Cortical connectivity is embedded in resting state at columnar resolution

Card, Nicholas S.; Gharbawie, Omar A.

doi:10.1016/j.pneurobio.2022.102263

Cited by 8 publications

(4 citation statements)

References 87 publications

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“…In particular, ICMS has also been used in conjunction with fMRI or intrinsic optical imaging to measure intra- and interregional connectivity (22-26, 44). Furthermore, similar to our findings, ICMS-evoked neural activity measured with intrinsic optical imaging corresponds with both anatomical connectivity and resting-state functional connectivity (45). However, the stimulation amplitudes in these studies were several times higher than the amplitudes used here, increasing the volume of direct activation, and potentially the risk of cortical damage with repeated stimulation (46).…”

Section: Discussionsupporting

confidence: 89%

Stimulation-Evoked Effective Connectivity (SEEC): An in-vivo approach for defining mesoscale corticocortical connectivity

Bundy

Barbay

Hudson

et al. 2022

Preprint

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BackgroundCortical stimulation has been a versatile technique for examining the structure and function of cortical regions as well as for implementing novel therapies. While stimulation has been used to examine the local spread of neural activity, it may also enable longitudinal examination of mesoscale interregional connectivity. Recent studies have used focal intracortical microstimulation with optical imaging to show cross-region spread of neural activity, but the exact neural mechanisms elucidated by these modalities is uncertain.ObjectiveHere, we sought to use intracortical microstimulation (ICMS) in conjunction with recordings of multi-unit action potentials to assess the mesoscale effective connectivity within sensorimotor cortex.MethodsNeural recordings were made from multielectrode arrays placed into sensory, motor, and premotor regions during surgical experiments in three squirrel monkeys. During each recording, single-pulse ICMS was repeatably delivered to a single region. Mesoscale effective connectivity was calculated from ICMS-evoked changes in multi-unit firing.ResultsMulti-unit action potentials were able to be detected on the order of 1 ms after each ICMS pulse. Across sensorimotor regions, short-latency (<2.5 ms) ICMS-evoked neural activity strongly correlated with known anatomic connections. Additionally, ICMS-evoked responses remained stable across the experimental period, in spite of small changes in electrode locations and anesthetic state.ConclusionsThese results show that monitoring ICMS-evoked neural activity is a viable way to longitudinally assess effective connectivity, enabling studies comparing the time course of connectivity changes with the time course of changes in behavioral function.HighlightsShort-latency neural responses to single-pulse intra-cortical microstimulation (ICMS) was evaluated as a surrogate for anatomical connectivity.Across three new-world monkeys, the strength of neural responses strongly correlated with known anatomical connections.Neural responses to stimulation were repeatable across the duration of the experiments and were invariant to minor deviations in electrode positions and anesthetic state.

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Section: Discussionsupporting

confidence: 89%

Stimulation-Evoked Effective Connectivity (SEEC): An in-vivo approach for defining mesoscale corticocortical connectivity

Bundy

Barbay

Hudson

et al. 2022

Preprint

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“…7, A and D ; r = 0.23; P = 0 with Fisher’s z transformation; 27,871 voxels; and Dice overlap index = 0.38), which showed the greatest [ 18 F]FES signal in the PPC, as well as with the smaller [ 18 F]FES PPC signal observed in squirrel monkey #2 (fig. S8; r = 0.08; P = 0 with Fisher’s z transformation; 29,529 voxels; and Dice overlap index = 0.44) and is consistent with known anatomical and functional connectivity of M1 in New World monkeys ( 37 – 40 ). Collectively, these findings highlight the utility of [ 18 F]FES-PET and ChRERα for in vivo mapping of anatomical projections for informing the structural basis of functional connectivity maps.…”

Section: Resultssupporting

confidence: 77%

Expression of the excitatory opsin ChRERα can be traced longitudinally in rat and nonhuman primate brains with PET imaging

et al. 2023

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Optogenetics is a widely used technology with potential for translational research. A critical component of such applications is the ability to track the location of the transduced opsin in vivo. To address this problem, we engineered an excitatory opsin, ChRERα (hChR2(134R)-V5-ERα-LBD), that could be visualized using positron emission tomography (PET) imaging in a noninvasive, longitudinal, and quantitative manner. ChRERα consists of the prototypical excitatory opsin channelrhodopsin-2 (ChR2) and the ligand-binding domain (LBD) of the human estrogen receptor α (ERα). ChRERα showed conserved ChR2 functionality and high affinity for [ 18 F]16α-fluoroestradiol (FES), an FDA-approved PET radiopharmaceutical. Experiments in rats demonstrated that adeno-associated virus (AAV)–mediated expression of ChRERα enables neural circuit manipulation in vivo and that ChRERα expression could be monitored using FES-PET imaging. In vivo experiments in nonhuman primates (NHPs) confirmed that ChRERα expression could be monitored at the site of AAV injection in the primary motor cortex and in long-range neuronal terminals for up to 80 weeks. The anatomical connectivity map of the primary motor cortex identified by FES-PET imaging of ChRERα expression overlapped with a functional connectivity map identified using resting state fMRI in a separate cohort of NHPs. Overall, our results demonstrate that ChRERα expression can be mapped longitudinally in the mammalian brain using FES-PET imaging and can be used for neural circuit modulation in vivo.

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“…If anything, ISOI sensitivity to subthreshold electrophysiological signals can lead to overestimation of the spatial extent of modulated neural activity ( Frostig et al, 2017 ; Grinvald et al, 1994 ). The issue is minimized by focusing on early segments of the ISOI response, which reports cortical organization and connectivity at columnar resolution ( Bonhoeffer and Grinvald, 1991 ; Card and Gharbawie, 2022 ; Card and Gharbawie, 2020 ; Friedman et al, 2020b ; Lu and Roe, 2007 ; Vanzetta et al, 2004 ). (2) Task overtraining .…”

Section: Discussionmentioning

confidence: 99%

Motor actions are spatially organized in motor and dorsal premotor cortex

Chehade,

Gharbawie

2023

eLife

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Frontal motor areas are central to controlling voluntary movements. In non-human primates, the motor areas contain independent, somatotopic, representations of the forelimb (i.e., motor maps). But are the neural codes for actions spatially organized within those forelimb representations? Addressing this question would provide insight into the poorly understood structure-function relationships of the cortical motor system. Here, we tackle the problem using high resolution optical imaging and motor mapping in motor (M1) and dorsal premotor (PMd) cortex. Two macaque monkeys performed an instructed reach-to-grasp task while cortical activity was recorded with intrinsic signal optical imaging (ISOI). The spatial extent of activity in M1 and PMd was then quantified in relation to the forelimb motor maps, which we obtained from the same hemisphere with intracortical microstimulation. ISOI showed that task-related activity was concentrated in patches that collectively overlapped <40% of the M1 and PMd forelimb representations. The spatial organization of the patches was consistent across task conditions despite small variations in forelimb use. Nevertheless, the largest condition differences in forelimb use were reflected in the magnitude of cortical activity. Distinct time course profiles from patches in arm zones and patches in hand zones suggest functional differences within the forelimb representations. The results collectively support an organizational framework wherein the forelimb representations contain subzones enriched with neurons tuned for specific actions. Thus, the often-overlooked spatial dimension of neural activity appears to be an important organizing feature of the neural code in frontal motor areas.

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Cortical connectivity is embedded in resting state at columnar resolution

Cited by 8 publications

References 87 publications

Stimulation-Evoked Effective Connectivity (SEEC): An in-vivo approach for defining mesoscale corticocortical connectivity

Stimulation-Evoked Effective Connectivity (SEEC): An in-vivo approach for defining mesoscale corticocortical connectivity

Expression of the excitatory opsin ChRERα can be traced longitudinally in rat and nonhuman primate brains with PET imaging

Motor actions are spatially organized in motor and dorsal premotor cortex

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