BACKGROUND & AIMS Changes in gut microbiota have been reported to alter signaling mechanisms, emotional behavior, and visceral nociceptive reflexes in rodents. However, alteration of the intestinal microbiota with antibiotics or probiotics has not been shown to produce these changes in humans. We investigated whether consumption of a fermented milk product with probiotic (FMPP) for 4 weeks by healthy women altered brain intrinsic connectivity or responses to emotional attention tasks. METHODS Healthy women with no gastrointestinal or psychiatric symptoms were randomly assigned to groups given FMPP (n = 12), a nonfermented milk product (n = 11, controls), or no intervention (n = 13) twice daily for 4 weeks. The FMPP contained Bifidobacterium animalis subsp Lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, and Lactococcus lactis subsp Lactis. Participants underwent functional magnetic resonance imaging before and after the intervention to measure brain response to an emotional faces attention task and resting brain activity. Multivariate and region of interest analyses were performed. RESULTS FMPP intake was associated with reduced task-related response of a distributed functional network (49% cross-block covariance; P = .004) containing affective, viscerosensory, and somatosensory cortices. Alterations in intrinsic activity of resting brain indicated that ingestion of FMPP was associated with changes in midbrain connectivity, which could explain the observed differences in activity during the task. CONCLUSIONS Four-week intake of an FMPP by healthy women affected activity of brain regions that control central processing of emotion and sensation.
Alterations in gray matter (GM) density/ volume and cortical thickness (CT) have been demonstrated in small and heterogeneous samples of subjects with different chronic pain syndromes, including irritable bowel syndrome (IBS). Aggregating across 7 structural neuroimaging studies conducted at UCLA between August 2006 and April 2011, we examined group differences in regional GM volume in 201 predominantly premenopausal female subjects (82 IBS, mean age: 32 ± 10 SD, 119 Healthy Controls [HCs], 30± 10 SD). Applying graph theoretical methods and controlling for total brain volume, global and regional properties of large-scale structural brain networks were compared between IBS and HC groups. Relative to HCs, the IBS group had lower volumes in bilateral superior frontal gyrus, bilateral insula, bilateral amygdala, bilateral hippocampus, bilateral middle orbital frontal gyrus, left cingulate, left gyrus rectus, brainstem, and left putamen. Higher volume was found for the left postcentral gyrus. Group differences were no longer significant for most regions when controlling for Early Trauma Inventory global score with the exception of the right amygdala and the left post central gyrus. No group differences were found for measures of global and local network organization. Compared to HCs, the right cingulate gyrus and right thalamus were identified as significantly more critical for information flow. Regions involved in endogenous pain modulation and central sensory amplification were identified as network hubs in IBS. Overall, evidence for central alterations in IBS was found in the form of regional GM volume differences and altered global and regional properties of brain volumetric networks.
Purpose The pathophysiology of interstitial cystitis/painful bladder syndrome (IC/PBS) remains incompletely understood, but is thought to involve a central disturbance in the processing of pain and viscerosensory signals. We aimed to identify differences in brain activity and connectivity between female IC/PBS patients and healthy controls in order to advance clinical phenotyping and treatment efforts for IC/PBS. Materials and Methods We examined oscillation dynamics of intrinsic brain activity in a large sample of well-phenotyped female IC/PBS patients and female healthy controls collected during a 10-minute resting fMRI scan as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network* project. The BOLD signal was transformed to the frequency domain and relative power was computed for multiple frequency bands. Results The results demonstrated altered frequency distributions in a viscerosensory region (post Insula) and sensorimotor cortices (postcentral gyrus, paracentral lobule, supplementary motor area (SMA), including a region likely involved in control of pelvic floor muscles (PelMotor). Additionally, the SMA, paracentral lobule and PelMotor all demonstrated increased functional connectivity to the midbrain (red nucleus) and cerebellum. This increased functional connectivity was greatest in patients reporting pain during bladder filling. Conclusions These findings suggest that women with IC/PBS have a neuromotor component to their pathology involving an alteration in the intrinsic oscillations and connectivity within a cortico-cerebellar network previously associated with urinary bladder function.
Rapidly responsive and flexible photonic papers are manufactured by coassembly of cellulose nanocrystals (CNCs) and waterborne polyurethane (WPU) latex for fully taking advantage of the chiral nematic structure of CNCs and the flexibility of WPU elastomer. The resulting CNC/WPU composite papers exhibit not only tunable iridescent colors by adjusting the helical pitch size, but also instant optical responses to water and wet gas, ascribed to the easy chain movement of the elastomeric WPU that does not restrict the fast water absorption-induced swelling of CNCs. By choosing water or NaCl aqueous solutions as inks, the colorful patterns on the CNC/WPU photonic paper can be made temporary, durable, or even disguisable. In addition, the photonic paper is simultaneously rewritable for all these three types of patterns, and the disguisable patterns, which are invisible at normal times and show up under stimuli, exhibit a quick reveal conversion just by exhaling on the paper. The rewritability, rapid responsibility, easy fabrication, and the eco-friendly nature of the inks make the flexible photonic paper/ink combination highly promising in sensors, displays, and photonic circuits.
Abnormal responses of the brain to delivered and expected aversive gut stimuli have been implicated in the pathophysiology of irritable bowel syndrome (IBS), a visceral pain syndrome occurring more commonly in women. Task-free resting-state functional magnetic resonance imaging (fMRI) can provide information about the dynamics of brain activity that may be involved in altered processing and/or modulation of visceral afferent signals. Fractional amplitude of low-frequency fluctuation is a measure of the power spectrum intensity of spontaneous brain oscillations. This approach was used here to identify differences in the resting-state activity of the human brain in IBS subjects compared with healthy controls (HCs) and to identify the role of sex-related differences. We found that both the female HCs and female IBS subjects had a frequency power distribution skewed toward high frequency to a greater extent in the amygdala and hippocampus compared with male subjects. In addition, female IBS subjects had a frequency power distribution skewed toward high frequency in the insula and toward low frequency in the sensorimotor cortex to a greater extent than male IBS subjects. Correlations were observed between resting-state blood oxygen level-dependent signal dynamics and some clinical symptom measures (e.g., abdominal discomfort). These findings provide the first insight into sex-related differences in IBS subjects compared with HCs using resting-state fMRI.
Background & AimsRegional reductions in gray matter (GM) have been reported in several chronic somatic and visceral pain conditions, including irritable bowel syndrome (IBS) and chronic pancreatitis. Reported GM reductions include insular and anterior cingulate cortices, even though subregions are generally not specified. The majority of published studies suffer from limited sample size, heterogeneity of populations, and lack of analyses for sex differences. We aimed to characterize regional changes in cortical thickness (CT) in a large number of well phenotyped IBS patients, taking into account the role of sex related differences.MethodsCortical GM thickness was determined in 266 subjects (90 IBS [70 predominantly premenopausal female] and 176 healthy controls (HC) [155 predominantly premenopausal female]) using the Laboratory of Neuro Imaging (LONI) Pipeline. A combined region of interest (ROI) and whole brain approach was used to detect any sub-regional and vertex-level differences after removing effects of age and total GM volume. Correlation analyses were performed on behavioral data.ResultsWhile IBS as a group did not show significant differences in CT compared to HCs, sex related differences were observed both within the IBS and the HC groups. When female IBS patients were compared to female HCs, whole brain analysis showed significant CT increase in somatosensory and primary motor cortex, as well as CT decrease in bilateral subgenual anterior cingulate cortex (sgACC). The ROI analysis showed significant regional CT decrease in bilateral subregions of insular cortex, while CT decrease in cingulate was limited to left sgACC, accounting for the effect of age and GM volume. Several measures of IBS symptom severity showed significant correlation with CT changes in female IBS patients.ConclusionsSignificant, sex related differences in CT are present in both HCs and in IBS patients. The biphasic neuroplastic changes in female IBS patients are related to symptom severity.
Fatigue caused by sustaining submaximal-intensity muscle contraction(s) involves increased activation in the brain such as primary motor cortex (M1), primary sensory cortex (S1), Premotor and supplementary motor area (PM&SMA) and prefrontal cortex (PFC). The synchronized increases in activation level in these cortical areas suggest fatigue-related strengthening of functional coupling within the motor control network. In the present study, this hypothesis was tested using the cross-correlation based functional connectivity (FC) analysis method. Ten subjects performed a 20-minute intermittent (3.5s ON/6.5s OFF, 120 trials total) handgrip task using the right hand at 50% maximal voluntary contraction (MVC) force level while their brain was scanned by a 3T Siemens Trio scanner using echo planar imaging (EPI) sequence. A representative signal time course of the left M1 was extracted by averaging the time course data of a 2-mm cluster of neighboring voxels of local maximal activation foci, which was identified by a general linear model. Two FC activation maps were created for each subject by cross-correlating the time course data of the minimal (the first 10 trials) and significant (the last 10 trials) fatigue stages across all the voxels in the brain to the corresponding representative time course. Histogram and quantile regression analysis were used to compare the FC between the minimal and significant fatigue stages and the results showed a significant increase in FC among multiple cortical regions, including right M1 and bilateral PM&SMA, S1 and PFC. This strengthened FC indicates that when muscle fatigue worsens, many brain regions increase their coupling with the left M1, the primary motor output control center for the right handgrip, to compensate for diminished force generating capability of the muscle in a coordinated fashion by enhancing the descending command for greater muscle recruitment to maintain the same force.
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