Cocaine use disorder (CUD) is a significant public health problem with few treatment options. Repetitive Transcranial Magnetic Stimulation (rTMS) targeting the left dorsolateral prefrontal cortex has shown promise as a therapeutic tool for neural alterations in CUD. However, its effects on white matter (WM) microstructure and their role in treatment efficacy remain uncertain. This study aimed to assess the global impact of rTMS on WM microstructure in CUD patients. In this study, we made a longitudinal correlational tractography analysis that was conducted using Quantitative Anisotropy (QA) on diffusion MRI data from CUD patients who received either active rTMS (n = 22) or sham rTMS (n = 18) treatment. Imaging data were collected before (T0) and after two weeks of treatment (T1). Correlations were derived using nonparametric Spearman partial correlation, accounting for gender, age, and age at substance initiation through multiple regression. Tracks were selected using a p-FDR threshold of 0.05. A significant QA increase was found in 9718 tracts across the whole brain in the active rTMS group compared to the sham group, with no observed reduction in QA. The affected WM tracts included cerebellar, commissural, associative, and projective fibers, mainly in the left hemisphere. The study suggests that rTMS induces widespread changes in WM microstructure, potentially improving communication between brain regions and cognitive control in CUD patients. However, the small sample size limits the findings’ generalizability, highlighting the need for larger, longitudinal studies.

We aim to investigate the progression of aging-related white matter (WM) degeneration, measured by fractional anisotropy (FA), in cognitively normal, healthy individuals over a long-term follow-up of 8.68 years. The study population consisted of 177 right-handed, healthy participants aged 21–89 years. Participants underwent cognitive assessments and MRI scans at three time points (Wave 1 = baseline; Wave 2 = approximately 4 years after Wave 1; Wave 3 = approximately 8 years after Wave 1). Three distinct Differential Tractography Analyses (DTA) were performed using the “Wave – previous Wave” scheme to evaluate long-term (Wave 3 – Wave 1) and short-term (Wave 2 – Wave 1 and Wave 3 – Wave 2) changes in FA. Correlational tractography with a nonparametric Spearman partial correlation was used for each DTA to visualize WM pathways that shown longitudinal change in FA, and the effects of covariates (including age and sex) were controlled for using a multiple regression model. For each analysis, a T-score threshold of 3.5 was applied in the fiber tracking algorithm, and a p-value corrected for False Discovery Rate (p-FDR) threshold of 0.001 was used to select tracks. FA decreased significantly over time in all three DTA (p-FDR < 0.001), showing a distinct left-dominant pattern characterized by initial involvement of the left hemisphere (mainly the temporal lobe) and later spreading to the entire brain. The results of this study suggest a “left-to-whole” pattern of WM degeneration during physiological aging, which may partially explain the loss of brain lateralization observed in aging. Question: Is there a pattern of progression of aging-related Fractional Anisotropy (FA) changes in cognitively normal, healthy individuals? Findings: The decline in FA during aging seems to follow a ‘left-to-whole’ pattern in cognitively healthy individuals. Clinical relevance statement: Understanding the pattern of white matter degeneration in healthy aging could improve our knowledge of the physiological mechanisms of cerebral aging, as well as help to identify new imaging biomarkers for diagnosing and monitoring neurodegenerative disorders.

Vagus nerve stimulation (VNS) is an established adjunctive therapy for drug-resistant epilepsy. Experimental and clinical evidence indicates that its therapeutic effects involve distributed brain networks and multiple neurochemical pathways. Electroencephalography (EEG) has been widely used to characterize VNS-related neurophysiological changes, including alterations in conventional oscillatory activity, functional connectivity, and, more recently, aperiodic spectral components such as the spectral exponent and spectral offset. However, these EEG findings are often interpreted without sufficient consideration of the neurochemical intermediates that may contribute to the observed electrophysiological changes. In this structured narrative review, primarily focused on epilepsy, we examine how VNS-related EEG findings can be interpreted in light of noradrenergic, serotonergic, cholinergic, GABAergic, and neurotrophic mechanisms. We also discuss methodological challenges in the analysis of periodic and aperiodic EEG components and outline how machine learning approaches and adaptive closed-loop neuromodulation strategies may support the development of clinically useful VNS biomarkers.

This study explores white matter (WM) microstructural changes across different phases of the menstrual cycle (MC) in healthy women. Using the publicly available Hormon Health Study dataset, we performed a differential tractography study on Q-space Trajectory Imaging sequences from 22 participants, assessing WM microstructural changes between three specific time points: (a) Menses phase (M-phase), (b) Ovulation phase (O-phase), and (c) Mid-Luteal phase (ML-phase). The difference between specific MC-phase scans were calculated by the scheme “phase - previous phase” of the MC in three distinct analyses: (a) Analysis 1 (O-phase – M-Phase); (b) Analysis 2 (ML-phase – O-phase); (c) Analysis 3 (M-phase – ML-phase). Quantitative anisotropy (QA), was employed to quantify changes in WM structure. A p-value corrected for false discovery rate (p-FDR) < 0.05 was used to identify statistically significant results. Significant reductions in QA were widespread observed in Analysis 1 (O-phase – M-Phase; p-FDR = 0.00026802), and Analysis 2 (ML-phase – O-phase; p-FDR = 0.00000242), while increased QA values were observed in Analysis 3 (M-phase – ML-phase; p-FDR = 0.00002051). This study provides evidence of cyclic WM microstructural changes during the MC. These results may offer insights into the mechanisms underlying MC-related brain physiological and pathological changes.

Patients with Parkinson’s Disease (PD) commonly experience Olfactory Dysfunction (OD). Our exploratory study examined hippocampal volumetric and resting-state functional magnetic resonance imaging (rs-fMRI) variations in a Healthy Control (HC) group versus a cognitively normal PD group, further categorized into PD with No/Mild Hyposmia (PD-N/MH) and PD with Severe Hyposmia (PD-SH). We calculated participants’ relative Total Hippocampal Volume (rTHV) and performed Spearman’s partial correlations, controlled for age and gender, to examine the correlation between rTHV and olfactory performance assessed by the Odor Stick Identification Test for the Japanese (OSIT-J) score. Mann-Whitney U tests assessed rTHV differences across groups and subgroups, rejecting the null hypothesis for p < 0.05. Furthermore, a seed-based rs-fMRI analysis compared hippocampal connectivity differences using a one-way ANCOVA covariate model with controls for age and gender. Spearman’s partial correlations indicated a moderate positive correlation between rTHV and OSIT-J in the whole study population (ρ = 0.406; p = 0.007), PD group (ρ = 0.493; p = 0.008), and PD-N/MH subgroup (ρ = 0.617; p = 0.025). Mann-Whitney U tests demonstrated lower rTHV in PD-SH subgroup compared to both HC group (p = 0.013) and PD-N/MH subgroup (p = 0.029). Seed-to-voxel rsfMRI analysis revealed reduced hippocampal connectivity in PD-SH subjects compared to HC subjects with a single cluster of voxels. Although the design of the study do not allow to make firm conclusions, it is reasonable to speculate that the progressive involvement of the hippocampus in PD patients is associated with the progression of OD.

Background: Alzheimer’s disease (AD) is a complex condition that affects various aspects of a patient’s life. Music therapy may be considered a beneficial supplementary tool to traditional therapies, that not fully address the range of AD manifestations. Objective: The purpose of this systematic review is to investigate whether music therapy can have a positive impact on AD patients and on which symptoms. Methods: The main research databases employed have been PubMed and Cochrane, using the keywords “dementia”, “music therapy”, “Alzheimer”, “fMRI”, “music”, and “EEG”. Results: After removing duplicates and irrelevant studies, 23 were screened using set criteria, resulting in the final inclusion of 15 studies. The total number of participants included in these studies has been of 1,196 patients. For the fMRI analysis the search resulted in 28 studies on PubMed, two of which were included in the research; the total number of participants was of 124 individuals. The studies conducted with EEG were found using PubMed. The initial search resulted in 15 studies, but after a more accurate evaluation only 2 have been included in the analysis. Conclusions: Even though the data currently available is not sufficient to draw conclusions supported by robust statistical power, the impact of music therapy on AD neuropsychiatric symptoms deserves great interest. Further research should be ushered, possibly multicentric studies, led with neuroimaging and other recent techniques, which can eventually open views on the music role in improving the cognitive status in AD.

To examine the corpus callosum’s (CC) integrity in terms of fractional anisotropy (FA) and how it affects resting-state hemispheric connectivity (rs-IHC) and cognitive function in healthy individuals. Sixty-eight healthy individuals were recruited for the study. The global FA (gFA) and FA values of each CC tract (forceps minor, body, tapetum, and forceps major) were evaluated using diffusion-weighted imaging (DWI) sequences. The homotopic functional connectivity technique was used to quantify the effects of FA in the CC tracts on bilateral functional connectivity, including the confounding effect of gFA. Brain regions with higher or lower rs-IHC were identified using the threshold-free cluster enhancement family-wise error-corrected p -value of 0.05. The null hypothesis was rejected if the p -value was ≤ 0.05 for the nonparametric partial correlation technique. Several clusters of increased rs-IHC were identified in relation to the FA of individual CC tracts, each with a unique topographic distribution and extension. Only forceps minor FA values correlated with cognitive scores. The integrity of CC influences rs-IHC differently in healthy subjects. Specifically, forceps minor anisotropy impacts rs-IHC and cognition more than other CC tracts do.

INTRODUCTION. Recent neuroimaging studies suggest that dental loss replacements induce changes in neuroplasticity as well as in correlated connectivity between brain networks. However, as the typical temporal delay in detecting brain activity by neuroimaging cannot account for the influence one neural system exerts over another in a context of real activation (“effective” connectivity), it seems of interest to approach this dynamic aspect of brain networking in the time frame of milliseconds by exploiting electroencephalographic (EEG) data. MATERIAL AND METHODS. The present study describes one subject who received a new prosthodontic provisional implant in substitution for previous dental repairs. Two EEG sessions led with a portable device were recorded before and after positioning the new dental implant. By following MATLAB-EEGLAB processing supported by the plugins FIELDTRIP and SIFT, the independent component analysis (ICA) derived from EEG raw signals was rendered as current density fields and interpolated with the dipoles generated by each electrode for a dynamic study of the effective connectivity. One more recording session was undertaken six months after the placement of the final implant. RESULTS. Compared to the baseline, the new prosthodontic implant induced a novel modulation of the neuroplasticity in sensory-motor areas which was maintained following the definitive implant after six months, as revealed by changes in the effective connectivity from the basal strong enslavement of a single brain area over the others, to an equilibrate inter-related connectivity evenly distributed along the frontotemporal regions of both hemispheres. CONCLUSIONS. The rapid shift of the effective connectivity after positioning the new prosthodontic implant and its substantial stability after six months suggest the possibility that synaptic modifications, induced by novel sensory motor conditions, modulate the neuroplasticity and reshape the final dynamic frame of the interarea connectivity. Moreover, given the viability of the EEG practice, this approach could be of some interest in assessing the association between oral pathophysiology and neuronal networking.

INTRODUCTION:Spinal cord injuries (SCIs) represent a severe neuro-traumatic occurrence and an excruciating social burden. Though the hyperbaric oxygen (HBO2) has been credited as a first line therapeutic resource for SCIs, its mechanism of action in the spine is only partially known, while the impingement upon other areas of the nervous system deserves additional investigation. In this study we deem to describe a novel effect of HBO2 in a subject affected by SCI who, along with the clinical improvement, showed a reshaped connectivity in cortical sensory-motor areas.CASE PRESENTATION:A 45 years male presenting severe sensory-motor symptoms following a spinal lesion partially involving the C1 segment was successfully treated with HBO2 cycles. After the dramatic improvement reflected by an excellent optimization of the single performances, it has been investigated whether this result would reveal not only an intrinsic effect upon the spinal cord, but also a better connectivity strength in sensory-motor cortical regions. The results obtained by implementing EEG recordings with EEGLAB auto regressive vector plugins indeed suggest a substantial reshaping of cortico-cortical connectivity after HBO2.DISCUSSION:These results show a correlation between positive clinical evolution and a new modulation of cortical connectivity. Though further clinical investigations would clarify as to whether HBO2 might be directly or epiphenomenally involved in this aspect of the network architecture, our report suggests that a comparison between clinical results and the study of brain connectivity represent a holistic approach in investigating the physiopathology of SCIs and in monitoring the treatment.

The frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non Asian populations. Here we present two studies performed in Sardinia, a large mediterranean island that's considered a genetic isolated: a study of HD incidence over a ten-years period, 2009 to 2018, in overall Island, and a prevalence study in the southern part of it.

BACKGROUND:The frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non-Asian populations. We have recently examined the prevalence of HD in the southern part of Sardinia, a large Italian Mediterranean island that is considered a genetic isolate. We observed regional microgeographic differences in the prevalence of HD across the study area similar to those recently reported in other studies conducted in European countries. To explore the basis for this variability, we undertook a study of the incidence of HD in Sardinia over a 10-year period, 2009 to 2018.METHODS:Our research was conducted in the 5 administrative areas of Sardinia island. Case patients were ascertained through multiple sources in Sardinia and Italy.RESULTS:During the incidence period 53 individuals were diagnosed with clinically manifested HD. The average annual incidence rate 2009-2018 was 2.92 per 106 persons-year (95% CI, 2.2 to 3.9). The highest incidence rate was observed in South Sardinia (6.3; 95% CI, 4.2-9.5). This rate was significantly higher (p<0.01) than the rates from Cagliari, Oristano, and Sassari provinces but did not significantly differ (p = 0.38) from the Nuoro rate.CONCLUSIONS:The overall incidence of HD in Sardinia is close to the correspondent estimates in Mediterranean countries. Our findings highlight also the possibility of local microgeographic variations in the epidemiology of HD that might reflect several factors, including a possible founder effect in the rural areas of South Sardinia and Nuoro.

Purpose:To investigate the relationships between white matter hyperintensities (WMH) and hippocampal volume and their influence on brain networks by using resting-state functional connectivity (rs-fc) magnetic resonance (MR) according to their localization. Methods:In this exploratory cross-sectional study, 38 subjects from the public "Leipzig Study for Mind/Body/Emotion Interactions" (LEMON) data set were selected. Morphometric analyses of both WMH burden and the total hippocampal relative volume (tHRV) were performed for each subject with two automated software. The WMH were then categorized as total (tWMH), periventricular (pvWMH), deep (dWMH), and juxtacortical (jcWMH). Spearman's correlation analyses were performed to evaluate the relationships between the following variables: age, tWMH, pvWMH, dWMH, jcWMH, and tHRV. Subsequently, three different rs-fc MR group analyses were performed using a multiple regression model that included age, pvWMH, dWMH, and jcWMH as second-level covariates. The graph theoretical analysis was applied to evaluate the effects of pvWMH (analysis 1), jcWMH (analysis 2), and dWMH (analysis 3). Results:Spearman's correlation analysis revealed several statistically significant (p < 0.05) positive and negative correlations, in particular positive between age and tWMH, and negative between dWMH and tHRV. rs-fc MR analysis 1 and 2 did not reveal statistically significant results; analysis 3 revealed that dWMH influenced network properties of several cerebral regions, in particular global and local efficiency of both the hippocampi. Conclusion:The localization of WMH influences brain activity in healthy subjects. In particular, dWMH are inversely correlated with tHRV and influence several properties of different cerebral areas, included both the hippocampi. Impact statement In this exploratory research we evidenced how both the load and the localization of white matter hyperintensities influence brain activity; in particular, we evidenced an inverse correlation between the volume of the deep white matter hyperintensities and hippocampal volume, as well as a direct influence on the connectivity properties of this important cerebral region. This finding represent a new element for understanding the effects of white matter hyperintensities on brain networking, and a cue that could be taken into account for possible future studies investigating brain connectivity and cognitive functions in healthy and pathological conditions.

Background: The frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non Asian populations. In Italy, two recent studies performed in Ferrara county and Molise provided different prevalence estimates, varying from 4.2 x 10(5) to 10.8 x 10(5). Here we present a study performed in the Southern part of Sardinia, a large Italian mediterranean island that is considered a genetic isolate. Methods: The study area included the two neighbouring counties of South Sardinia and Cagliari with 353,830 and 431,955 inhabitants respectively on December 31st, 2017 (prevalence date). Case-patients were ascertained through multiple sources in Sardinia and Italy. Results: We identified 54 individuals with HD, of whom 47 were alive on prevalence date. The resulting prevalence rate was 5.98 x 10(5) in the overall study area, however with marked variations between South Sardinia and Cagliari (9.6 x 10(5) vs. 3.0 x 10(5), p = 0.02). In the two study areas, we found similar CAG repeat length in normal alleles (17.5 2.1 vs. 17.7 +/- 2.2, p = 0.5). Conclusions: The overall prevalence of HD in Sardinia is close to the correspondent estimates in Europeans. Our findings also highlighted the possibility of local microgeographic variations in the epidemiology of HD.

Patients with Parkinson's Disease (PD) experience bothersome motor fluctuations and Levodopa-induced Dyskinesias (LIDs). Cerebellar continuous theta burst stimulation (cTBS) was used as an inhibitory protocol of repetitive transcranial magnetic stimulation (rTMS) to reduce LIDs in PD patients. The influence of Val66Met polymorphism of Brain Derived Neurotrophic Factor (BDNF) gene on the therapeutic response to cTBS was investigated and the serum levels of BDNF were measured before and after treatment. Eleven patients were exposed to a session of cTBS and sham stimulation (one week apart) after the administration of 125 % of their usual morning dose of Levodopa and LIDs were video-recorded and evaluated at different time points (0, 15, 30, 45, 60, 90 min after Levodopa). Cerebellar cTBS significantly reduced LIDs with respect to sham stimulation and decreased serum BDNF levels. These effects were evident in the Val66Val group (7 subjects) but not in the Val66Met group (4 subjects). These data confirm the efficacy of cerebellar cTBS in reducing LIDs in PD patients and show that the clinical effect is accompanied by a decrease in serum BDNF levels. Moreover, they suggest that BDNF Val66Met polymorphism may influence the clinical and biological response to cTBS.

OBJECTIVES:Among different exercise models proposed for individuals with Parkinson's disease (IwPD), the popularity of traditional forms of dance is increasing. The aim of this study was to evaluate the effects of Sardinian folk dance (Ballu Sardu, BS) on functional performance and motor and nonmotor symptoms in IwPD. DESIGN:Single-blind, randomized controlled pilot trial. SETTINGS:Outpatient health clinic. SUBJECTS AND INTERVENTIONS:Twenty IwPD (13M, 7F; 67.4 ± 6.1 years) were randomly assigned to BS (n = 10) or usual care (n = 10). The dance program consisted of two sessions/week, 90-min/class, for 12 weeks. OUTCOME MEASURES:Motor and nonmotor symptoms, as well as functional performance, were evaluated using different questionnaires and tests such as the Unified Parkinson's Disease Rating Scale Part-III (UPDRS-III), 6-min walking test (6MWT), Berg Balance Scale (BBS), Timed Up-and-Go (TUG) test, Five Times Sit-to-Stand Test (FTSST), Back Scratch Test (BST), Sit-and-Reach Test (SRT), instrumented gait analysis, Parkinson's Disease Fatigue Scale (PFS-16), Beck Depression Inventory, Starkstein Apathy Scale (SAS), and Montreal Cognitive Assessment (MOCA) scale. RESULTS:Repeated-measures analysis of variance revealed significant Time × Group interactions for UPDRS-III and functional variables such as the 6MWT, BBS, FTSST, TUG (all, p < 0.001), BST (p = 0.04), and gait analysis parameters (stride length, p = 0.031; gait speed, p = 0.049; and gait fatigue index (GFI), p = 0.005). For nonmotor symptoms, significant Time × Group interactions for depression (p < 0.001), apathy (p = 0.016), and MOCA scores (p = 0.012) were observed. Of note, for GFI and SAS, the BS group only showed a trend toward improvement, while the condition of the controls worsened significantly. No between-group differences were observed for SRT and PFS-16. CONCLUSIONS:BS is an enjoyable activity, which has been proved to be superior to usual care alone in inducing changes in different motor and nonmotor symptoms associated with PD. Results show that BS can be considered a safe tool for contrasting impairments observed in IwPD due to the intrinsic nature of the neurodegenerative disease.

Objective: Electroencephalography (EEG) is widely employed in the study of sleep disorders. This paper exploits the identification of cyclic alternating patterns (CAPs), a periodic ubiquitous phenomenon nested in the sleep stages, to analyze the EEG spectral coherence in subjects affected by nocturnal frontal lobe epilepsy (NFLE) and healthy controls. Methods: For each EEG recording, we extracted several CAP A1 subtype 4 s time series. We analyze the coherence between each pair of electrodes for each individual to obtain its distribution for each frequency range of interest to investigate differences between cases and controls. In addition, the imaginary and real parts of the spectral coherence were calculated and plotted to assess their likelihood of segregation into different classes and anatomical regions. Results: The results of this study suggest a relevant frontal-temporal neural circuitry difference between individuals affected by epilepsy and controls. Conclusion: This supports the observation that, though highly variable, a broad range of executive, cognitive and attentional deficit observed in subjects affected by NFLE might depend on frontal-temporal altered networking. Significance: The investigation of EEG activity in the domain of the complex sleep architecture represents a challenging topic in neurophysiology and needs new methods to explore the manifold aspects of sleep. This work aims to provide a simple method to distinguish NFLE from healthy subjects from a functional connectivity point of view and to explore the possibility of using a smaller EEG channel set to support diagnosis.

Human beings are “rule-following animals” or “nomic animals” whose behaviour is strictly supported by social norms that reflect shared expectations on what a particular social context considers as appropriate behaviour. Yet, little is known about the biological processes that determine how we learn to accept a particular social behaviour as the most appropriate, and even less is available to highlight the deepest levels/reasons that motivate the trade-off between the daily practice of individual habits and the processes involved in conforming them to such codified social expectations as norms are. In this essay, the authors set out to investigate this particular human ability which is indeed fundamental to understanding our social world: in doing so we hypothesise that the biologically hardwired structural organization and the phenotype expressed by individual habits are the benchmark where social norms are challenged. However, by suggesting that the manifold modalities of observing or violating the norms can be subtly constrained by the individual neurobiological milieu, one can only add another problem as the essay cannot account for the very essence of this trade-off which remains largely unexplored and open to new exciting questions.