Search

Background Borderline Personality Disorder (BPD) is a complex and debilitating disorder, characterized by deficits in metacognition and emotion dysregulation. The “gold standard” treatment for this disorder is psychotherapy with pharmacotherapy as an adjunctive treatment to target state symptoms. The present randomized clinical trial aims to assess the clinical and neurobiological changes following Metacognitive Interpersonal Therapy (MIT) compared with Structured Clinical Management (SCM) derived from specific recommendations in APA (American Psychiatric Association) guidelines for BPD. Methods The study design is a randomized parallel controlled clinical trial and will include 80 BPD outpatients, aged 18–45 enrolled at 2 recruitment centers. Primary outcome will be the clinical change in emotion regulation capacities assessed with the Difficulties in Emotion Regulation Scale (DERS). We will also investigated the effect of psychotherapy on metacognitive abilities and several clinical features such as BPD symptomatology, general psychopathology, depression, personal functioning, and trait dimensions (anger, impulsivity, alexithymia). We will evaluate changes in brain connectivity patterns and during the view of emotional pictures. A multidimensional assessment will be performed at the baseline, at 6, 12, 18 months. We will obtain structural and functional Magnetic Resonance Images (MRIs) in MIT-Treated BPD (N = 30) and SCM-treated BPD (N = 30) at baseline and after treatment, as well as in a group of 30 healthy and unrelated volunteers that will be scanned once for comparison. Discussion The present study could contribute to elucidate the neurobiological mechanisms underlying psychotherapy efficacy. The inclusion of a multidisciplinary study protocol will allow to study BPD considering different features that can affect the treatment response and their reciprocal relationships. Trial registration NCT02370316. Registered 02/24/2015. Electronic supplementary material The online version of this article (10.1186/s12888-019-2127-2) contains supplementary material, which is available to authorized users.

none 28 no BACKGROUND: The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. METHOD: A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. RESULTS: We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (⩾14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI

Background: Default mode network (DMN) dysfunction is well established in Alzheimer’s disease (AD) and documented in both preclinical stages and at-risk subjects, thus representing a potential disease target. Multi-sessions of repetitive transcranial magnetic stimulation (rTMS) seem capable of modulating DMN dynamics and memory in healthy individuals and AD patients; however, the potential of this approach in at-risk subjects has yet to be tested. Objective: This study will test the effect of rTMS on the DMN in healthy older individuals carrying the strongest genetic risk factor for AD, the Apolipoprotein E (APOE) ɛ4 allele. Methods: We will recruit 64 older participants without cognitive deficits, 32 APOE ɛ4 allele carriers and 32 non-carriers as a reference group. Participants will undergo four rTMS sessions of active (high frequency) or sham DMN stimulation. Multimodal imaging exam (including structural, resting-state, and task functional MRI, and diffusion tensor imaging), TMS with concurrent electroencephalography (TMS-EEG), and cognitive assessment will be performed at baseline and after the stimulation sessions. Results: We will assess changes in DMN connectivity with resting-state functional MRI and TMS-EEG, as well as changes in memory performance in APOE ɛ4 carriers. We will also investigate the mechanisms underlying DMN modulation through the assessment of correlations with measures of neuronal activity, excitability, and structural connectivity with multimodal imaging. Conclusion: The results of this study will inform on the physiological and cognitive outcomes of DMN stimulation in subjects at risk for AD and on the possible mechanisms. These results may outline the design of future non-pharmacological preventive interventions for AD.

Background and purpose In multiple sclerosis (MS), depression is a common disorder whose pathophysiology is still debated. To gain insights into the pathophysiology of depression in MS, resting-state (RS) functional connectivity (FC) changes of the default mode network (DMN), salience network (SN) and executive control network (ECN) were assessed in a group of depressed MS (D-MS) patients and in appropriately matched control groups. Methods Sixteen D-MS patients, 17 non-depressed MS (ND-MS) patients, 17 non-depressed healthy controls and 15 depressed subjects (D-S), age, sex and education matched, cognitively preserved and non-fatigued, were enrolled. All participants underwent a neuropsychological evaluation and RS functional magnetic resonance imaging study. Results Comparing D-MS patients with D-S, within the DMN, a significant RS-FC suppression was found in the posterior cingulate cortex (PCC); comparing D-MS with ND-MS, FC was significantly increased in the anterior cingulate cortex and significantly reduced in the PCC. Within the SN increased FC in the right supramarginal gyrus and right middle frontal gyrus was found in D-MS patients compared to D-S and to ND-MS; within the ECN increased FC in the right inferior parietal cortex was found in D-MS patients compared to ND-MS patients. Conclusions In cognitively preserved D-MS patients, FC derangement occurs in the SN, ECN and DMN. In the latter, changes occurring both in the anterior cingulate cortex and PCC suggest that depression in MS may be linked to MS itself and, in particular, to a peculiar pattern of network abnormalities favored by MS pathology through disconnection mechanisms. Reduced FC in the PCC, similar to MS patients with cognitive impairment, suggests a functional link between depression and cognitive impairment in MS.

Background: The default-mode network (DMN) has been increasingly recognized as relevant to cognitive status. Objectives: To explore DMN changes in patients with relapsing–remitting (RR) multiple sclerosis (MS) and to relate these to the cognitive status. Methods: Eighteen cognitively impaired (CI) and eighteen cognitively preserved (CP) RRMS patients and eighteen healthy controls (HCs), matched for age, sex and education, underwent neuropsychological evaluation and anatomical and resting-state functional MRI (rs-fMRI). DMN functional connectivity was evaluated from rs-fMRI data via independent component analysis. T2 lesion load (LL) was computed by a semi-automatic method and global and local atrophy was estimated by SIENAX and SPM8 voxel-based morphometry analyses from 3D-T1 images. Results: When the whole group of RRMS patients was compared with HCs, DMN connectivity was significantly weaker in the anterior cingulate cortex, whereas it was significantly weaker in the core but stronger at the periphery of the posterior cingulate cortex. These findings were more evident in CP than CI patients. Observed DMN changes did not correlate with global atrophy or T2-LL, but were locally associated with regional grey matter loss. Conclusion: Relapsing–remitting multiple sclerosis patients show a consistent dysfunction of DMN at the level of the anterior node. DMN distribution changes in the posterior node may reflect a possible compensatory effect on cognitive performance.

Objective To evaluate the executive control network connectivity integrity in patients with migraine with aura, in the interictal period, in comparison to patients with migraine without aura and healthy controls. Methods Using resting-state functional magnetic resonance imaging, we compared executive control network functional connectivity in 20 patients with migraine with aura vs 20 sex and age-matched patients with migraine without aura and 20 healthy controls, and assessed the correlation between executive control network functional connectivity and clinical features of patients with migraine. We used voxel-based morphometry and diffusion tensor imaging to investigate potential structural or microstructural changes. Results Neuropsychological data revealed no significant executive dysfunction in patients with migraine. Resting-state functional magnetic resonance imaging showed significant group differences in right middle frontal gyrus (Talairach coordinates x, y, z: +26, +2, +48) and dorsal anterior cingulate cortex (Talairach coordinates x, y, z: +6, +13, +49), indicating that these areas had a decreased component activity in both patients with migraine with and without aura when compared with healthy controls. Conversely, there were no significant differences in the executive control network functional connectivity between patients with migraine with and without aura (P

To better understand the effects of short-term computer-based cognitive rehabilitation (cCR) on cognitive performances and default mode network (DMN) intrinsic functional connectivity (FC) in cognitively impaired relapsing remitting (RR) multiple sclerosis (MS) patients. Eighteen cognitively impaired RRMS patients underwent neuropsychological evaluation by the Rao's brief repeatable battery and resting-state functional magnetic resonance imaging to evaluate FC of the DMN before and after a short-term (8 weeks, twice a week) cCR. A control group of 14 cognitively impaired RRMS patients was assigned to an aspecific cognitive training (aCT), and underwent the same study protocol. Correlations between DMN and cognitive performances were also tested. After cCR, there was a significant improvement of the following tests: SDMT (p < 0.01), PASAT 3" (p < 0.00), PASAT 2" (p < 0.03), SRT-D (p < 0.02), and 10/36 SPART-D (p < 0.04); as well as a significant increase of the FC of the DMN in the posterior cingulate cortex (PCC) and bilateral inferior parietal cortex (IPC). After cCR, a significant negative correlation between Stroop Color-Word Interference Test and FC in the PCC emerged. After aCT, the control group did not show any significant effect either on FC or neuropsychological tests. No significant differences were found in brain volumes and lesion load in both groups when comparing data acquired at baseline and after cCR or aCT. In cognitively impaired RRMS patients, cCR improves cognitive performances (i.e., processing speed and visual and verbal sustained memory), and increases FC in the PCC and IPC of the DMN. This exploratory study suggests that cCR may induce adaptive cortical reorganization favoring better cognitive performances, thus strengthening the value of cognitive exercise in the general perspective of building either cognitive or brain reserve.

Amyotrophic lateral sclerosis (ALS) and behavioral variant frontotemporal dementia (bvFTD) lie on a clinical, pathologic, and genetic continuum. Neuroimaging techniques have proven to be potentially useful to unravel the shared features of these syndromes. Using resting-state functional magnetic resonance imaging (RS-fMRI), we investigated functional connectivity of brain networks in 15 ALS and 15 bvFTD patients in early stages of disease and 15 healthy controls, looking expressly for connectivity pattern divergence or overlap between the 2 disorders. Compared with controls, we found decreased RS-fMRI signals within sensorimotor, right frontoparietal, salience, and executive networks in both patient groups. Within the default mode network (DMN), divergent connectivity patterns were observed, with RS-fMRI signals in the posterior cingulate cortex enhanced in bvFTD patients and suppressed in ALS patients. Our findings confirm that ALS and bvFTD not only broadly share common RS-fMRI connectivity patterns, probably representing different phenotypical expressions of the same neurodegenerative process, but also differ in the DMN, probably reflecting a different stage of neurodegeneration.

Neurodegenerative process in amyotrophic lateral sclerosis (ALS) has been proven to involve several cortical and subcortical brain regions within and beyond motor areas. However, how ALS pathology spreads progressively during disease evolution is still unknown. In this cross-sectional study we investigated 54 ALS patients, divided into 3 subsets according to the clinical stage, and 18 age and sex-matched healthy controls, by using tract-based spatial statistics (TBSS) diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) analyses. We aimed to identify white (WM) and gray matter (GM) patterns of disease distinctive of each clinical stage, corresponding to specific clinical milestones. ALS cases in stage 2A (i.e., at diagnosis) were characterized by GM and WM impairment of left motor and premotor cortices and brainstem at ponto-mesenchephalic junction. ALS patients in clinical stage 2B (with impairment of two functional regions) exhibited decreased fractional anisotropy (FA) (p

Diffusion-weighted magnetic resonance imaging (DWMRI) is used to study white matter (WM) in normal and clinical populations. In DWMRI studies, diffusion tensor imaging (DTI) models the WM anisotropy with one dominant direction, detecting possible pathway abnormalities only in large and highly coherent fiber tracts. However, more general anisotropy models like Q-ball imaging (QBI) may provide more sensitive WM descriptors in single patients. The present study aimed to compare DTI and QBI models in a group-level population analysis, using Amyotrophic Lateral Sclerosis (ALS) as a pathological case model of WM tract degeneration. DWMRI was performed in 19 ALS patients and 19 age and sex-matched healthy controls. DTI and QBI estimates were compared in whole-brain tract-based spatial statistics (TBSS) and volume of interest (VOI) analyses, and correlated with ALS clinical scores of disability. A significant decrease of the QBI-derived generalized fractional anisotropy (GFA) was observed in both motor and extramotor fibers of ALS patients compared to controls. Homologue DTI-derived FA maps were only partially overlapping with GFA maps. Particularly, the left corticospinal tracts resulted more markedly depicted by the QBI than by the DTI model, with GFA predicting ALS disability better than FA. The present findings demonstrate that QBI model is suitable for studying WM tract degeneration in population-level clinical studies. Particularly, group-level studies of fiber integrity may benefit from QBI when DTI is biased towards low values, such as in cases of fiber degeneration, and in regions with more than one dominant fiber direction.

Cognitive impairment is common in PD, even in early stages. The construct of mild cognitive impairment has been used to identify clinically evident cognitive impairment without functional decline in PD patients (PD-MCI). The aim of the present study was to investigate brain connectivity associated with PD-MCI through RS-fMRI. RS-fMRI at 3T was collected in 42 PD patients and 20 matched healthy controls. Among PD patients, 21 were classified as having MCI (PD-MCI) and 21 as cognitively unimpaired (PD-nMCI) based on criteria for possible PD-MCI (level I category). Single-subject and group-level ICA was used to investigate the integrity of brain networks related to cognition in PD patients with and without MCI. Image data processing and statistical analysis were performed in BrainVoyager QX. In addition, we used VBM to test whether functional connectivity differences were related to structural abnormalities. PD-nMCI and PD-MCI patients compared with controls showed decreased DMN connectivity. PD-MCI patients, but not PD-nMCI, compared with controls, showed decreased functional connectivity of bilateral prefrontal cortex within the frontoparietal network. The decreased prefrontal cortex connectivity correlated with cognitive parameters but not with clinical variables. VBM analysis did not reveal any difference in local gray matter between patients and controls. Our findings suggest that an altered DMN connectivity characterizes PD patients, regardless of cognitive status, whereas a functional disconnection of the frontoparietal network could be associated with MCI in PD in the absence of detectable structural changes.

Background: The North American Alzheimer's Disease Neuroimaging Initiative (NA-ADNI) was the first program to develop standardized procedures for Alzheimer's disease (AD) imaging biomarker collection. Objective: We describe the validation of acquisition and processing of structural magnetic resonance imaging (MRI) in different Italian academic AD clinics following NA-ADNI procedures. Methods: 373 patients with subjective memory impairment (n = 12), mild cognitive impairment (n = 92), Alzheimer's dementia (n = 253), and frontotemporal dementia (n = 16) were enrolled in 9 Italian centers. Also included were 22 cognitively healthy elderly controls. MRI site qualification and MP-RAGE quality assessment was applied following the NA-ADNI procedures. Indices of validity were: (i) AN-ADNI phantom's signal-to-noise and contrast-to-noise ratio, (ii) proportion of images passing quality control, (iii) comparability of automated intracranial volume (ICV) estimates across scanners, and (iv) known-group validity of manual hippocampal volumetry. Results: Results on Phantom and Volunteers scans showed that I-ADNI acquisition parameters were comparable with those one of the ranked-A ADNI scans. Eighty-seven percent of I-ADNI MPRAGE images were ranked of high quality in comparison of 69% of NA-ADNI. ICV showed homogeneous variances across scanners except for Siemens scanners at 3.0 Tesla (p = 0.039). A significant difference in hippocampal volume was found between AD and controls on 1.5 Tesla scans (p < 0.001), confirming known group validity test. Conclusion: This study has provided standardization of MRI acquisition and imaging marker collection across different Italian clinical units and equipment. This is a mandatory step to the implementation of imaging biomarkers in clinical routine for early and differential diagnosis.

In patients with progressive supranuclear palsy (PSP), previous reports have shown a severe white matter (WM) damage involving supra and infratentorial regions including cerebellum. In the present study, we investigated potential correlations between WM integrity loss and clinical-cognitive features of patients with PSP. By using magnetic resonance imaging and diffusion tensor imaging with tract based spatial statistic analysis, we analyzed WM volume in 18 patients with PSP and 18 healthy controls (HCs). All patients and HCs underwent a detailed clinical and neuropsychological evaluation. Relative to HCs, patients with PSP showed WM changes encompassing supra and infratentorial areas such as corpus callosum, fornix, midbrain, inferior fronto-occipital fasciculus, anterior thalamic radiation, superior cerebellar peduncle, superior longitudinal fasciculus, uncinate fasciculus, cingulate gyrus, and cortico-spinal tract bilaterally. Among different correlations between motor-cognitive features and WM structural abnormalities, we detected a significant association between fronto-cerebellar WM loss and executive cognitive impairment in patients with PSP. Our findings, therefore, corroborate the hypothesis that cognitive impairment in PSP may result from both "intrinsic" and "extrinsic" frontal lobe dysfunction, likely related to cerebellar disconnection.

Diffusion tensor imaging (DTI) has become a useful tool for investigating early white matter (WM) abnormalities in motor neuron disease. Furthermore, fiber tracking packages that apply multi-tensorial algorithms, such as q-ball imaging (QBI), have been proposed as alternative approaches to overcome DTI limitations in depicting fiber tracts with different orientations within the same voxel. We explored motor and extra-motor WM tract abnormalities in phenotypically heterogeneous amyotrophic lateral sclerosis (ALS) cases aiming to establish a consistent QBI-based WM signature of disease. We performed a whole-brain, QBI tract-based spatial statistics analysis with deterministic tractography of genu, body and splenium of corpus callosum (CC) and corticospinal tracts (CST) in 20 ALS patients (12 classical and 8 lower motor neuron variants) compared to 20 healthy controls. Mean tract length, fiber volume and density, and generalized fractional anisotropy were extracted and related to clinical indices of pyramidal impairment (upper motor neuron score), disease disability (ALS functional rating scale-revised) and progression. ALS patients showed significantly decreased fiber density and volume, and increased tract length in all regions of CC and left CST (p < 0.05, corrected). In CC body, pyramidal impairment was inversely correlated to fiber density (p = 0.01), while in CC splenium, clinical disability (p = 0.01) and progression (p = 0.02) were inversely correlated to tract length. Our findings further suggest that QBI tractography might represent a promising approach for investigating structural alterations in neurodegenerative diseases and confirm that callosal involvement is a consistent feature of most ALS variants, significantly related to both pyramidal dysfunction and disease disability.

BACKGROUND AND PURPOSE: The extensive application of advanced MR imaging techniques has undoubtedly improved our knowledge of the pathophysiology of amyotrophic lateral sclerosis. Nevertheless, the precise extent of neurodegeneration throughout the central nervous system is not fully understood. In the present study, we assessed the spatial distribution of cortical damage in amyotrophic lateral sclerosis by using a cortical thickness measurement approach. MATERIALS AND METHODS: Surface-based morphometry was performed on 20 patients with amyotrophic lateral sclerosis and 18 ageand sex-matched healthy control participants. Clinical scores of disability and disease progression were correlated with measures of cortical thickness. RESULTS: The patients with amyotrophic lateral sclerosis showed a significant cortical thinning in multiple motor and extramotor cortical areas when compared with healthy control participants. Gray matter loss was significantly related to disease disability in the left lateral orbitofrontal cortex (P .04), to disease duration in the right premotor cortex (P .007), and to disease progression rate in the left parahippocampal cortex (P .03). CONCLUSIONS: Cortical thinning of the motor cortex might reflect upper motor neuron impairment, whereas the extramotor involvement seems to be related to disease disability, progression, and duration. The cortical pattern of neurodegeneration depicted resembles what has already been described in frontotemporal dementia, thereby providing further structural evidence of a continuum between amyotrophic lateral sclerosis and frontotemporal dementia. ABBREVIATIONS: ALS amyotrophic lateral sclerosis; ALSFRS-R ALS Functional Rating Scale-Revised; CTh cortical thickness; FrSBe Frontal Systems Behavior Scale; FTD frontotemporal dementia; HCs healthy control participants; PMC primary motor cortex; SBM surface-based morphometry; TDP-43 transactivating responsive sequence DNA-binding protein 43-kDa; UMN upper motor neuron; VBM voxel-based morphometry

Background: Converging neuropsychological evidence suggests that in migraine executive functions (EF) may be affected during interictal periods. Objective: To evaluate the functional connectivity of the fronto-parietal networks (FPN) known to be associated with EF, in migraine without aura (MwoA) patients, in the interictal period, in comparison to healthy controls (HC). Methods: Using resting-state functional MRI (RS-fMRI), we compared functional connectivity within the FPN in 14 patients with MwoA versus 14 sex- and age-matched HC, and assessed the correlation between functional connectivity within FPN, clinical features of MwoA patients, and EF. We used voxel-based morphometry to assess whether between-group differences in functional connectivity were dependent on structural differences. Results: Neuropsychological data revealed no significant executive dysfunction in MwoA patients. RS-fMRI showed that MwoA patients, compared to HC, had significant functional connectivity reduction within the right FPN and specifically in the middle frontal gyrus (MFG) and the dorsal anterior cingulate cortex. In addition, we found that MFG reduced connectivity was negatively correlated with the pain intensity of migraine attacks. There were no structural differences between the two groups. Conclusions: Our data suggest that, even in the absence of clinically evident EF deficits, MwoA is associated with reduced FPN functional connectivity. This study provides further insights into the complex scenario of migraine mechanisms.

Objective: To investigate functional connectivity of the visual resting-state network (V-RSN) in normal-sighted relapsing-remitting multiple sclerosis (RRMS) patients with and without previous optic neuritis (ON).Methods: Thirty normal-sighted RRMS patients, 16 without (nON-MS) and 14 with (ON-MS) previous ON, and 15 age-and sex-matched healthy controls (HCs) underwent a neuro-ophthalmologic evaluation, including automated perimetry and retinal nerve fiber layer (RNFL) measurement, as well as an MRI protocol, including structural and resting-state fMRI (RS-fMRI) sequences. Functional connectivity of the V-RSN was evaluated by independent component analysis (ICA). Regional gray matter atrophy was assessed by voxel-based morphometry (VBM). A correlation analysis was performed between RS-fMRI results and clinical, neuro-ophthalmologic, and structural MRI variables.Results: Compared to HCs, patients with RRMS showed a reduced functional connectivity in the peristriate visual cortex, bilaterally. Compared to nON-MS, ON-MS patients revealed a region of stronger functional connectivity in the extrastriate cortex, at the level of right lateral middle occipital gyrus, as well as a region of reduced functional connectivity at the level of right inferior peristriate cortex. These latter changes correlated with the number of previous ON. All detected V-RSN changes did not colocalize with regional gray matter atrophy.Conclusions: Normal-sighted RRMS patients show a significant functional disconnection in the V-RSN. RRMS patients recovered from a previous ON show a complex reorganization of the V-RSN, including an increased functional connectivity at the level of extrastriate visual areas. Neurology (R) 2012;79:1458-1465

BACKGROUND AND PURPOSE: FOG is a troublesome symptom of PD. Despite growing evidence suggesting that FOG in PD may be associated with cognitive dysfunction, the relationship between regional brain atrophy and FOG has been poorly investigated. MATERIALS AND METHODS: Optimized VBM was applied to 3T brain MR images of 24 patients with PD and 12 HC. Patients were classified as either FOG− or FOG+ (n = 12) based on their responses to a validated FOG Questionnaire and clinical observation. All patients with PD also underwent a detailed neuropsychological evaluation. RESULTS: The VBM analysis in patients with FOG+ showed a reduced GM volume in the left cuneus, precuneus, lingual gyrus, and posterior cingulate cortex compared with both patients with FOG− and HC. We did not detect any significant change of GM volume when comparing HC versus all patients with PD (FOG− and FOG+). FOG clinical severity was significantly correlated with GM loss in posterior cortical regions. Finally, patients with FOG+ scored lower on tests of frontal lobe function. CONCLUSIONS: Our findings provide the first evidence that the development of FOG in patients with PD is associated with posterior GM atrophy, which may play a role in the complex pathophysiology of this disabling symptom.

Objective: Using resting-state (RS) fMRI, we investigated the functional integrity of the defaultmode network (DMN) in cognitively unimpaired patients with Parkinson disease (PD). Methods: RS fMRI at 3 T was collected in 16 cognitively unimpaired patients with PD and 16 ageand gender-matched healthy controls. Single-subject and group-level independent component analysis was used to investigate differences in functional connectivity within the DMN in patients with PD and healthy controls. Statistical analysis was performed using BrainVoyager QX. In addition, we used voxel-based morphometry to test whether between-group differences in RS functional connectivity were related to structural abnormalities. Results: Patients with PD compared with controls showed a decreased functional connectivity of the right medial temporal lobe and bilateral inferior parietal cortex within the DMN. Although patients with PD were cognitively unimpaired, the decreased DMN connectivity significantly correlated with cognitive parameters but not with disease duration, motor impairment, or levodopa therapy. The analysis of regional volume differences did not reveal any differences in local gray matter between patients and controls. Conclusions: Our findings revealed a functional disruption of the DMN in cognitively unimpaired patients with PD, in the absence of significant structural differences between patients and controls. Wehypothesize that a dysfunction of theDMNconnectivitymay have a role in the development of cognitive decline in PD. © 2012 American Academy of Neurology.

We assessed the spontaneous blood-oxygen-level-dependent signal fluctuations in the resting-state brain networks of amyotrophic lateral sclerosis patients and their relation to physiologically sensitive and disease modified functional magnetic resonance imaging parameters. Resting-state functional magnetic resonance imaging was performed at 3 Tesla on 20 amyotrophic lateral sclerosis patients with minimal frontal cognitive dysfunction and 20 age- and sex-matched healthy volunteers. Resting-state network maps were extracted with independent component analysis and group-level statistical analyses were performed to detect disease and disease-by-age interaction effects. Whole-brain global and regional atrophy measures were obtained from same-session structural scans. The sensori-motor network showed significant disease effects, with signals suppressed in patients bilaterally in the primary motor cortex. The default-mode network showed a significant disease-by-age interaction in the posterior cingulate cortex, where signals correlated with age positively in patients and negatively in controls. Both disease and disease-by-age interaction effects were detected in the right fronto-parietal network. Although global atrophy did not show significant differences, regions of reduced gray matter volume were detected in patients compared with controls adjacent to regions of reduced functional connectivity. Our results confirm that resting-state functional magnetic resonance imaging signals in the sensori-motor network are suppressed in amyotrophic lateral sclerosis. A similar suppression is evident in the right fronto-parietal network, possibly reflecting the patients' frontal dysfunction and right-lateralized patterns of regional atrophy. The interaction between disease and aging in the default-mode network unravels a possible mechanism of compensation between motor and extramotor systems emerging as a supplementary functional push to help motor disturbances.