Intrinsic functional architecture predicts electrically evoked responses in the human brain

Corey Keller (Albert Einstein College of Medicine), Stephan Bickel (North Shore LIJ Health System), Laszlo Entz (eInstitute for Psychology of the Hungarian Academy of Sciences), Fred Lado (Department of Neurology, Montefiore Medical Center), Istvan Ulbert (eInstitute for Psychology of the Hungarian Academy of Sciences), Clare Kelly (New York University Child Study Center), Michael Milham (New York University Child Study Center), Ashesh Mehta (North Shore LIJ Health System)

Introduction: Functional MRI studies carried out during rest (R-fMRI) suggest that this architecture is represented in low frequency (< 0.1Hz) spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal that are correlated within spatially distributed networks of brain areas. These networks, collectively referred to as the brain’s intrinsic functional architecture, exhibit a remarkable correspondence with patterns of task-evoked co-activation as well as maps of anatomical connectivity. Despite this striking correspondence, there is no direct evidence that this intrinsic architecture forms the scaffold that gives rise to faster processes relevant to information processing and seizure spread. Here, we demonstrate that the spatial distribution and magnitude of temporally correlated low-frequency fluctuations observed with fMRI during rest predict the pattern and magnitude of cortico-cortical evoked potentials (CCEPs) elicited within 500 milliseconds after single-pulse electrical stimulation of the cerebral cortex with intracranial electrodes.

Methods: 6 patients with medically-intractable epilepsy underwent intracranial electrode implantation for monitoring of epileptic activity. Pre-operatively, patients performed rfMRI scanning. Post-implantation, single pulse electrical stimulation was performed at adjacent electrode sites and cortico-cortical evoked potentials (CCEP) were measured. Subdural electrodes were localized to the underlying anatomical structures by co-registering the pre-operative MRI and post-operative CT. Seeds were placed over electrode locations where single pulse stimulation was performed and resting state functional connectivity (RSFC) z-values were calculated at electrode sites where CCEPs were measured. The correlation of these modalities was then determined by comparing CCEPs and RSFC values.

Results: The correlation between all CCEPs and RSFCs in each subject was significant (P<0.05). Across individuals, this relationship was found to be independent of the specific regions and functional systems probed. Positive RSFC values were shown to be tightly correlated with CCEPs (6/6 subjects; P<0.01), but negative RSFC values (anti-correlated regions) failed to show a significant difference to those RSFC values centered around zero.

Discussion: Here we demonstrate that the spatial pattern and magnitude of evoked activity in response to direct cortical stimulation (CCEPs) was predicted by the pattern and strength of correlations among low-frequency BOLD signal fluctuations (RSFC). Our findings provide strong empirical support for the idea that correlated slow BOLD signal fluctuations provide an intrinsic representation of the brain’s repertoire of functional responses. Analysis of negative RSFC did not demonstrate a direct correlation with CCEPs, suggesting that the CCEP-RSFC relationship is not simply linear and requires further study. Finally, the present findings suggest that rfMRI approaches may provide a non-invasive alternative to more traditional invasive measures to clinically map spatially distributed networks underlying brain function and pathological networks underlying seizure spread.

Preferred presentation format: Poster
Topic: Neuroimaging

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