Characteristic BOLD signals are detectable in white matter of the spinal cord at rest and after a stimulus.

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions.

Disrupting nociceptive information processing flow through transcranial focused ultrasound neuromodulation of thalamic nuclei.

BACKGROUND: MRI-guided transcranial focused ultrasound (MRgFUS) as a next-generation neuromodulation tool can precisely target and stimulate deep brain regions with high spatial selectivity. Combined with MR-ARFI (acoustic radiation force imaging) and using fMRI BOLD signal as functional readouts, our previous studies have shown that low-intensity FUS can excite or suppress neural activity in the somatosensory cortex. OBJECTIVE: To investigate whether low-intensity FUS can suppress nociceptive heat stimulation-induced responses in thalamic nuclei during hand stimulation, and to determine how this suppression influences the information processing flow within nociception networks. FINDINGS: BOLD fMRI activations evoked by 47.5 °C heat stimulation of hand were detected in 24 cortical regions, which belong to sensory, affective, and cognitive nociceptive networks. Concurrent delivery of low-intensity FUS pulses (650 kHz, 550 kPa) to the predefined heat nociceptive stimulus-responsive thalamic centromedial_parafascicular (CM_para), mediodorsal (MD), ventral_lateral (VL_ and ventral_lateral_posteroventral (VLpv) nuclei suppressed their heat responses. Off-target cortical areas exhibited reduced, enhanced, or no significant fMRI signal changes, depending on the specific areas. Differentiable thalamocortical information flow during the processing of nociceptive heat input was observed, as indicated by the time to reach 10% or 30% of the heat-evoked BOLD signal peak. Suppression of thalamic heat responses significantly altered nociceptive processing flow and direction between the thalamus and cortical areas. Modulation of contralateral versus ipsilateral areas by unilateral thalamic activity differed. Signals detected in high-order cortical areas, such as dorsal frontal (DFC) and ventrolateral prefrontal (vlPFC) cortices, exhibited faster response latencies than sensory areas. CONCLUSIONS: The concurrent delivery of FUS suppressed nociceptive heat response in thalamic nuclei and disrupted the nociceptive network. This study offers new insights into the causal functional connections within the thalamocortical networks and demonstrates the modulatory effects of low-intensity FUS on nociceptive information processing.

Detection and characterization of resting state functional networks in squirrel monkey brain.

Resting-state fMRI based on analyzing BOLD signals is widely used to derive functional networks in the brain and how they alter during disease or injury conditions. Resting-state networks can also be used to study brain functional connectomes across species, which provides insights into brain evolution. The squirrel monkey (SM) is a non-human primate (NHP) that is widely used as a preclinical model for experimental manipulations to understand the organization and functioning of the brain. We derived resting-state networks from the whole brain of anesthetized SMs using Independent Component Analysis of BOLD acquisitions. We detected 15 anatomically constrained resting-state networks localized in the cortical and subcortical regions as well as in the white-matter. Networks encompassing visual, somatosensory, executive control, sensorimotor, salience and default mode regions, and subcortical networks including the Hippocampus-Amygdala, thalamus, basal-ganglia and brainstem region correspond well with previously detected networks in humans and NHPs. The connectivity pattern between the networks also agrees well with previously reported seed-based resting-state connectivity of SM brain. This study demonstrates that SMs share remarkable homologous network organization with humans and other NHPs, thereby providing strong support for their suitability as a translational animal model for research and additional insight into brain evolution across species.

Longitudinal multiparametric MRI of traumatic spinal cord injury in animal models.

Multi-parametric MRI (mpMRI) technology enables non-invasive and quantitative assessments of the structural, molecular, and functional characteristics of various neurological diseases. Despite the recognized importance of studying spinal cord pathology, mpMRI applications in spinal cord research have been somewhat limited, partly due to technical challenges associated with spine imaging. However, advances in imaging techniques and improved image quality now allow longitudinal investigations of a comprehensive range of spinal cord pathological features by exploiting different endogenous MRI contrasts. This review summarizes the use of mpMRI techniques including blood oxygenation level-dependent (BOLD) functional MRI (fMRI), diffusion tensor imaging (DTI), quantitative magnetization transfer (qMT), and chemical exchange saturation transfer (CEST) MRI in monitoring different aspects of spinal cord pathology. These aspects include cyst formation and axonal disruption, demyelination and remyelination, changes in the excitability of spinal grey matter and the integrity of intrinsic functional circuits, and non-specific molecular changes associated with secondary injury and neuroinflammation. These approaches are illustrated with reference to a nonhuman primate (NHP) model of traumatic cervical spinal cord injuries (SCI). We highlight the benefits of using NHP SCI models to guide future studies of human spinal cord pathology, and demonstrate how mpMRI can capture distinctive features of spinal cord pathology that were previously inaccessible. Furthermore, the development of mechanism-based MRI biomarkers from mpMRI studies can provide clinically useful imaging indices for understanding the mechanisms by which injured spinal cords progress and repair. These biomarkers can assist in the diagnosis, prognosis, and evaluation of therapies for SCI patients, potentially leading to improved outcomes.

Identification of synchronous BOLD signal patterns in white matter of primate spinal cord.

Functional MRI studies of the brain have shown that blood-oxygenation-level-dependent (BOLD) signals are robustly detectable not only in gray matter (GM) but also in white matter (WM). Here, we report the detection and characteristics of BOLD signals in WM of spinal cord (SC) of squirrel monkeys. Tactile stimulus-evoked BOLD signal changes were detected in the ascending sensory tracts of SC using a General-Linear Model (GLM) as well as Independent Component Analysis (ICA). ICA of resting state signals identified coherent fluctuations from eight WM hubs which correspond closely with known anatomical locations of SC WM tracts. Resting state analyses showed that the WM hubs exhibited correlated signal fluctuations within and between SC segments in specific patterns that correspond well with the known neurobiological functions of WM tracts in SC. Overall, these findings suggest WM BOLD signals in SC show similar features as GM both at baseline and under stimulus conditions.

Do working and living conditions influence brick-kiln productivity? Evidence from Nepal.

The brick-kiln (BK) sector in Nepal is largely an informal sector. This study investigated the influence of working and living conditions (WLCs) in BKs on productivity at two levels - BK level and workers' level - using primary data collected from 781 workers and 80 BK entrepreneurs in 12 districts of Nepal. WLCs were assessed based on the provision of nine amenities to workers at BKs. Correlation and regression analyses revealed that WLCs have a positive influence on both BK level as well as workers' level productivity. Moreover, large BKs with better investment in zig-zag technology and mechanization are more likely to spend on improving WLCs than small BKs, who are reluctant to invest in WLCs due mainly to a lack of financial resources. The study suggests an integrated approach emphasizing equally improved WLCs and cleaner technology in the BK sector to transform it into a healthier and socio-environmentally responsible industry.

Forgotten Contributors in the Brick Sector in Nepal.

Brick making in Nepal is an informal sector that is still highly labor intensive. It employs transient workers who are extremely marginalized and exposed to poor working and living conditions. This study assesses the working and living conditions of male and female brick workers and their children and looks to address the main issues and challenges to promote decent living and working conditions in the brick factories through action research. A rapid needs assessment was conducted to take stock of the working and living conditions of male and female workers across five provinces in Nepal. Subsequently, selected pilot interventions through stakeholder consultations were initiated to address these issues and challenges. There are a host of challenges faced by these workers in the factories, with the main issues being occupational health and safety and childcare/education for workers' children. The study suggests that the working and living conditions of the workers can be improved by incentivizing the brick entrepreneurs to invest in them, thus creating a more productive workforce. Moreover, the findings from the pilot interventions can help in the design of effective solutions.

Determinants of crop residue burning practice in the Terai region of Nepal.

The open burning of agricultural crop residue is a key environmental issue facing the Hindu Kush Himalaya region, the Indo-Gangetic plain in particular. There is a varying intensity in the incidence of open agricultural burning in this region, and multiple drivers that determine why farmers in this region decide to burn their crop residues. While there have been research studies conducted for other countries in the region, research into the determinants of crop-burning in the Nepalese context is missing. Using primary data from a survey of 388 farming households across three districts of the Nepal Terai-Nawalparasi, Rupandehi and Kapilvastu-applying a recursive bivariate probit model, this study seeks to find out what drives the Nepalese farmers to burn their crop residue instead of using them in a sustainable manner and suggest policy recommendations for mitigation. Our findings show that the major determining factors that influence the farmers' behavior in Nepal are livestock ownership, combine harvester use and awareness level of the farmers. While the effects of crop residue burning is transboundary in nature, the mitigation measures require to be region specific. Based on the findings, the study proposes raising livestock, using technology like Happy Seeders or upgrade the combine harvesters, raising awareness and changing perception of farmers, and promoting alternative uses of crop residue as viable mitigation measures.

Functional networks in non-human primate spinal cord and the effects of injury.

Spontaneous fluctuations of Blood Oxygenation-Level Dependent (BOLD) MRI signal in a resting state have previously been detected and analyzed to describe intrinsic functional networks in the spinal cord of rodents, non-human primates and human subjects. In this study we combined high resolution imaging at high field with data-driven Independent Component Analysis (ICA) to i) delineate fine-scale functional networks within and between segments of the cervical spinal cord of monkeys, and also to ii) characterize the longitudinal effects of a unilateral dorsal column injury on these networks. Seven distinct functional hubs were revealed within each spinal segment, with new hubs detected at bilateral intermediate and gray commissure regions in addition to the bilateral dorsal and ventral horns previously reported. Pair-wise correlations revealed significantly stronger connections between hubs on the dominant hand side. Unilateral dorsal-column injuries disrupted predominantly inter-segmental rather than intra-segmental functional connectivities as revealed by correlation strengths and graph-theory based community structures. The effects of injury on inter-segmental connectivity were evident along the length of the cord both below and above the lesion region. Connectivity strengths recovered over time and there was revival of inter-segmental communities as animals recovered function. BOLD signals of frequency 0.01-0.033 Hz were found to be most affected by injury. The results in this study provide new insights into the intrinsic functional architecture of spinal cord and underscore the potential of functional connectivity measures to characterize changes in networks after an injury and during recovery.

Socio-Economic Implications of COVID-19 Pandemic in South Asia: Emerging Risks and Growing Challenges.

The dramatic spread of COVID-19 has threatened human lives, disrupted livelihoods, and affected trade, economy and businesses across the globe. The global economy has begun to show major disruptions and is heading toward a severe recession with an unprecedented economic crisis. As the global economy is highly integrated and interdependent through the global supply chains, it has been profoundly affected by the COVID-19 pandemic. Although all countries have faced difficulties due to Covid-19, South Asian countries in particular have had to deal with a more challenging situation due to their large population, weak health facilities, high poverty rates, low socio-economic conditions, poor social protection systems, limited access to water and sanitation, and inadequate living space, necessary to maintain physical distancing and take other required measures to contain this pandemic. To contain the spread of the virus, South Asian countries have imposed stringent lockdowns, which have consequently affected the lives and livelihoods of millions of people in the region, where a third of world's poor live. Against this backdrop, this paper examines the existing and prospective impacts, risks and challenges of Covid-19 on key social and economic sectors including migration, tourism, informal sector, agriculture and rural livelihoods. The analysis revealed that COVID-19 is likely to affect economic growth, increase fiscal deficit and monetary burden, increase the risks of macroeconomic instability, decrease migration and remittance, reduce income from travel and tourism, and result in dwindling micro-small and medium industries and informal businesses. This is likely to deepen poverty and increase unemployment and the risks of hunger and food insecurity. If not addressed properly, this may reinforce existing inequalities, break social harmony, and increase tension and turbulence. The economic and social costs of the COVID-19 outbreak are therefore likely to be significant and long-lasting in South Asia.

Longitudinal changes in DTI parameters of specific spinal white matter tracts correlate with behavior following spinal cord injury in monkeys.

This study aims to evaluate how parameters derived from diffusion tensor imaging reflect axonal disruption and demyelination in specific white matter tracts within the spinal cord of squirrel monkeys following traumatic injuries, and their relationships to function and behavior. After a unilateral section of the dorsal white matter tract of the cervical spinal cord, we found that both lesioned dorsal and intact lateral tracts on the lesion side exhibited prominent disruptions in fiber orientation, integrity and myelination. The degrees of pathological changes were significantly more severe in segments below the lesion than above. The lateral tract on the opposite (non-injured) side was minimally affected by the injury. Over time, RD, FA, and AD values of the dorsal and lateral tracts on the injured side closely tracked measurements of the behavioral recovery. This unilateral section of the dorsal spinal tract provides a realistic model in which axonal disruption and demyelination occur together in the cord. Our data show that specific tract and segmental FA and RD values are sensitive to the effects of injury and reflect specific behavioral changes, indicating their potential as relevant indicators of recovery or for assessing treatment outcomes. These observations have translational value for guiding future studies of human subjects with spinal cord injuries.

Concomitant modulation of BOLD responses in white matter pathways and cortex.

In response to a flickering visual stimulus, the BOLD response in primary visual cortex varies with the flickering frequency and is maximal when it is close to 8Hz. In previous studies we demonstrated that BOLD signals in specific white matter (WM) pathways covary with the alternations between stimulus conditions in a block design in similar manner to gray matter (GM) regions. Here we investigated whether WM tracts show varying responses to changes in flicker frequency and are modulated in the same manner as cortical areas. We used a Fourier analysis of BOLD signals to measure the signal amplitude and phase at the fundamental frequency of a block-design task in which flickering visual stimuli alternated with blank presentations, avoiding the assumption of any specific hemodynamic response function. The BOLD responses in WM pathways and the primary visual cortex were evaluated for flicker frequencies varying between 2 and 14Hz. The variations with frequency of BOLD signals in specific WM tracts followed closely those in primary visual cortex, suggesting that variations in cortical activation are directly coupled to corresponding BOLD signals in connected WM tracts. Statistically significant differences in the timings of BOLD responses were also measured between visual cortex and specific WM bundles. These results confirm that when cortical BOLD responses are modulated by selecting different task parameters, relevant WM tracts exhibit corresponding BOLD signals that are also affected.

Longitudinal assessment of recovery after spinal cord injury with behavioral measures and diffusion, quantitative magnetization transfer and functional magnetic resonance imaging.

Spinal cord injuries (SCIs) are a leading cause of disability and can severely impact the quality of life. However, to date, the processes of spontaneous repair of damaged spinal cord remain incompletely understood, partly due to a lack of appropriate longitudinal tracking methods. Noninvasive, multiparametric magnetic resonance imaging (MRI) provides potential biomarkers for the comprehensive evaluation of spontaneous repair after SCI. In this study in rats, a clinically relevant contusion injury was introduced at the lumbar level that impairs both hindlimb motor and sensory functions. Quantitative MRI measurements were acquired at baseline and serially post-SCI for up to 2 wk. The progressions of injury and spontaneous recovery in both white and gray matter were tracked longitudinally using pool-size ratio (PSR) measurements derived from quantitative magnetization transfer (qMT) methods, measurements of water diffusion parameters using diffusion tensor imaging (DTI) and intrasegment functional connectivity derived from resting state functional MRI. Changes in these quantitative imaging measurements were correlated with behavioral readouts. We found (a) a progressive decrease in PSR values within 2 wk post-SCI, indicating a progressive demyelination at the center of the injury that was validated with histological staining, (b) PSR correlated closely with fractional anisotropy and transverse relaxation of free water, but did not show significant correlations with behavioral recovery, and (c) preliminary evidence that SCI induced a decrease in functional connectivity between dorsal horns below the injury site at 24 h. Findings from this study not only confirm the value of qMT and DTI methods for assessing the myelination state of injured spinal cord but indicate that they may also have further implications on whether therapies targeted towards remyelination may be appropriate. Additionally, a better understanding of changes after SCI provides valuable information to guide and assess interventions.

Functional MRI and resting state connectivity in white matter - a mini-review.

Functional MRI (fMRI) signals are robustly detectable in white matter (WM) but they have been largely ignored in the fMRI literature. Their nature, interpretation, and relevance as potential indicators of brain function remain under explored and even controversial. Blood oxygenation level dependent (BOLD) contrast has for over 25 years been exploited for detecting localized neural activity in the cortex using fMRI. While BOLD signals have been reliably detected in grey matter (GM) in a very large number of studies, such signals have rarely been reported from WM. However, it is clear from our own and other studies that although BOLD effects are weaker in WM, using appropriate detection and analysis methods they are robustly detectable both in response to stimuli and in a resting state. BOLD fluctuations in a resting state exhibit similar temporal and spectral profiles in both GM and WM, and their relative low frequency (0.01-0.1 Hz) signal powers are comparable. They also vary with baseline neural activity e.g. as induced by different levels of anesthesia, and alter in response to a stimulus. In previous work we reported that BOLD signals in WM in a resting state exhibit anisotropic temporal correlations with neighboring voxels. On the basis of these findings, we derived functional correlation tensors that quantify the correlational anisotropy in WM BOLD signals. We found that, along many WM tracts, the directional preferences of these functional correlation tensors in a resting state are grossly consistent with those revealed by diffusion tensors, and that external stimuli tend to enhance visualization of specific and relevant fiber pathways. These findings support the proposition that variations in WM BOLD signals represent tract-specific responses to neural activity. We have more recently shown that sensory stimulations induce explicit BOLD responses along parts of the projection fiber pathways, and that task-related BOLD changes in WM occur synchronously with the temporal pattern of stimuli. WM tracts also show a transient signal response following short stimuli analogous to but different from the hemodynamic response function (HRF) characteristic of GM. Thus there is converging and compelling evidence that WM exhibits both resting state fluctuations and stimulus-evoked BOLD signals very similar (albeit weaker) to those in GM. A number of studies from other laboratories have also reported reliable observations of WM activations. Detection of BOLD signals in WM has been enhanced by using specialized tasks or modified data analysis methods. In this mini-review we report summaries of some of our recent studies that provide evidence that BOLD signals in WM are related to brain functional activity and deserve greater attention by the neuroimaging community.

Intrinsic functional architecture of the non-human primate spinal cord derived from fMRI and electrophysiology.

Resting-state functional MRI (rsfMRI) has recently revealed correlated signals in the spinal cord horns of monkeys and humans. However, the interpretation of these rsfMRI correlations as indicators of functional connectivity in the spinal cord remains unclear. Here, we recorded stimulus-evoked and spontaneous spiking activity and local field potentials (LFPs) from monkey spinal cord in order to validate fMRI measures. We found that both BOLD and electrophysiological signals elicited by tactile stimulation co-localized to the ipsilateral dorsal horn. Temporal profiles of stimulus-evoked BOLD signals covaried with LFP and multiunit spiking in a similar way to those observed in the brain. Functional connectivity of dorsal horns exhibited a U-shaped profile along the dorsal-intermediate-ventral axis. Overall, these results suggest that there is an intrinsic functional architecture within the gray matter of a single spinal segment, and that rsfMRI signals at high field directly reflect this underlying spontaneous neuronal activity.

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

Whereas resting state blood oxygenation-level dependent (BOLD) functional MRI has been widely used to assess functional connectivity between cortical regions, the laminar specificity of such measures is poorly understood. This study aims to determine: (a) whether the resting state functional connectivity (rsFC) between two functionally related cortical regions varies with cortical depth, (b) the relationship between layer-resolved tactile stimulus-evoked activation pattern and interlayer rsFC pattern between two functionally distinct but related somatosensory areas 3b and 1, and (c) the effects of spatial resolution on rsFC measures. We examined the interlayer rsFC between areas 3b and 1 of squirrel monkeys under anesthesia using tactile stimulus-driven and resting state BOLD acquisitions at submillimeter resolution. Consistent with previous observations in the areas 3b and 1, we detected robust stimulus-evoked BOLD activations with foci were confined mainly to the upper layers (centered at 21% of the cortical depth). By carefully placing seeds in upper, middle, and lower layers of areas 3b and 1, we observed strong rsFC between upper and middle layers of these two areas. The layer-resolved activation patterns in areas 3b and 1 agree with their interlayer rsFC patterns, and are consistent with the known anatomical connections between layers. In summary, using BOLD rsFC pattern, we identified an interlayer interareal microcircuit that shows strong intrinsic functional connections between upper and middle layer areas 3b and 1. RsFC can be used as a robust invasive tool to probe interlayer corticocortical microcircuits.

Multiple sclerosis lesions affect intrinsic functional connectivity of the spinal cord.

Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.

Resting-state functional connectivity in the rat cervical spinal cord at 9.4 T.

PURPOSE: Numerous studies have adopted resting-state functional MRI methods to infer functional connectivity between cortical regions, but very few have translated them to the spinal cord, despite its critical role in the central nervous system. Resting-state functional connectivity between gray matter horns of the spinal cord has previously been shown to be detectable in humans and nonhuman primates, but it has not been reported previously in rodents. METHODS: Resting-state functional MRI of the cervical spinal cord of live anesthetized rats was performed at 9.4 T. The quality of the functional images acquired was assessed, and quantitative analyses of functional connectivity in C4-C7 of the spinal cord were derived. RESULTS: Robust gray matter horn-to-horn connectivity patterns were found that were statistically significant when compared with adjacent control regions. Specifically, dorsal-dorsal and ventral-ventral connectivity measurements were most prominent, while ipsilateral dorsal-ventral connectivity was also observed but to a lesser extent. Quantitative evaluation of reproducibility also revealed moderate robustness in the bilateral sensory and motor networks that was weaker in the dorsal-ventral connections. CONCLUSIONS: This study reports the first evidence of resting-state functional circuits within gray matter in the rat spinal cord, and verifies their detectability using resting-state functional MRI at 9.4 T. Magn Reson Med 79:2773-2783, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

High spatial correspondence at a columnar level between activation and resting state fMRI signals and local field potentials.

Although blood oxygenation level-dependent (BOLD) fMRI has been widely used to map brain responses to external stimuli and to delineate functional circuits at rest, the extent to which BOLD signals correlate spatially with underlying neuronal activity, the spatial relationships between stimulus-evoked BOLD activations and local correlations of BOLD signals in a resting state, and whether these spatial relationships vary across functionally distinct cortical areas are not known. To address these critical questions, we directly compared the spatial extents of stimulated activations and the local profiles of intervoxel resting state correlations for both high-resolution BOLD at 9.4 T and local field potentials (LFPs), using 98-channel microelectrode arrays, in functionally distinct primary somatosensory areas 3b and 1 in nonhuman primates. Anatomic images of LFP and BOLD were coregistered within 0.10 mm accuracy. We found that the point spread functions (PSFs) of BOLD and LFP responses were comparable in the stimulus condition, and both estimates of activations were slightly more spatially constrained than local correlations at rest. The magnitudes of stimulus responses in area 3b were stronger than those in area 1 and extended in a medial to lateral direction. In addition, the reproducibility and stability of stimulus-evoked activation locations within and across both modalities were robust. Our work suggests that the intrinsic resolution of BOLD is not a limiting feature in practice and approaches the intrinsic precision achievable by multielectrode electrophysiology.

Biophysical and neural basis of resting state functional connectivity: Evidence from non-human primates.

Functional MRI (fMRI) has evolved from simple observations of regional changes in MRI signals caused by cortical activity induced by a task or stimulus, to task-free acquisitions of images in a resting state. Such resting state signals contain low frequency fluctuations which may be correlated between voxels, and strongly correlated regions are deemed to reflect functional connectivity within synchronized circuits. Resting state functional connectivity (rsFC) measures have been widely adopted by the neuroscience community, and are being used and interpreted as indicators of intrinsic neural circuits and their functional states in a broad range of applications, both basic and clinical. However, there has been relatively little work reported that validates whether inter-regional correlations in resting state fluctuations of fMRI (rsfMRI) signals actually measure functional connectivity between brain regions, or to establish how MRI data correlate with other metrics of functional connectivity. In this mini-review, we summarize recent studies of rsFC within mesoscopic scale cortical networks (100µm-10mm) within a well defined functional region of primary somatosensory cortex (S1), as well as spinal cord and brain white matter in non-human primates, in which we have measured spatial patterns of resting state correlations and validated their interpretation with electrophysiological signals and anatomic connections. Moreover, we emphasize that low frequency correlations are a general feature of neural systems, as evidenced by their presence in the spinal cord as well as white matter. These studies demonstrate the valuable role of high field MRI and invasive measurements in an animal model to inform the interpretation of human imaging studies.