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EPM1 (epilepsy, progressive myoclonic 1; Unverricht-Lundborg disease, OMIM #254800) is the most frequent form of progressive myoclonus epilepsy. Previous findings have suggested that its pathophysiology mainly involves the cerebellum, but the evaluation of cerebellar dysfunction is still unsatisfactory. The aim of this study was to assess the structural and functional involvement of the cerebellum in EPM1. We used voxel-based morphometry and spatially unbiased infra-tentorial template analyses of structural magnetic resonance imaging (MRI) scans, and functional MRI (fMRI) scans during block and event-related go/no-go motor tasks to study 13 EPM1 patients with mild to moderate myoclonus. We compared the results with those obtained in 12 age-matched healthy controls (HCs) and in 12 patients with hereditary spinocerebellar ataxia (SCA). Structural analyses revealed different patterns of atrophic changes in the EPM1 and SCA patients: in the former, they involved both cerebrum and cerebellum but, in the latter, only the cerebellum. During fMRI, block and event-related go/no-go tasks similarly activated the cerebellum and cerebrum in the EPM1 patients and HCs, whereas both tasks revealed much less cerebellar activation in the SCA patients than in the other two groups. Volumetric evaluation of the EPM1 patients showed that the cerebellum seemed to be marginally involved in a widespread atrophic process, and fMRI showed that it was not functionally impaired during motor tasks.

Electrophysiological studies indicate that Unverricht-Lundborg's disease (ULD), the most common form of progressive myoclonus epilepsy in Europe, is characterized by the involvement of multiple cortical regions in degenerative changes that lead to enhanced excitation and deficient inhibition. We searched for the haemodynamic correlates of these effects using functional MRI (fMRI) of self-paced index extensions, a well-accepted task highlighting significant differences. EEG and fMRI were simultaneously acquired in 11 ULD patients and 16 controls, performing the index extensions individually (event-related task) as well as repetitively (block task). ERD/ERS analysis was performed for the EEG data in the alpha and beta bands. fMRI time-series were analyzed using the traditional general linear model, as well as with an assumption-free approach, and by means of cross-region correlations representing functional connectivity. In line with the existing literature, ULD patients had enhanced desynchronization in the alpha band and reduced post-movement synchronization in the beta band. By contrast, fMRI did not reveal any difference between the two groups; there were no activation intensity, latency or extent effects, no significant engagement of additional regions, and no changes to functional connectivity. We conclude that, so long as the patients are executing a task which does not induce obvious action myoclonus, the hypothesized abnormalities in pyramidal neuron and interneuron dynamics are relatively subtle, embodied in processes which are not metabolically-demanding and take place at a time-scale invisible to fMRI.

We investigated the spatial correspondence between functional MRI (fMRI) activations and cortical current density maps of event-related potentials (ERPs) reconstructed without fMRI priors. The presence of a significant spatial correspondence is a prerequisite for direct integration of the two modalities, enabling to combine the high spatial resolution of fMRI with the high temporal resolution of ERPs. Four separate tasks were employed: visual stimulation with a pattern-reversal chequerboard, recognition of images of nameable objects, recognition of written words, and auditory stimulation with a piano note. ERPs were acquired with 19 recording channels, and source localisation was performed using a realistic head model, a standard cortical mesh and the multiple sparse priors method. Spatial correspondence was evaluated at group level over 10 subjects, by means of a voxel-by-voxel test and a test on the distribution of local maxima. Although not complete, it was significant for the visual stimulation task, image and word recognition tasks (P < 0.001 for both types of test), but not for the auditory stimulation task. These findings indicate that partial but significant spatial correspondence between the two modalities can be found even with a small number of channels, for three of the four tasks employed. Absence of correspondence for the auditory stimulation task was caused by the unfavourable situation of the activated cortex being perpendicular to the overlying scalp, whose consequences were exacerbated by the small number of channels. The present study corroborates existing literature in this field, and may be of particular relevance to those interested in combining fMRI with ERPs acquired with the standard 10-20 system.