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Background and ObjectivesNeuroimaging studies suggest that changes in the cerebellar-basal ganglia-thalamo-cortical sensorimotor circuit are a pathophysiologic feature of focal dystonia. However, it remains unclear whether structural and functional alterations vary in different forms of focal dystonia. Thus, in patients with cervical dystonia (CD) and blepharospasm (BSP), we aimed to investigate structural damage and resting-state functional alterations using whole-brain and seed-based approaches to test the hypothesis of possible functional connectivity (FC) alterations in specific circuits, including the cerebellum, basal ganglia, and cerebral cortex, in the context of preserved global FC.MethodsIn this cross-sectional study, we applied a multimodal 3T MRI protocol, including 3-dimensional T1-weighted images to extract brain volumes and cortical thickness, and fMRI at rest to study FC of the dentate nucleus and globus pallidus with a seed-based approach and whole-brain FC with a graph theory approach.ResultsThis study included 33 patients (17 with CD [14 female] age 55.7 ± 10.1 years, 16 with BSP [11 female] age 62.9 ± 8.8 years) and 16 age- and sex-matched healthy controls (HC) (7 female) 54.3 ± 14.3 years if age. Patients with CD, patients with BSP, and HC did not differ in terms of cortical or subcortical volume. Compared to HC, both patients with CD and patients with BSP had a loss of dentate FC anticorrelation with the sensorimotor cortex. Patients with CD and those with BSP showed increased pallidal FC with the cerebellum, supplementary motor area, and prefrontal cortices with respect to HC. Increased dentate FC with the cerebellum and thalamus and increased pallidal FC with the bilateral thalamus, sensorimotor and temporo-occipital cortices, and right putamen were present in patients with CD but not patients with BSP compared to HC. Measures of global FC, that is, global efficiency and small-worldness, did not differ between patients and HC.DiscussionBoth patients with CD and those with BSP showed altered dentate and pallidal FC with regions belonging to the integrated cerebellar-basal ganglia-thalamo-cortical sensorimotor circuit, supporting the concept that focal dystonia is a disorder of specific networks and not merely a result of basal ganglia alterations in the context of a preserved whole-brain functional architecture. Differences in functional interplay among specific brain structures may distinguish CD and BSP.

As atrophy represents the most relevant driver of progression in multiple sclerosis (MS), we investigated the impact of different patterns of brain and spinal cord atrophy on disability worsening in MS. We acquired clinical and MRI data from 90 patients with relapsing–remitting MS and 24 healthy controls (HC). Clinical progression at follow-up (mean 3.7 years) was defined according to the Expanded Disability Status Scale-Plus. Brain and spinal cord volumes were computed on MRI brain scans. After normalizing each participants’ brain and spine volume to the mean of the HC, z-score cut-offs were applied to separate pathologically atrophic from normal brain and spine volumes (accepting a 2.5% error probability). Accordingly, MS patients were classified into four groups (Group I: no brain or spinal cord atrophy N = 40, Group II: brain atrophy/no spinal cord atrophy N = 11, Group III: no brain atrophy/ spinal cord atrophy N = 32, Group IV: both brain and spinal cord atrophy N = 7). All patients’ groups showed significantly lower brain volume than HC (p p p = 0.049) and Group IV (p = 0.023) vs Group I, and in Group IV (p = 0.048) vs Group III. Spinal cord atrophy (OR = 3.75, p = 0.018) and brain + spinal cord atrophy (OR = 5.71, p = 0.046) were significant predictors of disability progression. The presence of concomitant brain and spinal cord atrophy is the strongest correlate of progression over time. Isolated spinal cord atrophy exerts a similar effect, confirming the leading role of spinal cord atrophy in the determination of motor disability.

Background: Damage to the cerebellar sensorimotor and cognitive domains may underlie physical and cognitive disability. Objective: To investigate resting-state functional connectivity (FC) of sensorimotor and cognitive cerebellum, and clinical correlates in multiple sclerosis (MS). Methods: A total of 119 patients with MS and 42 healthy subjects underwent multimodal 3T-magnetic resonance imaging (MRI). Patients were evaluated using the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite Scale. After parcellation of sensorimotor (lobules I–V + VIII) and cognitive cerebellum (lobules VI, VII, IX, X), we calculated cerebellar resting-state FC using a seed-based approach. Results: In patients with MS, the sensorimotor cerebellum showed increased FC mainly with cerebellar, thalamic, and cortical (frontal, parietal, temporal) areas and decreased FC with insular areas; the cognitive cerebellum showed increased FC mainly with thalamic and cortical (temporal-occipital) areas, and decreased FC with frontal-insular areas. Both sensorimotor and cognitive cerebellar FC negatively correlated with disability, and positively with cognitive scores. Cerebellar structural damage only partially influenced results. Conclusion: The two neocerebellar circuits showed altered FC with subcortical and cortical areas. The association between increased sensorimotor and cognitive cerebellar FC and low levels of physical and cognitive disability suggests that altered FC might modulate the effects of cerebellar structural damage on clinical condition.

Tourette syndrome (TS) and early-onset obsessive-compulsive disorder (OCD) are frequently associated and conceptualized as distinct phenotypes of a common disease spectrum. However, the nature of their relationship is still largely unknown on a pathophysiological level. In this study, early structural white matter (WM) changes investigated through diffusion tensor imaging (DTI) were compared across four groups of drug-naïve children: TS-pure (n = 16), TS+OCD (n = 14), OCD (n = 10), and 11 age-matched controls. We analyzed five WM tracts of interest, i.e., cortico-spinal tract (CST), anterior thalamic radiations (ATR), inferior longitudinal fasciculus (ILF), corpus callosum (CC), and cingulum and evaluated correlations of DTI changes to symptom severity. Compared to controls, TS-pure and TS+OCD showed a comparable pattern of increased fractional anisotropy (FA) in CST, ATR, ILF and CC, with FA changes displaying negative correlation to tic severity. Conversely, in OCD, FA decreased in all WM tracts (except for the cingulum) compared to controls and negatively correlated to symptoms. We demonstrate different early WM microstructural alterations in children with TS-pure/TS+OCD as opposed to OCD. Our findings support the conceptualization of TS+OCD as a subtype of TS while suggesting that OCD is characterized by independent pathophysiological mechanisms affecting WM development.

Essential tremor (ET) is one of the most common movement disorders. Over the last 10 years, magnetic resonance imaging (MRI) has shed light on the structural and functional abnormalities possibly involved in ET pathophysiology. In this systematic review, we aimed to identify the cortical and subcortical structures involved and the role that different brain areas play in the pathophysiology of motor and non-motor ET features. We found that structural (grey and white matter) cerebellar damage and connectivity alterations between the cerebellum and various cortical areas play a role in both motor and non-motor symptoms of ET. In particular, many studies found an association between MRI findings and non-motor symptoms.

Cognitive fatigability in multiple sclerosis represents the decrease in cognitive performance over time. It is a frequent symptom that negatively affects quality of life and ability to work. There are no objective measures of cognitive fatigability. This study aimed at quantifying cognitive fatigability despite the learning effect and to clarify whether cognitive fatigability represents a free-standing phenomenon rather than an aspect of cognitive impairment. We measured information processing speed with the Symbol Digit Modalities Test, and the number of right answers was recorded every 30 s for 180 s. We approximated the number of right answers as function of time with two logarithmic models, one including a first-order term alone and the other adding also a second-order term. The coefficient of the latter (B) may quantify performance deflection and may represent cognitive fatigability. We tested 173 patients with multiple sclerosis, including 119 cognitively impaired and 54 cognitively preserved patients, and 35 healthy subjects. The performance of cognitively preserved patients showed a deflection at the end of task that was detected neither in controls nor in cognitively impaired patients and needed a second-order term to be approximated (p < .03, F = 14.02). B was explained neither by depression nor fatigue. We proposed for the first time a method to quantify cognitive fatigue via a second-order least square fit model, easily usable in the clinical practice. By using this novel approach, cognitive fatigability results to be a free-standing phenomenon that is more evident in cognitively preserved than in cognitive impaired patients.

We investigated changes in gray matter (GM) and white matter (WM) in the whole brain, including both cortical and subcortical structures, and their relationship with tremor severity, psychiatric symptoms, and cognitive impairment in patients affected by essential tremor (ET). We studied 19 ET patients and 15 healthy subjects (HS). All the subjects underwent a 3-T MRI study based on 3D-T1 and diffusion tensor images. For the GM analysis, cortical thickness was assessed by using the Computational Anatomy Tool, basal ganglia and thalamus volumes by using the FMRIB software library, and cerebellum lobular volumes by using the spatial unbiased atlas template. For the WM assessment, we performed a voxel-wise analysis by means of tract-based spatial statistics. Patients’ tremor severity and psychiatric and cognitive disorders were evaluated by means of standard clinical scales. Neuroimaging data were correlated with clinical scores. We found significantly smaller right and left thalamic volumes in ET patients than in HS, which correlated with cognitive scores. We did not observe any significant differences either in cortical thickness or in cerebellar lobular volumes between patients and HS. WM abnormalities were detected in most hemisphere bundles, particularly in the corticospinal tract, cerebellar peduncles, and corpus callosum. The WM abnormalities significantly correlated with tremor severity, cognitive profile, and depression. Our study indicates that ET is characterized by several GM and WM changes of both infra- and supratentorial brain structures. The results may help to better understand mechanisms underlying tremor severity and psychiatric and cognitive impairment in ET. • We performed a comprehensive evaluation of gray and white matter in the same sample of patients with essential tremor using recently developed data analysis methods. • Essential tremor is characterized by widespread gray and white matter changes in both infra- and supratentorial brain structures. The results may help to better understand motor and non-motor symptoms in patients with essential tremor.

Multiple Sclerosis (MS) is a chronic neurological disease that represents a leading cause of disability in young adults and is characterized by inflammation and degeneration of both white matter (WM) and gray matter (GM). Defining the presence or absence of inflammation on individual basis is a key point in choosing the therapy and monitoring the treatment response. Magnetic resonance imaging (MRI) represents the most sensitive non-invasive tool to monitor inflammation in the clinical practice. Indeed, in the early phase of inflammation MRI detects new lesions as extrusion of gadolinium contrast agents across the altered blood-brain-barrier (BBB). The occurrence of MRI lesions is used to confirm diagnosis and has been validated as surrogate marker of relapse to monitor response to treatments. However, focal gadolinium-enhancing lesions represent only an aspect of neuroinflammation. Recent studies have suggested the presence of a widespread inflammation of the central nervous system (CNS), which is mainly related to microglial cells activation occurring both at the edge of chronic focal lesions and throughout the normal-appearing brain tissue. New imaging techniques have been developed to study diffuse inflammation taking place outside the focal plaques. The scope of this review is to examine the various neuroimaging techniques and those biophysical quantities that can be non-invasively detected to enlighten the different aspects of neuroinflammation. Some techniques are commonly used in the clinical practice, while others are used in the research field to better understand the pathophysiological mechanisms of the disease and the role of inflammation.

Short-term disability progression was predicted from a baseline evaluation in patients with multiple sclerosis (MS) using their three-dimensional T1-weighted (3DT1) magnetic resonance images (MRI). One-hundred-and-eighty-one subjects diagnosed with MS underwent 3T-MRI and were followed up for two to six years at two sites, with disability progression defined according to the expanded-disability-status-scale (EDSS) increment at the follow-up. The patients’ 3DT1 images were bias-corrected, brain-extracted, registered onto MNI space, and divided into slices along coronal, sagittal, and axial projections. Deep learning image classification models were applied on slices and devised as ResNet50 fine-tuned adaptations at first on a large independent dataset and secondly on the study sample. The final classifiers’ performance was evaluated via the area under the curve (AUC) of the false versus true positive diagram. Each model was also tested against its null model, obtained by reshuffling patients’ labels in the training set. Informative areas were found by intersecting slices corresponding to models fulfilling the disability progression prediction criteria. At follow-up, 34% of patients had disability progression. Five coronal and five sagittal slices had one classifier surviving the AUC evaluation and null test and predicted disability progression (AUC > 0.72 and AUC > 0.81, respectively). Likewise, fifteen combinations of classifiers and axial slices predicted disability progression in patients (AUC > 0.69). Informative areas were the frontal areas, mainly within the grey matter. Briefly, 3DT1 images may give hints on disability progression in MS patients, exploiting the information hidden in the MRI of specific areas of the brain.

In‐scanner head motion represents a major confounding factor in functional connectivity studies and it raises particular concerns when motion correlates with the effect of interest. One such instance regards research focused on functional connectivity modulations induced by sustained cognitively demanding tasks. Indeed, cognitive engagement is generally associated with substantially lower in‐scanner movement compared with unconstrained, or minimally constrained, conditions. Consequently, the reliability of condition‐dependent changes in functional connectivity relies on effective denoising strategies. In this study, we evaluated the ability of common denoising pipelines to minimize and balance residual motion‐related artifacts between resting‐state and task conditions. Denoising pipelines—including realignment/tissue‐based regression, PCA/ICA‐based methods (aCompCor and ICA‐AROMA, respectively), global signal regression, and censoring of motion‐contaminated volumes—were evaluated according to a set of benchmarks designed to assess either residual artifacts or network identifiability. We found a marked heterogeneity in pipeline performance, with many approaches showing a differential efficacy between rest and task conditions. The most effective approaches included aCompCor, optimized to increase the noise prediction power of the extracted confounding signals, and global signal regression, although both strategies performed poorly in mitigating the spurious distance‐dependent association between motion and connectivity. Censoring was the only approach that substantially reduced distance‐dependent artifacts, yet this came at the great cost of reduced network identifiability. The implications of these findings for best practice in denoising task‐based functional connectivity data, and more generally for resting‐state data, are discussed., We showed the inefficacy of many denoising strategies in balancing motion‐related artifacts between functional conditions that are differently prone to motion, such as rest and cognitively demanding conditions. While no pipeline was able to completely suppress motion artifacts and simultaneously maximize network identifiability, we found that strategies exploiting an optimized aCompCor yielded the best results. Importantly, we advocate the use of censoring with caution, since we found the method to be cost ineffective, prone to introduce biases and to reduce network identifiability.

Objective: To evaluate baseline characteristics predictive of improving information processing speed in multiple sclerosis (MS) and the relationship between cognitive and motor response to dalfampridine (DA) treatment. Methods: This is a post hoc analysis of a randomized, double-blind, placebo-controlled trial in patients with MS randomized to receive DA 10 mg or placebo twice daily for 12 consecutive weeks. Here, we include only data from 71 patients in the arm treated with DA. According to the median value of Symbol Digit Modalities Test (SDMT) response, patients were categorized as “full responders” (FR) or “partially responders” (PR). Results: There was higher possibility of being FR in the presence of a baseline lower Expanded Disability Status Scale [odds ratio (OR) 0.69; 95% confidence interval (CI) 0.5–0.97, p = 0.034], a higher Multiple Sclerosis Functional Composite value (OR 1.37; 95%CI 1.05–1.8, p = 0.022), a lower Timed 25-Foot Walk Test (OR 0.76; 95% CI 0.6–0.98, p = 0.033), and a lower 9-Hole Peg Test with dominant hand (OR 0.92; 95% CI 0.86–0.99, p = 0.029). FR group did not show any significant improvement of motor performance compared with PR group. Conclusion: The current analysis shows that in MS patients with cognitive deficit, the greatest improvement in SDMT provided by DA was observed in patients with milder motor impairment; cognitive and motor responses to treatments are not related. Trial registration: EU Clinical Trials Register; ID 2013-002558-64 ( https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-002558-64 )

Tourette syndrome (TS) and obsessive–compulsive disorder (OCD) are two neurodevelopmental disorders characterized by repetitive behaviors. Our recent study in drug-naive children with TS and OCD provided evidence of cerebellar involvement in both disorders. In addition, cerebellar functional connectivity (FC) was similar in TS patients without comorbidities (TSpure) and TS patients with OCD comorbidity (TS + OCD), but differed in pure OCD patients. To investigate in detail the cerebellar involvement in the pathophysiology of TS and OCD, we explored cerebellar structural and functional abnormalities in drug-naive children with TSpure, TS + OCD, and OCD and assessed possible correlations with severity scores. We examined 53 drug-naive children, classified as TSpure (n = 16), TS + OCD (n = 14), OCD (n = 11), or controls (n = 12). All subjects underwent a multimodal 3T magnetic resonance imaging examination. Cerebellar lobular volumes and quantitative diffusion tensor imaging parameters of cerebellar peduncles were used as measures of structural integrity. The dentate nucleus was selected as a region of interest to examine cerebello-cerebral functional connectivity alterations. Structural analysis revealed that both TSpure and TS + OCD patients had higher fractional anisotropy in cerebellar peduncles than controls. Conversely, OCD patients were characterized by lower fractional anisotropy than both controls and TSpure and TS + OCD patients. Lastly, cerebellar functional connectivity analysis revealed significant alterations in the cerebello-thalamo-cortical circuit in TSpure, TS + OCD, and OCD patients. Early cerebellar structural and functional changes in drug-naive pediatric TSpure, TS + OCD, and OCD patients support a primary role of the cerebellum in the pathophysiology of these disorders.

BACKGROUND AND PURPOSE: Conventional MR imaging explains only a fraction of the clinical outcome variance in multiple sclerosis. We aimed to evaluate machine learning models for disability prediction on the basis of radiomic, volumetric, and connectivity features derived from routine brain MR images. MATERIALS AND METHODS: In this retrospective cross-sectional study, 3T brain MR imaging studies of patients with multiple sclerosis, including 3D T1-weighted and T2-weighted FLAIR sequences, were selected from 2 institutions. T1-weighted images were processed to obtain volume, connectivity score (inferred from the T2 lesion location), and texture features for an atlas-based set of GM regions. The site 1 cohort was randomly split into training (n = 400) and test (n = 100) sets, while the site 2 cohort (n = 104) constituted the external test set. After feature selection of clinicodemographic and MR imaging–derived variables, different machine learning algorithms predicting disability as measured with the Expanded Disability Status Scale were trained and cross-validated on the training cohort and evaluated on the test sets. The effect of different algorithms on model performance was tested using the 1-way repeated-measures ANOVA. RESULTS: The selection procedure identified the 9 most informative variables, including age and secondary-progressive course and a subset of radiomic features extracted from the prefrontal cortex, subcortical GM, and cerebellum. The machine learning models predicted disability with high accuracy (r approaching 0.80) and excellent intra- and intersite generalizability (r ≥ 0.73). The machine learning algorithm had no relevant effect on the performance. CONCLUSIONS: The multidimensional analysis of brain MR images, including radiomic features and clinicodemographic data, is highly informative of the clinical status of patients with multiple sclerosis, representing a promising approach to bridge the gap between conventional imaging and disability.

Objective To explore whether abnormal thalamic resting-state functional connectivity (rsFC) contributes to altered sensorimotor integration and hand dexterity impairment in multiple sclerosis (MS). Methods To evaluate sensorimotor integration, we recorded kinematic features of index finger abductions during somatosensory temporal discrimination threshold (STDT) testing in 36 patients with relapsing-remitting MS and 39 healthy controls (HC). Participants underwent a multimodal 3T structural and functional MRI protocol. Results Patients had lower index finger abduction velocity during STDT testing compared to HC. Thalamic rsFC with the precentral and postcentral gyri, supplementary motor area (SMA), insula, and basal ganglia was higher in patients than HC. Intrathalamic rsFC and thalamic rsFC with caudate and insula bilaterally was lower in patients than HC. Finger movement velocity positively correlated with intrathalamic rsFC and negatively correlated with thalamic rsFC with the precentral and postcentral gyri, SMA, and putamen. Conclusions Abnormal thalamic rsFC is a possible substrate for altered sensorimotor integration in MS, with high intrathalamic rsFC facilitating finger movements and increased thalamic rsFC with the basal ganglia and sensorimotor cortex contributing to motor performance deterioration. Significance The combined study of thalamic functional connectivity and upper limb sensorimotor integration may be useful in identifying patients who can benefit from early rehabilitation to prevent upper limb motor impairment.

To evaluate the role of iron deposition in subcortical nuclei of patients with essential tremor (ET). Twenty-three patients with ET underwent a standardized 3T-MRI protocol. We specifically assessed iron deposition using susceptibility-weighted angiography (SWAN) images in seven specific regions of interest (ROIs): the thalamus, putamen, globus pallidus, caudate nucleus, substantia nigra, red nucleus, and dentate nucleus. Tremor in ET patients was clinically assessed using the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). ET patient data were compared with data obtained from 23 Parkinson’s disease (PD) patients and 14 healthy subjects (HS). No differences in iron deposition in the seven ROIs were found between ET patients and HS. Conversely, PD patients showed increased iron deposition in the substantia nigra in comparison with both ET patients and HS. Our results indicate the absence of iron deposition in subcortical nuclei of ET patients, which is generally considered a marker of neurodegeneration.

Previous studies in cohorts of Tourette syndrome (TS) or obsessive-compulsive disorder (OCD) patients have not clarified whether these two disorders represent two clinical conditions or they are distinct clinical phenotypes of a common disease spectrum. The study aimed to compare functional connectivity (FC) patterns in a pediatric drug-naive cohort of 16 TS patients without any comorbidity (TS), 14 TS patients with OCD (TS + OCD), and 10 pure OCD patients as well as 11 matched controls that underwent resting state fMRI. Via independent component analysis, we examined FC in the basal ganglia (BGN), sensorimotor (SMN), cerebellum (CBN), frontoparietal (FPN), default-mode (DMN), orbitofrontal (OBFN), and salience (SAN) networks among the above cohorts and their association with clinical measures. Compared to controls, TS and TS + OCD patients showed higher FC in the BGN, SMN, CBN and DMN and lower FC in the FPN and SAN. The TS and TS + OCD groups showed comparable FC in all networks. In contrast to controls, OCD patients exhibited increased FC in the BGN, SMN, CBN, DMN, FPN, and SAN. OCD patients also showed higher FC in CBN and FPN when compared with TS and TS + OCD patients both separately and as one group. Tic severity negatively correlated with FC in CBN and FPN in the TS group, while the compulsiveness scores positively correlated with the same two networks in OCD patients. Our findings suggest common FC changes in TS and TS + OCD patients. In contrast, OCD is characterized by a distinctive pattern of FC changes prominently involving the CBN and FPN.

Highlights • This systematic review focuses on structural and functional neuroimaging findings in PD patients with FOG. • The existing neuroimaging literature may explain several mechanisms underpinning FOG in PD. • FOG in PD reflect structural or functional damage in brain regions responsible for human locomotion., Freezing of gait (FOG) is a paroxysmal gait disorder that often occurs at advanced stages of Parkinson's disease (PD). FOG consists of abrupt walking interruption and severe difficulty in locomotion with an increased risk of falling. Pathophysiological mechanisms underpinning FOG in PD are still unclear. However, advanced MRI and nuclear medicine studies have gained relevant insights into the pathophysiology of FOG in PD. Neuroimaging studies have demonstrated structural and functional abnormalities in a number of cortical and subcortical brain regions in PD patients with FOG. In this paper, we systematically review existing neuroimaging literature on the structural and functional brain changes described in PD patients with FOG, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We evaluate previous studies using various MRI techniques to estimate grey matter loss and white matter degeneration. Moreover, we review functional brain changes by examining functional MRI and nuclear medicine imaging studies. The current review provides up-to-date knowledge in this field and summarizes the possible mechanisms responsible for FOG in PD.

Despite previous functional MRI studies on alterations within the cerebello-thalamo-cortical circuit in patients with essential tremor (ET), the specific role of disconnection of the dentate nucleus (DN), the main output cerebellar pathway, still needs clarification. In this study, we evaluated DN functional connectivity (FC) changes and their relationship with motor and non-motor symptoms in ET. We studied 25 ET patients and 26 healthy controls. Tremor severity was assessed using the Fahn–Tolosa–Marin tremor rating scale (FTM-TRS) and tremor amplitude and frequency were evaluated using kinematic techniques. Cognitive profile was assessed by montreal cognitive assessment (MoCA) and frontal assessment battery (FAB). All participants underwent a 3 T MRI protocol including resting-state blood oxygenation level dependent and diffusion tensor sequences. We used a seed-based approach to investigate DN FC and to explore the diffusion properties of cerebellar peduncles. There was significantly decreased DN FC with cortical, subcortical, and cerebellar areas in ET patients compared with healthy controls. Correlation analysis showed that: (1) the DN FC with the supplementary motor area, pre and postcentral gyri, and prefrontal cortex negatively correlated with FTM-TRS score and disease duration; (2) DN FC changes in the thalamus and caudate negatively correlated with peak tremor frequency, changes in the cerebellum positively correlated with tremor amplitude, and changes in the bilateral thalamus negatively correlated with tremor amplitude, and (3) DN FC with the associative prefrontal and parietal cortices, basal ganglia, and thalamus positively correlated with the MoCA score. Diffusion abnormalities were found in the three cerebellar peduncles, which did not correlate with clinical scores.

To characterize the relation between brain functional connectivity and disability in patients with multiple sclerosis; to investigate the existence of critical values of both disability and functional connectivity corresponding to exhaustion of functional adaptive mechanisms.Hundred-and-nineteen patients with no-to-severe disability and 42 healthy subjects were studied via 3T resting state functional MRI. Out of 116 regions extracted from Automated Anatomical Labeling atlas, pairs of regions whose functional connectivity correlated with Expanded Disability Status Score were identified. In patients, mathematical modeling was applied to find the best models describing Expanded-Disability-Status-Score vs structural or functional measures. Functional vs structural models intersecting points were identified.Disability had direct linear relation with lesion load (r = 0.40, p 5E-6), inverse of thalamic volume (r = 0.31 p 1E-3) and functional connectivity in bi-frontal pairs of regions (r 0.40, p 0.04), while being non-linearly associated with functional connectivity in cerebello-temporal and cerebello-frontal pairs of regions (F 1.73, p 0.02). Structural vs functional models intersecting points corresponded to Expanded Disability Status Score of 3.0. 85% of patients scoring more than 3.0 showed functional connectivity in cerebello-temporal and cerebello-frontal pairs of regions below confidence intervals (z = [2.28-2.88] 95% CI) measured in healthy subjects.Functional brain connectivity changes may represent mechanisms of adaptation to structural damage and inflammation and may be not always clinically beneficial. Functional connectivity decreases in comparison with structural measure at Expanded Disability Status Score greater than 3.0, which may be critical and indicate exhaustion of compensatory mechanisms.

Neuroplasticity, which is the ability of the brain to adapt to internal and external environmental changes, physiologically occurs during growth and in response to damage. The brain’s response to damage is of particular interest in multiple sclerosis, a chronic disease characterized by inflammatory and neurodegenerative damage to the central nervous system. Functional MRI (fMRI) is a tool that allows functional changes related to the disease and to its evolution to be studied in vivo. Several studies have shown that abnormal brain recruitment during the execution of a task starts in the early phases of multiple sclerosis. The increased functional activation during a specific task observed has been interpreted mainly as a mechanism of adaptive plasticity designed to contrast the increase in tissue damage. More recent fMRI studies, which have focused on the activity of brain regions at rest, have yielded nonunivocal results, suggesting that changes in functional brain connections represent mechanisms of either adaptive or maladaptive plasticity. The few longitudinal studies available to date on disease evolution have also yielded discrepant results that are likely to depend on the clinical features considered and the length of the follow-up. Lastly, fMRI has been used in interventional studies to investigate plastic changes induced by pharmacological therapy or rehabilitation, though whether such changes represent a surrogate of neuroplasticity remains unclear. The aim of this paper is to systematically review the existing literature in order to provide an overall description of both the neuroplastic process itself and the evolution in the use of fMRI techniques as a means of assessing neuroplasticity. The quantitative and qualitative approach adopted here ensures an objective analysis of published, peer-reviewed research and yields an overview of up-to-date knowledge.

We present low-resolution 5.5-35 um spectra for 103 galaxies from the 12 um Seyfert sample, a complete unbiased 12 um flux limited sample of local Seyfert galaxies selected from the IRAS Faint Source Catalog, obtained with the Infrared Spectrograph (IRS) on-board Spitzer Space Telescope. For 70 of the sources observed in the IRS mapping mode, uniformly extracted nuclear spectra are presented for the first time. We performed an analysis of the continuum emission, the strength of the Polycyclic Aromatic Hydrocarbon (PAH) and astronomical silicate features of the sources. We find that on average, the 15-30 um slope of the continuum is alpha_{15-30}=-0.85+-0.61 for Seyfert 1s and -1.53+-0.84 for Seyfert 2s, and there is substantial scatter in each type. Moreover, nearly 32% of Seyfert 1s, and 9% of Seyfert 2s, display a peak in the mid-infrared spectrum at 20 um, which is attributed to an additional hot dust component. The PAH equivalent width decreases with increasing dust temperature, asindicated by the global infrared color of the host galaxies. However, no statistical difference in PAH equivalent width is detected between the two Seyfert types, 1 and 2, of the same bolometric luminosity. The silicate features at 9.7 and 18um in Seyfert 1 galaxies are rather weak, while Seyfert 2s are more likely to display strong silicate absorption. Those Seyfert 2s with the highest silicate absorption also have high infrared luminosity and high absorption (hydrogen column density N_H>10^23 cm^-2 as measured from the X-rays. Finally, we propose a new method to estimate the AGN contribution to the integrated 12 um galaxy emission, by subtracting the "star formation" component in the Seyfert galaxies, making use of the tight correlation between PAH 11.2 um luminosity and 12 um luminosity for star forming galaxies., accepted for publication in ApJ

We present the results of a Herschel-PACS study of a sample of 97 LINERs at redshift z\sim 0.3 selected from the zCOSMOS survey. Of these sources, 34 are detected in a least one PACS band, enabling reliable estimates of the far-infrared L(FIR) luminosities, and a comparison to the FIR luminosities of local LINERs. Many of our PACS-detected LINERs are also UV sources detected by Galex. Assuming that the FIR is produced in young dusty star-forming regions, the typical star-formation rates (SFRs) for the host galaxies in our sample is \sim 10 M_Sun yr-1, 1-2 orders of magnitude larger than in many local LINERs. Given stellar masses inferred from optical/NIR photometry of the (unobscured) evolved stellar populations, we find that the entire sample lies close to the star-forming "main sequence" for galaxies at redshift 0.3. For young star-forming regions, the H\alpha- and UV-based estimates of the SFRs are much smaller than the FIR-based estimates, by factors \sim 30, even assuming that all of the H\alpha\ emission is produced by O-star ionization rather than by the AGNs. These discrepancies may be due to large (and uncertain) extinctions towards the young stellar systems. Alternatively, the H\alpha\ and UV emissions could be tracing residual star-formation in an older less obscured population with decaying star formation. We also compare L(SF) and L(AGN) in local LINERs and in our sample and comment on the problematic use of several line diagnostic diagrams in cases similar to the sample under study., Comment: Tommasin et al. 2012, ApJ, 753, 155

We present spectroscopic observations of FIR fine-structure lines of 26 Seyfert galaxies obtained with the Herschel-PACS spectrometer. These observations are complemented by spectroscopy with Spitzer-IRS and Herschel-SPIRE. The ratios of the OIII, NII, SIII and NeV lines have been used to determine electron densities in the ionised gas regions. The CI lines, observed with SPIRE, have been used to measure the densities in the neutral gas, while the OI lines provide a measure of the gas temperature, at densities below 10000 cm-3. Using the OI145/63um and SIII33/18um line ratios we find an anti-correlation of the temperature with the gas density. Using various fine-structure line ratios, we find that density stratification is common in these active galaxies. On average, the electron densities increase with the ionisation potential of the ions producing the NII, SIII and NeV emission. The infrared emission lines arise partly in the Narrow Line Region (NLR) photoionised by the AGN central engine, partly in HII regions photo ionised by hot stars and partly in neutral gas in photo-dissociated regions (PDRs). We attempt to separate the contributions to the line emission produced in these different regions by comparing our emission line ratios to empirical and theoretical values. In particular, we tried to separate the contribution of AGN and star formation by using a combination of Spitzer and Herschel lines, and we found that, besides the well known mid-IR line ratios, the mixed mid-IR/far-IR line ratio of OIII88um/OIV26um can reliably discriminate the two emission regimes, while the far-IR line ratio of CII157um/OI63um is only able to mildly separate the two regimes. By comparing the observed CII157um/NII205um ratio with photoionisation models, we also found that most of the CII emission in the galaxies we examined is due to PDRs., Comment: Accepted for publication in ApJ Main Journal on the 5th November 2014, 25 pages, 16 figures

We present the Spitzer 10-37um IRS high resolution (R~600) spectroscopic survey of the Seyfert galaxies of the 12 micron Galaxy Sample. The new spectra of 61 galaxies, with those already published, gives us a total of 91 12micron Seyfert galaxies observed, out of 112. We use an improved AGN classification for Seyfert galaxies: instead of the type 1 and 2 classes, we use the spectropolarimetric data to divide them into "AGN 1" and "AGN 2", where AGN 1's include all broad-line objects, including the Seyfert 2's showing hidden broad lines in polarized light, while AGN 2's contains only Seyferts with no detectable broad lines at all. We present various mid-IR observables and we find that these properties characterize the AGN 1's objects as a single family, with strongly AGN-dominated spectra. In contrast, the AGN 2's can be divided in two groups, the first one with properties similar to the AGN 1's and the second similar to the non-Seyfert galaxies, such as LINERs or starburst galaxies. We computed a semianalytical model to estimate the AGN and the starburst contributions to the mid-IR galaxy emission at 19um. We find that AGN 1 have an AGN contribution >73% and AGN 2 >45% of their total emission at 19um. The detection of [NeV] lines is an almost perfect signature of energy production by an AGN. We present mean spectra of the various AGN categories. We derive the first local luminosity functions for the mid-infrared lines and the PAH feature. No statistical difference is found in the space densities for Seyfert 1's and 2's, nor for the new classes of AGN 1's and 2's. The global output of accretion-powered galactic nuclei in the local universe is derived from the correlation between [NeV] line and the nonstellar IR continuum luminosity.

We performed an analysis of the mid-infared properties of the 12micron Seyfert sample, a complete unbiased 12micron flux limited sample of local Seyfert galaxies selected from the IRAS Faint Source Catalog, based on low resolution spectra obtained with the Infrared Spectrograph (IRS) on-board Spitzer Space Telescope. A detailed presentation of this analysis is dicussed in Wu et al. (2009). We find that on average, the 15-30micron slope of the continuum is -0.85+/-0.61 for Seyfert 1s and -1.53+/-0.84 for Seyfert 2s, and there is substantial scatter in each type. Moreover, nearly 32% of Seyfert 1s, and 9% of Seyfert 2s, display a peak in the mid-infrared spectrum at 20micron, which is attributed to an additional hot dust component. The Polycyclic Aromatic Hydrocarbon (PAH) equivalent width decreases with increasing dust temperature, as indicated by the global infrared color of the host galaxies. However, no statistical difference in PAH equivalent width is detected between the two Seyfert types, 1 and 2, of the same bolometric luminosity. Finally, we propose a new method to estimate the AGN contribution to the integrated 12micron galaxy emission, by subtracting the "star formation" component in the Seyfert galaxies, making use of the tight correlation between PAH 11.2micron luminosity and 12micron luminosity for star forming galaxies., Comment: Oral Contribution to Proceedings of IAU Symp. 267, "Co-evolution of Central Black Holes and Galaxies", 6 pages, 2 figures

The first high resolution Spitzer IRS 9-37um spectra of 29 Seyfert galaxies (about one quarter) of the 12um Active Galaxy Sample are presented and discussed. The high resolution spectroscopy was obtained with corresponding off-source observations. This allows excellent background subtraction, so that the continuum levels and strengths of weak emission lines are accurately measured. The result is several new combinations of emission line ratios, line/continuum and continuum/continuum ratios that turn out to be effective diagnostics of the strength of the AGN component in the IR emission of these galaxies. The line ratios [NeV]/[NeII], [OIV]/[NeII], already known, but also [NeIII]/[NeII] and [NeV]/[SiII] can all be effectively used to measure the dominance of the AGN. We extend the analysis, already done using the 6.2um PAH emission feature, to the equivalent width of the 11.25um PAH feature, which also anti-correlates with the dominance of the AGN. We measure that the 11.25um PAH feature has a constant ratio with the H_2 S(1) irrespective of Seyfert type, approximately 10 to 1. Using the ratio of accurate flux measurements at about 19um with the two spectrometer channels, having aperture areas differing by a factor 4, we measured the source extendness and correlated it with the emission line and PAH feature equivalent widths. The extendness of the source gives another measure of the AGN dominance and correlates both with the EWs of [NeII] and PAH emission. Using the rotational transitions of H$_2$ we were able to estimate temperatures (200-300K) and masses (1-10 x 10^6 M_sun), or significant limits on them, for the warm molecular component in the galaxies observed., Comment: submitted to ApJ, Aug.2007, revised, in the refereeing process

Spontaneous low-frequency Blood–Oxygenation Level–Dependent (BOLD) signals acquired during resting state are characterized by spatial patterns of synchronous fluctuations, ultimately leading to the identification of robust brain networks. The resting-state brain networks, including the Default Mode Network (DMN), are demonstrated to persist during sustained task execution, but the exact features of task-related changes of network properties are still not well characterized. In this work we sought to examine in a group of 20 healthy volunteers (age 33±6 years, 8F/12M) the relationship between changes of spectral and spatiotemporal features of one prominent resting-state network, namely the DMN, during the steady-state execution of a sustained working memory n-back task. We found that the steady state execution of such a task impacted on both functional connectivity and amplitude of BOLD fluctuations within large parts of the DMN, but these changes correlated between each other only in a small area of the posterior cingulate. We conclude that combined analysis of multiple parameters related to connectivity, and their changes during the transition from resting state to steady-state task execution, can contribute to a better understanding of how brain networks rearrange themselves in response of a task.