Functional connectivity MR imaging of the language network in patients with drug-resistant epilepsy

BACKGROUND AND PURPOSE:Subtle linguistic dysfunction and reorganization of the language network were described in patients with epilepsy, suggesting the occurrence of plasticity changes. We used resting state FC-MRI to investigate the effects induced by chronic epilepsy on the connectivity of the language-related brain regions and correlated it with language performance.MATERIALS AND METHODS:FC-MRI was evaluated in 22 right-handed patients with drug-resistant epilepsy (11 with LE and 11 with RE) and in 12 healthy volunteers. Neuropsychological assessment of verbal IQ was performed. Patients and controls underwent BOLD fMRI with a verb-generation task, and language function was lateralized by an LI. Intrinsic activity fluctuations for FC analysis were extracted from data collected during the task. Six seeding cortical regions for speech in both hemispheres were selected to obtain a measure of the connectivity pattern among the language networks.RESULTS:Patients with LE presented atypical language lateralization and an overall reduced connectivity of the language network with respect to controls. In patients with both LE and RE, the mean FC was significantly reduced within the left (dominant) hemisphere and between the 2 hemispheres. In patients with LE, there was a positive correlation between verbal IQ scores and the left intrahemispheric FC.CONCLUSIONS:In patients with intractable epilepsy, FC-MRI revealed an overall reduction and reorganization of the connectivity pattern within the language network. FC was reduced in the left hemisphere regardless of the epileptogenic focus side and was positively correlated with linguistic performance only in patients with LE.

MR imaging plays a crucial role in the preoperative assessment of patients with intractable epilepsy. Structural MR imaging is routinely used for the detection of epileptogenic brain lesions, whereas fMRI localizes brain functions on the cerebral cortex and establishes their spatial relationship with lesions. One of the most frequent applications of fMRI is presurgical mapping of language functions and identification of the dominant hemisphere for speech.^1,2Subtle linguistic dysfunction affects up to one-third of adults with chronic epilepsy,^3–5 even in the absence of a direct injury to the brain language network. Functional neuroimaging has demonstrated different patterns of activation and reorganization of the language network in patients with epilepsy compared with healthy subjects. Using fMRI, Brázdil et al⁶ described a different activation pattern of the Broca area in a group of patients with left mesial-temporal epilepsy. In addition, task-evoked BOLD activity within the language network was found to be less unbalanced toward the dominant hemisphere in patients with epilepsy, compared with the healthy controls, especially in patients with early seizure onset.² Taken as a whole, these results suggest the possibility that epilepsy may induce functional changes across remote cortical regions, including those specialized for speech.In addition to task-evoked fMRI studies, resting state FC-MRI can reveal the cortical connectivity among language-network regions by evaluating correlations of spontaneous BOLD signal-intensity fluctuations.^7–10 FC-MRI has attracted growing interest and new applications and can be reasonably considered a marker of neural connectivity.¹¹ Most important, FC-MRI seems particularly suited for clinical populations because subjects lie in the scanner without any imposed task, thus eliminating the need for complying with task instructions.¹² Similarly, FC analysis of intrinsic brain activity, typically performed on resting state data, can be performed on task-related data by subtracting the contribution of the BOLD activation response.^12,13Recently, Waites et al¹⁴ found a decreased resting state FC-MRI connectivity among language regions and an increased connectivity between the left inferior frontal gyrus and part of the DMN in a group of patients with left temporal lobe epilepsy compared with controls. These observations further confirm the influence of epilepsy on language-network activity and possibly account for subtle language impairments that may affect patients with epilepsy. However, we have little information about potential hemispheric differences in these patients; and most important, the changes in FC associated with verbal performance have not been studied previously, to our knowledge.In the present retrospective analysis, we investigated the FC pattern among language-network nodes in a group of patients (n = 22) with either left- or right-lateralized drug-resistant epilepsy and in a group of matched healthy subjects (n = 12). First, we evaluated the pattern of cortical activation during a conventional block-designed verb-generation task assessing the degree of language function lateralization across hemispheres. We then used FC-MRI to investigate the pattern of functional connectivity among 6 regions of the language network in the 2 hemispheres. Finally, we investigated the correlation between the pattern of FC-MRI and the neuropsychological evaluation of language performance.