Morphological changes of the limbic system associated with acute and chronic low-back pain: A UK biobank imaging study.

BACKGROUND: Low back pain (LBP) is a major public health issue that influences physical and emotional factors integral to the limbic system. This study aims to investigate the association between LBP and brain morphometry alterations as the duration of LBP increases (acute vs. chronic). METHODS: We used the UK Biobank data to investigate the morphological features of the limbic system in acute LBP (N = 115), chronic LBP (N = 243) and controls (N = 358), and tried to replicate our findings with an independent dataset composed of 45 acute LBP participants evaluated at different timepoints throughout 1 year from the OpenPain database. RESULTS: We found that in comparison with chronic LBP and pain-free controls, acute LBP was associated with increased volumes of the nucleus accumbens, amygdala, hippocampus, and thalamus, and increased grey matter volumes in the hippocampus and posterior cingulate gyrus. In the replication cohort, we found non-significantly larger hippocampus and thalamus volumes in the 3-month visit (acute LBP) compared to the 1-year visit (chronic LBP), with similar effect sizes as the UK Biobank dataset. CONCLUSIONS: Our results suggest that acute LBP is associated with dramatic morphometric increases in the limbic system and mesolimbic pathway, which may reflect an active brain response and self-regulation in the early stage of LBP. SIGNIFICANCE: Our study suggests that LBP in the acute phase is associated with the brain morphometric changes (increase) in some limbic areas, indicating that the acute phase of LBP may represent a crucial stage of self-regulation and active response to the disease's onset.

The modulation effects of repeated transcutaneous auricular vagus nerve stimulation on the functional connectivity of key brainstem regions along the vagus nerve pathway in migraine patients.

Background: Previous studies have shown a significant response to acute transcutaneous vagus nerve stimulation (taVNS) in regions of the vagus nerve pathway, including the nucleus tractus solitarius (NTS), raphe nucleus (RN) and locus coeruleus (LC) in both healthy human participants and migraine patients. This study aims to investigate the modulation effect of repeated taVNS on these brainstem regions by applying seed-based resting-state functional connectivity (rsFC) analysis. Methods: 70 patients with migraine were recruited and randomized to receive real or sham taVNS treatments for 4 weeks. fMRI data were collected from each participant before and after 4 weeks of treatment. The rsFC analyses were performed using NTS, RN and LC as the seeds. Results: 59 patients (real group: n = 33; sham group: n = 29) completed two fMRI scan sessions. Compared to sham taVNS, real taVNS was associated with a significant reduction in the number of migraine attack days (p = 0.024) and headache pain intensity (p = 0.008). The rsFC analysis showed repeated taVNS modulated the functional connectivity between the brain stem regions of the vagus nerve pathway and brain regions associated with the limbic system (bilateral hippocampus), pain processing and modulation (bilateral postcentral gyrus, thalamus, and mPFC), and basal ganglia (putamen/caudate). In addition, the rsFC change between the RN and putamen was significantly associated with the reduction in the number of migraine days. Conclusion: Our findings suggest that taVNS can significantly modulate the vagus nerve central pathway, which may contribute to the potential treatment effects of taVNS for migraine.Clinical Trial Registration: http://www.chictr.org.cn/hvshowproject.aspx?id=11101, identifier ChiCTR-INR-17010559.

Scalp Stimulation Targets for Neurological Conditions-Evidence from Large-Scale Meta-Analyses.

BACKGROUND: Neurological disorders are a major source of suffering for patients worldwide. Scalp stimulation methods have been widely applied in treating a number of neurological disorders. Recently, our understanding of pathological mechanisms associated with neurological disorders has been enhanced significantly. Nevertheless, these findings have yet to be well-integrated into scalp stimulation treatments for neurological disorders. METHODS: In a previous study, we proposed new brain targets for scalp stimulation in the treatment of eight common mental disorders based on the results of a large-scale meta-analyses using Neurosynth. This study aims to extend our previous findings in identifying surface brain targets for seven common neurological disorders: Alzheimer's disease, aphasia, chronic pain, dementia, dyslexia, mild cognitive impairment, and Parkinson's disease, utilizing a similar method. RESULTS: We hidentified seven to eight potential scalp stimulation targets for each disorder and used both 10-20 EEG system and acupuncture points to locate these targets to facilitate its clinical application. CONCLUSIONS: The proposed target protocols may facilitate and extend clinical applications of scalp stimulation methods such as transcranial electrical stimulation and scalp acupuncture in the treatment of neurological disorders.

Potential scalp stimulation targets for mental disorders: evidence from neuroimaging studies.

Mental disorders widely contribute to the modern global disease burden, creating a significant need for improvement of treatments. Scalp stimulation methods (such as scalp acupuncture and transcranial electrical stimulation) have shown promising results in relieving psychiatric symptoms. However, neuroimaging findings haven't been well-integrated into scalp stimulation treatments. Identifying surface brain regions associated with mental disorders would expand target selection and the potential for these interventions as treatments for mental disorders. In this study, we performed large-scale meta-analyses separately on eight common mental disorders: attention deficit hyperactivity disorder, anxiety disorder, autism spectrum disorder, bipolar disorder, compulsive disorder, major depression, post-traumatic stress disorder and schizophrenia; utilizing modern neuroimaging literature to summarize disorder-associated surface brain regions, and proposed neuroimaging-based target protocols. We found that the medial frontal gyrus, the supplementary motor area, and the dorsal lateral prefrontal cortex are commonly involved in the pathophysiology of mental disorders. The target protocols we proposed may provide new brain targets for scalp stimulation in the treatment of mental disorders, and facilitate its clinical application.

Perturbing fMRI brain dynamics using transcranial direct current stimulation.

The dynamic nature of resting-state functional magnetic resonance imaging (fMRI) brain activity and connectivity has drawn great interest in the past decade. Specific temporal properties of fMRI brain dynamics, including metrics such as occurrence rate and transitions, have been associated with cognition and behaviors, indicating the existence of mechanism distruption in neuropsychiatric disorders. The development of new methods to manipulate fMRI brain dynamics will advance our understanding of these pathophysiological mechanisms from native observation to experimental mechanistic manipulation. In the present study, we applied repeated transcranial direct current stimulation (tDCS) to the right dorsolateral prefrontal cortex (rDLPFC) and the left orbitofrontal cortex (lOFC), during multiple simultaneous tDCS-fMRI sessions from 81 healthy participants to assess the modulatory effects of stimulating target brain regions on fMRI brain dynamics. Using the rDLPFC and the lOFC as seeds, respectively, we first identified two reoccurring co-activation patterns (CAPs) and calculated their temporal properties (e.g., occurrence rate and transitions) before administering tDCS. The spatial maps of CAPs were associated with different cognitive and disease domains using meta-analytical decoding analysis. We then investigated how active tDCS compared to sham tDCS in the modulation of the occurrence rates of these different CAPs and perturbations of transitions between CAPs. We found that by enhancing neuronal excitability of the rDLPFC and the lOFC, the occurrence rate of one CAP was significantly decreased while that of another CAP was significantly increased during the first 6 min of stimulation. Furthermore, these tDCS-associated changes persisted over subsequent testing sessions (both during and before/after tDCS) across three consecutive days. Active tDCS could perturb transitions between CAPs and a non-CAP state (when the rDLPFC and the lOFC were not activated), but not the transitions within CAPs. These results demonstrate the feasibility of modulating fMRI brain dynamics, and open new possibilities for discovering stimulation targets and dynamic connectivity patterns that can ensure the propagation of tDCS-induced neuronal excitability, which may facilitate the development of new treatments for disorders with altered dynamics.