Changes In Resting-state Brain Activity Research Articles

Changes in Resting-State Brain Activity After Cognitive Behavioral Therapy for Chronic Pain: A Magnetoencephalography Study

Cognitive behavioral therapy (CBT) is believed to be an effective treatment for chronic pain due to its association with cognitive and emotional factors. Nevertheless, there is a paucity of magnetoencephalography (MEG) investigations elucidating its underlying mechanisms. This study investigated the neurophysiological effects of CBT employing MEG and analytical techniques. We administered resting-state MEG scans to 30 patients with chronic pain and 31 age-matched healthy controls. Patients engaged in a 12-session group CBT program. We conducted pretreatment (T1) and post-treatment (T2) MEG and clinical assessments. MEG data were examined within predefined regions of interest, guided by the authors’ and others’ prior magnetic resonance imaging studies. Initially, we selected regions displaying significant changes in power spectral density and multiscale entropy between patients at T1 and healthy controls. Then, we examined the changes within these regions after conducting CBT. Furthermore, we applied support vector machine analysis to MEG data to assess the potential for classifying treatment effects. We observed normalization of power in the gamma2 band (61–90 Hz) within the right inferior frontal gyrus (IFG) and multiscale entropy within the right dorsolateral prefrontal cortex (DLPFC) of patients with chronic pain after CBT. Notably, changes in pain intensity before and after CBT positively correlated with the alterations of multiscale entropy. Importantly, responders predicted by the support vector machine classifier had significantly higher treatment improvement rates than nonresponders. These findings underscore the pivotal role of the right IFG and DLPFC in ameliorating pain intensity through CBT. Further accumulation of evidence is essential for future applications. PerspectiveWe conducted MEG scans on 30 patients with chronic pain before and after a CBT program, comparing results with 31 healthy individuals. There were CBT-related changes in the right IFG and DLPFC. These results highlight the importance of specific brain regions in pain reduction through CBT.

Two Distinct Neural Mechanisms Underlying Acupuncture Analgesia.

Acupuncture analgesia is a traditional treatment with a long history, although it lacks scientific evidence. It is reportedly associated with the central nervous system, including various brain regions, from the cortices to the brain stem. However, it remains unclear whether the distributed regions behave as a single unit or consist of multiple sub-units playing different roles. Magnetoencephalography is a neuroimaging technique that can measure the oscillatory frequency of neural signals and brain regions. The frequency band of neural signals allows further understanding of the characteristics of the acupuncture-related neural systems. This study measured resting-state brain activity using magnetoencephalography in 21 individuals with chronic pain before and after acupuncture treatment. The subjective level of pain was assessed using a visual analog scale, and brain activity was compared to identify the brain regions and the frequencies associated with acupuncture analgesia. Here, we categorized the changes in resting-state brain activity into two groups: low-frequency oscillatory activity (<3 Hz) in the left middle occipital and right superior partial lobule and high-frequency oscillatory activity (81–120 Hz) on both sides of the prefrontal, primary sensory, and right fusiform gyri. These findings suggest that acupuncture analgesia influences two or more sub-units of the neural systems, which helps us understand the neural mechanisms underlying acupuncture analgesia.

Distinctive effects of executive dysfunction and loss of learning/memory abilities on resting-state brain activity

Dementia is a syndrome characterised by cognitive impairments, with a loss of learning/memory abilities at the earlier stages and executive dysfunction at the later stages. However, recent studies have suggested that impairments in both learning/memory abilities and executive functioning might co-exist. Cognitive impairments have been primarily evaluated using neuropsychological assessments, such as the Mini-Mental State Examination (MMSE). Recently, neuroimaging techniques such as magnetoencephalography (MEG), which assess changes in resting-state brain activity, have also been used as biomarkers for cognitive impairment. However, it is unclear whether these changes reflect dysfunction in executive function as well as learning and memory. In this study, parameters from the MEG for brain activity, MMSE for learning/memory, and Frontal Assessment Battery (FAB) for executive function were compared within 207 individuals. Three MEG parameters were used as representatives of resting-state brain activity: median frequency, individual alpha frequency, and Shannon’s spectral entropy. Regression analysis showed that median frequency was predicted by both the MMSE and FAB scores, while individual alpha frequency and Shannon’s spectral entropy were predicted by MMSE and FAB scores, respectively. Our results indicate that MEG spectral parameters reflect both learning/memory and executive functions, supporting the utility of MEG as a biomarker of cognitive impairment.

Anterior Cingulate Cortex Activity During Rest Is Related to Alterations in Pain Perception in Aging.

Alterations in the affective component of pain perception are related to the development of chronic pain and may contribute to the increased vulnerability to pain observed in aging. The present study analyzed age-related changes in resting-state brain activity and their possible relation to an increased pain perception in older adults. For this purpose, we compared EEG current source density and fMRI functional-connectivity at rest in older (n = 20, 66.21 ± 3.08 years) and younger adults (n = 21, 20.71 ± 2.30 years) and correlated those brain activity parameters with pain intensity and unpleasantness ratings elicited by painful stimulation. We found an age-related increase in beta2 and beta3 activity in temporal, frontal, and limbic areas, and a decrease in alpha activity in frontal areas. Moreover, older participants displayed increased functional connectivity in the anterior cingulate cortex (ACC) and the insula with precentral and postcentral gyrus. Finally, ACC beta3 activity was positively correlated with pain intensity and unpleasantness ratings in older, and ACC-precentral/postcentral gyrus connectivity was positively correlated with unpleasantness ratings in older and younger participants. These results reveal that ACC resting-state hyperactivity is a stable trait of brain aging and may underlie their characteristic altered pain perception.

Acute ketamine administration attenuates lipopolysaccharide-induced depressive-like behavior by reversing abnormal regional homogeneity in the nucleus accumbens.

Ketamine has rapid antidepressant effects, but no study to date has investigated changes in resting-state brain activity following ketamine administration in inflammation-induced depression. The purpose of this study was to use blood oxygen level-dependent functional MRI to explore changes in the resting-state brain activity in a rat model of depression induced by lipopolysaccharide (LPS, 1 mg/kg) challenge and to examine whether acute ketamine administration can reverse LPS-induced depressive-like behavior. Here, we showed LPS-induced depressive-like behavior as evidenced by significantly reduced motility in the forced swim test. In addition, LPS-induced increases in plasma levels of proinflammatory cytokines were not completely reversed by acute ketamine administration, suggesting that ketamine exerts its antidepressant effects independently of a possible interference with LPS-induced inflammatory signaling. However, increased regional homogeneity (ReHo) was observed in some brain regions of LPS-exposed animals, including bilateral caudate putamen and nucleus accumbens, which were parts of the mood-regulating circuit. Moreover, ReHo values of bilateral caudate putamen and nucleus accumbens showed significant positive correlations with immobility time. Notably, the LPS-induced depressive-like behavior and increase of ReHo value in the right nucleus accumbens was reversed by acute ketamine administration. In summary, this study suggests that acute ketamine administration is capable of attenuating LPS-induced depressive-like behavior, at least partially by reversing abnormal ReHo in the right nucleus accumbens.

Differences in regional homogeneity between patients with Crohn's disease with and without abdominal pain revealed by resting-state functional magnetic resonance imaging.

Abnormal pain processing in the central nervous system may be related to abdominal pain in patients with Crohn's disease (CD). The purpose of this study was to investigate changes in resting-state brain activity in patients with CD in remission and its relationship with the presence of abdominal pain. Twenty-five patients with CD and with abdominal pain, 25 patients with CD and without abdominal pain, and 32 healthy subjects were scanned using a 3.0-T functional magnetic resonance imaging scanner. Regional homogeneity (ReHo) was used to assess resting-state brain activity. Daily pain scores were collected 1 week before functional magnetic resonance imaging. We found that patients with abdominal pain exhibited lower ReHo values in the insula, middle cingulate cortex (MCC), and supplementary motor area and higher ReHo values in the temporal pole. In contrast, patients without abdominal pain exhibited lower ReHo values in the hippocampal/parahippocampal cortex and higher ReHo values in the dorsomedial prefrontal cortex (all P < 0.05, corrected). The ReHo values of the insula and MCC were significantly negatively correlated with daily pain scores for patients with abdominal pain (r = -0.53, P = 0.008 and r = -0.61, P = 0.002, respectively). These findings suggest that resting-state brain activities are different between remissive patients with CD with and without abdominal pain and that abnormal activities in insula and MCC are closely related to the severity of abdominal pain.

Altered fMRI resting-state connectivity in individuals with fibromyalgia on acute pain stimulation.

Fibromyalgia is a chronic widespread pain condition, with patients commonly reporting other symptoms such as sleep difficulties, memory complaints and fatigue. The use of magnetic resonance imaging (MRI) in fibromyalgia has allowed for the detection of neural abnormalities, with alterations in brain activation elicited by experimental pain and alterations in resting state connectivity related to clinical pain. In this study, we sought to monitor state changes in resting brain connectivity following experimental pressure pain in fibromyalgia patients and healthy controls. Twelve fibromyalgia patients and 15 healthy controls were studied by applying discrete pressure stimuli to the thumbnail bed during MRI. Resting-state functional MRI scanning was performed before and immediately following experimental pressure pain. We investigated changes in functional connectivity to the thalamus and the insular cortex. Acute pressure pain increased insula connectivity to the anterior cingulate and the hippocampus. Additionally, we observed increased thalamic connectivity to the precuneus/posterior cingulate cortex, a known part of the default mode network, in patients but not in controls. This connectivity was correlated with changes in clinical pain. These data reporting changes in resting-state brain activity following a noxious stimulus suggest that the acute painful stimuli may contribute to the alteration of the neural signature of chronic pain. WHAT DOES THIS STUDY/ADD?: In this study acute pain application shows an echo in functional connectivity and clinical pain changes in chronic pain.

325 Abnormal Regional Homogeneity in Patients With Crohn's Disease and Its Relationship With Abdominal Pain

Background & aims: Increasing evidence indicates abnormal pain processing in the central nervous system in patients with Crohn's disease (CD). The purpose of this study was to understand changes in resting-state brain activity in CD patients in remission and its relationship with abdominal pain. Methods: Twenty-five CD patients with abdominal pain, 24 CD patients without abdominal pain, and 33 healthy control subjects were scanned using a 3.0 T functional magnetic resonance imaging (fMRI) scanner. Regional Homogeneity (ReHo) was used to assess resting-state brain activity among the three groups. Daily pain scores were collected 1 week before fMRI scanning. Results: Patients with abdominal pain exhibited lower ReHo values in the insula, middle cingulate cortex (MCC), supplementary motor area, and higher ReHo value in the temporal pole, whereas patients without abdominal pain exhibited lower ReHo value in the hippocampal/parahippocampal cortex and higher ReHo value in the dorsomedial prefrontal cortex (dmPFC) (all P<0.05). The ReHo values of the insula and MCC were significantly negatively correlated with abdominal pain scores (r=0.53, P=0.008, and r=-0.61, P=0.002, respectively) (Figure 1). Conclusion: We suggest that there exist different changes in resting-state brain activity between CD patients in remission with and without abdominal pain. The negative correlations between pain severity and ReHo values of the insula and MCC in the painful CD patients suggest the involvement of these brain regions in visceral pain processing.

326 Effects of CT Reconstruction Algorithm on the Quantitative Assessment of Crohn's Disease: A Comparison of Standard and Low Dose CT Enterography

Background & aims: Increasing evidence indicates abnormal pain processing in the central nervous system in patients with Crohn's disease (CD). The purpose of this study was to understand changes in resting-state brain activity in CD patients in remission and its relationship with abdominal pain. Methods: Twenty-five CD patients with abdominal pain, 24 CD patients without abdominal pain, and 33 healthy control subjects were scanned using a 3.0 T functional magnetic resonance imaging (fMRI) scanner. Regional Homogeneity (ReHo) was used to assess resting-state brain activity among the three groups. Daily pain scores were collected 1 week before fMRI scanning. Results: Patients with abdominal pain exhibited lower ReHo values in the insula, middle cingulate cortex (MCC), supplementary motor area, and higher ReHo value in the temporal pole, whereas patients without abdominal pain exhibited lower ReHo value in the hippocampal/parahippocampal cortex and higher ReHo value in the dorsomedial prefrontal cortex (dmPFC) (all P<0.05). The ReHo values of the insula and MCC were significantly negatively correlated with abdominal pain scores (r=0.53, P=0.008, and r=-0.61, P=0.002, respectively) (Figure 1). Conclusion: We suggest that there exist different changes in resting-state brain activity between CD patients in remission with and without abdominal pain. The negative correlations between pain severity and ReHo values of the insula and MCC in the painful CD patients suggest the involvement of these brain regions in visceral pain processing.

Longitudinal changes in resting-state brain activity in a capsular infarct model.

Strokes attributable to subcortical infarcts have been increasing recently in elderly patients. To gain insight how this lesion influences the motor outcome and responds to rehabilitative training, we used circumscribed photothrombotic capsular infarct models on 36 Sprague-Dawley rats (24 experimental and 12 sham-operated). We used 2-deoxy-2-[(18)F]-fluoro-D-glucose-micro positron emission tomography (FDG-microPET) to assess longitudinal changes in resting-state brain activity (rs-BA) and daily single-pellet reaching task (SPRT) trainings to evaluate motor recovery. Longitudinal FDG-microPET results showed that capsular infarct resulted in a persistent decrease in rs-BA in bilateral sensory and auditory cortices, and ipsilesional motor cortex, thalamus, and inferior colliculus (P<0.0025, false discovery rate (FDR) q<0.05). The decreased rs-BA is compatible with diaschisis and contributes to manifest the malfunctions of lesion-specific functional connectivity. In contrast, capsular infarct resulted in increase of rs-BA in the ipsilesional internal capsule, and contralesional red nucleus and ventral hippocampus in recovery group (P<0.0025, FDR q<0.05), implying that remaining subcortical structures have an important role in conducting the recovery process in capsular infarct. The SPRT training facilitated motor recovery only in rats with an incomplete destruction of the posterior limb of the internal capsule (PLIC) (Pearson's correlation, P<0.05). Alternative therapeutic interventions are required to enhance the potential for recovery in capsular infarct with complete destruction of PLIC.

Altered regional homogeneity in experimentally induced low back pain: a resting-state fMRI study.

BackgroundFunctional imaging studies have indicated that patients with low back pain can have significant reductions in cerebral cortex grey matter. However, the mechanisms governing the nociceptive pathways in the human brain are unclear. The aim of this study was to use functional magnetic resonance imaging (fMRI) and regional homogeneity (ReHo) to investigate changes in resting-state brain activity in subjects that experienced experimentally induced low back pain.MethodsHealthy subjects (n = 15) underwent fMRI (3.0 T) at baseline and during painful stimulation (intramuscular injection of 3% hypertonic saline).ResultsCompared to the scans conducted at baseline, scans conducted during experimentally induced low back pain showed increased ReHo on the right side in the medial prefrontal cortex, precuneus, insula, parahippocampal gyrus and cerebellum (posterior lobe), but decreased ReHo in the primary somatosensory cortex, anterior cingulate cortex and parahippocampal gyrus on the left side. The right inferior parietal lobule also showed a decreased ReHo (P < 0.05, cluster threshold ≥10).ConclusionsThese findings suggest that abnormally spontaneous resting-state activity in some brain regions may be associated with pain processing. These changes in neural activity may contribute to the recognition, execution, memory and emotional processing of acute low back pain.

The Time Course of Task-Specific Memory Consolidation Effects in Resting State Networks

Previous studies have reported functionally localized changes in resting-state brain activity following a short period of motor learning, but their relationship with memory consolidation and their dependence on the form of learning is unclear. We investigate these questions with implicit or explicit variants of the serial reaction time task (SRTT). fMRI resting-state functional connectivity was measured in human subjects before the tasks, and 0.1, 0.5, and 6 h after learning. There was significant improvement in procedural skill in both groups, with the group learning under explicit conditions showing stronger initial acquisition, and greater improvement at the 6 h retest. Immediately following acquisition, this group showed enhanced functional connectivity in networks including frontal and cerebellar areas and in the visual cortex. Thirty minutes later, enhanced connectivity was observed between cerebellar nuclei, thalamus, and basal ganglia, whereas at 6 h there was enhanced connectivity in a sensory-motor cortical network. In contrast, immediately after acquisition under implicit conditions, there was increased connectivity in a network including precentral and sensory-motor areas, whereas after 30 min a similar cerebello-thalamo-basal ganglionic network was seen as in explicit learning. Finally, 6 h after implicit learning, we found increased connectivity in medial temporal cortex, but reduction in precentral and sensory-motor areas. Our findings are consistent with predictions that two variants of the SRTT task engage dissociable functional networks, although there are also networks in common. We also show a converging and diverging pattern of flux between prefrontal, sensory-motor, and parietal areas, and subcortical circuits across a 6 h consolidation period.

Modeling the outcome of structural disconnection on resting-state functional connectivity

A growing body of experimental evidence suggests that functional connectivity at rest is shaped by the underlying anatomical structure. Furthermore, the organizational properties of resting-state functional networks are thought to serve as the basis for an optimal cognitive integration. A disconnection at the structural level, as occurring in some brain diseases, would then lead to functional and presumably cognitive impairments. In this work, we propose a computational model to investigate the role of a structural disconnection (encompassing putative local/global and axonal/synaptic mechanisms) on the organizational properties of emergent functional networks. The brain's spontaneous neural activity and the corresponding hemodynamic response were simulated using a large-scale network model, consisting of local neural populations coupled through white matter fibers. For a certain coupling strength, simulations reproduced healthy resting-state functional connectivity with graph properties in the range of the ones reported experimentally. When the structural connectivity is decreased, either globally or locally, the resultant simulated functional connectivity exhibited a network reorganization characterized by an increase in hierarchy, efficiency and robustness, a decrease in small-worldness and clustering and a narrower degree distribution, in the same way as recently reported for schizophrenia patients. Theoretical results indicate that most disconnection-related neuropathologies should induce the same qualitative changes in resting-state brain activity.