White matter substrates of functional connectivity dynamics in the human brain.

The contribution of structural connectivity to functional connectivity dynamics is still far from being elucidated. Herein, we applied track-weighted dynamic functional connectivity (tw-dFC), a model integrating structural, functional, and dynamic connectivity, on high quality diffusion weighted imaging and resting-state fMRI data from two independent repositories. The tw-dFC maps were analyzed using independent component analysis, aiming at identifying spatially independent white matter components which support dynamic changes in functional connectivity. Each component consisted of a spatial map of white matter bundles that show consistent fluctuations in functional connectivity at their endpoints, and a time course representative of such functional activity. These components show high intra-subject, inter-subject, and inter-cohort reproducibility. We provided also converging evidence that functional information about white matter activity derived by this method can capture biologically meaningful features of brain connectivity organization, as well as predict higher-order cognitive performance.

Effects of diffusion signal modeling and segmentation approaches on subthalamic nucleus parcellation.

The subthalamic nucleus (STN) is commonly used as a surgical target for deep brain stimulation in movement disorders such as Parkinson's Disease. Tractography-derived connectivity-based parcellation (CBP) has been recently proposed as a suitable tool for non-invasive in vivo identification and pre-operative targeting of specific functional territories within the human STN. However, a well-established, accurate and reproducible protocol for STN parcellation is still lacking. The present work aims at testing the effects of different tractography-based approaches for the reconstruction of STN functional territories. We reconstructed functional territories of the STN on the high-quality dataset of 100 unrelated healthy subjects and on the test-retest dataset of the Human Connectome Project (HCP) repository. Connectivity-based parcellation was performed with a hypothesis-driven approach according to cortico-subthalamic connectivity, after dividing cortical areas into three groups: associative, limbic and sensorimotor. Four parcellation pipelines were compared, combining different signal modeling techniques (single-fiber vs multi-fiber) and different parcellation approaches (winner takes all parcellation vs fiber density thresholding). We tested these procedures on STN regions of interest obtained from three different, commonly employed, subcortical atlases. We evaluated the pipelines both in terms of between-subject similarity, assessed on the cohort of 100 unrelated healthy subjects, and of within-subject similarity, using a second cohort of 44 subjects with available test-retest data. We found that each parcellation provides converging results in terms of location of the identified parcels, but with significative variations in size and shape. All pipelines obtained very high within-subject similarity, with tensor-based approaches outperforming multi-fiber pipelines. On the other hand, higher between-subject similarity was found with multi-fiber signal modeling techniques combined with fiber density thresholding. We suggest that a fine-tuning of tractography-based parcellation may lead to higher reproducibility and aid the development of an optimized surgical targeting protocol.

In Vivo Super-Resolution Track-Density Imaging for Thalamic Nuclei Identification.

The development of novel techniques for the in vivo, non-invasive visualization and identification of thalamic nuclei has represented a major challenge for human neuroimaging research in the last decades. Thalamic nuclei have important implications in various key aspects of brain physiology and many of them show selective alterations in various neurologic and psychiatric disorders. In addition, both surgical stimulation and ablation of specific thalamic nuclei have been proven to be useful for the treatment of different neuropsychiatric diseases. The present work aimed at describing a novel protocol for histologically guided delineation of thalamic nuclei based on short-tracks track-density imaging (stTDI), which is an advanced imaging technique exploiting high angular resolution diffusion tractography to obtain super-resolved white matter maps. We demonstrated that this approach can identify up to 13 distinct thalamic nuclei bilaterally with very high inter-subject (ICC: 0.996, 95% CI: 0.993-0.998) and inter-rater (ICC:0.981; 95% CI:0.963-0.989) reliability, and that both subject-based and group-level thalamic parcellation show a fair share of similarity to a recent standard-space histological thalamic atlas. Finally, we showed that stTDI-derived thalamic maps can be successfully employed to study structural and functional connectivity of the thalamus and may have potential implications both for basic and translational research, as well as for presurgical planning purposes.

Ventral intermediate nucleus structural connectivity-derived segmentation: anatomical reliability and variability.

The Ventral intermediate nucleus (Vim) of thalamus is the most targeted structure for the treatment of drug-refractory tremors. Since methodological differences across existing studies are remarkable and no gold-standard pipeline is available, in this study, we tested different parcellation pipelines for tractography-derived putative Vim identification. Thalamic parcellation was performed on a high quality, multi-shell dataset and a downsampled, clinical-like dataset using two different diffusion signal modeling techniques and two different voxel classification criteria, thus implementing a total of four parcellation pipelines. The most reliable pipeline in terms of inter-subject variability has been picked and parcels putatively corresponding to motor thalamic nuclei have been selected by calculating similarity with a histology-based mask of Vim. Then, spatial relations with optimal stimulation points for the treatment of essential tremor have been quantified. Finally, effect of data quality and parcellation pipelines on a volumetric index of connectivity clusters has been assessed. We found that the pipeline characterized by higher-order signal modeling and threshold-based voxel classification criteria was the most reliable in terms of inter-subject variability regardless data quality. The maps putatively corresponding to Vim were those derived by precentral and dentate nucleus-thalamic connectivity. However, tractography-derived functional targets showed remarkable differences in shape and sizes when compared to a ground truth model based on histochemical staining on seriate sections of human brain. Thalamic voxels connected to contralateral dentate nucleus resulted to be the closest to literature-derived stimulation points for essential tremor but at the same time showing the most remarkable inter-subject variability. Finally, the volume of connectivity parcels resulted to be significantly influenced by data quality and parcellation pipelines. Hence, caution is warranted when performing thalamic connectivity-based segmentation for stereotactic targeting.

New insights into cortico-basal-cerebellar connectome: clinical and physiological considerations.

The current model of the basal ganglia system based on the 'direct', 'indirect' and 'hyperdirect' pathways provides striking predictions about basal ganglia function that have been used to develop deep brain stimulation approaches for Parkinson's disease and dystonia. The aim of this review is to challenge this scheme in light of new tract tracing information that has recently become available from the human brain using MRI-based tractography, thus providing a novel perspective on the basal ganglia system. We also explore the implications of additional direct pathways running from cortex to basal ganglia and between basal ganglia and cerebellum in the pathophysiology of movement disorders.

Spatially coherent and topographically organized pathways of the human globus pallidus.

Internal and external segments of globus pallidus (GP) exert different functions in basal ganglia circuitry, despite their main connectional systems share the same topographical organization, delineating limbic, associative, and sensorimotor territories. The identification of internal GP sensorimotor territory has therapeutic implications in functional neurosurgery settings. This study is aimed at assessing the spatial coherence of striatopallidal, subthalamopallidal, and pallidothalamic pathways by using tractography-derived connectivity-based parcellation (CBP) on high quality diffusion MRI data of 100 unrelated healthy subjects from the Human Connectome Project. A two-stage hypothesis-driven CBP approach has been carried out on the internal and external GP. Dice coefficient between functionally homologous pairs of pallidal maps has been computed. In addition, reproducibility of parcellation according to different pathways of interest has been investigated, as well as spatial relations between connectivity maps and existing optimal stimulation points for dystonic patients. The spatial organization of connectivity clusters revealed anterior limbic, intermediate associative and posterior sensorimotor maps within both internal and external GP. Dice coefficients showed high degree of coherence between functionally similar maps derived from the different bundles of interest. Sensorimotor maps derived from the subthalamopallidal pathway resulted to be the nearest to known optimal pallidal stimulation sites for dystonic patients. Our findings suggest that functionally homologous afferent and efferent connections may share similar spatial territory within the GP and that subcortical pallidal connectional systems may have distinct implications in the treatment of movement disorders.

Improving motor performance in Parkinson's disease: a preliminary study on the promising use of the computer assisted virtual reality environment (CAREN).

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by various motor symptoms including balance and gait impairment. Several studies have shown that physiotherapy, cueing techniques, treadmill training, and cognitive movement strategies are useful in improving balance and gait in patients with PD. Devices employing virtual reality (VR) have been shown to be promising in neurorehabilitation as they can provide the patients with multisensory stimulation creating a realistic environment and improve the motivation and the adhesion of patients to the rehabilitation program. This preliminary study is aimed at testing the efficacy and feasibility of gait training based on the computer-assisted virtual reality environment (CAREN) in a sample of PD. METHODS: In this preliminary study, 22 outpatients affected by PD who attended the Behavioral and Robotic Neurorehab Laboratory of the IRCCS Neurolesi between August 2017 and October 2018 were enrolled. All PD patients underwent 20 conventional physiotherapy sessions followed by 3-month of rest. Then, the patients were provided with 20 sessions of CAREN training. Gait and balance performances were rated before, after each training protocol, and 3 months later. Gait analysis was also performed before and after CAREN training. RESULTS: All patients completed both of the rehabilitation trainings without any adverse event. All considered scales improved significantly at the end of both rehabilitation treatments. However, patients presented with a greater clinical improvement after the CAREN training, compared with conventional physiotherapy. In particular, patients walked faster and with more stability, with wider, longer steps. CONCLUSIONS: Even though further neurophysiological details are required to identify the patients who may benefit from CAREN training, our findings suggest that this innovative device is an effective and feasible tool to train balance and gait in patients with PD.

Effects of robotic neurorehabilitation through lokomat plus virtual reality on cognitive function in patients with traumatic brain injury: A retrospective case-control study.

Background: Traumatic brain injury (TBI) is a clinical condition characterized by damage due to a mechanical physical event, which has a devastating impact on both the patient and his/her family. The purpose of this study is to evaluate the effects of robotic neurorehabilitation using Lokomat with virtual reality (VR) on attention processes and executive functions in patients with TBI.Materials and Methods: This is a retrospective case-control study. Fifty-six TBI patients have been included in the analysis, using an electronic recovery data system. The enrolled patients were divided into two groups: the experimental group (LPG) underwent rehabilitation training with Lokomat Pro, equipped with a VR screen, whereas the control group (LNG) performed rehabilitation training using Lokomat Nanos, without VR. The two groups matched for age, sex, education, brain lesions, interval from TBI. The rehabilitation protocol consisted of a total of 40 training sessions.Results: LPG and LNG had a significant improvement in mood and in the perception of physical well-being. However, only the LPG had a significant improvement in global cognitive, executive and attention functions. Furthermore, LPG presented a significant enhancement of the quality of life, with regard to the perception of the mental and physical state.Conclusion: Our study supports the idea that Lokomat is a useful tool in the rehabilitation of patients with TBI; in particular, the integration of the VR device can implement the cognitive and behavioral functions of TBI patients, enhancing also their physical and mental well-being.

Anatomical Characterization of the Human Structural Connectivity between the Pedunculopontine Nucleus and Globus Pallidus via Multi-Shell Multi-Tissue Tractography.

Background and objectives: The internal (GPi) and external segments (GPe) of the globus pallidus represent key nodes in the basal ganglia system. Connections to and from pallidal segments are topographically organized, delineating limbic, associative and sensorimotor territories. The topography of pallidal afferent and efferent connections with brainstem structures has been poorly investigated. In this study we sought to characterize in-vivo connections between the globus pallidus and the pedunculopontine nucleus (PPN) via diffusion tractography. Materials and Methods: We employed structural and diffusion data of 100 subjects from the Human Connectome Project repository in order to reconstruct the connections between the PPN and the globus pallidus, employing higher order tractography techniques. We assessed streamline count of the reconstructed bundles and investigated spatial relations between pallidal voxels connected to the PPN and pallidal limbic, associative and sensorimotor functional territories. Results: We successfully reconstructed pallidotegmental tracts for the GPi and GPe in all subjects. The number of streamlines connecting the PPN with the GPi was greater than the number of those joining it with the GPe. PPN maps within pallidal segments exhibited a distinctive spatial organization, being localized in the ventromedial portion of the GPi and in the ventral-anterior portion in the GPe. Regarding their spatial relations with tractography-derived maps of pallidal functional territories, the highest value of percentage overlap was noticed between PPN maps and the associative territory. Conclusions: We successfully reconstructed the anatomical course of the pallidotegmental pathways and comprehensively characterized their topographical arrangement within both pallidal segments. PPM maps were localized in the ventromedial aspect of the GPi, while they occupied the anterior pole and the most ventral portion of the GPe. A better understanding of the spatial and topographical arrangement of the pallidotegmental pathways may have pathophysiological and therapeutic implications in movement disorders.

Structural Connectivity-Based Parcellation of the Dopaminergic Midbrain in Healthy Subjects and Schizophrenic Patients.

Background and objectives: Functional deregulation of dopaminergic midbrain regions is a core feature of schizophrenia pathophysiology. Anatomical research on primates suggests that these regions may be subdivided into distinct, topographically organized functional territories according to their connectivity to the striatum. The aim of the present work was the reconstruction of dopaminergic midbrain subregions in healthy subjects and schizophrenic patients and the evaluation of their structural connectivity profiles. Materials and Methods: A hypothesis-driven connectivity-based parcellation derived from diffusion tractography was applied on 24 healthy subjects and 30 schizophrenic patients to identify distinct territories within the human dopaminergic midbrain in vivo and non-invasively. Results: We identified a tripartite subdivision of dopaminergic midbrain, including limbic, prefrontal and sensorimotor territories. No significant differences in structural features or connectivity were found between subjects and patients. Conclusions: The parcellation scheme proposed herein may help to achieve detailed characterization of structural and functional anomalies of the dopaminergic midbrain in schizophrenic patients.

Structural connectivity-based topography of the human globus pallidus: Implications for therapeutic targeting in movement disorders.

BACKGROUND: Understanding the topographical organization of the cortico-basal ganglia circuitry is of pivotal importance because of the spreading of techniques such as DBS and, more recently, MR-guided focused ultrasound for the treatment of movement disorders. A growing body of evidence has described both direct cortico- and dento-pallidal connections, although the topographical organization in vivo of these pathways in the human brain has never been reported. OBJECTIVE: To investigate the topographical organization of cortico- and dento-pallidal pathways by means of diffusion MRI tractography and connectivity based parcellation. METHODS: High-quality data from 100 healthy subjects from the Human Connectome Project repository were utilized. Constrained spherical deconvolution-based tractography was used to reconstruct structural cortico- and dento-pallidal connectivity. Connectivity-based parcellation was performed with a hypothesis-driven approach at three different levels: functional regions (limbic, associative, sensorimotor, and other), lobes, and gyral subareas. RESULTS: External globus pallidus segregated into a ventral associative cluster, a dorsal sensorimotor cluster, and a caudal "other" cluster on the base of its cortical connectivity. Dento-pallidal connections clustered only in the internal globus pallidus, where also associative and sensorimotor clusters were identified. Lobar parcellation revealed the presence in the external globus pallidus of dissociable clusters for each cortical lobe (frontal, parietal, temporal, and occipital), whereas in internal globus pallidus only frontal and parietal clusters were found out. CONCLUSION: We mapped the topographical organization of both internal and external globus pallidus according to cortical and cerebellar connections. These anatomical data could be useful in DBS, radiosurgery and MR-guided focused ultrasound targeting for treating motor and nonmotor symptoms in movement disorders. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Paving the way for a better understanding of the pathophysiology of gait impairment in myotonic dystrophy: a pilot study focusing on muscle networks.

BACKGROUND: A proper rehabilitation program targeting gait is mandatory to maintain the quality of life of patients with Myotonic dystrophy type 1 (DM1). Assuming that gait and balance impairment simply depend on the degree of muscle weakness is potentially misleading. In fact, the involvement of the Central Nervous System (CNS) in DM1 pathophysiology calls into account the deterioration of muscle coordination in gait impairment. Our study aimed at demonstrating the presence and role of muscle connectivity deterioration in patients with DM1 by a CNS perspective by investigating signal synergies using a time-frequency spectral coherence and multivariate analyses on lower limb muscles while walking upright. Further, we sought at determining whether muscle networks were abnormal secondarily to the muscle impairment or primarily to CNS damage (as DM1 is a multi-system disorder also involving the CNS). In other words, muscle network deterioration may depend on a weakening in signal synergies (that express the neural drive to muscles deduced from surface electromyography data). METHODS: Such an innovative approach to estimate muscle networks and signal synergies was carried out in seven patients with DM1 and ten healthy controls (HC). RESULTS: Patients with DM1 showed a commingling of low and high frequencies among muscle at both within- and between-limbs level, a weak direct neural coupling concerning inter-limb coordination, a modest network segregation, high integrative network properties, and an impoverishment in the available signal synergies, as compared to HCs. These network abnormalities were independent from muscle weakness and myotonia. CONCLUSIONS: Our results suggest that gait impairment in patients with DM1 depends also on a muscle network deterioration that is secondary to signal synergy deterioration (related to CNS impairment). This suggests that muscle network deterioration may be a primary trait of DM1 rather than a maladaptive mechanism to muscle degeneration. This information may be useful concerning the implementation of proper rehabilitative strategies in patients with DM1. It will be indeed necessary not only addressing muscle weakness but also gait-related muscle connectivity to improve functional ambulation in such patients.

Biased Visuospatial Attention in Cervical Dystonia.

OBJECTIVES: There is increasing evidence of non-motor, sensory symptoms, mainly involving the spatial domain, in cervical dystonia (CD). These manifestations are likely driven by dysfunctional overactivity of the parietal cortex during the execution of a sensory task. Few studies also suggest the possibility that visuospatial attention might be specifically affected in patients with CD. Therefore, we asked whether non-motor manifestations in CD might also comprise impairment of higher level visuospatial processing. METHODS: To this end, we investigated visuospatial attention in 23 CD patients and 12 matched healthy controls (for age, gender, education, and ocular dominance). The patients were identified according to the dystonia pattern type (laterocollis vs. torticollis). Overall, participants were right-handers, and the majority of them was right-eye dominant. Visuospatial attention was assessed using a line bisection task. Participants were asked to bisect horizontal lines, using their right or left hand. RESULTS: Participants bisected more to the left of true center when using their left hand to perform the task than when using their right hand. However, overall, torticollis patients produced a significantly greater leftward deviation than controls. CONCLUSIONS: These data are consistent with preliminary findings suggesting the presence of biased spatial attention in patients with idiopathic cervical dystonia. The presence of an attentional bias in patients with torticollis seem to indicate that alterations of attentional circuits might be implicated in the pathophysiology of this type of CD. (JINS, 2018, 24, 23-32).

Bridging the Gap Towards Awareness Detection in Disorders of Consciousness: An Experimental Study on the Mirror Neuron System.

Advanced functional neuroimaging approaches dealing with motor imagery have disclosed covert cognitive processes in patients with disorders of consciousness (DoC). However, motor impairment and cognitive-motor dissociation can bias such approaches. Fourteen patients with post-traumatic DoC and ten healthy controls (HC) were provided with three motor tasks related to mirror neuron system (MNS) activation (movement observation, movement execution, and passive motor imagery of a movement) while recording electroencephalographic (EEG) metrics [EEG power and Granger Casualty Index (GCI)] to detect residual signs of conscious awareness. The most relevant finding was that all HCs, all patients with Minimally Conscious State and one with Unresponsive Wakefulness Syndrome demonstrated an event-related synchronization in the gamma range over left frontal regions, with high GCI values, in the passive motor imagery condition. These data significantly correlated with the level of behavioral responsiveness measured by the Coma Recovery Scale-Revised. Thus, our findings may indicate that motor tasks related to MNS can activate frontoparietal networks, although leading to different conscious processes. Hence, MNS assessment can be usefully employed to differentiate among patients with DoC.

Functional MRI and laser-evoked potentials evaluation in Charcot-Marie-Tooth syndrome.

Charcot-Marie-Tooth (CMT) disease is a genetically heterogeneous group of disorders. Pain is a less common symptom complained by CMT patients. We described a case of a 39-year-old male patient affect by Charcot-Marie-Tooth (CMT) disease compared to five healthy controls (HC), to assess the sensory and the nociceptive pathways by using LEPs recording associated to fMRI examination, to find an "objective" marker which could be used in the management of CMT patient. The nociceptive system was evaluated by laser-evoked potentials (LEPs). Moreover, fMRI (functional magnetic resonance imaging) examination, by using laser stimuli, was performed. LEPs' examination showed an increase of latency and an amplitude reduction respect to HC. The laser stimulation during fMRI showed a decreased cortical activations if compared to HC. The originality of this paper, although limited to a single case, resides in a detailed evaluation of CMT1 patient performed by using neurophysiologic and neuroimaging methods to investigate extensively the sensory nociceptive pathways.

The role of music therapy in rehabilitation: improving aphasia and beyond.

Music is part of the human nature, and it is also philogenically relevant to language evolution. Language and music are bound together in the enhancement of important social functions, such as communication, cooperation and social cohesion. In the last few years, there has been growing evidence that music and music therapy may improve communication skills (but not only) in different neurological disorders. One of the plausible reasons concerning the rational use of sound and music in neurorehabilitation is the possibility to stimulate brain areas involved in emotional processing and motor control, such as the fronto-parietal network. In this narrative review, we are going to describe the role of music therapy in improving aphasia and other neurological disorders, underlying the reasons why this tool could be effective in rehabilitative settings, especially in individuals affected by stroke.

Visual System Involvement in Patients with Newly Diagnosed Parkinson Disease.

Purpose To assess intracranial visual system changes of newly diagnosed Parkinson disease in drug-naïve patients. Materials and Methods Twenty patients with newly diagnosed Parkinson disease and 20 age-matched control subjects were recruited. Magnetic resonance (MR) imaging (T1-weighted and diffusion-weighted imaging) was performed with a 3-T MR imager. White matter changes were assessed by exploring a white matter diffusion profile by means of diffusion-tensor imaging-based parameters and constrained spherical deconvolution-based connectivity analysis and by means of white matter voxel-based morphometry (VBM). Alterations in occipital gray matter were investigated by means of gray matter VBM. Morphologic analysis of the optic chiasm was based on manual measurement of regions of interest. Statistical testing included analysis of variance, t tests, and permutation tests. Results In the patients with Parkinson disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density (F, -8.28; P < .05), a significant increase in optic radiation mean diffusivity (F, 7.5; P = .014), and a significant reduction in white matter concentration. VBM analysis also showed a significant reduction in visual cortical volumes (P < .05). Moreover, the chiasmatic area and volume were significantly reduced (P < .05). Conclusion The findings show that visual system alterations can be detected in early stages of Parkinson disease and that the entire intracranial visual system can be involved. © RSNA, 2017 Online supplemental material is available for this article.

What Do We Know About the Influence of the Cerebellum on Walking Ability? Promising Findings from Transcranial Alternating Current Stimulation.

Several cerebellar functions related to upper limb motor control have been studied using non-invasive brain stimulation paradigms. We have recently shown that transcranial alternating current stimulation (tACS) may be a promising approach in shaping the plasticity of cerebellum-brain pathways in a safe and effective manner. This study aimed to assess whether cerebellar tACS at different frequencies may tune M1-leg excitability and modify gait control in healthy human subjects. To this end, we tested the effects of different cerebellar tACS frequencies over the right cerebellar hemisphere (at 10, 50, and 300 Hz, besides a sham-tACS) on M1-leg excitability, cerebellum-brain inhibition (CBI), and gait parameters in a sample of 25 healthy volunteers. Fifty and 300 Hz tACS differently modified M1-leg excitability and CBI from both lower limbs, without significant gait perturbations. We hypothesize that tACS aftereffect may depend on a selective entrainment of distinct cerebellar networks related to lower limb motor functions. Therefore, cerebellar tACS might represent a useful tool to modulate walking training in people with cerebellum-related gait impairment, given that tACS may potentially reset abnormal cerebellar circuitries.

Constrained Spherical Deconvolution Tractography Reveals Cerebello-Mammillary Connections in Humans.

According to the classical view, the cerebellum has long been confined to motor control physiology; however, it has now become evident that it exerts several non-somatic features other than the coordination of movement and is engaged also in the regulation of cognition and emotion. In a previous diffusion-weighted imaging-constrained spherical deconvolution (CSD) tractography study, we demonstrated the existence of a direct cerebellum-hippocampal pathway, thus reinforcing the hypothesis of the cerebellar role in non-motor domains. However, our understanding of limbic-cerebellar interconnectivity in humans is rather sparse, primarily due to the intrinsic limitation in the acquisition of in vivo tracing. Here, we provided tractographic evidences of connectivity patterns between the cerebellum and mammillary bodies by using whole-brain CSD tractography in 13 healthy subjects. We found both ipsilateral and contralateral connections between the mammillary bodies, cerebellar cortex, and dentate nucleus, in line with previous studies performed in rodents and primates. These pathways could improve our understanding of cerebellar role in several autonomic functions, visuospatial orientation, and memory and may shed new light on neurodegenerative diseases in which clinically relevant impairments in navigational skills or memory may become manifest at early stages.

Does the radiologically isolated syndrome exist? A dual-task cost pilot study.

Simultaneous performance of motor and cognitive tasks may compete for common brain network resources in aging or patients with some neurological diseases, suggesting the occurrence of a cognitive-motor interference. While this phenomenon has been well described for multiple sclerosis (MS) patients, it never has been tested on asymptomatic subject with magnetic resonance imaging (MRI) findings suggestive of demyelinating disease (i.e., radiologically isolated syndrome: RIS). In this pilot study, 10 RIS subjects and 10 sex/age-matched healthy controls were tested by means of static posturography under eyes opened (single-task trial) and while performing two different cognitive tasks (semantic modified word list generation for first dual-task trial and phonemic semantic modified word list generation for second dual-task trial), to estimate the dual-task cost (DTC) of standing balance. In our sample, under cognitive interference (without any substantial differences between semantic and phonemic modified word list generation), the RIS group showed significance differences in CoP (center of pressure) total sway area, ellipse eccentricity, CoP sway path length, CoP median sway velocity along the AP (anteroposterior) axis and along the ML (mediolateral) axis, reflecting a higher negative DTC respect to healthy subjects (which have simply shown a statistical trend, failing to reach a significance, in some trials). The phenomenon of cognitive-motor interference might be unmasked by a dual-task posturography in RIS subjects, too. We hypothesize that this approach could be useful to early reveal the presence of a demyelinating disease and to reach a MS diagnosis in subjects otherwise classified as RIS.