Re-learning mental representation of walking after a brain lesion. Effects of a cognitive-motor training with a robotic orthosis.

Introduction: Stroke-related deficits often include motor impairments and gait dysfunction, leading to a limitation of social activities and consequently affecting the quality of life of stroke survivors. Neurorehabilitation takes advantage of the contribution of different techniques in order to achieve more benefits for patients. Robotic devices help to improve the outcomes of physical rehabilitation. Moreover, motor imagery seems to play a role in neurological rehabilitation since it leads to the activation of the same brain areas as actual movements. This study investigates the use of a combined physical and cognitive protocol for gait rehabilitation in stroke patients. Methods: Specifically, we tested the efficacy of a 5-week training program using a robotic orthosis (P.I.G.R.O.) in conjunction with motor imagery training. Twelve chronic stroke patients participated in the study. We evaluated balance and gait performance before and after the training. Six of them underwent fMRI examination before and after the training to assess the effects of the protocol on brain plasticity mechanisms in motor and imagery tasks. Results: Our results show that the rehabilitation protocol can effectively improve gait performance and balance and reduce the risk of falls in stroke patients. Furthermore, the fMRI results suggest that rehabilitation is associated with cerebral plastic changes in motor networks. Discussion: The present findings, if confirmed by future research, have the potential to advance the development of new, more effective rehabilitation approaches for stroke patients, improving their quality of life and reducing the burden of stroke-related disability.

Embolic Stroke of Undetermined Source: Role of Implantable Loop Recorder in Secondary Prevention.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most important cause of embolic stroke of undetermined source (ESUS). Implantable loop recorder (ILR) demonstrated the highest sensitivity for detecting it. This register was created to confirm the high prevalence of AF in patients after ESUS and to verify possible benefits on clinical outcomes such as TIA (Transient Ischaemic Attack)/stroke recurrence and death using ILR. METHODS: A total of 278 patients admitted to "Molinette" Hospital in Stroke Unit department between 2011 and 2016, diagnosed with ESUS, underwent ILR implantation if they had at least one risk factor for AF. A total of 165 patients admitted to other departments in the same center for the same pathology, without ILR, represent the control group. We used propensity score to select 132 patients from each group (matching age, sex, CHADS-VASC, and HAS-BLEED baseline characteristics). RESULTS: The detection rate of AF episodes was significantly higher in the ILR group (p < 0.001). No significant protective role of ILR for clinical endpoints was found on univariate analysis, although a trend towards significance has been pointed for the composite outcome of death and ischemic events recurrence (OR 0.52, CI 0.26-1.04, p = 0.06). A protective role of ILR was found for deaths (OR 0.4, CI 0.17-0.94, p 0.03) and for the composite outcome (OR 0.41, CI 0.19-0.87, p 0.02) on multivariate analysis in the best subsets. CONCLUSION: With our statistical models, we identified a significant clinical benefit from ILR monitoring, evidenced by a trend of less death and TIA/stroke recurrence and relevant ILR protection for prediction of TIA/stroke recurrence.

Physical but not virtual presence of others potentiates implicit and explicit learning.

E-learning activities are becoming more and more common. Whilst it is well known that the physical presence of others motivates individuals to engage in perceptual and learning tasks, systematic investigations comparing the effects of physical and virtual co-presence of others on knowledge acquisition are still scarce. Here we investigate the effects of physical and virtual co-presence of others on explicit and implicit learning. In Experiment 1 (discovery sample), retrieval accuracy in a spatial memory task and EEG indexes (mismatch negativity-MMN) of implicit perceptual learning were recorded when participants were alone or in presence of another individual. In Experiment 2 (replicating sample), we added a "virtual" condition, where the same tasks were performed during a video-conference call. In both experiments, MMN was demonstrated to encode for perceptual learning as revealed by the significant correlation with Bayesian Surprise (a consolidated information-theoretic index of Bayesian learning). Furthermore, In Experiments 1 and 2 physical co-presence systematically ameliorated memorization performances and increased MMN indexes related to implicit learning. These positive effects were absent in the virtual condition, thus suggesting that only physical, but not virtual co-presence is effective in potentiating learning dynamics.

Investigation of Brain Activation Patterns Related to the Feminization or Masculinization of Body and Face Images across Genders.

Previous studies demonstrated sex-related differences in several areas of the human brain, including patterns of brain activation in males and females when observing their own bodies and faces (versus other bodies/faces or morphed versions of themselves), but a complex paradigm touching multiple aspects of embodied self-identity is still lacking. We enrolled 24 healthy individuals (12 M, 12 F) in 3 different fMRI experiments: the vision of prototypical body silhouettes, the vision of static images of the face of the participants morphed with prototypical male and female faces, the vision of short videos showing the dynamic transformation of the morphing. We found differential sexual activations in areas linked to self-identity and to the ability to attribute mental states: In Experiment 1, the male group activated more the bilateral thalamus when looking at sex congruent body images, while the female group activated more the middle and inferior temporal gyrus. In Experiment 2, the male group activated more the supplementary motor area when looking at their faces; the female group activated more the dorsomedial prefrontal cortex (dmPFC). In Experiment 3, the female group activated more the dmPFC when observing either the feminization or the masculinization of their face. The defeminization produced more activations in females in the left superior parietal lobule and middle occipital gyrus. The performance of all classifiers built using single ROIs exceeded chance level, reaching an area under the ROC curves > 0.85 in some cases (notably, for Experiment 2 using the V1 ROI). The results of the fMRI tasks showed good agreement with previously published studies, even if our sample size was small. Therefore, our functional MRI protocol showed significantly different patterns of activation in males and females, but further research is needed both to investigate the gender-related differences in activation when observing a morphing of their face/body, and to validate our paradigm using a larger sample.

How does decision-making change during challenging times?

Prospect Theory, proposed and developed by Kahneman and Tversky, demonstrated that people do not make rational decisions based on expected utility, but are instead biased by specific cognitive tendencies leading to neglect, under- or over- consider information, depending on the context of presentation. In this vein, the present paper focuses on whether and how individual decision-making attitudes are prone to change in the presence of globally challenging events. We ran three partial replications of the Kahneman and Tversky (1979) paper, focusing on a set of eight prospects, after a terror attack (Paris, November 2015, 134 subjects) and during the Covid-19 pandemic, both during the first lockdown in Italy (Spring 2020, 176 subjects) and after the first reopening (140 subjects). The results confirm patterns of choice characterizing uncertain times, as shown by previous literature. In particular, we note significant increase of risk aversion, both in the gain and in the loss domains, that consistently emerged in the three replications. Given the nature of our sample, and the heterogeneity between the three periods investigated, we suggest that the phenomenon we present can be explained stress-related effects on decision making rather than by other economic effects, such as the income effect.

A Virtual Navigation Training Promotes the Remapping of Space in Allocentric Coordinates: Evidence From Behavioral and Neuroimaging Data.

Allocentric space representations demonstrated to be crucial to improve visuo-spatial skills, pivotal in every-day life activities and for the development and maintenance of other cognitive abilities, such as memory and reasoning. Here, we present a series of three different experiments: Experiment 1, Discovery sample (23 young male participants); Experiment 2, Neuroimaging and replicating sample (23 young male participants); and Experiment 3 (14 young male participants). In the experiments, we investigated whether virtual navigation stimulates the ability to form spatial allocentric representations. With this aim, we used a novel 3D videogame (MindTheCity!), focused on the navigation of a virtual town. We verified whether playing at MindTheCity! enhanced the performance on spatial representational tasks (pointing to a specific location in space) and on a spatial memory test (asking participant to remember the location of specific objects). Furthermore, to uncover the neural mechanisms underlying the observed effects, we performed a preliminary fMRI investigation before and after the training with MindTheCity!. Results show that our virtual training enhances the ability to form allocentric representations and spatial memory (Experiment 1). Experiments 2 and 3 confirmed the behavioral results of Experiment 1. Furthermore, our preliminary neuroimaging and behavioral results suggest that the training activates brain circuits involved in higher-order mechanisms of information encoding, triggering the activation of broader cognitive processes and reducing the working load on memory circuits (Experiments 2 and 3).

Emotional imagination of negative situations: Functional neuroimaging in anorexia and bulimia.

AIM: The present study aims to extend the knowledge of the neural correlates of emotion processing in first episode subjects affected by anorexia nervosa (AN) or bulimia nervosa (BN). We applied an emotional distress paradigm targeting negative emotions thought to be relevant for interpersonal difficulties and therapeutic resistance mechanisms. METHODS: The current study applied to 44 female participants with newly diagnosed AN or BN and 20 matched controls a neuroimaging paradigm eliciting affective responses. The measurements also included an extensive assessment comprising clinical scales, neuropsychological tests, measures of emotion processing and empathy. RESULTS: AN and BN did not differ from controls in terms of emotional response, emotion matching, self-reported empathy and cognitive performance. However, eating disorder and psychopathological clinical scores, as well as alexithymia levels, were increased in AN and BN. On a neural level, no significant group differences emerged, even when focusing on a region of interest selected a priori: the amygdala. Some interesting findings put in relation the hippocampal activity with the level of Body Dissatisfaction of the participants, the relative importance of the key nodes for the common network in the decoding of different emotions (BN = right amygdala, AN = anterior cingulate area), and the qualitative profile of the deactivations. CONCLUSIONS: Our data do not support the hypothesis that participants with AN or BN display reduced emotional responsiveness. However, peculiar characteristics in emotion processing could be associated to the three different groups. Therefore, relational difficulties in eating disorders, as well as therapeutic resistance, could be not secondary to a simple difficulty in feeling and identifying basic negative emotions in AN and BN participants.

Following the gold trail: Reward influences on spatial exploration in neglect.

Spatial attention is guided by the perceived salience and relevance of objects in the environment, a process considered to depend on a broad parieto-frontal cortical network. Signals arising from the limbic and nigrostriatal pathways conveying affective and motivational cues are also known to modulate visual selection, but the nature of this contribution and its relation to spatial attention remain unclear. We investigated the role of reward information in 15 patients with left hemispatial neglect and 15 control subjects playing multiple rounds of a virtual foraging game. Participants' exploration tracked dynamically adjusted underlying reward distributions, largely unbeknownst to them. Both control and neglect participants showed typical exploration/exploitation balance, dependent on abundance or scarcity of rewards. De-reinforcing previously favored, mostly right, regions of space attenuated left space under-exploration in patients. Multiple regression analysis indicates that such reward-based training may benefit mostly patients early after lesion onset, with mild neglect and small lesions sparing subcortical regions. Our findings support the view that spatial exploration recruits heavily right hemispheric visuospatial attentional mechanisms as well as reward signals processed by basal ganglia and prefrontal cortical circuits, which serve to learn about the motivational relevance of environmental stimuli and help prioritize attention and motor response selection.

A review of the recent advances in neuroimaging of frontotemporal lobar degeneration.

INTRODUCTION: The term "frontotemporal lobar degeneration" (FTLD) includes a large set of neurodegenerative diseases, which are heterogeneous in their genetic, pathologic and clinical aspects. This review will focus on the most recent contribution of neuroimaging tools on the diagnosis, characterization and pathogenesis of FTLD. EVIDENCE ACQUISITION: Scopus, Ovid, PubMed and MEDLINE were searched for articles published from January 2012 up to December 2014. Searches were limited to articles published in English. Frontotemporal lobar degeneration as a key word was always in the search queries in combination with logic AND, and at least one other key word. EVIDENCE SYNTHESIS: We found 91 papers of interest and reviewed their contents, finding in particular 4 major topics: the contribution of neuroimaging on the differential diagnosis; patients' functional characterization; new neuroimaging tools under development and pre-symptomatic genetic forms. CONCLUSIONS: Neuroimaging techniques have shown to be useful supporting tools in diagnosis, even if not always determinant to reach a conclusive decision, and quite important to identify phenocopies. At the moment, there is not a neuroimaging biomarker that could track the progressive course of dementias and the effect of therapies, but it is possible that in the future Diffusion Tensor Imaging and molecular imaging could fill this void. Monitoring the evolution of the pathology in vivo for at least 5 years is essential, and this would only be possible in a large multicenter study; asymptomatic forms would require even longer observation periods.

Cognitive and Neurophysiological Effects of Non-invasive Brain Stimulation in Stroke Patients after Motor Rehabilitation.

The primary aim of this study was to evaluate and compare the effectiveness of two specific Non-Invasive Brain Stimulation (NIBS) paradigms, the repetitive Transcranial Magnetic Stimulation (rTMS), and transcranial Direct Current Stimulation (tDCS), in the upper limb rehabilitation of patients with stroke. Short and long term outcomes (after 3 and 6 months, respectively) were evaluated. We measured, at multiple time points, the manual dexterity using a validated clinical scale (ARAT), electroencephalography auditory event related potentials, and neuropsychological performances in patients with chronic stroke of middle severity. Thirty four patients were enrolled and randomized. The intervention group was treated with a NIBS protocol longer than usual, applying a second cycle of stimulation, after a washout period, using different techniques in the two cycles (rTMS/tDCS). We compared the results with a control group treated with sham stimulation. We split the data analysis into three studies. In this first study we examined if a cumulative effect was clinically visible. In the second study we compared the effects of the two techniques. In the third study we explored if patients with minor cognitive impairment have most benefit from the treatment and if cognitive and motor outcomes were correlated. We found that the impairment in some cognitive domains cannot be considered an exclusion criterion for rehabilitation with NIBS. ERP improved, related to cognitive and attentional processes after stimulation on the motor cortex, but transitorily. This effect could be linked to the restoration of hemispheric balance or by the effects of distant connections. In our study the effects of the two NIBS were comparable, with some advantages using tDCS vs. rTMS in stroke rehabilitation. Finally we found that more than one cycle (2-4 weeks), spaced out by washout periods, should be used, only in responder patients, to obtain clinical relevant results.

Neurologic and cognitive outcomes after aortic arch operation with hypothermic circulatory arrest.

BACKGROUND: Neurologic injury is still a frequent cause of mortality, morbidity, and long-lasting disability in patients undergoing an aortic arch operation with hypothermic circulatory arrest. The aim of this analysis was to evaluate short- and long-term outcomes in neurologic and cognitive functions in this group of high-risk patients. METHODS: A total of 333 patients undergoing an aortic arch operation between February 2004 and June 2010 were retrospectively reviewed. Cerebral protection was obtained with deep hypothermic circulatory arrest in 220 patients (66%) or with moderate hypothermic circulatory arrest in 113 cases (34%). Straight deep hypothermic circulatory arrest was adopted in 35 cases (11%), while the association with antegrade cerebral perfusion was adopted in 271 cases (81%) and with retrograde cerebral perfusion in 27 cases (8%). Seventy-eight patients were enrolled in a case control prospective study (mean follow-up time = 42 months) and underwent neuropsychologic evaluations; data were compared with those of a matched-control group of hypertensive patients without history of cardiac operations. RESULTS: Forty-one out of 333 patients experienced permanent neurologic dysfunction (12%) and 83 experienced temporary neurologic dysfunctions (25%). Acute aortic dissection and deep hypothermic circulatory arrest were significant predictors of mortality and permanent neurologic dysfunction. Acute aortic dissection and hypothermic circulatory arrest duration >30 minutes were significant predictors of temporary neurologic dysfunction, while antegrade cerebral perfusion was protective on mortality. Neuropsychologic evaluations showed no significant differences between the groups. The operative group showed worse verbal and working memory (P = .003), worse semantic fluency (P = .036), higher degree of alexithymia (P = .004), and a lower quality of life (P = .007). CONCLUSION: Although moderate hypothermic circulatory arrest with antegrade cerebral perfusion demonstrated a lower mortality compared with deep hypothermic arrest, neurocognitive testing demonstrated no difference between the groups. Additionally, patients undergoing an aortic arch operation demonstrated long-term cognitive deficits and psychological dysfunction when compared to a matched cohort of nonoperative patients.

Selective Vulnerability of Cortical Border Zone to Microembolic Infarct.

BACKGROUND AND PURPOSE: Endovascular procedures, including atrial fibrillation transcatheter ablation, may cause microembolization of brain arteries. Microemboli often cause small sized and clinically silent cerebral ischemias (SCI). These lesions are clearly visible on early postoperative magnetic resonance diffusion-weighted images. We analyzed SCI distribution in a population of patients submitted to atrial fibrillation transcatheter ablation. METHODS: Seventy-eight of 927 consecutive patients submitted to atrial fibrillation transcatheter ablation were found positive for acute SCI on a postoperative magnetic resonance. SCI were identified and marked, and their coordinates were transformed from native space into the International Consortium for Brain Mapping/Montreal Neurological Institute space. We then computed the voxel-wise probability distribution map of the SCI using the activation likelihood estimation approach. RESULTS: SCI were more commonly found in the cortex. In supratentorial regions, SCI selectively involved cortical border zone between anterior, middle, and posterior cerebral arteries; in infratentorial regions, distal territory of posteroinferior cerebellar artery. Possible explanations include selective embolization, linked to the vascular anatomy of pial arteries supplying those territories, reduced clearance of emboli in a relatively hypoperfused zone, or a combination of both. This particular distribution of lesions has been reported in both animal models and in patients with microemboli of different sources. CONCLUSIONS: A selective vulnerability of cortical border zone to microemboli occurring during atrial fibrillation transcatheter ablation was observed. We hypothesize that such selectivity may apply to microemboli of different sources.

Double-Cone Coil TMS Stimulation of the Medial Cortex Inhibits Central Pain Habituation.

OBJECTIVE: The aim of this study was to investigate whether Transcranial Magnetic Stimulation (TMS) applied over the medial line of the scalp affects the subjective perception of continuous pain induced by means of electric stimulation. In addition, we wanted to identify the point of stimulation where this effect was maximum. METHODS: Superficial electrical stimulation was used to induce continuous pain on the dominant hand. At the beginning of the experiment we reached a pain rating of 5 on an 11-point numeric rating scale (NRS; 0 = no pain and 10 = maximum tolerable pain) for each subject by setting individually the current intensity. The TMS (five pulses at increasing intensities) was applied on 5 equidistant points (one per session) over the medial line of the scalp in 13 healthy volunteers using a double-cone coil to stimulate underlying parts of the brain cortex. In every experimental session the painful stimulation lasted 45 minutes, during which pain and distress intensities NRS were recorded continuously. We calculated the effect of adaptation and the immediate effect of the TMS stimulation for all locations. Additionally, an ALE (Activation Likelihood Estimation) meta-analysis was performed to compare our results with the neuroimaging literature on subjective pain rating. RESULTS: TMS stimulation temporarily decreased the pain ratings, and pain adaptation was suppressed when applying the TMS over the FCz site on the scalp. No effect was found for distress ratings. CONCLUSIONS: The present data suggest that the medial cortex in proximity of the cingulated gyrus has a causal role in adaptation mechanisms and in processing ongoing pain and subjective sensation of pain intensity.

Paroxysmal non-kinesigenic dyskinesia, post-streptococcal syndromes and psychogenic movement disorders: a diagnostic challenge.

We report a case of a 15-year-old boy presenting with sudden attacks of hyperkinetic movements of the limbs, trunk and neck. Clinical features were suggestive of paroxysmal non-kinesigenic dyskinesia, but the elevated antistreptolysin O antibody titre and history of recurrent upper airways infection led us to consider a post-streptococcal syndrome as a possible diagnosis. The patient started therapy with benzathine penicillin, sodium valproate and clonazepam without any significant improvement. A successive psychiatric assessment revealed the presence of a psychogenic movement disorder. Psychodynamic psychotherapy and individual counselling were started with progressive improvement of psychological symptoms and gradual resolution of hyperkinetic episodes, without any recurrence recorded during the follow-up (10 months).

A kinematic analysis of age-related changes in grasping to use and grasping to move common objects.

Grasping is a complex action which requires high-level motor control. Although the impact of aging on grasping has been investigated in some studies, to date little is known as to how the aging process interacts with the purpose of the movement. The aims of the present study were (i) to investigate the effect of aging on grasping movements, and to explore on how this effect is modulated by (ii) the goal of the task, and by (iii) the characteristics of the target such as its location in the visual field, its orientation and its size. Young and elderly adults were asked to grasp to move or to grasp to use objects of different sizes and orientations, presented either in the central or the peripheral visual field. Movement duration did not differ between the two groups. However, elderly participants required a longer approach phase and showed a different grasping strategy, characterized by larger grip aperture and smaller percentage of wrist rotation in comparison to young adults. Elderly adults showed a decrease in accuracy when grasping objects presented in the peripheral, but not in the central visual field. A similar modulation of the kinematic parameters consisting in longer planning and execution phases in the grasp to use in comparison to the grasp to move condition was observed in both groups, suggesting that the effect of aging might be minimized and compensated in more goal-directed tasks.