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Many activities of daily living require quick shifts between symmetric and asymmetric bimanual actions. Bimanual motor control has been mostly studied during continuous repetitive tasks, while little research has been carried out in experimental settings requiring dynamic changes in motor output generated by both hands. Here, we performed functional magnetic resonance imaging (MRI) while healthy volunteers performed a visually guided, bimanual pinch force task. This enabled us to map functional activity and connectivity of premotor and motor areas during bimanual pinch force control in different task contexts, requiring mirror-symmetric or inverse-asymmetric changes in discrete pinch force exerted with the right and left hand. The bilateral dorsal premotor cortex showed increased activity and effective coupling to the ipsilateral supplementary motor area (SMA) in the inverse-asymmetric context compared to the mirror-symmetric context of bimanual pinch force control while the SMA showed increased negative coupling to visual areas. Task-related activity of a cluster in the left caudal SMA also scaled positively with the degree of synchronous initiation of bilateral pinch force adjustments, irrespectively of the task context. The results suggest that the dorsal premotor cortex mediates increasing complexity of bimanual coordination by increasing coupling to the SMA while SMA provides feedback about motor actions to the sensory system.

Background: There is evidence that temporal duration is spatially represented on a horizontal mental timeline (MTL) with relatively short durations represented on the left and long duration on the right side. Most of this evidence comes from the visual domain. Objective: With the present study, we investigated whether temporal duration judgements of visual and auditory stimuli might be affected by spatial biases in time representation. Methods: Participants were asked to estimate the temporal duration of a target with respect to a reference stimulus. Two different exposure times were used for the reference (fast and slow), and three exposure times for the target with respect to the reference (shorter, equal, longer). Two versions of the task were implemented to probe visual and auditory temporal processing. Results: Participants showed enhanced performance when the target had longer duration than the reference independently of the type of task, but they were affected in opposite ways by the reference exposure time, in the two tasks. Best performance was observed for the fast reference in the visual domain and for the slow reference in the auditory one. Discussion: We argue that these findings provide evidence that temporal judgments of visual and auditory stimuli are affected by the duration of the reference stimulus, besides the duration of the target stimulus. Interestingly, they suggest putative leftward and rightward spatial biases in time representation for the visual and auditory domains, respectively, although future studies are necessary to further investigate these initial findings.

Visuospatial attention is asymmetrically distributed with a leftward bias (i.e. pseudoneglect), while evidence for asymmetries in auditory spatial attention is still controversial. In the present study, we investigated putative asymmetries in the distribution of auditory spatial attention and the influence that visual information might have on its deployment. A modified version of the Posner task (i.e. the visuo-audio spatial task [VAST]) was used to investigate spatial processing of auditory targets when endogenous orientation of spatial attention was mediated by visual cues in healthy adults. A line bisection task (LBT) was also administered to assess the presence of a leftward bias in deployment of visuospatial attention. Overall, participants showed rightward and leftward biases in the VAST and the LBT, respectively. In the VAST, sound localization was enhanced by visual cues. Altogether, these findings support the existence of a facilitation effect for auditory targets originating from the right side of space and provide new evidence for crossmodal links in endogenous spatial attention between vision and audition. Keywords: Auditory system, Endogenous spatial attention, Pseudoneglect, Visual system, Visuo-audio task

Transcranial Magnetic Stimulation (TMS) may affect attentional processing when applied to the right posterior parietal cortex (PPC) of healthy participants in line with neuropsychological and neuroimaging evidence on the neural bases of this cognitive function. Specifically, the application of TMS to right PPC induces a rightward attentional bias on line length estimation in healthy participants (i.e., neglect-like bias), mimicking the rightward bias shown by patients with unilateral spatial neglect after damage of the right PPC. With the present study, we investigated whether right PPC might play a crucial role in attentional processing of illusory depth perception, given the evidence that a rightward bias may be observed in patients with neglect during perception of the Necker Cube (NC). To this end, we investigated the effects of low-frequency rTMS applied to the right or left PPC on attentional disambiguation of the NC in two groups of healthy participants. To control for the effectiveness of TMS on visuospatial attention, rTMS effects were also assessed on a frequently used line length estimation (i.e., the Landmark Task or LT). Both groups also received sham stimulation. RTMS of the right or left PPC did not affect NC perception. On the other hand, rTMS of the right PPC (but not left PPC) induces neglect-like bias on the LT, in line with previous studies. These findings confirm that right PPC is involved in deployment of spatial attention on line length estimation. Interestingly, they suggest that this brain region does not critically contribute to deployment of visuospatial attention during attentional disambiguation of the Necker Cube. Future investigations, targeting different areas of fronto-parietal circuits, are necessary to further explore the neuro-functional bases of attentional contribution to illusory depth perception.

Several techniques and protocols of non-invasive transcranial brain stimulation (NIBS), including transcranial magnetic and electrical stimuli, have been developed in the past decades. These techniques can induce long lasting changes in cortical excitability by promoting synaptic plasticity and thus may represent a therapeutic option in neuropsychiatric disorders. On the other hand, despite these techniques have become popular, the fragility and variability of the after effects are the major challenges that non-invasive transcranial brain stimulation currentlyfaces. Several factors may account for such a variability such as biological variations, measurement reproducibility, and the neuronal state of the stimulated area. One possible strategy, to reduce this variability is to monitor the neuronal state in real time using EEG and trigger TMS pulses only at pre-defined state. In addition, another strategy under study is to use the spaced application of multiple NIBS protocols within a session to improve the reliability and extend the duration of NIBS effects. Further studies, although time consuming, are required for improving the so far limited effect sizes of NIBS protocols for treatment of neurological or psychiatric disorders.

In the last decades, a number of Diffusion Weighted Imaging (DWI) based techniques have been developed to study non-invasively human brain tissues, especially white matter (WM). In this context, Constrained Spherical Deconvolution (CSD) is recognized as being able to accurately characterize water molecules displacement, as they emerge from the observation of MR diffusion weighted (MR-DW) images. CSD is suggested to be applied on MR-DW datasets consisting of b-values around 3,000 s/mm2 and at least 45 unique diffusion weighting directions. Below such technical requirements, Diffusion Tensor Imaging (DT) remains the most widely accepted model. Unlike CSD, DTI is unable to resolve complex fiber geometries within the brain, thus affecting related tissues quantification. In addition, thanks to CSD, an index called Apparent Fiber Density (AFD) can be measured to estimate intra-axonal volume fraction within WM. In standard clinical settings, diffusion based acquisitions are well below such technical requirements. Therefore, in this study we wanted to extensively compare CSD and DTI model outcomes on really low demanding MR-DW datasets, i.e., consisting of a single shell (b-value = 1,000 s/mm2) and only 30 unique diffusion encoding directions. To this end, we performed deterministic and probabilistic tractographic reconstruction of two major WM pathways, namely the Corticospinal Tract and the Arcuate Fasciculus. We estimated and analyzed tensor based features as well as, for the first time, AFD interpretability in our data. By performing multivariate statistics and tract-based ROI analysis, we demonstrate that WM quantification is affected by both the diffusion model and threshold applied to noisy tractographic maps. Consistently with existing literature, we showed that CSD outperforms DTI even in our scenario. Most importantly, for the first time we address the problem of accuracy and interpretation of AFD in a low-demanding DW setup, and show that it is still a biological meaningful measure for the analysis of intra-axonal volume even in clinical settings.

The current model of basal ganglia circuits has been introduced almost two decades ago and has settled the basis for our understanding of basal ganglia physiology and movement disorders. Although many questions are yet to be answered, several efforts have been recently made to shed new light on basal ganglia function. The traditional concept of “direct” and “indirect” pathways, obtained from axonal tracing studies in non-human primates and post-mortem fiber dissection in the human brain, still retains a remarkable appeal but is somehow obsolete. Therefore, a better comprehension of human structural basal ganglia connectivity in vivo, in humans, is of uttermost importance given the involvement of these deep brain structures in many motor and non-motor functions as well as in the pathophysiology of several movement disorders. By using diffusion magnetic resonance imaging and tractography, we have recently challenged the traditional model of basal ganglia network by showing the possible existence, in the human brain, of cortico-pallidal, cortico-nigral projections, which could be mono- or polysynaptic, and an extensive subcortical network connecting the cerebellum and basal ganglia. Herein, we aimed at reconstructing the basal ganglia connectome providing a quantitative connectivity analysis of the reconstructed pathways. The present findings reinforce the idea of an intricate, not yet unraveled, network involving the cerebral cortex, basal ganglia, and cerebellum. Our findings may pave the way for a more comprehensive and holistic pathophysiological model of basal ganglia circuits.

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive methods for stimulating cortical neurons that have been increasingly used in the neurology realm and in the neurosciences applied to movement disorders. In addition, these tools have the potential to be delivered as clinically therapeutic approach. Despite several studies support this hypothesis, there are several limitations related to the extreme variability of the stimulation protocols, clinical enrolment and variability of rTMS and tDCS after effects that make clinical interpretation very difficult. Aim of the present study will be to critically discuss the state of art therapeutically applications of rTMS and tDCS in dystonia.