Rosa De Micco

Resting-state functional connectivity associated with mild cognitive impairment in Parkinson’s disease

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.

Cortical thickness changes in patients with Parkinson's disease and impulse control disorders

INTRODUCTION To investigate gray matter (GM) and cortical thickness (CTh) changes in patients with Parkinsons disease (PD) with and without Impulse Control Disorders (ICDs). METHODS Fifteen patients with PD with ICDs (ICD+), 15 patients with PD without ICDs (ICD-) and 24 age and sex-matched healthy controls (HCs) were enrolled in the study. Patients were screened for ICDs by the Minnesota Impulsive Disorders Interview (MIDI) and underwent an extensive neuropsychological evaluation. Whole brain structural imaging was performed on a 3T GE MR scanner. Surface-based investigation of CTh was carried out by using Freesurfer Software. We also used voxel-based morphometry to investigate the pattern of GM atrophy. RESULTS The voxel-wise analysis of the regional differences in CTh revealed that ICD+ patients showed a statistically significant (p<0.01 FDR) thicker cortex when compared to both ICD- patients and HCs in the anterior cingulate (ACC) and orbitofrontal (OFC) cortices. Moreover, cortical thickness abnormalities were positively correlated with ICD severity (p<0.05 FDR). VBM data did not reveal any statistically significant differences in local GM. CONCLUSIONS Our results demonstrate that ICD+ patients have an increased CTh in limbic regions when compared with ICD- patients at the same disease stage and with an equal daily levodopa equivalent dose. These corticometric changes may play a role in the lack of inhibition of compulsive behaviors. The presence of such structural abnormalities may result from a synergistic effect of dopaminergic therapy in patients with a pre-existing vulnerability to develop an abnormal behavioral response to external stimuli.

Sensorimotor connectivity in Parkinson's disease: the role of functional neuroimaging

The diagnosis of Parkinson’s disease (PD) remains still clinical; nevertheless, in the last decades, the rapid evolution of advanced MRI techniques has made it possible to detect structural and, increasingly, functional brain changes in patients with PD. Indeed, functional MRI (fMRI) techniques have offered the opportunity to directly measure the brain’s activity and connectivity in patients with PD both in early and complicated stage of the disease. The aims of the following review are (1) to present an overview of recent fMRI reports investigating the activity and connectivity of sensorimotor areas in patients with PD using both task-related and “resting-state” fMRI analysis (2) to elucidate potential pathophysiological mechanisms underlying dyskinetic motor complications in the advanced stage of PD.

Clinical and cognitive correlations of regional gray matter atrophy in progressive supranuclear palsy

BACKGROUND Progressive supranuclear palsy is the most common neurodegenerative bradykinetic-rigid syndrome after Parkinsons disease. Several volumetric studies have revealed a widespread cortical and subcortical gray matter atrophy, however the correlations between the pattern of gray matter loss and clinical-cognitive features have been poorly investigated. METHODS By using 3-T magnetic-resonance imaging and voxel-based morphometry we compared gray matter volume in 15 patients with progressive supranuclear palsy, 15 patients with Parkinsons disease and 15 healthy controls. All patients underwent a clinical and neuropsychological evaluation. RESULTS In agreement with previous studies, patients with progressive supranuclear palsy, compared to patients with Parkinsons disease and healthy controls, showed a reduced gray matter volume in several cortical and subcortical areas including cerebellum, frontal, temporal and parahippocampal cortical structures. We did not find any significant gray matter volume changes when comparing patients with Parkinsons disease vs healthy controls. Among different significant correlations between motor-cognitive features and gray matter loss, we detected a significant correlation between fronto-cerebellar gray matter atrophy and executive cognitive impairment in patients with progressive supranuclear palsy. CONCLUSIONS Our findings confirm that gray matter loss in patients with progressive supranuclear palsy involves several brain areas and suggest that cerebellar atrophy may play a role in the pathogenesis of cognitive dysfunction in patients with progressive supranuclear palsy due to a disruption of its modulation on executive functions.

Functional connectivity underpinnings of fatigue in "Drug-Naïve" patients with Parkinson's disease.

Fatigue is a common problem in PD either in the early or later stage of the disease. Using resting‐state functional MRI, we investigated the functional correlates of fatigue in a cohort of “drug‐naïve” patients with PD.

A transient third cranial nerve palsy as presenting sign of spontaneous intracranial hypotension

Spontaneous intracranial hypotension is an uncommon cause of sudden and persistent headache: associated symptoms are common, among which there are cranial nerve palsies, especially of the abducens nerve. We report a case of a 21-year-old man with a transient and isolated third nerve palsy due to spontaneous intracranial hypotension. To our knowledge, there are only few reports in the literature of such association.

Functional Changes of the Perigenual Part of the Anterior Cingulate Cortex after External Trigeminal Neurostimulation in Migraine Patients

Objective To explore the functional reorganization of the pain processing network during trigeminal heat stimulation (THS) after 60 days of external trigeminal neurostimulation (eTNS) in migraine without aura (MwoA) patients between attacks. Methods Using whole-brain BOLD-fMRI, functional response to THS at two different intensities (41 and 51°C) was investigated interictally in 16 adults MwoA patients before and after eTNS with the Cefaly® device. We calculated the percentage of patients having at least a 50% reduction of monthly migraine attacks and migraine days between baseline and the last month of eTNS. Secondary analyses evaluated associations between BOLD signal changes and clinical features of migraine. Results Before eTNS treatment, there was no difference in BOLD response between MwoA patients and healthy controls (HC) during low-innocuous THS at 41°C, whereas the perigenual part of the right anterior cingulate cortex (ACC) revealed a greater BOLD response to noxious THS at 51°C in MwoA patients when compared to HC. The same area demonstrated a significant reduced BOLD response induced by the noxious THS in MwoA patients after eTNS (p = 0.008). Correlation analyses showed a significant positive correlation between ACC BOLD response to noxious THS before eTNS treatment and the decrease of ACC BOLD response to noxious THS after eTNS. Moreover, a significant negative correlation in the migraine group after eTNS treatment between ACC functional activity changes and both the perceived pain ratings during noxious THS and pre-treatment migraine attack frequency has been found. Conclusion Our findings suggest that eTNS treatment with the Cefaly® device induces a functional antinociceptive modulation in the ACC that is involved in the mechanisms underlying its preventive anti-migraine efficacy. Nevertheless, further observations to confirm whether the observed fMRI effects of eTNS are both related to clinical improvement and specific to antinociceptive modulation in migraine patients are mandatory.

Intrinsic brain connectivity predicts impulse control disorders in patients with Parkinson's disease

Background: Impulse control disorders can be triggered by dopamine replacement therapies in patients with PD. Using resting‐state functional MRI, we investigated the intrinsic brain network connectivity at baseline in a cohort of drug‐naive PD patients who successively developed impulse control disorders over a 36‐month follow‐up period compared with patients who did not.

Central pain processing in “drug‐naïve” pain‐free patients with Parkinson's disease

Despite its clinical relevance, the pathophysiology of pain in Parkinsons disease (PD) is still largely unknown, and both central and peripheral mechanisms have been invoked.

Structural MRI in Idiopathic Parkinson's Disease

Among modern neuroimaging modalities, magnetic resonance imaging (MRI) is a widely available, non-invasive, and cost-effective method to detect structural and functional abnormalities related to neurodegenerative disorders. In the last decades, MRI have been widely implemented to support PD diagnosis as well as to provide further insights into motor and non-motor symptoms pathophysiology, complications and treatment-related effects. Different aspects of the brain morphology and function may be derived from a single scan, by applying different analytic approaches. Biomarkers of neurodegeneration as well as tissue microstructural changes may be extracted from structural MRI techniques. In this chapter, we analyze the role of structural imaging to differentiate PD patients from controls and to define neural substrates of motor and non-motor PD symptoms. Evidence collected in the premotor PD phase will be also critically discussed. White matter as well as gray matter integrity imaging studies has been reviewed, aiming to highlight points of strength and limits to their potential application in clinical settings.