SUMMARY
Perampanel, a non-competitive antagonist of the post-synaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic-clonic seizures but also known to increase feelings of anger. Using statistical parametric mapping–derived measures of activation and task-modulated functional connectivity (psychophysiologic interaction), we investigated 14 people with focal epilepsy who had verbal fluency fMRI twice, before and after the add-on treatment of perampanel. For comparison, we included 28 people with epilepsy, propensity-matched for clinical characteristics, who had two scans but no change in ASM regime in-between. After commencing perampanel, individuals had higher task-related activations in left orbito-frontal cortex (OFC), less task-related activations in subcortical regions including left thalamus and left caudate, and lower task-related thalamo-caudate and caudate-subtantial nigra connectivity. Decreased task-related connectivity is observed between left OFC and precuneus and left medial frontal lobe. Our results highlight the brain regions associated with the beneficiary therapeutic effects on focal to bilateral tonic-clonic seizures (thalamus and caudate) but also the undesired affective side effects of perampanel with increased anger and aggression (OFC).
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