Abstracts

Rationale: The insular-cingulate connectivity is involved in physiologic networks like salience network (William W. Seeley, J of Neuroscience, 2019; 39; 9878) or in pathologic network such as epilepsy.

Methods: We retrospectively included patients with drug resistant epilepsy that underwent invasive Stereo-electroencephalographic (SEEG) presurgical work-up at the University Emergency Hospital Bucharest between 2012-2021. We selected only those patients that had at least one pair of contacts placed within the cingulate and insular cortex. Resting state effective connectivity was determined by electrical intracranial stimulation (using a cortical stimulator Guideline 4000 - FHC, Bowdoin, ME): single pulses (20 pulses, amplitude between 0 to 5 mA range, biphasic, 3 ms pulse duration, 15 sec inter-pulse interval) and high frequency with alternating polarity (43Hz, 1ms pulse duration, 5 seconds stimulation trial, amplitude increased based on clinical effects from 0.25 to 3mA). In a subset of patients, we have highlighted symptoms-related connectivity based on clinical effects elicited by high frequency stimulation of the insular and cingulate cortex. The high frequency connectivity metric was chosen as the RMS of the AC component of the averaged waveforms, in a 5-23 ms window following stimulation pulses, that does not include the early ( < 5 ms) residual artifact. A threshold of Z=3 for the Z-test statistic comparing the set of RMS values for the responses to individual stimulation pulses during the response versus baseline intervals was used to select most robust connections between stimulated site and the rest of implanted areas.

Results: We included 51 patients that underwent single pulse electrical stimulation and 28 in whom we performed high-frequency stimulation with alternating polarity. Significant cortico-cortical evoked potentials (Spearman’s correlation coefficient, p< 0.05 and ρ >0.5 between the RMS of the response and the current intensity) with a mean amplitude of 47 mV in cingulate and 65 mV in insula when stimulating the opposite area, point out to a bi-directional insular-cingulate connectivity (16% asymmetry), following also an anterior to posterior pattern (Figure 1, patient 99 example). Most common clinical effects were autonomic, somatosensory, vestibular, motor or language-related and connectivity analysis highlights a network comprising both the insular and the cingulate cortex.

Conclusions: There is a bidirectional connectivity between the insular and the cingulate cortex organized in an anterior-posterior pattern that generates specific clinical effects like vestibular, autonomic or somatosensory.

Funding: Please list any funding that was received in support of this abstract.: UEFISCDI COFUND-FLAGERA II-CAUSALTOMICS, PN-III-P4-ID-PCE-2020-0935, PN-III-P1-1.1-TE-2019-0502.