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.

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 neuropsychiatric symptoms following stroke using virtual reality: A case report.

RATIONALE: Post-stroke cognitive impairment occurs frequently in patients with stroke, with a 20% to 80% prevalence. Anxiety is common after stroke, and is associated with a poorer quality of life. The use of standard relaxation techniques in treating anxiety in patients undergoing post-stroke rehabilitation have shown some positive effects, whereas virtual reality seems to have a role in the treatment of anxiety disorders, especially when associated to neurological damage. PATIENTS CONCERNS: A 50-year-old woman, smokers, affected by hypertension and right ischemic stroke in the chronic phase (i.e., after 12 months by cerebrovascular event), came to our observation for a severe anxiety state and a mild cognitive deficit, mainly involving attention and visuo-executive processes, besides a mild left hemiparesis. DIAGNOSIS: Anxiety in a patient with ischemic stroke. INTERVENTIONS: Standard relaxation techniques alone in a common clinical setting or the same psychological approach in an immersive virtual environment (i.e., Computer Assisted Rehabilitation Environment - CAREN). OUTCOMES: The patient's cognitive and psychological profile, with regard to attention processes, mood, anxiety, and coping strategies, were evaluated before and after the 2 different trainings. A significant improvement in the functional and behavioral outcomes were observed only at the end of the combined approach. LESSONS: The immersive virtual reality environment CAREN might be useful to improve cognitive and psychological status, with regard to anxiety symptoms, in post-stroke individuals.

Motor imagery in stroke patients: a descriptive review on a multidimensional ability.

Purpose/aim: Motor imagery (MI) is the mental representation of a movement without engaging its actual execution. MI shares neuroanatomical correlates with brain motor networks. Neurologic disorders affecting motor skills, such as stroke, have been related to impairments in MI. A descriptive review was conducted to explore the effects of stroke on MI ability and its background mechanisms. Materials and Methods: We searched on PubMed and Web of Science databases and screening references of included studies and review articles for additional citations. Results: On a total of 885 studies, only 15 articles met inclusion criteria. Results suggested that MI is impaired after stroke, in implicit and explicit abilities. Impairments in mental chronometry as well as in accuracy and reaction times were observed. Conclusions: Neuroimaging findings confirmed a brain reorganization after a stroke and a compensatory over-usage of contralesional hemisphere was highlighted.

Naturally occurring compounds in differentiation based therapy of cancer.

Differentiation of cancer cells entails the reversion of phenotype from malignant to the original. The conversion to cell type characteristic for another tissue is named transdifferentiation. Differentiation/transdifferentiation of malignant cells in high grade tumor mass could serve as a nonaggressive approach that potentially limits tumor progression and augments chemosensitivity. While this therapeutic strategy is already being used for treatment of hematological cancers, its feasibility for solid malignancies is still debated. We will presently discuss the natural compounds that show these properties, with focus on anthraquinones from Aloe vera, Senna, Rheum sp. and hop derived prenylflavonoids.

Evaluating Peripersonal Space through the Functional Transcranial Doppler: Are We Paving the Way for Early Detecting Mild Cognitive Impairment to Dementia Conversion?

BACKGROUND: Identifying the patients with mild cognitive impairment (MCI) who may develop dementia (MDC) is challenging. The study of peripersonal space (PPS) by using functional transcranial Doppler (fTCD) could be used for this purpose. OBJECTIVE: To identify changes in cerebral blood flow (CBF) during motor tasks targeting PPS, which can predict MDC. METHODS: We evaluated the changes in CBF in 22 patients with MCI and 23 with dementia [Alzheimer's disease (AD) and vascular dementia (VaD)] during a motor task (passive mobilization, motor imagery, and movement observation) in which the hand of the subject moved forward and backward the face. RESULTS: CBF increased when the hand approached the face and decreased when the hand moved from the face in the healthy controls (HCs). CBF changed were detectable only in patients with MCI but not in those with the AD and those who were MDC after 8-month follow-up. On the other hand, the patients with VaD presented a paradoxical response to the motor task (i.e., a decrease of CBF rather than an increase, as observed in HCs and MCI). Therefore, we found a modulation of PPS-related CBF only in HCs and patients with stable MCI (at the 8-month follow-up). CONCLUSIONS: fTCD may allow preliminarily differentiating and following-up the patients with MCI and MDC, thus allowing the physician to plan beforehand more individualized cognitive rehabilitative training.

Reducing the rate of misdiagnosis in patients with chronic disorders of consciousness: Is there a place for audiovisual stimulation?

BACKGROUND: The patients with chronic Disorders of Consciousness (DoC) mostly present with extremely challenging differential diagnosis. The advanced analysis of electroencephalographic (EEG) signals induced by brain stimulation paradigms may provide an appropriate approach to differentiate patients with DoC, besides the clinical assessment. OBJECTIVE: This study was performed with an objective of identifying residual brain network perturbations following an innovative, non-invasive audiovisual stimulation protocol, which could be related to behavioral responsiveness in patients with DoC. METHODS: The study comprised of ten healthy controls (HC), seven patients with Minimally Conscious State (MCS), and nine patients with Unresponsive Wakefulness Syndrome (UWS). Both synchronous as well as asynchronous transorbital and transauricolar alternating current were employed as stimuli and their effects were measured in terms of functional and effective connectivity. RESULTS: A more noticeable deterioration of long range connectivity patterns were found in patients with UWS than in those with MCS, with an exception of two patients with UWS, who showed connectivity values similar to those of MCS patients. CONCLUSION: The audiovisual stimulation paradigm used in the present study may be employed as a supportive bedside tool for improving the differential diagnosis in patients with DoC.

Breakthroughs in the spasticity management: Are non-pharmacological treatments the future?

The present paper aims at providing an objective narrative review of the existing non-pharmacological treatments for spasticity. Whereas pharmacologic and conventional physiotherapy approaches result well effective in managing spasticity due to stroke, multiple sclerosis, traumatic brain injury, cerebral palsy and incomplete spinal cord injury, the real usefulness of the non-pharmacological ones is still debated. We performed a narrative literature review of the contribution of non-pharmacological treatments to spasticity management, focusing on the role of non-invasive neurostimulation protocols (NINM). Spasticity therapeutic options available to the physicians include various pharmacological and non-pharmacological approaches (including NINM and vibration therapy), aimed at achieving functional goals for patients and their caregivers. A successful treatment of spasticity depends on a clear comprehension of the underlying pathophysiology, the natural history, and the impact on patient's performances. Even though further studies aimed at validating non-pharmacological treatments for spasticity should be fostered, there is growing evidence supporting the usefulness of non-pharmacologic approaches in significantly helping conventional treatments (physiotherapy and drugs) to reduce spasticity and improving patient's quality of life. Hence, non-pharmacological treatments should be considered as a crucial part of an effective management of spasticity.

Twist and turn into chronic disorders of consciousness: Potential role of the auditory stapedial reflex.

BACKGROUND: Patients suffering from chronic disorders of consciousness (DOC), including minimally conscious state (MCS) and unresponsive wakefulness syndrome (UWS), typically show an awareness impairment paralleled by a significant reflex hyper-excitability, which depend on the cortical deafferentation following brain-damage-induced thalamocortical system deterioration. Nonetheless, recent studies have shown a residual preservation of cortico-subcortical pathways that may sustain residual fragments of awareness in some DOC patients. OBJECTIVE: The aim of our study was to assess whether the cortical modulation of auditory stapedial reflex (ASR) could be a marker of a higher degree of brain network connectivity, which is a fundamental prerequisite for awareness generation and maintenance. METHODS: We applied a repetitive transcranial magnetic stimulation (rTMS) protocol over the primary auditory area and measured the neuromodulation effects on ASR threshold (ASRt) in a DOC sample and a healthy control group (HC). RESULTS: We observed an ASRt reduction in all the HC and MCS individuals, in parallel to a better sound-induced motor responsiveness in MCS sample, while all the UWS patients, but two, did not show any significant ASRt modulation. CONCLUSION: We hypothesize that our conditioning protocol may have entrained and potentiated some spared cortico-subcortical networks that sustained the clinical and electrophysiological amelioration we found. Our data electrophysiologically demonstrate for the first time that primary the auditory area can influence ASR elicitation, and such finding may support the DOC differential diagnosis.