Brain Advance Access published online on May 6, 2009
Brain, doi:10.1093/brain/awp095
Neurobiological mechanisms underlying emotional processing in relapsing-remitting multiple sclerosis
1 Istituto di Scienze Neurologiche, Consiglio Nazionale delle Ricerche, Cosenza, 87050, Italy 2 Istituto di Neurologia, Università ‘Magna Graecia’, Catanzaro, 88100, Italy 3 Cognition and Brain Sciences Unit, Medical Research Council, Cambridge, CB2 7EF, UK 4 Center for Neurological Imaging, Harvard Medical School, Boston, MA 02115, USA 5 Unita’ di Neuroradiologia, Università ‘Magna Graecia’, Catanzaro 88100, Italy
Correspondence to:
Prof. Francesco Fera, MD, University of Catanzaro, ‘Magna Graecia’, Building B, Level 0, Room 86, Viale Europa, Germaneto (CZ), 88100, Italy. E-mail: fera{at}unicz.it
Affective disorders are frequent and disabling conditions in multiple sclerosis; however, the underlying neurobiological mechanisms are still poorly understood and investigated. Previous structural imaging studies have suggested that damage of frontal and temporal cortices plays an important role in the genesis of emotional disorders in multiple sclerosis, although psychosocial factors have been also implicated. However, this initial research may not have fully characterized the brain's functional dynamics of emotional processes in multiple sclerosis. Functional magnetic resonance imaging (fMRI) appears, therefore, to be a sensible tool to explore neurobiological mechanisms of emotions in multiple sclerosis since it also allows investigation of the functional connectivity or ‘communication’ between critical regions in affective behaviour [e.g. the prefrontal cortex (PFC) and amygdala]. In the present study, functional imaging was used to investigate the neural substrate of processing emotions in 12 multiple sclerosis patients relative to 12 healthy subjects matched for age and educational level. Only relapsing-remitting multiple sclerosis patients, who were cognitively unimpaired and who did not assume disease-modifying therapies, were included, given the potential confounding effect of these variables in the genesis of emotional symptoms. Brain responses were recorded in all participants while they executed an active task that consisted of processing emotional relative to neutral stimuli. Structural measures (i.e. total lesion load, grey matter, white matter and total brain volume) were also recorded to control for any effect of these variables. Despite similar performances during the task, and no differences in structural measures, multiple sclerosis patients displayed significantly greater responses within the ventrolateral PFC [t's > 5, P's < 0.02, Family Wise Error (FWE), small volume correction (svc)], compared to controls. Multiple sclerosis patients also showed a lack of functional connectivity between two prefrontal areas and the amygdala, a subcortical region critically involved in the generation of negative feelings (t's > 4, P's < 0.05, FWE, svc). It is likely that pathological changes related to the disease are reflected in an abnormal ‘communication’ between key emotional regions and that adaptive processes take place and become evident as enhanced responses of task-specific areas (i.e. the ventrolateral PFC). Local reorganizations in the brain can be viewed as compensatory mechanisms aimed to limit the clinical expression of emotional symptoms in multiple sclerosis. Overall our findings offer new insights into the neurobiological mechanisms of emotions in multiple sclerosis and provide evidence that they resemble those described for some psychiatric disorders.
Key Words: multiple sclerosis; fMRI; emotion; prefrontal cortex; amygdala
Abbreviations: BOLD, blood oxygenation level dependant; CMDI, Chicago Multiscale Depression Inventory; DSM, diagnostic and statistical manual of mental disorders; EPI, echo planar image; FWE, family wise error; FMRI, functional magnetic resonance imaging; FWHM, full width half maximum; JLO, judgement of line orientation; MNI, Montreal Neurological Institute; RAVLT, rey auditory-verbal learning test; ROCFT, Rey–Osterrieth complex figure test; SIENA, structural image evaluation using normalization of atrophy; SPM, statistical parametric mapping; WAIS-R, Wechsler Adult Intelligence Scale-Revised
Received January 8, 2009. Revised February 27, 2009. Accepted March 11, 2009.