Abstract
Objective
Cognitive impairment often impacts quality of life in epilepsy even if seizures are controlled. Word-finding difficulty is particularly prevalent and often attributed to etiological (static, baseline) circuit alterations. We sought to determine whether interictal discharges convey significant superimposed contributions to word-finding difficulty in patients, and if so, through which cognitive mechanism(s).
Methods
Twenty-three patients undergoing intracranial monitoring for drug-resistant epilepsy participated in multiple tasks involving word-production (auditory naming, short-term verbal free recall, repetition) to probe word-finding difficulty across different cognitive domains. We compared behavioral performance between trials with vs. without interictal discharges across six major brain areas and adjusted for inter-subject differences using mixed-effects models. We also evaluated for subjective word finding difficulties through retrospective chart review.
Results
Subjective word-finding difficulty was reported by the majority (79%) of studied patients pre-operatively. During intracranial recordings, IEDs in the medial temporal lobe were associated with long-term lexico-semantic memory impairments as indexed by auditory naming (p=0.009), in addition to their established impact on short-term verbal memory as indexed by free recall (p=0.004). Interictal discharges involving the lateral temporal cortex and lateral frontal cortex were associated with delayed reaction time in the auditory naming task (p=0.016 and p=0.018), as well as phonological working memory impairments as indexed by repetition reaction time (p=0.002). Effects of IEDs across anatomical regions were strongly dependent on their precise timing within the task.
Significance
IEDs appear to act through multiple cognitive mechanisms to form a convergent basis for the debilitating clinical word-finding difficulty reported by patients with epilepsy. This was particularly notable for medial temporal spikes which are quite common in adult focal epilepsy. In parallel with the treatment of seizures, the modulation of interictal discharges through emerging pharmacological means and neurostimulation approaches may be an opportunity to help address devastating memory and language impairments in epilepsy.
OCT