Pathophysiology of Migraine

Objective To study the resting-state functional connectivity(FC) changes of anterior cingulate cortex(ACC) and amygdala in adolescent patients with medication-naive first-episode major depressive disorder(MDD). Methods Medication-naive first-episode MDD adolescents(n=30) and pair-wise matched healthy controls(HCs, n=29) underwent resting-state functional magnetic resonance images(fMRI). To study whether there were different in FC changes between amygdala and ACC and whole brain regions, and whether abnormal FC was related to clinical characteristics. Results Compared with HCs, the adolescent MDD patients showed decreased FC between the left amygdala and right thalamus(MNI x, y, z: 15, -21, 18)(t=-2.85)and increased FC between the left amygdala and the bilateral temporal middle gyrus, left occipital gyrus, right medial prefrontal cortex(MPFC)(MNI x, y, z: 9, 66, 15)(t=2.80). The right amygdale showed decreased FC with bilateral middle frontal gyrus, left caudate(MNI x, y, z: -15, -9, 21)(t=-2.53), right thalamus(MNI x, y, z: 12, -36, 12)(t=-3.01), right cerebellum(MNI x, y, z: 3, -84, -33)(t=-2.45) and increased FC with right temporal middle gyrus, right MPFC(MNI x, y, z: 6, 69, 12)(t=2.41). The left ACC showed decreased FC with left cerebellum(MNI x, y, z: 12, -87, -24)(t=-2.36), left frontal inferior triangle gyrus, right frontal inferior orbital gyrus and increased FC with right frontal middle orbital gyrus.The right ACC showed decreased FC with left caudate(MNI x, y, z: -15, 21, 6)(t=-2.29), right temporal middle gyrus, right MPFC(MNI x, y, z: 9, 54, 36)(t=-2.29), right frontal inferior orbital gyrus, right angular(MNI x, y, z: 45, -51, 21)(t=-3.01), left dorsolateral prefrontal cortex(MNI x, y, z: -21, 33, 36)(t=-2.61). The increased FC between the left amygdale and bilateral temporal middle gyrus showed positive correlation with the score of HAMD(r=0.50, P<0.05; r=0.45, P<0.05). And the FC between the right amygdale and right middle frontal gyrus was positive correlation with duration of disease(r=0.63, P<0.05). Conclusion There is widespread FC disorder in amygdala and ACC in adolescents patients with first-episode depression.Abnormal FC changes may be the neuropathological mechanism of depression. Key words: Adolescent major depressive disorder; Resting-state fMRI; Functional connectivity; Amygdala; Anterior cingulated cortex

Altered gray matter morphometry and resting-state functional and structural connectivity in social anxiety disorder

Functional dyspepsia (FD) is a common functional gastrointestinal disorder. Accumulating evidence suggests the crucial role of central nervous system in the development and maintenance of FD. In particular, periaqueductal gray (PAG) has demonstrated an important role in modulation of pain and emotion, which may be related to FD. However, the study of the PAG in FD is still limited. This study aimed to assess intrinsic connectivity of the PAG in FD patients. Resting-state functional magnetic imaging (fMRI) data were collected from 66 FD patients and 42 healthy controls (HCs). Functional connectivity analysis was performed to investigate the PAG connectivity pattern differences between the patients and HCs. We then examined the relationships between functional connectivity within the PAG networks and FD symptoms. Compared to HCs, patients had increased PAG connectivity with the insula, and decreased PAG connectivity with the orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (dlPFC) and hippocampus/parahippocampus (HIPP/paraHIPP). There were positive correlations between disease duration and PAG connectivity with the putamen and supplementary motor area (SMA), and positive correlations between symptom severity and PAG connectivity with the insula. FD patients with high level of anxiety and depression had altered PAG connectivity with the anterior cingulate cortex (ACC), precuneus, dlPFC and caudate, compared to other patients. These findings indicate that abnormal intrinsic network of the PAG might be associated with abnormality of pain processing and disruption of emotion processing in FD patients. Our study further complements neuroimaging findings about FD.

ObjectiveNumerous studies suggest that hypnosis has significant potential in mental health and cognitive disorder treatments. However, the mechanisms by which hypnosis influences brain activity and functional network connectivity remain unclear. This study employed functional near-infrared spectroscopy (fNIRS) to investigate resting-state functional connectivity (rsFC) under hypnosis.MethodsTwenty-six healthy college students participated in the study. Resting-state oxygenated hemoglobin (HbO) data were collected from the prefrontal cortex (PFC) during both control aware and hypnotic states. Functional connectivity strengths between these states were analyzed to assess changes in brain activity associated with deep hypnosis.ResultsA total of 55 paired samples t-tests were conducted across 11 regions of interest (ROIs), revealing statistically significant differences (p < 0.05) in functional connectivity strength between the control state and hypnotic state in 10 paired comparisons. Increased connectivity during hypnosis (6 pairs): LBA9-RBA10 (t = −2.672, p = 0.013), LBA6-RBA46 (t = −2.948, p = 0.007), LBA46-RBA46 (t = −2.516, p = 0.019), RBA8-RBA46 (t = −2.689, p = 0.013), RBA9-RBA46 (t = −2.090, p = 0.047), LBA10-RBA10 (t = −2.315, p = 0.029); Decreased connectivity during hypnosis (4 pairs): LBA9-LBA45 (t = 2.064, p = 0.049), LBA6-LBA45 (t = 3.151, p = 0.004), LBA8-LBA45 (t = 2.438, p = 0.022), LBA8-RBA9 (t = 2.085, p = 0.047). No significant differences were observed in connectivity strength between other ROI pairs.ConclusionHypnosis appears to modulate the function of the DLPFC, PFC, and related regions, enhancing specific brain network functional connectivity. This preliminary study demonstrates that resting-state functional connectivity analysis using fNIRS is a valuable approach for studying brain activity during hypnosis.

Secular Mindfulness-Based Interventions: Efficacy and Neurobiology.

Modulatory effects of different exercise modalities on the functional connectivity of the periaqueductal grey and ventral tegmental area in patients with knee osteoarthritis: a randomised multimodal magnetic resonance imaging study

The current study examined the effects of a 16-week creative expression program on brain activity during a story creating task and resting-state functional network connectivity in mild cognitive impairment (MCI) adults. Thirty-six MCI adults were allocated to either the creative expression program (CrExp, n = 18) or control group (CG,n = 18). Before and after intervention, all participants were scanned with functional magnetic resonance imaging (fMRI) during story creating task performance and a resting state. The two-group comparison was calculated between the blood oxygenation level-dependent (BOLD) signal changes for each cluster to investigate the differences in fMRI activation and functional connectivity (FC) between two groups. Task activation analyses showed an increase in the right anterior cingulate gyrus (ACG), right medial frontal gyrus (MFG), right lentiform nucleus (LN), left hippocampus(HIP), left middle occipital gyrus (MOG), and left cerebellum posterior lobe (CPL) (p < 0.05). Story creating performance improvements were associated with greater activation in the left HIPregion. Resting-state functional connectivity (FC) between left HIP and certain other brain areas shown a significant interaction of creative expression group versus control group. Moreover, connectivity between the right angular gyrus (ANG), right inferior temporal gyrus (ITG), right superior occipital gyrus (SOG), left ANG, and left MFGwere related to improved cognitive performance (p < 0.05). These data extend current knowledge by indicating that the creative expression program can improve cognitive activation in MCI, and these enhancements may be related to the neurocognitive network plasticity changes induced by creative expression training.

This study aimed to investigate the resting-state functional connectivity of the hypothalamus and its relationships with gonadal steroid hormones and depression symptoms in perimenopausal women. Total 66 perimenopausal women voluntarily participated in this study from October 2012 to June 2013. Zung Self-rating Depression Scale (ZSDS) was used to assess depression symptoms. Plasma gonadal steroid hormones including estradiol, testosterone, and progesterone were determined by the chemiluminescence immunoassay. A 3.0 Tesla magnetic resonance imaging (MRI) scanner was utilized to acquire resting-state functional MRI data. The z-value functional connectivity map of each participant was calculated voxel-wisely based on the seed region of the hypothalamus. One sample t test of Statistical Parametric Mapping (SPM) were used to determine the brain areas with statistically significant functional connectivity to the hypothalamus, then multiple regression of SPM was used to calculate the correlated areas with 3 gonadal steroid hormones, respectively. Finally, Pearson correlation was performed to analyze bivariate correlations between mean z-values and ZSDS scores. Significant functional connectivity to the hypothalamus were found in brain areas as follows:the lateral inferior frontal gyrus, medial prefrontal cortex, dorsal lateral prefrontal cortex, orbitofrontal cortex, subgenual cortex, anterior cingulate cortex, posterior cingulate cortex, cuneus and precuneus, hippocampus and parahippocampal gyrus, and angular gyrus (False Discovery Rate q<0.05). Among these areas, the plasma testosterone level was positively related to the functional connectivity strength of the right angular gyrus, and negatively related to the strengths of the right subgenual cortex and bilateral medial superior frontal gyrus to the hypothalamus (PAlphaSim<0.05). Especially, mean z-value in the subgenual cortex was positively related to the ZSDS index score (r=0.279, P=0.023), and factor scores of the core depression symptoms (r=0.278, P=0.024) and somatic symptoms (r=0.357, P=0.003). In perimenopausal women, the hypothalamus has resting-state functional connectivity with widespread areas involved in the brain depression-related network and default mode network, and the plasma androgen level may modulate the functional connectivity strengths of the hypothalamus and decrease the susceptibility of perimenopausal women to depression.

There is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored. Here, we sought to determine brain regions mediating ANS and descending pain control associations. Thirty participants underwent conditioned pain modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between 'pressure-only' and 'pressure+cold' stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain-free and one during cold-pain were acquired. Heart rate variability (HRV) was simultaneously recorded. Normalised low-frequency HRV (LF-HRVnu) and the CPM score were negatively correlated; individuals with higher LF-HRVnu during pain reported reductions in pain during CPM. PAG-ventro-medial prefrontal cortex (vmPFC) and PAG-rostral ventromedial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG-vmPFC functional connectivity mediated the strength of the LF-HRVnu-CPM association. CPM response magnitude was also negatively correlated with vmPFC GM volume. Our multi-modal approach, using behavioural, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body-brain interactions in chronic pain patients may catalyse the development of new treatments. KEY POINTS: Heart rate variability (HRV) is associated with descending pain modulation as measured by the conditioned pain modulation protocol (CPM). There is an association between CPM scores and the functional connectivity between the periaqueductal grey (PAG) and ventro-medial prefrontal cortex (vmPFC). CPM scores are also associated with vmPFC grey matter volume. The strength of functional connectivity between the PAG and vmPFC mediates the association between HRV and CPM. Our data provide new evidence of interactions between the autonomic nervous system and descending pain mechanisms.

FRONTIERS COMMENTARY article Front. Psychiatry, 04 May 2016 Volume 7 - 2016 | https://doi.org/10.3389/fpsyt.2016.00078

Structural and functional correlates of olfactory reward processing in behavioral variant frontotemporal dementia

The resting-state cerebro-cerebellar function connectivity and associations with verbal working memory performance

Addiction related alteration in resting-state brain connectivity

The aim of the study was to elucidate the correlation between spatially distinct brain areas with a full bladder from the perspective of functional connectivity using resting-state functional magnetic resonance imaging (rs-fMRI) with simultaneous urodynamic testing in healthy volunteers. The brain regions with full and empty bladders were reported via rs-fMRI using a 3T magnetic resonance system. Then, we identified brain regions that are activated during bladder filling by calculating the amplitude of low-frequency fluctuation (ALFF) values using brain imaging software (DPABI and SPM8) and empirically derived six regions of interest (ROI) from analysis of activation were used as seeds for resting-state functional connectivity (rs-FC) analysis with the rest of the brain to examine differences in the two conditions. Statistical analysis was performed with a paired t-test and statistical significance was defined as a P < 0.01. Twenty-two healthy volunteers (11 men and 11 women) 35-64years of age were enrolled. The rs-fMRI scans of 22 healthy volunteers were analyzed. After motion correction, two subjects were excluded. Meaningful data were obtained on 20 of these subjects. Compared with an empty bladder, functional connection enhancement was noted mainly in the right inferior orbitofrontal cortex and bilateral calcarine gyrus, the left lingual gyrus, left fusiform gyrus, left superior occipital gyrus, right insula, right inferior temporal gyrus, superior parietal lobe, left insula, right lingual gyrus, right fusiform gyrus, left parahippocampal gyrus, right inferior temporal gyrus, superior parietal lobe, left calcarine gyrus, bilateral lingual gyrus, prefrontal cortex, including the middle frontal gyrus and superior frontal gyrus, the right middle temporal gyrus, bilateral posterior cingulate cortex, and right precuneus. The decrease in functional connection was mainly located in the right inferior orbitofrontal cortex, prefrontal cortex, including the superior frontal gyrus, orbitofrontal cortex, and anterior cingulate cortex, the left inferior orbitofrontal cortex, right insula, middle occipital gyrus, angular gyrus, inferior frontal gyrus, right insula, middle temporal gyrus, inferior parietal lobe, middle occipital gyrus, supplementary motor area, superior frontal gyrus, left insula, bilateral posterior cingulate cortex, bilateral precuneus, middle occipital gyrus, and right middle temporal lobe. There were significant changes in the functional connectivity of the brain between full and empty bladders in healthy volunteers, which suggests that the central neural processes involved in storage needs brain areas with integrated control. These findings are strong evidence for physicians to consider brain responses in urine storage and offer the provision of some normative data.

Emerging evidences suggest that cognitive deficits in individuals with mild cognitive impairment (MCI) are associated with disruptions in brain functional connectivity (FC). This systematic review and meta-analysis aimed to comprehensively evaluate alterations in FC between MCI individuals and healthy control (HC) using functional near-infrared spectroscopy (fNIRS). Thirteen studies were included in qualitative analysis, with two studies synthesized for quantitative meta-analysis. Overall, MCI patients exhibited reduced resting-state FC, predominantly in the prefrontal, parietal, and occipital cortex. Meta-analysis of two studies revealed a significant reduction in resting-state FC from the right prefrontal to right occipital cortex (standardized mean difference [SMD]=-.56; p<.001), left prefrontal to left occipital cortex (SMD=-.68; p<.001), and right prefrontal to left occipital cortex (SMD=-.53; p<.001) in MCI patients compared to HC. During naming animal-walking task, MCI patients exhibited enhanced FC in the prefrontal, motor, and occipital cortex, whereas a decrease in FC was observed in the right prefrontal to left prefrontal cortex during calculating-walking task. In working memory tasks, MCI predominantly showed increased FC in the medial and left prefrontal cortex. However, a decreased in prefrontal FC and a shifted in distribution from the left to the right prefrontal cortex were noted in MCI patients during a verbal frequency task. In conclusion, fNIRS effectively identified abnormalities in FC between MCI and HC, indicating disrupted FC as potential markers for the early detection of MCI. Future studies should investigate the use of task- and region-specific FC alterations as a sensitive biomarker for MCI.