Solid-state vs water-perfused catheters to measure colonic high-amplitude propagating contractions

Background Solid‐state (SS) manometry catheters with portable data loggers offer many potential advantages over traditional water‐perfused (WP) systems, such as prolonged recordings in a more physiologic ambulatory setting and the lack of risk for water overload. The use of SS catheters has not been evaluated in comparison with perfused catheters in children. This study aims to compare data provided by SS and WP catheters in children undergoing colonic manometry studies. Methods A SS catheter and a WP catheter were taped together such that their corresponding sensors were at the same location. Simultaneous recordings were obtained using the SS and WP catheters (both 8 channels, 10 cm apart) in 15 children with severe defecation disorders referred for colonic manometry. Signals were recorded for a minimum of 1 h during fasting, 1 h after ingestion of a meal, and 1 h after the administration of bisacodyl. Solid‐state signals from the data logger were analyzed against the perfused signals. All high‐amplitude propagated contractions (HAPCs), the most recognizable and interpreted colonic motor event, were evaluated for spatial and temporal features including their durations, amplitudes, and propagation velocities. Key Results A total of 107 HAPCs were detected with SS and 91 with WP catheters. All WP‐HAPC were also observed with SS. Linear regression analysis showed that SS catheters tended to give higher readings in the presence of amplitudes <102 mmHg and lower reading with amplitudes >102 mmHg. An opposite trend was found for the duration of contractions. No significant difference was found for HAPC velocity. Conclusions & Inferences SS catheters are more sensitive in recording HAPCs in children with defecation disorders compared with the more traditional WP assembly. There is a difference in measurements of amplitude between the two systems. Solid‐state catheters offer potential advantages over WP catheters in children, being portable, safer to use, and may provide data over a more prolonged period.     

Day‐to‐day reproducibility of prolonged ambulatory colonic manometry in healthy subjects

Background Although colonic manometry provides useful information regarding colonic physiology, considerable variability has been reported both for regional motility and manometric patterns. Whether colonic manometry is reproducible is not known. Methods Seven healthy volunteers (three men, four women, mean age = 34 years) underwent two studies of 24‐h ambulatory colonic manometry, each 2 weeks apart. Manometry was performed by placing a six‐sensor solid‐state probe, up to the hepatic flexure and anchored to colonic mucosa. Colonic motility was assessed by the number and area‐under‐curve (AUC) of pressure waves and motility patterns such as high‐amplitude propagating contractions (HAPC). Waking and meal‐induced gastrocolonic responses were also assessed. Paired t‐test was used to examine the reproducibility and intra and interindividual variability. Key Results The number of pressure waves and propagating pressure waves and HAPC, and AUC were similar between the two studies. Diurnal variation, waking and meal‐induced gastrocolonic responses were also reproducible. There was some variability in the incidence of individual colonic motor patterns. Conclusions & Inferences Colonic manometry findings were generally reproducible, particularly for the assessment of key physiologic changes, such as meal‐induced gastrocolonic, HAPC, and waking responses.     

Bowel preparation affects the amplitude and spatiotemporal organization of colonic propagating sequences

Background Colonic manometry is performed using either colonoscopically assisted catheter placement, after bowel preparation, or nasocolonic intubation of the unprepared bowel. There has been little systematic evaluation of the effects of bowel cleansing upon colonic propagating pressure wave sequences. Methods Eight healthy volunteers underwent nasocolonic placement of a water‐perfused silicone catheter which recorded pressures at 16 recording sites each spaced 7.5 cm apart in the unprepared colon for 24 h. These measures were compared with those obtained in another eight healthy volunteers in whom the catheter was placed to the caecum at colonoscopy in the prepared colon. Key Results The colonic motor responses to meals and morning waking, and the normal nocturnal suppression did not differ between the two groups, nor were the overall frequency, regional dependence nor extent of propagating sequences (PS) influenced by bowel preparation. Bowel preparation did result in a significant increase in the frequency of high amplitude PS (22 ± 7 vs 8 ± 4 HAPS/24 h; P = 0.003). Additionally, a number of the measures of spatiotemporal organization among consecutive PS (linkage among sequences and predefecatory stereotypical patterning) were significantly altered by bowel preparation. Conclusions & Inferences The overall frequency of PSs, the colonic responses to physiological stimuli such a meal and morning waking and nocturnal suppression, are not influenced by prior bowel preparation. However, investigators wishing to study HAPS frequency, or the more complex spatiotemporal relationships among consecutive PSs, should control for bowel preparation when making comparisons among study groups.     

High‐resolution manometry changes our views of gastrointestinal motility

High‐resolution manometry using catheters with 36 solid‐state sensors spaced 1 cm apart has already become an established technique for esophageal manometry where it has replaced water‐perfused and station pull‐through manometry. Spatiotemporal plots with color coding of pressure have greatly facilitated the analysis of esophageal peristalsis. Although suitable for the length of the esophagus, the solid‐state catheter is insufficient for the study of longer segments of the gastrointestinal tract. A new technique with fiber‐optic sensors has made it possible to construct catheters with 72–144 sensors. Studies of colonic motility have revealed that the most common motor pattern of the colon is a peristaltic contraction that travels 7–10 cm in the retrograde direction. Earlier studies using low‐resolution manometry with 7–45 cm between sensors led us to erroneous conclusions regarding direction and frequency of contractions and they largely missed both antegrade and retrograde contractions traveling short distances. Fiber‐optic high‐resolution manometry holds promise for greatly improving our understanding of gut motor physiology and hopefully also our understanding of patients with symptoms of disordered gut motility.     

Anatomical registration and three‐dimensional visualization of low and high‐resolution pan‐colonic manometry recordings

Background Colonic propagating sequences (PS) are important for the movement of colonic content and defecation, and aberrant PS patterning has been associated with slow transit constipation. However, because these motor patterns are typically recorded over long periods (24 h +), the visualization of PS spatiotemporal patterning is difficult. Here, we develop a novel method for displaying pan‐colonic motility patterns. Methods A 3D mesh representing the geometry of the human colon was created as follows: (i) Human colon images from the Visible Human Dataset were digitized to create a 3D data cloud, and (ii) A surface mesh was fitted to the cloud using a least‐squares minimization technique. Colonic manometry catheters were placed in the ascending colon of healthy controls and patients with slow transit constipation (STC), with the aid of a colonoscope. The colonic manometry data were interpolated and mapped to the model according to the following anatomical landmarks: cecum, hepatic flexure, splenic flexure, sigmoid‐descending junction, and anus. Key Results These 3D images clearly and intuitively communicate characteristics of normal and abnormal colonic motility. Specifically we have shown the reduced amplitude of the antegrade propagating pressure waves (PPW) throughout the colon and reduced frequency of PPWs at the mid‐colon in patients with STC. Conclusions and Inferences A novel method for the 3D visualization of PS is presented, providing an intuitive method for representing a large volume of physiological data. These techniques can be used to display frequency, amplitude or velocity data, and will help to convey regions of abnormally in patient populations.     

Classification of normal and abnormal colonic motility based on cross‐correlations of pancolonic manometry data

Background Manual analysis of data acquired from manometric studies of colonic motility is laborious, subject to laboratory bias and not specific enough to differentiate all patients from control subjects. Utilizing a cross‐correlation technique, we have developed an automated analysis technique that can reliably differentiate the motor patterns of patients with slow transit constipation (STC) from those recorded in healthy controls. Methods Pancolonic manometric data were recorded from 17 patients with STC and 14 healthy controls. The automated analysis involved calculation of an indicator value derived from cross‐correlations calculated between adjacent recording sites in a manometric trace. The automated technique was conducted on blinded real data sets (observed) and then to determine the likelihood of positive indicator values occurring by chance, the channel number within each individual data set were randomized (expected) and reanalyzed. Key Results In controls, the observed indicator value (3.2 ± 1.4) was significantly greater than that predicted by chance (0.8 ± 1.5; P < 0.0001). In patients, the observed indicator value (?2.7 ± 1.8) did not differ from that predicted by chance (?3.5 ± 1.6; P = 0.1). The indicator value for controls differed significantly from that of patients (P < 0.0001), with all individual patients falling outside of the range of indicator values for controls. Conclusions & Inferences Automated analysis of colonic manometry data using cross‐correlation separated all patients from controls. This automated technique indicates that the contractile motor patterns in STC patients differ from those recorded in healthy controls. The analytical technique may represent a means for defining subtypes of constipation.     

High amplitude propagated contractions

While most colonic motor activity is segmental and non‐propulsive, colonic high amplitude propagated contractions (HAPC) can transfer colonic contents over long distances and often precede defecation. High amplitude propagated contractions occur spontaneously, in response to pharmacological agents or colonic distention. A subset of patients with slow transit constipation have fewer HAPC. In this issue of Neurogastroenterology and Motility, Rodriguez et al. report that anal relaxation during spontaneous and bisacodyl‐induced HAPC exceeds anal relaxation during rectal distention in constipated children undergoing colonic manometry. Moreover, and consistent with a neural mechanism, anal relaxation often precedes arrival of HAPC in the left colon. High amplitude propagated contractions are also used to evaluate the motor response to a meal and pharmacological stimuli (e.g., bisacodyl, neostigmine) and to identify colonic inertia during colonic motility testing in chronic constipation. This editorial comprehensively reviews the characteristics, physiology and pharmacology of HAPC, their assessment by manometry, and relevance to constipation and diarrhea.     

Statins and cognition in late‐life bipolar disorder

Objectives

Recent data suggests that statins have positive effects on cognition in older adults. Studies in patients with mood disorders have found contradicting positive and negative effects of statins on mood and cognition, with limited data in bipolar disorder (BD). The objective of this study was to assess the association between statin use and cognition in older adults with BD.

Methods

In a cross‐sectional sample of 143 euthymic older adults with BD (age ≥ 50), statin users (n = 48) and nonusers (n = 95) were compared for cognitive outcomes: Global and cognitive domain z‐scores were calculated from detailed neuropsychological batteries using normative data from healthy comparators (n = 87).

Results

The sample had a mean age of 64.3 (±8.9) years, 65.0% were female, with an average of 15.1 (±2.79) years of education. Statin users did not differ from nonusers on global (?0.60 [±0.69] vs ?0.49 [±0.68], t[127] = 0.80, P = .42) or individual cognitive domains z‐score.

Conclusions

In older patients with BD, statin use is not independently associated with cognitive impairment. This suggests that in older BD patients, the cognitive dysfunction associated with BD trumps the potential cognitive benefit that is associated with statins in older adults without a psychiatric disorder. Further, statins do not seem to exacerbate this cognitive dysfunction. Future longitudinal studies are needed to confirm these findings.     

Risk of recurrence after a single manic or mixed episode – a systematic review and meta‐analysis

Objectives

For the first time to estimate the risk of recurrence among patients with a single manic/mixed episode by systematically reviewing prior studies on cohorts of adults, and cohorts of children and adolescents, respectively.

Methods

A systematic literature search up to August 2017 was carried out including studies in which < 25% of the participants were estimated to have had a mood episode that required pharmacological treatment prior to the index manic or mixed episode at inclusion.

Results

Three studies including a total of 293 adult patients with a single manic or mixed episode and three studies of children and adolescents including 126 patients were identified. In the adult studies, 31%, 40% and 42% experienced recurrence after recovery within 1 year, 59% after 2 years, and 58% after 4 years, respectively. In the studies on children and adolescents, 40% and 52% experienced recurrence after recovery within 1 year, 30% and 60% after 2 years and 64% and 67% after 4 to 5 years, respectively. Results from meta‐analyses showed a 1‐year rate of recurrence of 35% (95% confidence interval [CI]: 30‐41%) in adults, and in adolescents/children, a 1‐year rate of recurrence of 48% (95% CI: 38‐58%), a 2‐year rate of 46% (95% CI: 33‐60%) and a 4‐5‐year rate of recurrence of 65% (95% CI: 52‐77%; as data from different studies were included at 1, 2 and 5 years, rates of recurrence did not increase steadily with time).

Conclusions

The rate of recurrence is high among adults as well as children and adolescents. It is important that clinicians and patients as well as relatives are well informed about these high risks when deciding to start maintenance treatment or not following onset of a single manic or mixed episode.     

Criterion validity of the GMFM‐66 item set and the GMFM‐66 basal and ceiling approaches for estimating GMFM‐66 scores

Aim

The aim of this study was to compare the accuracy of two abbreviated approaches for estimating Gross Motor Function Measure 66 (GMFM‐66) scores against the full GMFM‐66 and to explore their strengths and limitations.

Method

An existing dataset (n=224) comprising children aged 1 to 13 years (mean age 6y 11mo, SD 4y 6mo; 132 males, 92 females) with cerebral palsy (CP) of all Gross Motor Function Classification System (GMFCS) levels was used to compare the validity of the item set version (GMFM‐66‐IS) and the basal and ceiling version (GMFM‐66‐B&C) with the full GMFM‐66 scores. Follow‐up assessment at 1 year (n=109) allowed evaluation of change scores and accuracy at a single point in time.

Results

The cross‐sectional agreement was excellent for both abbreviated measures (all intraclass correlation coefficients [ICCs] >0.98). When measuring change over time, both the GMFM‐66‐IS and the GMFM‐66‐B&C showed good agreement for children with bilateral CP (ICCs >0.9). However, the GMFM‐66‐IS assessed change over 1 year more accurately than the GMFM‐66‐B&C in children with unilateral CP (ICC=0.89 vs ICC=0.58; 95% confidence intervals do not overlap).

Interpretation

Both approaches for estimating GMFM‐66 scores are accurate at a single point in time. If the primary goal of assessment is to measure change, the full GMFM‐66 should still be regarded as the criterion standard. The GMFM‐66‐IS should be the preferred shortened measure for children with unilateral CP.     

Dynamics of movement‐related cortical potentials and sensorimotor oscillations during palmar grasp movements

Movement‐related cortical potentials (MRCP) and sensorimotor oscillatory electroencephalographic (EEG) activity (event‐related desynchronization/synchronization—ERD/ERS) provide complementary information of the associated motor activity. The aim of this study was to provide comparative spatio‐temporal analysis of both EEG phenomena associated with palmar grasping motions including hand opening and closing phases. Nine healthy participants were instructed to perform self‐paced, right hand grasping movements. EEG was recorded from 28 sites synchronous with electromyography (EMG) of wrist/fingers extensors and flexors. Statistical analysis of the EEG data revealed significant differences (p < .05) between the idle state (baseline) and motor preparation/execution periods in majority of recorded channels. The earliest statistical significance in MRCPs was observed for channel FC3 at ?460.9 ms, while the earliest significant ERD was observed at 164.1 ms for channel C3. MRCP and ERD/ERS topographies in our study are in line with the results of previous studies comparing MRCP and ERD/ERS spatio‐temporal patterns during upper limb movements, however, results of our study show that MRCP significant differences compared to the baseline appear in most channels earlier than ERD (on average 613.6 ± 191.5 ms earlier). This implies an advantage of MRCP signals for grasping movements' prediction, which is in contrast to previous reports. Moreover, combined spatio‐temporal information on MRCP and ERD/ERS presented in this paper may serve for future optimization of grasp movement prediction/detection hybrid algorithms in the context of restorative brain–computer interface technology.     

Abnormal small bowel motility in patients with hereditary transthyretin amyloidosis

Background

Gastrointestinal complications are common in hereditary transthyretin amyloid (ATTRm) amyloidosis. The underlying mechanisms have not been fully elucidated, and the patients’ small bowel function remains largely unexplored. The aim of the present study was to compare the small bowel motility in ATTRm amyloidosis patients with that in non‐amyloidosis patient controls.

Methods

ATTRm amyloidosis patients undergoing evaluation for liver transplantation were consecutively investigated with 24‐hour duodenojejunal manometry (n = 19). The somatostatin analogue octreotide was used to induce fasting motility. Patients with age at onset of ≥50 years were defined as late‐onset cases. For each patient, three age‐ and sex‐matched patient controls (n = 57) were selected from the total pool of investigated patients.

Key Results

Manometry was judged as abnormal in 58% of the patients and in 26% of the patient controls (P = .01). Patients displayed significantly more daytime phase III migrating motor complexes than patient controls (median 4 vs 2, P < .01), and had a higher frequency of low‐amplitude complexes (16% vs 4%; however, this difference did not reach statistical significance, P = .10). Furthermore, late‐onset patients showed a delay in octreotide response (5.4 vs 3.8 minutes, P < .01), but this was not observed for early‐onset patients or within the control group.

Conclusions and Inferences

Patients with ATTRm amyloidosis displayed abnormalities in their small bowel motility more frequently than non‐amyloidosis patient controls, and the manometric pattern was probably best consistent with a combined neuromyopathic disorder. The delayed octreotide response in late‐onset patients warrants further investigation.     

High‐resolution esophageal pressure topography is superior to conventional sleeve manometry for the detection of transient lower esophageal sphincter relaxations associated with a reflux event

Background Transient lower esophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro‐esophageal reflux and are detected during manometric studies using well defined criteria. Recently, high‐resolution esophageal pressure topography (HREPT) has been introduced and is now considered as the new standard to study esophageal and lower esophageal sphincter (LES) function. In this study we performed a head‐to‐head comparison between HREPT and conventional sleeve manometry for the detection of TLESRs. Methods A setup with two synchronized MMS‐solar systems was used. A solid state HREPT catheter, a water‐perfused sleeve catheter, and a multi intraluminal impedance pH (MII‐pH) catheter were introduced in 10 healthy volunteers (M6F4, age 19–56). Subjects were studied 0.5 h before and 3 h after ingestion of a standardized meal. Tracings were blinded and analyzed by the three authors according to the TLESR criteria. Key Results In the HREPT mode 156 TLESRs were scored, vs 143 during sleeve manometry (P = 0.10). Hundred and twenty‐three TLESRs were scored by both techniques. Of all TLESRs (177), 138 were associated with reflux (78%). High‐resolution esophageal pressure topography detected significantly more TLESRs associated with a reflux event (132 vs 119, P = 0.015) resulting in a sensitivity for detection of TLESRs with reflux of 96% compared to 86% respectively. Analysis of the discordant TLESRs associated with reflux showed that TLESRs were missed by sleeve manometry due to low basal LES pressure (N = 5), unstable pharyngeal signal (N = 4), and residual sleeve pressure >2 mmHg (N = 10). Conclusions & Inferences The HREPT is superior to sleeve manometry for the detection of TLESRs associated with reflux. However, rigid HREPT criteria are awaited.     

Long‐term safety and efficacy of acotiamide in functional dyspepsia (postprandial distress syndrome)—results from the European phase 3 open‐label safety trial

Backgrounds

Acotiamide is a novel acetylcholinesterase inhibitor for treatment of postprandial distress syndrome (PDS) symptoms of functional dyspepsia (FD). This European phase 3 open‐label safety trial has been conducted to evaluate the long‐term safety of acotiamide and explore the efficacy of acotiamide on PDS symptoms using the validated LPDS, quality of life using SF‐36 and SF‐NDI, and work productivity using WPAI.

Methods

FD‐PDS patients (defined by ROME III criteria) aged ≥18 years with active PDS symptoms and without predominant overlapping symptoms of epigastric pain syndrome and related disorders were enrolled to receive 100 mg acotiamide three times daily for 1 year. Patients' safety profile and efficacy of acotiamide were monitored.

Key Results

The majority of patients (81.6%) maintained exposure to acotiamide for >50 weeks, with a mean duration of 320.3 days. No specific clinically significant safety concerns have been shown, with no deaths, treatment‐related severe/serious adverse events, or any clinically significant laboratory test results. Although being an open‐label trial, acotiamide showed a change in severity larger than the minimum clinically important difference at weeks 1 and 2 for postprandial fullness and early satiation (meal‐related symptoms), and showed improvement of quality of life and work productivity from the first measurement (at week 12) up to 1 year.

Conclusions & Inferences

The long‐term safety of acotiamide treatment was confirmed. A clinically important change for PDS symptoms, QoL, and work productivity was suggested; however a controlled trial is required to confirm this hypothetic efficacy of acotiamide. (NCT01973790).     

Clozapine as a first‐ or second‐line treatment in schizophrenia: a systematic review and meta‐analysis

Objective

No consensus exists on whether clozapine should be prescribed in early stages of psychosis. This systematic review and meta‐analysis therefore focus on the use of clozapine as first‐line or second‐line treatment in non‐treatment‐resistant patients.

Methods

Articles were eligible if they investigated clozapine compared to another antipsychotic as a first‐ or second‐line treatment in non‐treatment‐resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We performed random‐effects meta‐analyses.

Results

Fifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800 on other antipsychotics). Our meta‐analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of clozapine (Hedges’ g = 0.220, P = 0.026, 95% CI = 0.026–0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a significant benefit of clozapine over risperidone (Hedges’ g = 0.274, P = 0.030, 95% CI = 0.027–0.521).

Conclusion

The few eligible trials on this topic suggest that clozapine may be more effective than other antipsychotics when used as first‐ or second‐line treatment. Only large clinical trials may comprehensively probe disease stage‐dependent superiority of clozapine and investigate overall tolerability.     

The presentation of depression symptoms in attention‐deficit/hyperactivity disorder: comparing child and parent reports

Background

Attention‐deficit/hyperactivity disorder (ADHD) frequently co‐occurs with depression, and outcomes are poor when both are present. Little is known about whether depression symptoms present differently in ADHD compared to the general population, or how reliable young people with ADHD are at reporting these symptoms. This study aimed to describe depression symptoms in a clinical ADHD sample compared to a population sample, and compare self‐reports of depression symptoms with parent‐reports.

Methods

Two hundred and forty‐nine children with ADHD and their parents completed follow‐up questionnaires around 5 years after taking part in a Cardiff University ADHD study. Child depression symptoms were measured using parent‐ and child‐reported Mood and Feelings Questionnaires (MFQ) and compared to a population sample with MFQ data (n = 1460). Within both samples, child‐ and parent‐reported depression symptoms were compared.

Results

Although the profile of depression symptoms was similar between young people with ADHD and those in the general population, depression symptoms were much more common in the ADHD sample (parent‐rated MFQ score = 24.52 vs. 9.39; child‐rated = 21.02 vs. 11.86). The most common symptoms in both samples included irritability, restlessness and concentration difficulties, with core depression symptoms such as feeling miserable/unhappy also prominent. Within the ADHD sample, but not the population sample, children reported depression symptoms less frequently than their parents.

Conclusions

Young people with ADHD are at high risk of experiencing symptoms of depression but may under‐report the severity of their symptoms. Obtaining parent reports of depression symptoms in this group may be important to avoid missing key indicators of risk.     

Domain‐specific cognitive impairment in non‐demented Parkinson's disease psychosis

Introduction

In Parkinson's disease (PD), psychosis is associated with cognitive impairment that may be more profound in particular cognitive domains. Our goal was to determine whether psychosis in non‐demented PD participants is associated with domain‐specific cognitive impairment on the Mini‐Mental State Exam (MMSE).

Methods

The Morris K. Udall Parkinson's Disease Research Center of Excellence Longitudinal Study at Johns Hopkins is a prospective study that was initiated in 1998. Clinical assessments are conducted at two‐year intervals at the Johns Hopkins Hospital. We analyzed data from 137 enrolled participants with idiopathic PD. Psychosis diagnoses were established by psychiatrist interview per DSM‐IV criteria. An incident dementia diagnosis resulted in exclusion from analysis for that evaluation and any future evaluations in that participant. We used logistic regression with generalized estimated equations (GEE) to model the time‐varying relationship between MMSE subscale scores and psychosis, adjusting for potential confounding variables identified through univariable analysis.

Results

Thirty‐one unique psychosis cases were recorded among non‐demented participants. Fifty total evaluations with psychosis present were analyzed. In multivariable regressions, psychosis was associated with lower scores on the orientation (relative odds ratio, rOR: 0.73; 95% CI: 0.58–0.93; p = 0.011), language (rOR: 0.64; 95% CI: 0.48–0.86; p = 0.003), and intersecting pentagon (rOR: 0.43; 95% CI: 0.20–0.92 p = 0.030) subscales of the MMSE.

Conclusions

In PD, executive dysfunction, disorientation, and impaired language comprehension may be associated with psychosis. Our findings suggest that the corresponding MMSE subscales may be useful in identifying participants with a higher likelihood of developing psychosis. Copyright © 2017 John Wiley & Sons, Ltd.     

Effect of phase‐encoding direction on group analysis of resting‐state functional magnetic resonance imaging

Aim

Echo‐planar imaging is a common technique used in functional magnetic resonance imaging (fMRI); however, it suffers from image distortion and signal loss because of large susceptibility effects that are related to the phase‐encoding direction of the scan. Despite this relation, the majority of neuroimaging studies has not considered the influence of phase‐encoding direction. Here, we aimed to clarify how phase‐encoding direction can affect the outcome of an fMRI connectivity study of schizophrenia (SCZ).

Methods

Resting‐state fMRI using anterior to posterior (A–P) and posterior to anterior (P–A) directions was used to examine 25 patients with SCZ and 37 matched healthy controls (HC). We conducted a functional connectivity (FC) analysis using independent component analysis and performed three group comparisons: (i) A–P versus P–A (all participants); (ii) SCZ versus HC for the A–P and P–A datasets; and (iii) the interaction between phase‐encoding direction and participant group.

Results

The estimated FC differed between the two phase‐encoding directions in areas that were more extensive than those where signal loss has been reported. Although FC in the SCZ group was lower than that in the HC group for both directions, the A–P and P–A conditions did not exhibit the same specific pattern of differences. Further, we observed an interaction between participant group and the phase‐encoding direction in the left temporoparietal junction and left fusiform gyrus.

Conclusion

Phase‐encoding direction can influence the results of FC studies. Thus, appropriate selection and documentation of phase‐encoding direction will be important in future resting‐state fMRI studies.

     

Sex‐related differences in resting‐state brain activity and connectivity in the orbital frontal cortex and insula in patients with functional constipation

Functional magnetic resonance imaging (fMRI) has been used to investigate sex‐related differences in brain abnormalities in patients with irritable bowel syndrome (IBS). Like IBS, women with functional constipation (FC) are 2.1 times as many as men. No study has been performed yet to examine sex‐related differences in brain activity and connectivity in patients with FC. Here, we employed resting‐state fMRI with amplitude of low‐frequency fluctuation (ALFF) to investigate brain functional differences in 51 patients with FC (34 females) and 52 healthy controls (34 females). Results showed abdominal pain and abdominal distension correlated with trait (TAI) and state (SAI) anxiety ratings in the female FC group, and abdominal distension correlated with sensation of incomplete evacuation in the male FC group. Two‐way ANOVA revealed sex effects on ALFF in precentral gyrus, thalamus, insula (INS), and orbital frontal cortex (OFC, P_FWE < 0.05). Post hoc test showed that the female FC group had lower ALFF than males in these brain regions (P < 0.01), and ALFF in INS and OFC was correlated with abdominal pain and difficulty of defecation, respectively. Seed voxel correlation analysis showed that the female FC group had weaker connectivity than males between INS and lateral OFC (lOFC). INS‐lOFC connectivity was negatively correlated with the anxiety score in the female FC group and was negatively correlated with abdominal distension in the male FC group. These findings provide the first insight into sex‐related differences in patients with FC and highlight that INS and OFC play an important role in modulating the intrinsic functional connectivity of the resting brain network showing that this role is influenced by sex.