Van der Waals Epitaxy of Weyl-Semimetal Td-WTe2.

Epitaxial growth of WTe2 offers significant advantages, including the production of high-quality films, possible long-range in-plane ordering, and precise control over layer thicknesses. However, the mean island size of WTe2 grown by molecular beam epitaxy (MBE) in the literature is only a few tens of nanometers, which is not suitable for the implementation of devices at large lateral scales. Here we report the growth of Td -WTe2 ultrathin films by MBE on monolayer (ML) graphene, reaching a mean flake size of ≃110 nm, which is, on overage, more than three times larger than previous results. WTe2 films thicker than 5 nm have been successfully synthesized and exhibit the expected Td phase atomic structure. We rationalize the epitaxial growth of Td-WTe2 and propose a simple model to estimate the mean flake size as a function of growth parameters that can be applied to other transition metal dichalcogenides (TMDCs). Based on nucleation theory and the Kolmogorov-Johnson-Meh-Avrami (KJMA) equation, our analytical model supports experimental data showing a critical coverage of 0.13 ML above which WTe2 nucleation becomes negligible. The quality of monolayer WTe2 films is demonstrated by electronic band structure analysis using angle-resolved photoemission spectroscopy (ARPES), which is in agreement with first-principles calculations performed on free-standing WTe2 and previous reports. We found electron pockets at the Fermi level, indicating a n-type doping of WTe2 with an electron density of n = 2.0 ± 0.5 × 1012 cm-2 for each electron pocket.

Functional Piezoresistive Polymer Composites Based on CO2 Laser-Irradiated Graphene Oxide-Loaded Polyurethane: Morphology, Structure, Electrical and Piezoresistive Properties.

Nanocomposite materials have recently attracted great attention for their wide range of applications, such as in smart materials, flexible electronics, and deformation sensing applications. Such materials make it possible to combine a polymer with functional fillers. In this study, flexible artificial leathers, exhibiting insulating properties and containing 1.5 or 2wt.% of graphene oxide (GO) in the polyurethane (PU) layer, were electrically activated via CO2 laser irradiation to obtain conductive paths at the surface exposed to the laser beam. As the material retained its insulating properties out of the irradiation areas, the laser scribing method allowed, at least in principle, a printed circuit to be easily and quickly fabricated. Combining a variety of investigation methods, including scanning electron microscopy (SEM), optical profilometry, IR and Raman spectroscopies, and direct current (DC) and alternate current (AC) electrical measurements, the effects of the laser irradiation were investigated, and the so-obtained electrical properties of laser-activated GO/PU regions were elucidated to unveil their potential use in both static and dynamic mechanical conditions. In more detail, it was shown that under appropriate CO2 laser irradiation, GO sheets into the GO/PU layer were locally photoreduced to form reduced-GO (RGO) sheets. It was verified that the RGO sheets were entangled, forming an accumulation path on the surface directly exposed to the laser beam. As the laser process was performed along regular paths, these RGO sheets formed electrically conductive wires, which exhibited piezoresistive properties when exposed to mechanical deformations. It was also verified that such piezoresistive paths showed good reproducibility when subjected to small flexural stresses during cyclic testing conditions. In brief, laser-activated GO/PU artificial leathers may represent a new generation of metal-free materials for electrical transport applications of low-current signals and embedded deformation sensors.

Abnormal cortical asymmetry as a target for neuromodulation in neuropsychiatric disorders: A narrative review and concept proposal.

Recent advances in knowledge relating to the organization of neural circuitry in the human brain have increased understanding of disorders involving brain circuit asymmetry. These asymmetries, which can be measured and identified utilizing EEG and LORETA analysis techniques, may be a factor in mental disorders. New treatments involving non-invasive brain stimulation (NIBS), including trans-cranial magnetic stimulation, direct current stimulation and vagal nerve stimulation, have emerged in recent years. We propose that EEG identification of circuit asymmetry geometries can direct non-invasive brain stimulation more specifically for treatments of mental disorders. We describe as a narrative review new NIBS therapies that have been developed and delivered, and suggest that they are proving effective in certain patient groups. A brief narrative of influence of classical and operant conditioning of neurofeedback on EEG coherence, phase, abnormalities and Loreta's significance is provided. We also discuss the role of Heart rate variability and biofeedback in influencing EEG co-relates. Clinical evidence is at an early stage, but the basic science evidence and early case studies suggest that this may be a promising new modality for treating mental disorders and merits further research.

Theta Burst Stimulation of the Precuneus Modulates Resting State Connectivity in the Left Temporal Pole.

It has been shown that continuous theta burst stimulation (cTBS) over the precuneus acts on specific memory retrieval abilities. In order to study the neural mechanisms beyond these findings, we combined cTBS and resting-state functional magnetic resonance imaging. Our experimental protocol involved stimulation and sham conditions on a group of healthy subjects, and each condition included a baseline and two follow-up acquisitions (5 and 15 min after baseline) after cTBS. We analysed brain functional connectivity by means of graph theoretical measures, with a specific focus on the network modular structure. Our results showed that cTBS of the precuneus selectively affects the left temporal pole, decreasing its functional connectivity in the first follow-up. Moreover, we observed a significant increase in the size of the module of the precuneus in the second follow-up. Such effects were absent in the sham condition. We observed here a modulation of functional connectivity as a result of inhibitory stimulation over the precuneus. Such a modulation first acts indirectly on the temporal area and then extends the connectivity of the precuneus itself by a feed-back mechanism. Our current findings extend our previous behavioural observations and increase our understanding of the mechanisms underlying the stimulation of the precuneus.

Resting-State Functional Connectivity Changes Between Dentate Nucleus and Cortical Social Brain Regions in Autism Spectrum Disorders.

Autism spectrum disorders (ASDs) are known to be characterized by restricted and repetitive behaviors and interests and by impairments in social communication and interactions mainly including "theory of mind" (ToM) processes. The cerebellum has emerged as one of the brain regions affected by ASDs. As the cerebellum is known to influence cerebral cortex activity via cerebello-thalamo-cortical (CTC) circuits, it has been proposed that cerebello-cortical "disconnection" could in part underlie autistic symptoms. We used resting-state (RS) functional magnetic resonance imaging (fMRI) to investigate the potential RS connectivity changes between the cerebellar dentate nucleus (DN) and the CTC circuit targets, that may contribute to ASD pathophysiology. When comparing ASD patients to controls, we found decreased connectivity between the left DN and cerebral regions known to be components of the ToM network and the default mode network, implicated in specific aspects of mentalizing, social cognition processing, and higher order emotional processes. Further, a pattern of overconnectivity was also detected between the left DN and the supramodal cerebellar lobules associated with the default mode network. The presented RS-fMRI data provide evidence that functional connectivity (FC) between the dentate nucleus and the cerebral cortex is altered in ASD patients. This suggests that the dysfunction reported within the cerebral cortical network, typically related to social features of ASDs, may be at least partially related to an impaired interaction between cerebellum and key cortical social brain regions.

Brain Connectomics' Modification to Clarify Motor and Nonmotor Features of Myotonic Dystrophy Type 1.

The adult form of myotonic dystrophy type 1 (DM1) presents with paradoxical inconsistencies between severity of brain damage, relative preservation of cognition, and failure in everyday life. This study, based on the assessment of brain connectivity and mechanisms of plasticity, aimed at reconciling these conflicting issues. Resting-state functional MRI and graph theoretical methods of analysis were used to assess brain topological features in a large cohort of patients with DM1. Patients, compared to controls, revealed reduced connectivity in a large frontoparietal network that correlated with their isolated impairment in visuospatial reasoning. Despite a global preservation of the topological properties, peculiar patterns of frontal disconnection and increased parietal-cerebellar connectivity were also identified in patients' brains. The balance between loss of connectivity and compensatory mechanisms in different brain networks might explain the paradoxical mismatch between structural brain damage and minimal cognitive deficits observed in these patients. This study provides a comprehensive assessment of brain abnormalities that fit well with both motor and nonmotor clinical features experienced by patients in their everyday life. The current findings suggest that measures of functional connectivity may offer the possibility of characterizing individual patients with the potential to become a clinical tool.

Longitudinal Changes in Functional Brain Connectivity Predicts Conversion to Alzheimer's Disease.

This longitudinal study investigates the modifications in structure and function occurring to typical Alzheimer's disease (AD) brains over a 2-year follow-up, from pre-dementia stages of disease, with the aim of identifying biomarkers of prognostic value. Thirty-one patients with amnestic mild cognitive impairment were recruited and followed-up with clinical, neuropsychological, and MRI assessments. Patients were retrospectively classified as AD Converters or Non-Converters, and the data compared between groups. Cross-sectional MRI data at baseline, assessing volume and functional connectivity abnormalities, confirmed previous findings, showing a more severe pattern of regional grey matter atrophy and default-mode network disconnection in Converters than in Non-Converters. Longitudinally, Converters showed more grey matter atrophy in the frontotemporal areas, accompanied by increased connectivity in the precuneus. Discriminant analysis revealed that functional connectivity of the precuneus within the default mode network at baseline is the parameter able to correctly classify patients in Converters and Non-Converters with high sensitivity, specificity, and accuracy.

Functional Anatomy of the Thalamus as a Model of Integrated Structural and Functional Connectivity of the Human Brain In Vivo.

While methods of measuring non-invasively both, functional and structural brain connectivity are available, the degree of overlap between them is still unknown. In this paper this issue is addressed by investigating the connectivity pattern of a brain structure with many, well characterized structural connections, namely the thalamus. Diffusion-weighted and resting state (RS) functional MRI (fMRI) data were collected in a group of 38 healthy participants. Probabilistic tractography was performed to parcellate the thalamus into regions structurally connected to different cortical areas. The resulting regions were used as seeds for seed-based analysis of RS fMRI data. The tractographic parcellation was thus cross-validated against functional connectivity data by evaluating the overlap between the functional and structural thalamo-cortical connections originating from the parcellated regions. Our data show only a partial overall correspondence between structural and functional connections, in the same group of healthy individuals, thus suggesting that the two approaches provide complementary and not overlapping information. Future studies are warranted to extend the results we obtained in the thalamus to other structures, and to confirm that the mechanisms behind functional connectivity are more complex than just expressing structural connectivity.

Cognitive reserve and the risk for Alzheimer's disease: a longitudinal study.

This study investigates how cognitive reserve (CR) interacts with neurodegeneration (quantified by medial temporal atrophy, MTA) and macroscopic white matter lesions (WMLs) in delaying the conversion from amnestic mild cognitive impairment to Alzheimer's disease (AD). Forty-two amnestic mild cognitive impairment patients were consecutively recruited. They underwent magnetic resonance imaging and a comprehensive questionnaire to classify them as individuals with low or high CR. Patients were then clinically followed-up for 2 years. The patients' risk for conversion to AD because of CR was estimated by controlling for cognitive efficiency, MTA, and WMLs at baseline. Global cognition was the best predictor of conversion to AD in low CR patients. Conversely, in high CR patients only, WMLs (but not MTA) highly contributed in increasing the risk for conversion to AD. In conclusion, CR interacts with both patients' cognitive features and WMLs in modulating the impact of AD pathology. This seems relevant for clinical prognosis and therapeutic strategies.

TMS evidence for a selective role of the precuneus in source memory retrieval.

The posteromedial cortex including the precuneus (PC) is thought to be involved in episodic memory retrieval. Here we used continuous theta burst stimulation (cTBS) to disentangle the role of the precuneus in the recognition memory process in a sample of healthy subjects. During the encoding phase, subjects were presented with a series of colored pictures. Afterwards, during the retrieval phase, all previously presented items and a sample of new pictures were presented in black, and subjects were asked to indicate whether each item was new or old, and in the latter case to indicate the associated color. cTBS was delivered over PC, posterior parietal cortex (PPC) and vertex before the retrieval phase. The data were analyzed in terms of hits, false alarms, source errors and omissions. cTBS over the precuneus, but not over the PPC or the vertex, induced a selective decrease in source memory errors, indicating an improvement in context retrieval. All the other accuracy measurements were unchanged. These findings suggest a direct implication of the precuneus in successful context-dependent retrieval.

Network based statistical analysis detects changes induced by continuous theta-burst stimulation on brain activity at rest.

We combined continuous theta-burst stimulation (cTBS) and resting state (RS)-fMRI approaches to investigate changes in functional connectivity (FC) induced by right dorsolateral prefrontal cortex (DLPFC)-cTBS at rest in a group of healthy subjects. Seed-based fMRI analysis revealed a specific pattern of correlation between the right prefrontal cortex and several brain regions: based on these results, we defined a 29-node network to assess changes in each network connection before and after, respectively, DLPFC-cTBS and sham sessions. A decrease of correlation between the right prefrontal cortex and right parietal cortex (Brodmann areas 46 and 40, respectively) was detected after cTBS, while no significant result was found when analyzing sham-session data. To our knowledge, this is the first study that demonstrates within-subject changes in FC induced by cTBS applied on prefrontal area. The possibility to induce selective changes in a specific region without interfering with functionally correlated area could have several implications for the study of functional properties of the brain, and for the emerging therapeutic strategies based on transcranial stimulation.

Abnormal functional brain connectivity and personality traits in myotonic dystrophy type 1.

IMPORTANCE: Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy observed in adults, is a genetic multisystem disorder affecting several other organs besides skeletal muscle, including the brain. Cognitive and personality abnormalities have been reported; however, no studies have investigated brain functional networks and their relationship with personality traits/disorders in patients with DM1. OBJECTIVE: To use resting-state functional magnetic resonance imaging to assess the potential relationship between personality traits/disorders and changes to functional connectivity within the default mode network (DMN) in patients with DM1. DESIGN, SETTING, AND PARTICIPANTS: We enrolled 27 patients with genetically confirmed DM1 and 16 matched healthy control individuals. Patients underwent personality assessment using clinical interview and Minnesota Multiphasic Personality Inventory-2 administration; all participants underwent resting-state functional magnetic resonance imaging. Investigations were conducted at the Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Catholic University of Sacred Heart, and Azienda Ospedaliera San Camillo Forlanini. INTERVENTION: Resting-state functional magnetic resonance imaging. MAIN OUTCOMES AND MEASURES: Measures of personality traits in patients and changes in functional connectivity within the DMN in patients and controls. Changes in functional connectivity and atypical personality traits in patients were correlated. RESULTS: We combined results obtained from the Minnesota Multiphasic Personality Inventory-2 and clinical interview to identify a continuum of atypical personality profiles ranging from schizotypal personality traits to paranoid personality disorder within our DM1 patients. We also demonstrated an increase in functional connectivity in the bilateral posterior cingulate and left parietal DMN nodes in DM1 patients compared with controls. Moreover, patients with DM1 showed strong associations between DMN functional connectivity and schizotypal-paranoid traits. CONCLUSIONS AND RELEVANCE: Our findings provide novel biological evidence that DM1 is a clinical condition that also involves an alteration of functional connectivity of the brain. We speculate that these functional brain abnormalities, similarly to frank psychiatric disorders, may account for the atypical personality traits observed in patients with DM1.

Widespread alterations in functional brain network architecture in amnestic mild cognitive impairment.

We investigated changes in functional network architecture in amnestic mild cognitive impairment using graph-based analysis of task-free functional magnetic resonance imaging and fine cortical parcellation. Widespread disconnection was observed primarily in cortical hubs known to manifest early Alzheimer's disease pathology, namely precuneus, parietal lobules, supramarginal and angular gyri, and cuneus, with additional involvement of subcortical regions, sensorimotor cortex and insula. The connectivity changes determined using graph-based analysis significantly exceed those detected using independent component analysis both in amplitude and topographical extent, and are largely decoupled from the presence of overt atrophy. This superior ability of graph-based analysis to detect disease-related disconnection highlights its potential use in the determination of biomarkers of early dementia. Graph-based analysis source code is provided as supplementary material.

Theta burst stimulation modulates cerebellar-cortical connectivity in patients with progressive supranuclear palsy.

BACKGROUND: Progressive Supranuclear Palsy (PSP) is an atypical degenerative Parkinsonism characterized by postural instability, supranuclear gaze palsy and frontal deficits. Recent imaging studies revealed that the volume of cerebellar peduncles and midbrain were reduced in PSP. Transcranial magnetic stimulation (TMS) studies demonstrated a cerebellar involvement in PSP showing an impairment of functional connectivity between the cerebellar hemisphere (Cb) and the contralateral primary motor cortex (M1) (cerebellar brain inhibition-CBI). OBJECTIVE: To investigate the plasticity of the cerebello-thalamo-cortical circuits in ten PSP patients after two-week course of cerebellar intermittent theta burst stimulation (iTBS), a form of repetitive TMS. METHODS: Before and after the iTBS sessions we measured functional connectivity between Cb and contralateral M1 (CBI), short intracortical inhibition (SICI) and intracortical facilitation (ICF) and short latency afferent inhibition (SLAI) in contralateral M1. We also performed resting state functional magnetic resonance (rs-fMRI) and we administered clinical rating scale (PSP-RS). RESULTS: At baseline PSP patients had decreased efficiency of CBI, SICI and SLAI in comparison to PD patients and healthy subjects. Cerebellar iTBS increased the deficient functional cerebellar-motor connectivity as assessed by CBI. No effect was seen for SICI/ICF and SLAI circuits. Following iTBS there was an increased signal in the head of the caudate nucleus bilaterally as shown by rs-fMRI. Moreover, PSP-RS showed an improvement of dysarthria in all patients. CONCLUSIONS: iTBS enhanced functional connectivity between the cerebellar hemisphere, the caudate nucleus and the cortex, that was paralleled by some clinical improvement. Future randomized, sham-stimulation controlled studies are warranted to support the clinical efficacy of this technique.

Theta burst stimulation improves visuo-spatial attention in a patient with traumatic brain injury.

Recent studies showed that non-invasive brain stimulation methods, such as repetitive transcranial magnetic stimulation (rTMS) can improve the symptoms of neglect in stroke patients. Here, we adopted this approach to improve visuo-spatial deficit in a patient with traumatic brain injury (TBI) that showed important symptoms of visuo-spatial neglect. We found that continuous theta burst stimulation (cTBS) applied over the left posterior parietal cortex (PPC) induced a clinical improvement of cognitive disorder associated to a functional changes of fronto-parietal network as assessed by means of TMS and resting state fMRI.

Microstructural damage of the posterior corpus callosum contributes to the clinical severity of neglect.

One theory to account for neglect symptoms in patients with right focal damage invokes a release of inhibition of the right parietal cortex over the left parieto-frontal circuits, by disconnection mechanism. This theory is supported by transcranial magnetic stimulation studies showing the existence of asymmetric inhibitory interactions between the left and right posterior parietal cortex, with a right hemispheric advantage. These inhibitory mechanisms are mediated by direct transcallosal projections located in the posterior portions of the corpus callosum. The current study, using diffusion imaging and tract-based spatial statistics (TBSS), aims at assessing, in a data-driven fashion, the contribution of structural disconnection between hemispheres in determining the presence and severity of neglect. Eleven patients with right acute stroke and 11 healthy matched controls underwent MRI at 3T, including diffusion imaging, and T1-weighted volumes. TBSS was modified to account for the presence of the lesion and used to assess the presence and extension of changes in diffusion indices of microscopic white matter integrity in the left hemisphere of patients compared to controls, and to investigate, by correlation analysis, whether this damage might account for the presence and severity of patients' neglect, as assessed by the Behavioural Inattention Test (BIT). None of the patients had any macroscopic abnormality in the left hemisphere; however, 3 cases were discarded due to image artefacts in the MRI data. Conversely, TBSS analysis revealed widespread changes in diffusion indices in most of their left hemisphere tracts, with a predominant involvement of the corpus callosum and its projections on the parietal white matter. A region of association between patients' scores at BIT and brain FA values was found in the posterior part of the corpus callosum. This study strongly supports the hypothesis of a major role of structural disconnection between the right and left parietal cortex in determining 'neglect'.