Alfonso Giordano

Rhythm-specific modulation of the sensorimotor network in drug-naive patients with Parkinson's disease by levodopa.

Brain activity during rest is characterized by slow (0.01-0.1 Hz) fluctuations of blood oxygenation level-dependent functional magnetic resonance imaging signals. These fluctuations are organized as functional connectivity networks called resting-state networks, anatomically corresponding to specific neuronal circuits. As Parkinsons disease is mainly characterized by a dysfunction of the sensorimotor pathways, which can be influenced by levodopa administration, the present study investigated the functional connectivity changes within the sensorimotor resting-state network in drug-naïve patients with Parkinsons disease after acute levodopa administration. Using a double-blind placebo-controlled design, resting-state functional magnetic resonance imaging was carried out in 20 drug-naïve patients with Parkinsons disease, immediately before and 60 min after, oral administration of either levodopa or placebo. Control resting-state functional magnetic resonance imaging data were recorded in 18 age- and sex-matched healthy volunteers. Independent component analysis was performed to extract resting-state network maps and associated time-course spectral features. At the anatomical level, levodopa enhanced the sensorimotor network functional connectivity in the supplementary motor area, a region where drug-naïve patients with Parkinsons disease exhibited reduced signal fluctuations compared with untreated patients. At the spectral frequency level, levodopa stimulated these fluctuations in a selective frequency band of the sensorimotor network. The reported effects induced by levodopa on sensorimotor network topological and spectral features confirm that the sensorimotor system is a target of acute levodopa administration in drug-naïve patients with Parkinsons disease. Moreover, while the regional changes in supplementary motor area reflect the functional improvement in motor function, the rhythm-specific modulation induced by the dopamine precursor discloses a novel aspect of pharmacological stimulation in Parkinsons disease, adding further insight to the comprehension of levodopa action.

Executive resting-state network connectivity in migraine without aura.

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.

Pain processing in patients with migraine: an event-related fMRI study during trigeminal nociceptive stimulation

We explored the functional pattern of the pain-processing network in patients with migraine, in the interictal periods, during trigeminal noxious stimulation. Contact heat evoked potential stimulation induced thermal pain and functional magnetic resonance imaging were used to measure whole-brain activation in 16 patients with episodic migraine without aura and 16 age- and gender-matched healthy controls in response to a severe (53°C) noxious, a moderate (51°C) noxious, and a control (41°C) stimulus applied to the maxillary skin. When comparing the fMRI activation over the entire brain, patients with migraine, with respect to healthy controls, showed a significantly greater activation in the perigenual part of anterior cingulate cortex at 51°C and less activation in the bilateral secondary somatosensory cortex at 53°C. A group-by-stimulus interaction analysis revealed a region in the pons showing a divergent response in patients and healthy controls. Correlation analyses demonstrated that the pons activation correlated with higher headache-related disability in patients. Our findings demonstrate increased antinociceptive activity in patients with migraine, which may represent a compensatory reorganization to modulate pain perception at the same intensity of healthy controls.

Disrupted default mode network connectivity in migraine without aura

BackgroundResting-state functional magnetic resonance imaging (RS-fMRI) has demonstrated disrupted default mode network (DMN) connectivity in a number of pain conditions, including migraine. However, the significance of altered resting-state brain functional connectivity in migraine is still unknown. The present study is aimed to explore DMN functional connectivity in patients with migraine without aura (MwoA) and investigate its clinical significance.MethodsTo calculate and compare the resting-state functional connectivity of the DMN in 20 patients with MwoA, during the interictal period, and 20 gender- and age-matched HC, Brain Voyager QX was used. Voxel-based morphometry was used to assess whether between-group differences in DMN functional connectivity were related to structural differences. Secondary analyses explored associations between DMN functional connectivity, clinical and neuropsychological features of migraineurs.ResultsIn comparison to HC, patients with MwoA showed decreased connectivity in prefrontal and temporal regions of the DMN. Functional abnormalities were unrelated to detectable structural abnormalities or clinical and neuropsychological features of migraineurs.ConclusionsOur study provides further evidence of disrupted DMN connectivity in patients with MwoA. We hypothesize that a DMN dysfunction may be related to behavioural processes such as a maladaptive response to stress which seems to characterize patients with migraine.

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.

Increased interictal visual network connectivity in patients with migraine with aura

Objective To evaluate the resting-state visual network functional connectivity in patients with migraine with aura and migraine without aura during the interictal period. Population and methods Using resting-state functional magnetic resonance imaging, the resting-state visual network integrity was investigated in 20 patients with migraine with aura, 20 age- and sex-matched patients with migraine without aura and 20 healthy controls. Voxel-based morphometry and diffusion tensor imaging were used to assess whether between-groups differences in functional connectivity were dependent on structural or microstructural changes. Results Resting-state functional magnetic resonance imaging data showed that patients with migraine with aura, compared to both patients with migraine without aura and healthy controls, had a significant increased functional connectivity in the right lingual gyrus within the resting-state visual network (p < 0.05, cluster-level corrected). This abnormal resting-state visual network functional connectivity was observed in the absence of structural or microstructural abnormalities and was not related to migraine severity. Conclusions Our imaging data revealed that patients with migraine with aura exhibit an altered resting-state visual network connectivity. These results support the hypothesis of an extrastriate cortex involvement, centred in the lingual gyrus, a brain region related to mechanisms underlying the initiation and propagation of the migraine aura. This resting-state functional magnetic resonance imaging finding may represent a functional biomarker that could differentiate patients experiencing the aura phenomenon from patients with migraine without aura, even between migraine attacks.

Abnormal Connectivity Within Executive Resting-State Network in Migraine With Aura.

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.

Interictal cortical reorganization in episodic migraine without aura: an event-related fMRI study during parametric trigeminal nociceptive stimulation

The aim of our study was to explore the pain processing network in patients with migraine during trigeminal nociceptive stimulation. Sixteen patients with episodic migraine without aura and 16 healthy controls performed functional magnetic resonance imaging during thermal stimuli (at 41, 51 and 53°C). Patients with migraine showed a greater activation in the perigenual part of anterior cingulate cortex at 51°C and less activation in the bilateral somatosensory cortex at 53°C compared to healthy controls. There were no differences in experimental pain perception between groups. Our findings demonstrate a functional reorganization of cerebral areas known to be involved in pain processing in patients with migraine.

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.