Motor imagery (MI) relies on conscious mental simulation of a motor act without overt motor output and can promote motor skill acquisition and facilitate rehabilitation for patients with stroke or ...neurological conditions. Although a plethora of neuroimaging studies have investigated the neural network of MI regarding different body parts, exploration of the neural correlates to facial MI remains warranted. Here, we used functional MRI with a large cohort of 41 participants who underwent motor execution (ME) and MI runs of mouth-stretching tasks. Then, we carried out conjunction and contrast analyses to investigate the commonalities and differences between the two conditions. Conjunction analysis, representing the shared neural network between ME and MI, showed activation in the primary motor cortex, primary and secondary somatosensory cortices, premotor cortex, parietal lobe, anterior insula, supplementary motor area (SMA) and pre-SMA, thalamus, putamen, and caudate. Contrast analysis showed greater activation of primary motor cortex, primary and secondary somatosensory cortices, SMA, anterior insula, and the thalamus in response to ME than MI and greater activation of the premotor cortex, pre-SMA, putamen, and caudate in response to MI than ME. Interestingly, we found exclusive activation in the anterior cingulate cortex and left ventrolateral prefrontal cortex in response to MI, reflecting the motor inhibition network responsible for blocking the transmission of motor commands to peripheral effectors during mental rehearsal. Taken together, these findings show that, despite the neural overlap between ME and MI, there are different degrees of activation within this overlap, and that MI normally involves motor command inhibition possibly mediated by the anterior cingulate cortex and ventrolateral prefrontal cortex.
Chronic pain is a highly prevalent disease with poorly understood pathophysiology. In particular, the brain mechanisms mediating the transition from acute to chronic pain remain largely unknown. ...Here, we identify a subcortical signature of back pain. Specifically, subacute back pain patients who are at risk for developing chronic pain exhibit a smaller nucleus accumbens volume, which persists in the chronic phase, compared to healthy controls. The smaller accumbens volume was also observed in a separate cohort of chronic low-back pain patients and was associated with dynamic changes in functional connectivity. At baseline, subacute back pain patients showed altered local nucleus accumbens connectivity between putative shell and core, irrespective of the risk of transition to chronic pain. At follow-up, connectivity changes were observed between nucleus accumbens and rostral anterior cingulate cortex in the patients with persistent pain. Analysis of the power spectral density of nucleus accumbens resting-state activity in the subacute and chronic back pain patients revealed loss of power in the slow-5 frequency band (0.01 to 0.027 Hz) which developed only in the chronic phase of pain. This loss of power was reproducible across two cohorts of chronic low-back pain patients obtained from different sites and accurately classified chronic low-back pain patients in two additional independent datasets. Our results provide evidence that lower nucleus accumbens volume confers risk for developing chronic pain and altered nucleus accumbens activity is a signature of the state of chronic pain.
•Human study measuring pandemic-related neuroinflammation in individuals negative to COVID-19 antibodies.•Multimodal PET/MR brain imaging shows elevation in two independent putative markers of glial ...activation.•PET signal increases are associated with physical/mental fatigue indices.•Imaging transcriptomics analyses reveal a spatial overlap with the expression of genes related to neuroimmune responses.•Marginally elevated serum inflammatory markers correlate with neuroimaging markers.
While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other “sickness behavior”-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus.
We compared fifty-seven ‘Pre-Pandemic’ and fifteen ‘Pandemic’ datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies. We used a combination of multimodal molecular brain imaging (simultaneous positron emission tomography / magnetic resonance spectroscopy), behavioral measurements, imaging transcriptomics and serum testing to uncover links between pandemic-related stressors and neuroinflammation.
Healthy individuals examined after the enforcement of 2020 lockdown/stay-at-home measures demonstrated elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown subjects. The serum levels of two inflammatory markers (interleukin-16 and monocyte chemoattractant protein-1) were also elevated, although these effects did not reach statistical significance after correcting for multiple comparisons. Subjects endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus and precuneus (physical fatigue), compared to those reporting little/no symptoms. Post-lockdown TSPO signal changes were spatially aligned with the constitutive expression of several genes involved in immune/neuroimmune functions.
This work implicates neuroimmune activation as a possible mechanism underlying the non-virally-mediated symptoms experienced by many during the COVID-19 pandemic. Future studies will be needed to corroborate and further interpret these preliminary findings.
Chronic low back pain (CLBP) is often treated with opioid analgesics (OA), a class of medications associated with a significant risk of misuse. However, little is known about how treatment with OA ...affect the brain in chronic pain patients. Gaining this knowledge is a necessary first step towards understanding OA associated analgesia and elucidating long-term risk of OA misuse. Here we study CLBP patients chronically medicated with opioids without any evidence of misuse and compare them to CLBP patients not on opioids and to healthy controls using structural and functional brain imaging. CLBP patients medicated with OA showed loss of volume in the nucleus accumbens and thalamus, and an overall significant decrease in signal to noise ratio in their sub-cortical areas. Power spectral density analysis (PSD) of frequency content in the accumbens’ resting state activity revealed that both medicated and unmedicated patients showed loss of PSD within the slow-5 frequency band (0.01–0.027 Hz) while only CLBP patients on OA showed additional density loss within the slow-4 frequency band (0.027–0.073 Hz). We conclude that chronic treatment with OA is associated with altered brain structure and function within sensory limbic areas.
Compartmentalized meningeal inflammation is thought to represent one of the key players in the pathogenesis of cortical demyelination in multiple sclerosis. Positron emission tomography targeting the ...18 kDa mitochondrial Translocator Protein (TSPO) is a molecular-specific approach to quantify immune cell-mediated density in the cortico-meningeal tissue compartment in vivo. The aim of this study was to characterize cortical and meningeal TSPO expression in a heterogeneous cohort of multiple sclerosis cases using in vivo simultaneous MR-PET with 11C-PBR28, a second-generation TSPO radioligand, and ex vivo immunohistochemistry. Forty-nine multiple sclerosis patients (21 with secondary progressive and 28 with relapsing-remitting multiple sclerosis) with mixed or high affinity binding for 11C-PBR28 underwent 90-min 11C-PBR28 simultaneous MR-PET. Tracer binding was measured using 60-90 min normalized standardized uptake value ratio values sampled at mid-cortical depth and ∼3 mm above the pial surface. Data in multiple sclerosis patients were compared to 21 age-matched healthy controls. To characterize the nature of 11C-PBR28 PET uptake, the meningeal and cortical lesion cellular expression of TSPO was further described in post-mortem brain tissue from 20 cases with secondary progressive multiple sclerosis and five age-matched healthy donors. Relative to healthy controls, patients with multiple sclerosis exhibited abnormally increased TSPO signal in the cortex and meningeal tissue, diffusively in progressive disease and more localized in relapsing-remitting multiple sclerosis. In multiple sclerosis, increased meningeal TSPO levels were associated with increased Expanded Disability Status Scale scores (p = 0.007, by linear regression). Immunohistochemistry, validated using in-situ sequencing analysis, revealed increased TSPO expression in the meninges and adjacent subpial cortical lesions of post-mortem secondary progressive multiple sclerosis cases relative to control tissue. In these cases, increased TSPO expression was related to meningeal inflammation. Translocator Protein immunostaining was detected on meningeal major histocompatibility complex (MHC)-class II + macrophages and cortical activated MHC-class II + transmembrane protein (TMEM)119+ microglia. In vivo arterial blood data and neuropathology showed that endothelial binding did not significantly account for increased TSPO cortico-meningeal expression in multiple sclerosis. Our findings support the use of TSPO-PET in multiple sclerosis for imaging in vivo inflammation in the cortico-meningeal brain tissue compartment and provide in vivo evidence implicating meningeal inflammation in the pathogenesis of the disease.
Sex-based differences in the prevalence of autism spectrum disorder (ASD) are well-documented, with a male-to-female ratio of approximately 4:1. The clinical presentation of the core symptoms of ASD ...can also vary between sexes. Previously, positron emission tomography (PET) studies have identified alterations in the in vivo levels of translocator protein (TSPO)-a mitochondrial protein-in primarily or only male adults with ASD, with our group reporting lower TSPO relative to whole brain mean in males with ASD. However, whether in vivo TSPO levels are altered in females with ASD, specifically, is unknown. This is the first pilot study to measure in vivo TSPO in the brain in adult females with ASD using
CPBR28 PET-magnetic resonance imaging (MRI). Twelve adult females with ASD and 10 age- and TSPO genotype-matched controls (CON) completed one or two
CPBR28 PET-MRI scans. Females with ASD exhibited elevated
CPBR28 standardized uptake value ratio (SUVR) in the midcingulate cortex and splenium of the corpus callosum compared to CON. No brain area showed lower
CPBR28 SUVR in females with ASD compared to CON. Test-retest over several months showed stable
CPBR28 SUVR across time in both groups. Elevated regional
CPBR28 SUVR in females with ASD stand in stark contrast to our previous findings of lower regional
CPBR28 SUVR in males with ASD. Preliminary evidence of regionally elevated mitochondrial protein TSPO relative to whole brain mean in ASD females may reflect neuroimmuno-metabolic alterations specific to females with ASD.
Mentorship facilitates personal growth through pairing trainees with mentors who can share their expertise. In times of global integration, geographical proximity between mentors and mentees is ...relevant to a lesser degree. This has led to popularization of online mentoring programs. In this editorial, we introduce the history and architecture of the International Online Mentoring Programme organized by the Student and Postdoc Special Interest Group of the Organization for Human Brain Mapping.
Early career researchers (ECRs) are faced with a range of competing pressures in academia, making self-management key to building a successful career. The Organization for Human Brain Mapping ...undertook a group effort to gather helpful advice for ECRs in self-management.
Although acupuncture is an effective therapeutic intervention for pain reduction, the exact difference between real and sham acupuncture has not been clearly understood because a somatosensory ...tactile component is commonly included in the existing sham acupuncture protocols. In an event-related fMRI experiment, we implemented a novel form of sham acupuncture, phantom acupuncture, that reproduces the acupuncture needling procedure without somatosensory tactile stimulation while maintaining the credibility of the acupuncture treatment context. Fifty-six non-specific low back pain patients received either real (REAL) or phantom (PHNT) acupuncture stimulation in a parallel group study. The REAL group exhibited greater activation in the posterior insula and anterior cingulate cortex, reflecting the needling-specific components of acupuncture. We demonstrated that PHNT could be delivered credibly. Interestingly, the PHNT-credible group exhibited bilateral activation in SI/SII and also reported vicarious acupuncture sensations without needling stimulation. The PHNT group showed greater activation in the bilateral dorsolateral/ventrolateral prefrontal cortex (dlPFC/vlPFC). Moreover, the PHNT group exhibited significant pain reduction, with a significant correlation between the subjective fMRI signal in the right dlPFC/vlPFC and a score assessing belief in acupuncture effectiveness. These results support an expectation-related placebo analgesic effect on subjective pain intensity ratings, possibly mediated by right prefrontal cortex activity.
Controversy exists regarding the involvement of the primary motor cortex (M1) during motor imagery (MI) and also regarding the differential somatotopic representation of motor execution (ME) and ...mental simulation of movement, that is, MI within M1. Although some research reported clear M1 involvement during MI without overt motor output, others did not. However, possible somatotopic representation between execution and imagery has not been clearly investigated to date. The aim of the present study was to aid in the resolution of this controversy by investigating the possible involvement of M1 during MI, and the differential, within M1, somatotopic representation between execution and imagery by quantitatively assessing different location markers such as activation peak and center of mass as well as intensity differences between the two tasks in case of with and without the overlap between the two representations. Forty-one healthy volunteers participated in two functional MRI runs of mouth-stretching ME and MI tasks. Our findings suggest the clear involvement of M1 (BA 4) during MI with lower signal intensity compared with ME, and further showed distinct centers for each representation along the y-axis (anteroposterior plane), with MI showing more involvement of the anterior sector of M1 (BA 4a), whereas ME recruited more of the posterior sector (BA 4p). These results parallel the pioneering findings of a functional distinction between BA 4a and BA 4p, where BA 4a is more involved in the cognitive aspects of MI, whereas BA 4p is more related to executive function, promoting the idea of distinctive somatotopic mapping between execution and imagery within M1 sectors.
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