Xiangyu Long

Resting developments: a review of fMRI post-processing methodologies for spontaneous brain activity.

Analytic tools for addressing spontaneous brain activity, as acquired with fMRI during the “resting-state,” have grown dramatically over the past decade. Along with each new technique, novel hypotheses about the functional organization of the brain are also available to researchers. We review six prominent categories of resting-state fMRI data analysis: seed-based functional connectivity, independent component analysis, clustering, pattern classification, graph theory, and two “local” methods. In surveying these methods, we address their underlying assumptions, methodologies, and novel applications.

Characterizing acupuncture stimuli using brain imaging with fMRI: A systematic review and meta-analysis of the literature

Background The mechanisms of action underlying acupuncture, including acupuncture point specificity, are not well understood. In the previous decade, an increasing number of studies have applied fMRI to investigate brain response to acupuncture stimulation. Our aim was to provide a systematic overview of acupuncture fMRI research considering the following aspects: 1) differences between verum and sham acupuncture, 2) differences due to various methods of acupuncture manipulation, 3) differences between patients and healthy volunteers, 4) differences between different acupuncture points. Methodology/Principal Findings We systematically searched English, Chinese, Korean and Japanese databases for literature published from the earliest available up until September 2009, without any language restrictions. We included all studies using fMRI to investigate the effect of acupuncture on the human brain (at least one group that received needle-based acupuncture). 779 papers were identified, 149 met the inclusion criteria for the descriptive analysis, and 34 were eligible for the meta-analyses. From a descriptive perspective, multiple studies reported that acupuncture modulates activity within specific brain areas, including somatosensory cortices, limbic system, basal ganglia, brain stem, and cerebellum. Meta-analyses for verum acupuncture stimuli confirmed brain activity within many of the regions mentioned above. Differences between verum and sham acupuncture were noted in brain response in middle cingulate, while some heterogeneity was noted for other regions depending on how such meta-analyses were performed, such as sensorimotor cortices, limbic regions, and cerebellum. Conclusions Brain response to acupuncture stimuli encompasses a broad network of regions consistent with not just somatosensory, but also affective and cognitive processing. While the results were heterogeneous, from a descriptive perspective most studies suggest that acupuncture can modulate the activity within specific brain areas, and the evidence based on meta-analyses confirmed some of these results. More high quality studies with more transparent methodology are needed to improve the consistency amongst different studies.

Identifying the perfusion deficit in acute stroke with resting-state functional magnetic resonance imaging.

Temporal delay in blood oxygenation level–dependent (BOLD) signals may be sensitive to perfusion deficits in acute stroke. Resting‐state functional magnetic resonance imaging (rsfMRI) was added to a standard stroke MRI protocol. We calculated the time delay between the BOLD signal at each voxel and the whole‐brain signal using time‐lagged correlation and compared the results to mean transit time derived using bolus tracking. In all 11 patients, areas exhibiting significant delay in BOLD signal corresponded to areas of hypoperfusion identified by contrast‐based perfusion MRI. Time delay analysis of rsfMRI provides information comparable to that of conventional perfusion MRI without the need for contrast agents. ANN NEUROL 2013.

Functional connectivity-based parcellation of the human sensorimotor cortex

Task‐based functional magnetic resonance imaging (fMRI) has been successfully employed to obtain somatotopic maps of the human sensorimotor cortex. Here, we showed through direct comparison that a similar functional map can be obtained, independently of a task, by performing a connectivity‐based parcellation of the sensorimotor cortex based on resting‐state fMRI. Cortex corresponding to two adjacent Brodmann areas (BA 3 and BA 4) was selected as the sensorimotor area. Parcellation was obtained along a medial–lateral axis, which was confirmed to be somatotopic (corresponding roughly to an upper, middle and lower limb, respectively) by comparing it with maps obtained using motoric task‐based fMRI in the same participants. Interestingly, the resting‐state parcellation map demonstrated higher correspondence to the task‐based divisions after individuals performed the motor task. Using the resting‐state fMRI data, we also observed higher functional correlations between the centrally located hand region and the other two regions, than between the foot and tongue. The functional relevance of these somatosensory parcellation results indicates the feasibility of a wide range of potential applications to brain mapping.

Imperceptible Somatosensory Stimulation Alters Sensorimotor Background Rhythm and Connectivity

Most sensory input to our body is not consciously perceived. Nevertheless, it may reach the cortex and influence our behavior. In this study, we investigated noninvasive neural signatures of unconscious cortical stimulus processing to understand mechanisms, which (1) prevent low-intensity somatosensory stimuli from getting access to conscious experience and which (2) can explain the associated impediment of conscious perception for additional stimuli. Stimulation of digit 2 in humans far below the detection threshold elicited a cortical evoked potential (P1) at 60 ms, but no further somatosensory evoked potential components. No event-related desynchronization was detected; rather, there was a transient synchronization in the alpha frequency range. Using the same stimulation during fMRI, a reduced centrality of contralateral primary somatosensory cortex (SI) was found, which appeared to be mainly driven by reduced functional connectivity to frontoparietal areas. We conclude that after subthreshold stimulation the (excitatory) feedforward sweep of bottom-up processing terminates in SI preventing access to conscious experience. We speculate that this interruption is due to a predominance of inhibitory processing in SI. The increase in alpha activity and the disconnection of SI from frontoparietal areas are likely correlates of an elevated perception threshold and may thus serve as a gating mechanism for the access to conscious experience.

Body Topography Parcellates Human Sensory and Motor Cortex

Abstract The cytoarchitectonic map as proposed by Brodmann currently dominates models of human sensorimotor cortical structure, function, and plasticity. According to this model, primary motor cortex, area 4, and primary somatosensory cortex, area 3b, are homogenous areas, with the major division lying between the two. Accumulating empirical and theoretical evidence, however, has begun to question the validity of the Brodmann map for various cortical areas. Here, we combined in vivo cortical myelin mapping with functional connectivity analyses and topographic mapping techniques to reassess the validity of the Brodmann map in human primary sensorimotor cortex. We provide empirical evidence that area 4 and area 3b are not homogenous, but are subdivided into distinct cortical fields, each representing a major body part (the hand and the face). Myelin reductions at the hand–face borders are cortical layer-specific, and coincide with intrinsic functional connectivity borders as defined using large-scale resting state analyses. Our data extend the Brodmann model in human sensorimotor cortex and suggest that body parts are an important organizing principle, similar to the distinction between sensory and motor processing.

Differential cerebral response to somatosensory stimulation of an acupuncture point vs. two non-acupuncture points measured with EEG and fMRI

Acupuncture can be regarded as a complex somatosensory stimulation. Here, we evaluate whether the point locations chosen for a somatosensory stimulation with acupuncture needles differently change the brain activity in healthy volunteers. We used EEG, event-related fMRI, and resting-state functional connectivity fMRI to assess neural responses to standardized needle stimulation of the acupuncture point ST36 (lower leg) and two control point locations (CP1 same dermatome, CP2 different dermatome). Cerebral responses were expected to differ for stimulation in two different dermatomes (CP2 different from ST36 and CP1), or stimulation at the acupuncture point vs. the control points. For EEG, mu rhythm power increased for ST36 compared to CP1 or CP2, but not when comparing the two control points. The fMRI analysis found more pronounced insula and S2 (secondary somatosensory cortex) activation, as well as precuneus deactivation during ST36 stimulation. The S2 seed-based functional connectivity analysis revealed increased connectivity to right precuneus for both comparisons, ST36 vs. CP1 and ST36 vs. CP2, however in different regions. Our results suggest that stimulation at acupuncture points may modulate somatosensory and saliency processing regions more readily than stimulation at non-acupuncture point locations. Also, our findings suggest potential modulation of pain perception due to acupuncture stimulation.

Sustained Effects of Acupuncture Stimulation Investigated with Centrality Mapping Analysis

Acupuncture can have instant and sustained effects, however, its mechanisms of action are still unclear. Here, we investigated the sustained effect of acupuncture by evaluating centrality changes in resting-state functional magnetic resonance imaging after manually stimulating the acupuncture point ST36 at the lower leg or two control point locations (CP1 same dermatome, CP2 different dermatome). Data from a previously published experiment evaluating instant BOLD effects and S2-seed-based resting state connectivity was re-analyzed using eigenvector centrality mapping and degree centrality mapping. These data-driven methods might add new insights into sustained acupuncture effects on both global and local inter-region connectivity (centrality) by evaluating the summary of connections of every voxel. We found higher centrality in parahippocampal gyrus and middle temporal gyrus after ST36 stimulation in comparison to the two control points. These regions are positively correlated to major hubs of the default mode network, which might be the primary network affected by chronic pain. The stronger integration of both regions within the whole-brain connectome after stimulation of ST36 might be a potential contributor to pain modulation by acupuncture. These findings highlight centrality mapping as a valuable analysis for future imaging studies investigating clinically relevant outcomes associated with physiological response to acupuncture stimulation. Clinical trial registration: NCT01079689, ClinicalTrials.gov.

Difficulties Choosing Control Points in Acupuncture Research. Response: Commentary: Differential Cerebral Response, Measured with Both an EEG and fMRI, to Somatosensory Stimulation of a Single Acupuncture Point vs. Two Non-Acupuncture Points

The existence of point specificity in acupuncture is still controversial (Choi et al., 2012). Therefore, a thoughtful choice of control points is very important when evaluating point specific effects in acupuncture research.

Characterizing acupuncture stimuli using brain imaging with fMRI — A systematic review and meta-analysis of the literature

BackgroundThe mechanisms of action underlying acupuncture, including acupuncture point specificity, are not well understood. In the previous decade, an increasing number of studies have applied fMRI to investigate brain response to acupuncture stimulation. Our aim was to provide a systematic overview of acupuncture fMRI research considering the following aspects: 1) differences between verum and sham acupuncture, 2) differences due to various methods of acupuncture manipulation, 3) differences between patients and healthy volunteers, 4) differences between different acupuncture points.Methodology/Principle FindingsWe systematically searched English, Chinese, Korean and Japanese databases for literature published from the earliest available up until September 2009, without any language restrictions. We included all studies using fMRI to investigate the effect of acupuncture on the human brain (at least one group that received needle-based acupuncture). 779 papers were identified, 149 met the inclusion criteria for the descriptive analysis, and 34 were eligible for the meta-analyses. From a descriptive perspective, multiple studies reported that acupuncture modulates activity within specific brain areas, including somatosensory cortices, limbic system, basal ganglia, brain stem, and cerebellum. Meta-analyses for verum acupuncture stimuli confirmed brain activity within many of the regions mentioned above. Differences between verum and sham acupuncture were noted in brain response in middle cingulate, while some heterogeneity was noted for other regions depending on how such meta-analyses were performed, such as sensorimotor cortices, limbic regions, and cerebellum.ConclusionsBrain response to acupuncture stimuli encompasses a broad network of regions consistent with not just somatosensory, but also affective and cognitive processing. While the results were heterogeneous, from a descriptive perspective most studies suggest that acupuncture can modulate the activity within specific brain areas, and the evidence based on meta-analyses confirmed some of these results. More high quality studies with more transparent methodology are needed to improve the consistency amongst different studies.