Functional topography of pulvinar–visual cortex networks in macaques revealed by INS–fMRI

Abstract

The pulvinar in the macaque monkey contains three divisions: the medial pulvinar (PM), the lateral pulvinar (PL), and the inferior pulvinar (PI). Anatomical studies have shown that connections of PM are preferentially distributed to higher association areas, those of PL are biased toward the ventral visual pathway, and those of PI are biased with the dorsal visual pathway. To study functional connections of the pulvinar at mesoscale, we used a novel method called INS–fMRI (infrared neural stimulation and functional magnetic resonance imaging). This method permits studies and comparisons of multiple pulvinar networks within single animals. As previously revealed, stimulations of different sites in PL and PI produced topographically organized focal activations in visual areas V1, V2, and V3. In contrast, PM stimulation elicited little or diffuse response. The relative activations of areas V1, V2, V3A, V3d, V3v, V4, MT, and MST revealed that connections of PL are biased to ventral pathway areas, and those of PI are biased to dorsal areas. Different statistical values of activated blood‐oxygen‐level‐dependent responses produced the same center of activation, indicating stability of connectivity; it also suggests possible dynamics of broad to focal responses from single stimulation sites. These results demonstrate that infrared neural stimulation‐induced connectivity is largely consistent with previous anatomical connectivity studies, thereby demonstrating validity of our novel method. In addition, it suggests additional interpretations of functional connectivity to complement anatomical studies.

A novel interface for cortical columnar neuromodulation with multi-point infrared neural stimulation

“…To increase flexibility of stimulation patterns, we have developed a 100-fiber bundle array and have applied this to cortex in anesthetized monkeys, with plans to do so in awake monkeys 25,71 . Note that deep brain stimulators may also be designed 72,73 .…”

Two-photon imaging of excitatory and inhibitory neural response to infrared neural stimulation

“…INS stimulation of visual cortex in anesthetized macaque monkeys produced responses typical of visually induced cortical intrinsic signals 7 and furthermore led to selective modulation of functionally matched ocular dominance domains, consistent with activation of local cortico-cortical connections. The demonstration that INS stimulation in ultrahigh-field MRI could lead to activation of anatomically predicted mesoscale global brain sites in the macaque monkey further suggested that projection cells (excitatory pyramidal neurons) are being activated by INS [10][11][12] . These INS-induced responses have been shown to be intensityand duration-dependent.…”

“…Thus, the advantages of INS over conventional electrical stimulation include high spatial selectivity, contactless delivery, and importantly for primate and human application, neuromodulation of brain sites without prior opsin expression 8,9 . Furthermore, with this precision of targeted optical fiber stimulation and MRI compatibility, focal INS combined with MRI can be used for in vivo mapping of brain networks in primates [10][11][12] and holds promise for neuromodulation in awake behaving monkeys. While such applications have demonstrated great promise for circuit neuromodulation in vivo, its mechanism of action or effect on individual cell types is currently still poorly understood.…”

Brainwide mesoscale functional networks revealed by focal infrared neural stimulation of the amygdala

“…Specifically, brief (0.25msec) pulses of infrared (1875nm wavelength) light delivered (via 200um optical fiber) in pulse trains (200hz, duration 0.5sec) stimulate submillimeter clusters of neurons, leading to specific activation of connected sites whose locations are mapped at brainwide scale by recording Blood Oxygen Level Dependent (BOLD) signals (for review of INS, see (Chernov and Roe, 2014; Goyal et al, 2012; Thompson, 2014); for membrane capacitance effects see (Shapiro et al, 2012); for safety and damage thresholds in primates, see (Chernov et al, 2014; Pan et al, 2023)). As INS reveals functional connectivity, extending two synapses from the stimulation site (Xu et al, 2019), it evokes brainwide activations that prove to be highly anatomically and functionally specific (Shi et al, 2021; Yao et al, 2023). INS thus provides distinct benefits for high resolution brainwide circuit mapping compared with other electrical, optogenetic, and anatomical tracing methods (Klink et al, 2017; Roe et al, 2015).…”

“…Previously, we established that the INS-fMRI method could be used to reveal statistically significant, mesoscale connectivity between subcortical nuclei and cortical areas (Shi et al, 2021; Yao et al, 2023). Our initial study of amygdala stimulation illustrated, via stimulation of a few sites in BA, the feasibility of detecting statistically significant BOLD signal at connected sites in the cingulate cortex and lateral sulcus areas (insular cortex and association sensory areas and auditory belt areas) (Shi et al, 2021).…”