Correlated Disruption of Resting-State fMRI, LFP, and Spike Connectivity between Area 3b and S2 following Spinal Cord Injury in Monkeys

Abstract

This study aims to understand how functional connectivity (FC) between areas 3b and S2 alters following input deprivation and the neuronal basis of disrupted FC of resting-state fMRI signals. We combined submillimeter fMRI with microelectrode recordings to localize the deafferented digit regions in areas 3b and S2 by mapping tactile stimulus-evoked fMRI activations before and after cervical dorsal column lesion in each male monkey. An average afferent disruption of 97% significantly reduced fMRI, local field potential (LFP), and spike responses to stimuli in both areas. Analysis of resting-state fMRI signal correlation, LFP coherence, and spike cross-correlation revealed significantly reduced functional connectivity between deafferented areas 3b and S2. The degrees of reductions in stimulus responsiveness and FC after deafferentation differed across fMRI, LFP, and spiking signals. The reduction of FC was much weaker than that of stimulus-evoked responses. Whereas the largest stimulus-evoked signal drop (∼80%) was observed in LFP signals, the greatest FC reduction was detected in the spiking activity (∼30%). fMRI signals showed mild reductions in stimulus responsiveness (∼25%) and FC (∼20%). The overall deafferentation-induced changes were quite similar in areas 3b and S2 across signals. Here we demonstrated that FC strength between areas 3b and S2 was much weakened by dorsal column lesion, and stimulus response reduction and FC disruption in fMRI covary with those of LFP and spiking signals in deafferented areas 3b and S2. These findings have important implications for fMRI studies aiming to probe FC alterations in pathological conditions involving deafferentation in humans. By directly comparing fMRI, local field potential, and spike signals in both tactile stimulation and resting states before and after severe disruption of dorsal column afferent, we demonstrated that reduction in fMRI responses to stimuli is accompanied by weakened resting-state fMRI functional connectivity (FC) in input-deprived and reorganized digit regions in area 3b of the S1 and S2. Concurrent reductions in local field potential and spike FC validated the use of resting-state fMRI signals for probing neural intrinsic FC alterations in pathological deafferented cortex, and indicated that disrupted FC between mesoscale functionally highly related regions may contribute to the behavioral impairments.

Functional connectivity with cortical depth assessed by resting state fMRI of subregions of S1 in squirrel monkeys

“…However, to date, there is no evidence suggesting that anesthesia alters synchronization of resting state signals between layers in two functionally highly related cortical areas. In contrast, our own studies found that rsFC patterns did not change as a function of anesthesia level, indicating that the core intrinsic patterns are preserved under the light anesthesia level we used in our studies (Wu, Yang, & Chen, ). Increases in anesthesia depth only reduced the overall rsFC strength with no noticeable area bias (Wu et al, ).…”

Neuromodulation of sensory networks in monkey brain by focused ultrasound with MRI guidance and detection

“…Two main features of the BOLD responses support the conclusion that FUS-induced effects are neural based and circuit specific. First, the overall shape of BOLD signal changes evoked by long FUS blocks is very similar to the typical hemodynamic signal changes evoked by natural tactile stimulation, which are known to be related to increases in spiking activities and local field potentials in areas 3b and 1 of S1, as well as S2, within the monkey somatosensory system 32 , 36 . Second, the FUS-induced responses in these regions differed in magnitude and temporal features between regions.…”

“…In the present study, we aimed to address several challenges and questions about the application of FUS neuromodulation of the non-human primate brain using MRI-guided FUS at 7 T. We chose to study the monkey somatosensory system because it has been well characterized using fMRI and intracranial electrophysiology as well as invasive and post-mortem studies 25 , 26 . We have developed robust fMRI paradigms that allow us to reliably map brain touch circuits in non-human primates 27 – 32 . We first established that a FUS transducer could be implemented in a 7 T human scanner, with an optical tracking system to guide transducer placement.…”

Bidirectional and state-dependent modulation of brain activity by transcranial focused ultrasound in non-human primates

“…Med-FUS induced BOLD signal changes in areas 3a/3b, MCC, and VPL exhibited a two-phase feature: an apparent signal drop at the beginning of the med-FUS stimulation followed by BOLD signal increases. The overall shape of the BOLD signal changes modulated by long med-FUS blocks is very similar to the typical hemodynamic signal changes evoked by natural tactile stimulation, which are believed to be related to increases in spiking activities and local field potentials in areas 3b and 1 of S1, as well as S2, within the monkey somatosensory system [ 34 , 62 ]. We interpret the responses of the off-target regions as neural-based and activated via inter-regional connections.…”

“…Macaque monkeys have been well characterized by fMRI and intracranial electrophysiology as well as by invasive and post-mortem studies [ 27 , 28 ]. We have developed robust fMRI paradigms that allow us to reliably map touch responses in the brains of non-human primates [ 29 – 34 ], and have demonstrated the ability to detect high-amplitude FUS-induced neuromodulation effects [ 23 ], in which the used FUS was twice as high in amplitude. we refer to the current parameters as “med-FUS” to indicate medium amplitude.…”