Connectivity Alterations in Emotional and Cognitive Networks During a Manic State Induced by Direct Electrical Stimulation.

Mania is characterized by affective and cognitive alterations, with heightened external and self-awareness that are opposite to the alteration of awareness during epileptic seizures. Electrical stimulations carried out routinely during stereotactic intracerebral EEG (SEEG) recordings for presurgical evaluation of epilepsy may represent a unique opportunity to study the pathophysiology of such complex emotional-behavioral phenomenon, particularly difficult to reproduce in experimental setting. We investigated SEEG signals-based functional connectivity between different brain regions involved in emotions and in consciousness processing during a manic state induced by electrical stimulation in a patient with drug-resistant focal epilepsy. The stimulation inducing manic state and an asymptomatic stimulation of the same site, as well as a seizure with alteration of awareness (AOA) were analyzed. Functional connectivity analysis was performed by measuring interdependencies (nonlinear regression analysis based on the h2 coefficient) between broadband SEEG signals and within typical sub-bands, before and after stimulation, or before and during the seizure with AOA, respectively. Stimulation of the right lateral prefrontal cortex induced a manic state lasting several hours. Its onset was associated with significant increase of broadband-signal functional coupling between the right hemispheric limbic nodes, the temporal pole and the claustrum, whereas significant decorrelation between the right lateral prefrontal and the anterior cingulate cortex was observed in theta-band. In contrast, ictal alteration of awareness was associated with increased broadband and sub-bands synchronization within and between the internal and external awareness networks, including the anterior and middle cingulate, the mesial and lateral prefrontal, the inferior parietal and the temporopolar cortex. Our data suggest the existence of network- and frequency-specific functional connectivity patterns during manic state. A transient desynchronization of theta activity between the external and internal awareness network hubs is likely to increase awareness, with potential therapeutic effect.