Stefania Ferraro

Chronic Migraine With Medication Overuse Pre–Post Withdrawal of Symptomatic Medication: Clinical Results and fMRI Correlations

(Headache 2010;50:998‐1004)

Pain Processing in Medication Overuse Headache: A Functional Magnetic Resonance Imaging (fMRI) Study

OBJECTIVE The primary aim was to investigate functional differences between medication overuse headache (MOH) patients and controls with the purpose of evaluating the presence of a global alteration in the processing of noxious stimuli throughout the pain matrix. The secondary aim was to investigate whether activations in MOH patients normalize after medication withdrawal, which would suggest a possible role of the pain matrix in headache chronification. DESIGN Functional magnetic resonance imaging was performed during painful mechanical stimulation in nine female patients with MOH immediately and at 6 months after beginning medication withdrawal, and in nine control participants. RESULTS Compared with controls, immediately after beginning withdrawal, the MOH patients showed reduced pain-related activity across the primary somatosensory cortex, inferior parietal lobule, and supramarginal gyrus, as well as in regions of the lateral pathway of the pain matrix. At 6 months, these differences were no longer detectable. CONCLUSION Our findings suggest that significant functional changes occur in the lateral pain pathway in MOH patients. These could result from different processes: 1) cortical down-regulation aimed at reducing painful input to the cortex; 2) activity-dependent plasticity induced by excessive painful input during migraine attacks; and 3) direct effect of medication overuse. At 6 months after withdrawal, activity in these regions normalized, suggesting that no irreversible changes occur due to medication overuse.

In medication-overuse headache, fMRI shows long-lasting dysfunction in midbrain areas.

The primary aim of our study was to evaluate if a group of medication‐overuse headache (MOH) patients present dysfunctions in the mesocorticolimbic dopamine circuit. The secondary aim was to disentangle the role of the medication overuse and of the acute/chronic headache in determining these alterations and to investigate their persistence.

Neuroimaging in chronic migraine.

Abstract In chronic migraine, many neuroimaging studies with advanced techniques showed abnormalities in several brain areas involved in pain processing. The structural and functional dysfunctions are reported in cerebral areas localized in the brainstem and in the lateral and medial pain pathways. Using the advanced technique of volumetric MRI (voxel-based morphometry), reduction in the grey and white matter in brain areas of the pain network and increased density of the structures of the brainstem were observed in patients with episodic or chronic migraine. Most of the studies of functional anatomy in chronic migraine uses positron emission tomography (PET) and functional RM. These techniques could detect cerebral areas with regional cerebral blood flow and blood level oxygenation-dependant (BOLD) signal changes. Several PET and functional MRI experiments in patients with chronic migraine and drugs overuse before and after the withdrawal showed hypometabolism and hypoactivation in cortical areas involved in pain processing. These areas normalize their activity after detoxification, indicating reversible metabolic changes and BOLD signal changes as observed in other chronic pain. Functional and structural alterations observed in the cerebral areas of the pain network could be a result of a selective dysfunction of these regions due to cortical overstimulation associated with chronic pain. Advanced neuroimaging techniques have revolutionized the knowledge on chronic migraine, determining specific cortical substrate that could explain different forms of chronic migraine and perhaps the predisposition of patients to different therapeutic responses and to possible relapse in drug abuse.

Connectivity of the amygdala, piriform, and orbitofrontal cortex during olfactory stimulation: a functional MRI study.

The majority of existing functional MRI studies on olfactory perception have addressed the relationship between stimulus features and the intensity of activity in separate regions considered in isolation. However, anatomical studies as well as neurophysiological recordings in rats and insects suggest that odor features may also be represented in a sparse manner through the simultaneous activity of multiple cortical areas interacting as a network. Here, we aimed to map the interdependence of neural activity among regions of the human brain, representing functional connectivity, during passive smelling. Seventeen healthy participants were scanned while performing a blocked-design task alternating exposure to two unpleasant odorants and breathing fresh air. High efferent connectivity was detected for the piriform cortex and the amygdala bilaterally. By contrast, the medial orbitofrontal cortex was characterized by high afferent connectivity, notably in the absence of an overall change in the intensity of hemodynamic activity during olfactory stimulation. Our results suggest that, even in the context of an elementary task, information on olfactory stimuli is scattered by the amygdala and piriform cortex onto an anatomically sparse representation and then gathered and integrated in the medial orbitofrontal cortex.

Multimodal study of default-mode network integrity in disorders of consciousness

Understanding residual brain function in disorders of consciousness poses extraordinary challenges, and imaging examinations are needed to complement clinical assessment. The default‐mode network (DMN) is known to be dysfunctional, although correlation with level of consciousness remains controversial. We investigated DMN activity with resting‐state functional magnetic resonance imaging (rs‐fMRI), alongside its structural and metabolic integrity, aiming to elucidate the corresponding associations with clinical assessment.

Direct skin-to-skin versus indirect touch modulates neural responses to stroking versus tapping.

It remains unclear whether direct interpersonal contact is processed differently from similar soft touch applied through inanimate objects. We performed a functional MRI experiment in healthy volunteers, whereby activity during gentle stroking or tapping was compared between stimuli delivered using the experimenters hand or a velvet stick. Stroking with a hand elicited larger responses than the other three conditions in the contralateral primary and secondary somatosensory areas and in the posterior insula. The observed effects likely originate from a combination of perceptual differences and cognitive and emotional correlates of contact with another person. This empirical observation indicates that, to ensure ecological validity, studies of affective touch processing should be performed with stimuli delivered with direct interpersonal contact rather than inanimate objects.

Functional-MRI evaluation of pain processing in chronic migraine with medication overuse

Withdrawal is the first step for treating patients with chronic migraine and medication overuse. Recent studies confirmed common elements in personality between these patients and subjects addicted; some neuroimaging researches showed that abnormalities revealed are related to a specific cerebral pattern and that they can return to the normal state after withdrawal. Aim of the study was to submit a group of patients suffering from chronic migraine and medication overuse (the diagnosis was made according to Silberstein-Lipton criteria) to a withdrawal, to evaluate by f-MRI the presence of specific cerebral patterns before treatment and their possible changes after withdrawal. f-MRI seems to be a useful technique to obtain information on particular neuronal changes of the pain network involved in this type of patients. The activated areas are congruent with some data of the literature and the data emerged are discussed according to preceding reports.

Frontal cortex BOLD signal changes in premanifest Huntington disease A possible fMRI biomarker

Objective: To identify a possible functional imaging biomarker sensitive to the earliest neural changes in premanifest Huntington disease (preHD), allowing early therapeutic approaches aimed at preventing or delaying clinical onset. Methods: Sixteen preHD and 18 healthy participants were submitted to anatomical acquisitions and functional MRI (fMRI) acquisitions during the execution of the exogenous covert orienting of attention task. Due to strong a priori hypothesis, all fMRI correlation analyses were restricted to the following: (1) the frontal oculomotor cortex identified by the means of a prosaccadic task, comprising frontal eye fields and supplementary frontal eye fields; and (2) the data collected during inhibition of return, a phenomenon occurring during the executed task. In preHD, multiple regression analysis was performed between fMRI data and the probability to develop the disease in the next 5 years (p5HD). Moreover, mean blood oxygen level–dependent (BOLD) signal changes in the frontal oculomotor cortex and striatal volumes were linearly correlated with p5HD. Results: In preHD, multiple regression analysis showed that clusters of activity strongly correlated with p5HD in the right frontal oculomotor cortex. Importantly, mean BOLD signal changes of this region correlated with p5HD (r2 = 0.52). Among the considered striatal volumes, a modest correlation (r2 = 0.29) was observed in the right putamen and p5HD. Conclusion: fMRI activations in the right-frontal oculomotor cortex during inhibition of return can be considered a possible functional imaging biomarker in preHD.

A Neural Network Approach to fMRI Binocular Visual Rivalry Task Analysis

The purpose of this study was to investigate whether artificial neural networks (ANN) are able to decode participants’ conscious experience perception from brain activity alone, using complex and ecological stimuli. To reach the aim we conducted pattern recognition data analysis on fMRI data acquired during the execution of a binocular visual rivalry paradigm (BR). Twelve healthy participants were submitted to fMRI during the execution of a binocular non-rivalry (BNR) and a BR paradigm in which two classes of stimuli (faces and houses) were presented. During the binocular rivalry paradigm, behavioral responses related to the switching between consciously perceived stimuli were also collected. First, we used the BNR paradigm as a functional localizer to identify the brain areas involved the processing of the stimuli. Second, we trained the ANN on the BNR fMRI data restricted to these regions of interest. Third, we applied the trained ANN to the BR data as a ‘brain reading’ tool to discriminate the pattern of neural activity between the two stimuli. Fourth, we verified the consistency of the ANN outputs with the collected behavioral indicators of which stimulus was consciously perceived by the participants. Our main results showed that the trained ANN was able to generalize across the two different tasks (i.e. BNR and BR) and to identify with high accuracy the cognitive state of the participants (i.e. which stimulus was consciously perceived) during the BR condition. The behavioral response, employed as control parameter, was compared with the network output and a statistically significant percentage of correspondences (p-value <0.05) were obtained for all subjects. In conclusion the present study provides a method based on multivariate pattern analysis to investigate the neural basis of visual consciousness during the BR phenomenon when behavioral indicators lack or are inconsistent, like in disorders of consciousness or sedated patients.