Investigation of the reorganisation of language and verbal memory systems in chronic temporal lobe epilepsy.

Part of the brain, the left temporal lobe, is important in the comprehension of language. The front (anterior) and inner (medial) part of the temporal lobe is sometimes removed to treat a form of epilepsy known as temporal lobe epilepsy (TLE). There is always concern that the operation may affect the patient‘s language and memory. However, repeated epileptic activity over years may result in reorganisation of the normal systems. If true, such evidence would be important both clinically and for theories about normal language organisation. Surgical removal of the anterior left temporal lobe usually causes little disturbance of language function, and some regard this as evidence that this part is not involved in language. However, other evidence, both from brain imaging studies on normal subjects and from patients with a type of dementia, suggests that this is not the case, and that normal function cannot be inferred from the outcome of therapeutic removal of brain tissue in epileptic patients. Further, language is the mental product of interactions between widely distributed brain regions, and we will investigate whether chronic epilepsy results in reorganisation of these connections as an adaptation. Therefore, this study addresses both theoretical and practical clinical issues.

Aims:
In healthy subjects: to determine, in this control group, the distributed systems engaged during speech comprehension and production.
In patients with chronic TLE, with either a left- or right-lateralised focus: to determine changes in the processing of language, and the episodic memory processes engaged in parallel; in particular, to determine whether patients with left TLE show evidence of a ‘laterality shift‘ of these systems, or whether reorganisation is expressed as a change in the functional connectivity between cortical and sub-cortical regions, both within and between cerebral hemispheres.

The absence of major aphasia following anterior temporal lobectomy to treat TLE has been interpreted as evidence that anterior temporal cortex has little role to play in speech comprehension and production. This contrasts with studies in patients with semantic dementia, and some functional imaging studies on normal subjects. My study will investigate the functional anatomy of speech comprehension and production, with emphasis on anterior and mesial temporal lobe structures, in patients with chronic TLE who have not undergone neurosurgery. In particular, it will assess whether reorganisation accompanies chronic focal temporal lobe epileptic activity, invalidating inferences about normal organisation drawn from the behavioural effects of anterior temporal lobectomy. In parallel, the study will investigate episodic verbal memory encoding and retrieval that accompanies speech comprehension and production.

The MRI protocols and results will be of direct relevance to the pre-operative assessment of epileptic or tumour patients prior to neurosurgical intervention.

I will recruit 20 healthy subjects and 30-40 patients with chronic temporal lobe epilepsy (left and right-lateralised foci). All groups will be matched, as closely as possible, for age, sex and I.Q. All subjects will undergo both anatomical (including diffusion tensor imaging to assess white matter integrity) and functional magnetic resonance imaging after comprehensive neuropsychological testing. I will use implicit speech comprehension and speech production as the activation tasks, with a range of baseline control conditions.

Behavioural scores will be analysed using appropriate SPSS analyses. Anatomical and functional imaging scan data will be analysed using SPM5 (Wellcome Department of Cognitive Neurology) and FSL (FMRIB, Oxford) software. In addition to planned contrasts, the functional imaging data will be subjected to analyses of functional connectivity and voxel-based morphometry. Random effects statistical analyses will be performed both within and between groups.