effects for all patients. Models derived from pre-stimulation data consistently outperformed the null model when predicting neurostimulation effects on both tasks' performance. Notably, we could predict behavioural declines just as well as improvements. In conclusion, inter-patient variation in online responses to neurostimulation is, to some extent, systematic and predictable. Since declines in performance were just as predictable as improvements, the behavioural effects of neurostimulation in patients with anomia are unlikely to be driven by placebo effects. However, the online effect of the intervention appears to be as likely to interfere with task performance as to improve it.

Sensitivity and Specificity of Qualitative Visual Field Tests for Screening Visual Hemifield Deficits in Right-Brain-Damaged Stroke Patients.

A timely detection of visual hemifield deficits (VHFDs; hemianopias or quadrantanopias) is critical for both the diagnosis and treatment of stroke patients. The present study determined the sensitivity and specificity of four qualitative visual field tests, including face description, confrontation tests (finger wiggle), and kinetic boundary perimetry, to screen large and dense VHFDs in right-brain-damaged (RBD) stroke patients. Previously, the accuracy of qualitative visual field tests was examined in unselected samples of patients with heterogeneous aetiology, in which stroke patients represented a very small fraction. Building upon existing tests, we introduced some procedural ameliorations (incl. a novel procedure for kinetic boundary perimetry) and provided a scoresheet to facilitate the grading. The qualitative visual field tests' outcome of 67 consecutive RBD stroke patients was compared with the standard automated perimetry (SAP; i.e., reference standard) outcome to calculate sensitivity and specificity, as well as positive and negative predictive values (PPV and NPV), both for each individual test and their combinations. The face description test scored the lowest sensitivity and NPV, while the kinetic boundary perimetry scored the highest. No test returned false positives. Combining the monocular static finger wiggle test (by quadrants) and the kinetic boundary perimetry returned the highest sensitivity and specificity, in line with previous studies, but with higher accuracy (100% sensitivity and specificity). These findings indicate that the combination of these two tests is a valid approach with RBD stroke patients, prompting referral for a formal visual field examination, and representing a quick, easy-to-perform, and inexpensive tool for improving their care and prognosis.

Mapping spoken language and cognitive deficits in post-stroke aphasia.

Aphasia is an acquired disorder caused by damage, most commonly due to stroke, to brain regions involved in speech and language. While language impairment is the defining symptom of aphasia, the co-occurrence of non-language cognitive deficits and their importance in predicting rehabilitation and recovery outcomes is well documented. However, people with aphasia (PWA) are rarely tested on higher-order cognitive functions, making it difficult for studies to associate these functions with a consistent lesion correlate. Broca's area is a particular brain region of interest that has long been implicated in speech and language production. Contrary to classic models of speech and language, cumulative evidence shows that Broca's area and surrounding regions in the left inferior frontal cortex (LIFC) are involved in, but not specific to, speech production. In this study we aimed to explore the brain-behaviour relationships between tests of cognitive skill and language abilities in thirty-six adults with long-term speech production deficits caused by post-stroke aphasia. Our findings suggest that non-linguistic cognitive functions, namely executive functions and verbal working memory, explain more of the behavioural variance in PWA than classical language models imply. Additionally, lesions to the LIFC, including Broca's area, were associated with non-linguistic executive (dys)function, suggesting that lesions to this area are associated with non-language-specific higher-order cognitive deficits in aphasia. Whether executive (dys)function - and its neural correlate in Broca's area - contributes directly to PWA's language production deficits or simply co-occurs with it, adding to communication difficulties, remains unclear. These findings support contemporary models of speech production that place language processing within the context of domain-general perception, action and conceptual knowledge. An understanding of the covariance between language and non-language deficits and their underlying neural correlates will inform better targeted aphasia treatment and outcomes.

Sensitivity and Specificity of the Brentano Illusion Test in the Detection of Visual Hemi-Field Deficits in Patients with Unilateral Spatial Neglect.

Stroke survivors with right-brain damage (RBD) often present with attentional deficits such as left unilateral spatial neglect. Some patients also present with contralesional visual hemi-field deficits. A late detection of visual hemi-field deficits (VHFD) contributes to hampering neurorehabilitation and functional outcome of patients with neglect. The Brentano Illusion Test (BRIT) may be used for an early detection of VHFD during the neuropsychological assessment. In the present study, we determined the sensitivity and specificity of the BRIT for screening VHFD in patients with neglect. Sixty-four consecutive RBD patients were examined. Forty-five presented with neglect. Of these, 23 presented with VHFD (hemianopia or quadrantanopia) as detected by the Humphrey automated static visual field testing (reference standard). Consecutive patients also included 19 participants without neglect, who did not have any VHFD. The sensitivity and specificity of the BRIT for neglect patients were 78.3% (95% CI: 61.4-95.1) and 90.9 (95% CI: 78.9-100.0), respectively. Positive predictive value (PPV) was 89.6% (95% CI: 76.4-100.0); negative predictive value (NPV) 80.7% (95% CI: 65.2-96.2). No false positives in the group without neglect were identified. We conclude that the BRIT is an effective tool for clinical neuropsychologists to screen for possible VHFD in neglect patients during the neuropsychological assessment, allowing the refinement of the clinical picture in the neuropsychological report. An early detection of VHFD also allows referring the patient to standard diagnostics for a formal visual field examination, right from the first neuropsychological assessment.

Left egocentric neglect in early subacute right-stroke patients is related to damage of the superior longitudinal fasciculus.

A typical consequence of stroke in the right hemisphere is unilateral spatial neglect. Distinct forms of neglect have been described, such as space-based (egocentric) and object-based (allocentric) neglect. However, the relationship between these two forms of neglect is still far from being understood, as well as their neural substrates. Here, we further explore this issue by using voxel lesion symptoms mapping (VLSM) analyses on a large sample of early subacute right-stroke patients assessed with the Apples Cancellation Test. This is a sensitive test that simultaneously measures both egocentric and allocentric neglect. Behaviourally, we found no correlation between egocentric and allocentric performance, indicating independent mechanisms supporting the two forms of neglect. This was confirmed by the VLSM analysis that pointed out a link between a damage in the superior longitudinal fasciculus and left egocentric neglect. By contrast, no association was found between brain damage and left allocentric neglect. These results indicate a higher probability to observe egocentric neglect as a consequence of white matter damages in the superior longitudinal fasciculus, while allocentric neglect appears more "globally" related to the whole lesion map. Overall, these findings on early subacute right-stroke patients highlight the role played by white matter integrity in sustaining attention-related operations within an egocentric frame of reference.

Lesion site and therapy time predict responses to a therapy for anomia after stroke: a prognostic model development study.

Stroke is a leading cause of disability, and language impairments (aphasia) after stroke are both common and particularly feared. Most stroke survivors with aphasia exhibit anomia (difficulties with naming common objects), but while many therapeutic interventions for anomia have been proposed, treatment effects are typically much larger in some patients than others. Here, we asked whether that variation might be more systematic, and even predictable, than previously thought. 18 patients, each at least 6 months after left hemisphere stroke, engaged in a computerised treatment for their anomia over a 6-week period. Using only: (a) the patients' initial accuracy when naming (to-be) trained items; (b) the hours of therapy that they devoted to the therapy; and (c) whole-brain lesion location data, derived from structural MRI; we developed Partial Least Squares regression models to predict the patients' improvements on treated items, and tested them in cross-validation. Somewhat surprisingly, the best model included only lesion location data and the hours of therapy undertaken. In cross-validation, this model significantly out-performed the null model, in which the prediction for each patient was simply the mean treatment effect of the group. This model also made promisingly accurate predictions in absolute terms: the correlation between empirical and predicted treatment response was 0.62 (95% CI 0.27, 0.95). Our results indicate that individuals' variation in response to anomia treatment are, at least somewhat, systematic and predictable, from the interaction between where and how much lesion damage they have suffered, and the time they devoted to the therapy.

Transcranial direct current stimulation with functional magnetic resonance imaging: a detailed validation and operational guide.

Introduction: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique used to modulate human brain and behavioural function in both research and clinical interventions. The combination of functional magnetic resonance imaging (fMRI) with tDCS enables researchers to directly test causal contributions of stimulated brain regions, answering questions about the physiology and neural mechanisms underlying behaviour. Despite the promise of the technique, advances have been hampered by technical challenges and methodological variability between studies, confounding comparability/replicability. Methods: Here tDCS-fMRI at 3T was developed for a series of experiments investigating language recovery after stroke. To validate the method, one healthy volunteer completed an fMRI paradigm with three conditions: (i) No-tDCS, (ii) Sham-tDCS, (iii) 2mA Anodal-tDCS. MR data were analysed in SPM12 with region-of-interest (ROI) analyses of the two electrodes and reference sites. Results: Quality assessment indicated no visible signal dropouts or distortions introduced by the tDCS equipment. After modelling scanner drift, motion-related variance, and temporal autocorrelation, we found no field inhomogeneity in functional sensitivity metrics across conditions in grey matter and in the three ROIs. Discussion: Key safety factors and risk mitigation strategies that must be taken into consideration when integrating tDCS into an fMRI environment are outlined. To obtain reliable results, we provide practical solutions to technical challenges and complications of the method. It is hoped that sharing these data and SOP will promote methodological replication in future studies, enhancing the quality of tDCS-fMRI application, and improve the reliability of scientific results in this field. Conclusions: The method and data provided here provide a technically safe, reliable tDCS-fMRI procedure to obtain high quality MR data. The detailed framework of the Standard Operation Procedure SOP ( https://doi.org/10.5281/zenodo.4606564) systematically reports the technical and procedural elements of our tDCS-fMRI approach, which we hope can be adopted and prove useful in future studies.

Intra-cortical connectivity in multiple sclerosis: a neurophysiological approach.

Multiple sclerosis is an autoimmune disease predominantly affecting the white matter of the CNS, causing--among functional sequelae-cortico--cortical partial or total disconnection. Since functional connectivity linking cerebral regions is reliably reflected by synchronization of their neuronal firing, in this study an electrophysiological parameter measured by magnetoencephalography was used to quantify an intra-cortical connectivity (ICC) index focused on the primary somatosensory cortical areas (S1). Twenty-one patients affected by mild (Extended Disability Scale Score, median 1,5) relapsing-remitting (RR) multiple sclerosis in the remitting phase without clinically evident sensory impairment were evaluated. Three dimensional MRI was used to quantify the lesion load, discriminating black hole and non-black hole portions, normalized by individual brain volumes. When matched with a control population, multiple sclerosis patients showed a reduced ICC combined with the complete loss of the finger-dependent functional specialization in S1 cortex of the dominant hemisphere. No association was found between ICC impairment and disease duration, or prolongation of the central sensory conduction time, presence of spinal cord lesions and ongoing disease modifying therapy. The ICC index slightly correlated with the lesion load. A local index of ICC in a circumscribed brain primary area was altered in mildly disabled RR-multiple sclerosis patients, also in absence of any impairment of central sensory conduction. In conclusion, the diffuse damage influencing the multi-nodal network subtending complex cerebral functions also affects intrinsic cortical connectivity. The S1 ICC index is proposed as a highly sensitive and simple-to-test functional measure for the evaluation of intra-cortical synchronization mechanisms in RR-multiple sclerosis.

Principal component analysis in mild and moderate Alzheimer's disease--a novel approach to clinical diagnosis.

Principal component analysis (PCA) provides a method to explore functional brain connectivity. The aim of this study was to identify regional cerebral blood flow (rCBF) distribution differences between Alzheimer's disease (AD) patients and controls (CTR) by means of volume of interest (VOI) analysis and PCA. Thirty-seven CTR, 30 mild AD (mildAD) and 27 moderate AD (modAD) subjects were investigated using single photon emission computed tomography with (99m)Tc-hexamethylpropylene amine oxime. Analysis of covariance (ANCOVA), PCA, and discriminant analysis (DA) were performed on 54 VOIs. VOI analysis identified in both mildAD and modAD subjects a decreased rCBF in six regions. PCA in mildAD subjects identified four principal components (PCs) in which the correlated VOIs showed a decreased level of rCBF, including regions that are typically affected early in the disease. In five PCs, including parietal-temporal-limbic cortex, and hippocampus, a significantly lower rCBF in correlated VOIs was found in modAD subjects. DA significantly discriminated the groups. The percentage of subjects correctly classified was 95, 70, and 81 for CTR, mildAD and modAD groups, respectively. PCA highlighted, in mildAD and modAD, relationships not evident when brain regions are considered as independent of each other, and it was effective in discriminating groups. These findings may allow neurophysiological inferences to be drawn regarding brain functional connectivity in AD that might not be possible with univariate analysis.

Left hemispatial neglect and overt orienting in naturalistic conditions: Role of high-level and stimulus-driven signals.

Deficits of visuospatial orienting in brain-damaged patients affected by hemispatial neglect have been extensively investigated. Nonetheless, spontaneous spatial orienting in naturalistic conditions is still poorly understood. Here, we investigated the role played by top-down and stimulus-driven signals in overt spatial orienting of neglect patients during free-viewing of short videos portraying everyday life situations. In Experiment 1, we assessed orienting when meaningful visual events competed on the left and right side of space, and tested whether sensory salience on the two sides biased orienting. In Experiment 2, we examined whether the spatial alignment of visual and auditory signals modulates orienting. The results of Experiment 1 showed that in neglect patients severe deficits in contralesional orienting were restricted to viewing conditions with bilateral visual events competing for attentional capture. In contrast, orienting towards the contralesional side was largely spared when the videos contained a single event on the left side. In neglect patients the processing of stimulus-driven salience was relatively spared and helped orienting towards the left side when multiple events were present. Experiment 2 showed that sounds spatially aligned with visual events on the left side improved orienting towards the otherwise neglected hemispace. Anatomical scans indicated that neglect patients suffered grey and white matter damages primarily in the ventral frontoparietal cortex. This suggests that the improvement of contralesional orienting associated with visual salience and audiovisual spatial alignment may be due to processing in the relatively intact dorsal frontoparietal areas. Our data show that in naturalistic environments, the presence of multiple meaningful events is a major determinant of spatial orienting deficits in neglect patients, whereas the salience of visual signals and the spatial alignment between auditory and visual signals can counteract spatial orienting deficits. These results open new perspectives to develop novel rehabilitation strategies based on the use of naturalistic stimuli.

Processing of inconsistent emotional information: an fMRI study.

Previous studies investigating the anterior cingulate cortex (ACC) have relied on a number of tasks which involved cognitive control and attentional demands. In this fMRI study, we tested the model that ACC functions as an attentional network in the processing of language. We employed a paradigm that requires the processing of concurrent linguistic information predicting that the cognitive costs imposed by competing trials would engender the activation of ACC. Subjects were confronted with sentences where the semantic content conflicted with the prosodic intonation (CONF condition) randomly interspaced with sentences which conveyed coherent discourse components (NOCONF condition). We observed the activation of the rostral ACC and the middle frontal gyrus when the NOCONF condition was subtracted from the CONF condition. Our findings provide evidence for the involvement of the rostral ACC in the processing of complex competing linguistic stimuli, supporting theories that claim its relevance as a part of the cortical attentional circuit. The processing of emotional prosody involved a bilateral network encompassing the superior and medial temporal cortices. This evidence confirms previous research investigating the neuronal network that supports the processing of emotional information.