Clinical correlates of hypothalamic functional changes in migraine patients.

OBJECTIVE: To elucidate the hypothalamic involvement in episodic migraine and investigate the association between hypothalamic resting state functional connectivity changes and migraine patients' clinical characteristics and disease progression over the years. METHODS: Ninety-one patients with episodic migraine and 73 controls underwent interictal resting state functional magnetic resonance imaging. Twenty-three patients and controls were re-examined after a median of 4.5 years. Hypothalamic resting state functional connectivity changes were investigated using a seed-based correlation approach. RESULTS: At baseline, a decreased functional interaction between the hypothalamus and the parahippocampus, cerebellum, temporal, lingual and orbitofrontal gyrus was found in migraine patients versus controls. Increased resting state functional connectivity between the hypothalamus and bilateral orbitofrontal gyrus was demonstrated in migraine patients at follow-up versus baseline. Migraine patients also experienced decreased right hypothalamic resting state functional connectivity with ipsilateral lingual gyrus. A higher migraine attack frequency was associated with decreased hypothalamic-lingual gyrus resting state functional connectivity at baseline, while greater headache impact at follow-up correlated with decreased hypothalamic-orbitofrontal gyrus resting state functional connectivity at baseline. At follow-up, a lower frequency of migraine attacks was associated with higher hypothalamic-orbitofrontal gyrus resting state functional connectivity. CONCLUSIONS: During the interictal phase, the hypothalamus modulates the activity of pain and visual processing areas in episodic migraine patients. The hypothalamic-cortical interplay changes dynamically over time according to patients' clinical features.

The organization of intrinsic brain activity differs between genders: a resting-state fMRI study in a large cohort of young healthy subjects.

OBJECTIVES: To investigate, using resting state (RS) functional MRI (fMRI), gender-related differences of functional connectivity (FC) and functional network connectivity (FNC) of the human brain. EXPERIMENTAL DESIGN: One-hundred and four young healthy subjects (48/56 men/women), aged between 20 and 29 years, underwent a 10-min RS fMRI acquisition. Independent component analysis (ICA) and statistical parametric mapping were used to assess gender-related differences in RSNs, with and without correction for regional gray matter (GM) volume. The relationships among all RSNs was also assessed using a FNC method. PRINCIPAL OBSERVATIONS: For all networks, significant between-group differences of RS activity were found. Between-group comparisons of RSNs changed when adjusting for GM volume, as follows: (1) there was only marginal effect on the analysis of sensory (i.e., sensorimotor, visual, and auditory) networks; and (2) there was a significantly increased difference when cognitive networks (apart from one related to attention) were considered. Compared with women, men experienced increased FC in parietal and occipital regions in most RSNs, whereas women experienced a higher RS FC in frontal and temporal regions, and in the cerebellum. When compared to women, increased FNC was found in men between several cognitive and sensory networks, whereas women showed an increased FNC only between attention and right working-memory networks. CONCLUSIONS: The organization of intrinsic FC and FNC differ between genders. The detected differences could contribute to the understanding of the known between-gender variation in task-related recruitments, and the patterns of abnormalities detected in neurologic and psychiatric diseases with a gender prevalence.

Large-scale neuronal network dysfunction in relapsing-remitting multiple sclerosis.

OBJECTIVES: Given that multiple sclerosis (MS) hits diffusely the brain hemispheres, we hypothesized that this should result in a distributed pattern of functional connectivity (FC) abnormalities. To this aim, we assessed, using resting-state (RS) fMRI, intrinsic FC and functional network connectivity (FNC) of brain large-scale neuronal networks from 85 patients with relapsing-remitting MS (RRMS) and 40 matched controls. METHODS: Independent component analysis was used to analyze RS fMRI data. Intrinsic FC of each cluster of each RS network (RSN) was compared between controls and patients (analysis of variance adjusted for age, gender, and gray matter volume). The FNC toolbox was used to assess interactions among RSNs. RESULTS: Compared to controls, patients with RRMS experienced a decreased RS FC in regions of the salience (SN), executive control (ECN), working memory (WMN), default mode (DMN), sensorimotor, and visual networks. They also had an increased RS FC in regions of the ECN and auditory RSN. Decreased RS FC was significantly correlated with disability and T2 lesion volumes. In patients with RRMS, when compared to controls, FNC analysis showed that the ECN had an increased connectivity with the SN and a decreased connectivity with the DMN. An abnormal connectivity between the WMNs and sensory networks was also found. CONCLUSIONS: Functional abnormalities within and between large-scale neuronal networks occur in patients with RRMS and are related to the extent of T2 lesions and the severity of disability. Longitudinal studies should ascertain whether such functional abnormalities confer a systematic vulnerability to disease progression or, conversely, protect against the onset of clinical deficits.