Functional Reorganization of the Mesial Frontal Premotor Cortex in Patients With Supplementary Motor Area Seizures

Neurosurgery 92:186–194, 2023

Direct cortical stimulation of the mesial frontal premotor cortex, including the supplementary motor area (SMA), is challenging in humans. Limited access to these brain regions impedes understanding of human premotor cortex functional organization and somatotopy.

OBJECTIVE: To test whether seizure onset within the SMA was associated with functional remapping of mesial frontal premotor areas in a cohort of patients with epilepsy who underwent awake brain mapping after implantation of interhemispheric subdural electrodes.

METHODS: Stimulation trials from 646 interhemispheric subdural electrodes were analyzed and compared between patients who had seizure onset in the SMA (n = 13) vs patients who had seizure onset outside of the SMA (n = 12). 1:1 matching with replacement between SMA and non-SMA data sets was used to ensure similar spatial distribution of electrodes. Centroids and 95% confidence regions were computed for clustered head, trunk, upper extremity, lower extremity, and vision responses. A generalized linear mixedeffects model was used to test for significant differences in the resulting functional maps. Clinical, radiographic, and histopathologic data were reviewed.

RESULTS: After analyzing direct cortical stimulation trials from interhemispheric electrodes, we found significant displacement of the head and trunk responses in SMA compared with non-SMA patients (P < .01 for both). These differences remained significant after accounting for structural lesions, preexisting motor deficits, and seizure outcome.

CONCLUSION: The somatotopy of the mesial frontal premotor regions is significantly altered in patients who have SMA-onset seizures compared with patients who have seizure onset outside of the SMA, suggesting that functional remapping can occur in these brain regions.

The frontal longitudinal system as revealed through the fiber microdissection technique

J Neurosurg 133:1503–1515, 2020

The purpose of this study was to investigate the morphology, connectivity, and correlative anatomy of the longitudinal group of fibers residing in the frontal area, which resemble the anterior extension of the superior longitudinal fasciculus (SLF) and were previously described as the frontal longitudinal system (FLS).

METHODS Fifteen normal adult formalin-fixed cerebral hemispheres collected from cadavers were studied using the Klingler microdissection technique. Lateral to medial dissections were performed in a stepwise fashion starting from the frontal area and extending to the temporoparietal regions.

RESULTS The FLS was consistently identified as a fiber pathway residing just under the superficial U-fibers of the middle frontal gyrus or middle frontal sulcus (when present) and extending as far as the frontal pole. The authors were able to record two different configurations: one consisting of two distinct, parallel, longitudinal fiber chains (13% of cases), and the other consisting of a single stem of fibers (87% of cases). The fiber chains’ cortical terminations in the frontal and prefrontal area were also traced. More specifically, the FLS was always recorded to terminate in Brodmann areas 6, 46, 45, and 10 (premotor cortex, dorsolateral prefrontal cortex, pars triangularis, and frontal pole, respectively), whereas terminations in Brodmann areas 4 (primary motor cortex), 47 (pars orbitalis), and 9 were also encountered in some specimens. In relation to the SLF system, the FLS represented its anterior continuation in the majority of the hemispheres, whereas in a few cases it was recorded as a completely distinct tract. Interestingly, the FLS comprised shorter fibers that were recorded to interconnect exclusively frontal areas, thus exhibiting different fiber architecture when compared to the long fibers forming the SLF.

CONCLUSIONS The current study provides consistent, focused, and robust evidence on the morphology, architecture, and correlative anatomy of the FLS. This fiber system participates in the axonal connectivity of the prefrontal-premotor cortices and allegedly subserves cognitive-motor functions. Based in the SLF hypersegmentation concept that has been advocated by previous authors, the FLS should be approached as a distinct frontal segment within the superior longitudinal system.