Functional MRI detection of blood-oxygenation-level-dependent responses in both white and gray matter of the spinal cord after optogenetic cortical stimulation

PNAS Nexus. 2025 Oct 7;4(11):pgaf321. doi: 10.1093/pnasnexus/pgaf321. eCollection 2025 Nov.

Abstract

We report the first demonstrations of neural activity detected using functional MRI within both the gray and white matters of the cervical spinal cord of nonhuman primates in response to stimulation by optogenetic excitation of brain cortex. The right secondary somatosensory cortices (S2) of two squirrel monkeys were transfected with Adeno-associated virus that introduced a light-sensitive cation channel (ChR2) into neurons. An optical fiber was inserted to selectively activate excitatory neurons in S2 targets using a blue laser. MRIs were acquired of the brain and cervical spine at 9.4 Tesla before, during, and after optical excitation. Robust blood-oxygenation-level-dependent (BOLD) signal changes (P < 0.05 post-FDR correction) were detected at the probe location in S2 region and in multiple connected brain regions as expected. At the same level of significance, we also detected robust and focal BOLD signal changes in spinal gray and white matters in response to the light stimulation of S2 cortex. For example, the gray matter of the ipsilateral ventral horn and left and right dorsal horns exhibited a classical BOLD signal hemodynamic response, with peak signal amplitudes of ∼0.5-0.9%. Several white matter tracts also demonstrated robust responses. For example, the right and left spinocerebellar, left corticospinal, and dorsal column tracts showed transient increases in BOLD signal that were comparable to those seen in gray matter, and with similar time courses. These effects may represent both antidromic and orthodromic excitation produced within the neurons that normally carry sensory information to S2.

Keywords: antidromic; fMRI; optogenetic; spinal cord; white matter.