Attenuated post-movement beta rebound associated with schizotypal features in healthy people

Introduction: Schizophrenia and Schizotypal Personality Disorder (SPD) lie on a single spectrum of mental illness and converging evidence suggests similarities in the etiology of the two conditions. However, schizotypy is a heterogeneous facet of personality in the healthy population and so may be seen as a bridge between health and mental illness. Neural evidence for such a continuity would have implications for the characterization and treatment of schizophrenia. Based on our previous work identifying a relationship between symptomology in Schizophrenia and abnormal movement-induced electrophysiological response (the post-movement beta rebound (PMBR)), we predicted that if subclinical schizotypy arises from similar neural mechanisms to schizophrenia, schizotypy in healthy individuals would be associated with reduced PMBR. Methods: 116 participants completed a visuomotor task whilst their neural activity was recorded by magnetoencephalography. Partial correlations were computed between a measure of PMBR extracted from left primary motor cortex and scores on the Schizotypal Personality Questionnaire (SPQ), a self-report measure of schizotypal personality. Correlations between PMBR and SPQ factor scores measuring Cognitive-Perceptual, Interpersonal and Disorganization dimensions of schizotypy were also computed. Effects of site, age, and sex were controlled for. Results: We found a significant negative correlation between total SPQ score and PMBR. This was most strongly mediated by variance shared between Interpersonal and Disorganization factor scores. Conclusion: These findings indicate a continuum of neural deficit between schizotypy and schizophrenia, with diminution of PMBR, previously reported in schizophrenia, also measurable in individuals with schizotypal features, particularly disorganization and impaired interpersonal relations

Attenuated post-movement beta rebound associated with schizotypal features in healthy people

Introduction: Schizophrenia and Schizotypal Personality Disorder (SPD) lie on a single spectrum of mental illness and converging evidence suggests similarities in the etiology of the two conditions. However, schizotypy is a heterogeneous facet of personality in the healthy population and so may be seen as a bridge between health and mental illness. Neural evidence for such a continuity would have implications for the characterization and treatment of schizophrenia. Based on our previous work identifying a relationship between symptomology in Schizophrenia and abnormal movement-induced electrophysiological response (the post-movement beta rebound (PMBR)), we predicted that if subclinical schizotypy arises from similar neural mechanisms to schizophrenia, schizotypy in healthy individuals would be associated with reduced PMBR. Methods: 116 participants completed a visuomotor task whilst their neural activity was recorded by magnetoencephalography. Partial correlations were computed between a measure of PMBR extracted from left primary motor cortex and scores on the Schizotypal Personality Questionnaire (SPQ), a self-report measure of schizotypal personality. Correlations between PMBR and SPQ factor scores measuring Cognitive-Perceptual, Interpersonal and Disorganization dimensions of schizotypy were also computed. Effects of site, age, and sex were controlled for. Results: We found a significant negative correlation between total SPQ score and PMBR. This was most strongly mediated by variance shared between Interpersonal and Disorganization factor scores. Conclusion: These findings indicate a continuum of neural deficit between schizotypy and schizophrenia, with diminution of PMBR, previously reported in schizophrenia, also measurable in individuals with schizotypal features, particularly disorganization and impaired interpersonal relations

The physiological bases of hidden noise-induced hearing loss: protocol for a functional neuroimaging study

Background: Rodent studies indicate that noise exposure can cause permanent damage to synapses between inner hair cells and high-threshold auditory nerve fibers, without permanently altering threshold sensitivity. These demonstrations of what is commonly known as “hidden hearing loss” have been confirmed in several rodent species, but the implications for human hearing are unclear. Objective: Our Medical Research Council (MRC) funded programme aims to address this unanswered question, by investigating functional consequences of the damage to the human peripheral and central auditory nervous system that results from cumulative lifetime noise exposure. Behavioral and neuroimaging techniques are being used in a series of parallel studies aimed at detecting hidden hearing loss in humans. The planned neuroimaging study aims to (1) identify central auditory biomarkers associated with hidden hearing loss, (2) investigate if there are any additive contributions from tinnitus or diminished sound tolerance, which are often comorbid with hearing problems, and (3) explore the relation between subcortical functional Magnetic Resonance Imaging (fMRI) measures and the auditory brainstem response (ABR). Methods: Individuals aged 25 to 40 years with pure tone hearing thresholds ≤ 20 dB HL over the range 500 Hz to 8 kHz and no contraindications for MRI or signs of ear disease will be recruited into the study. Lifetime noise exposure will be estimated using an in-depth structured interview. Auditory responses throughout the central auditory system will be recorded using ABR and fMRI. Analyses will focus predominantly on correlations between lifetime noise exposure and auditory response characteristics. Results: This article reports the study protocol. The programme grant was awarded in July 2013. Enrollment for the study described in this protocol commenced in February 2017 and was completed in December 2017. Results are expected in 2018. Conclusions: This challenging and comprehensive study will have the potential to impact diagnostic procedures for hidden hearing loss, enabling early identification of noise-induced auditory damage via the detection of changes in central auditory processing. Consequently, this will generate the opportunity to give personalized advice regarding provision of ear defense and monitoring of further damage, thus reducing the incidence of noise-induced hearing loss

Increased liver fat and glycogen stores after consumption of high versus low glycaemic index food: a randomized crossover study

Aim: To investigate the acute and longer-term effects of low (LGI) versus high glycaemic index (HGI) diets on hepatic fat and glycogen accumulation and related blood measures in healthy volunteers. Methods: Eight healthy men (age 20.1 � 0.4 years, body mass index 23.0 � 0.9 kg/m2) attended a test day before and after a 7-day macronutrient- and energy-matched HGI or LGI diet, followed by a minimum 4-week wash-out period, and then returned to repeat the intervention with the alternative diet. During test days, participants consumed either an HGI or an LGI test meal corresponding to their diet week, and liver fat [1H magnetic resonance spectroscopy (MRS)], glycogen (13C MRS) and gastric content volume (MRI) were measured. Blood samples were obtained regularly throughout the test day to assess plasma glucose and insulin levels. Results: Plasma glucose and insulin peak values and area under the curve were significantly greater after the HGI test meal compared with the LGI test meal, as expected. Hepatic glycogen concentrations increased more after the HGI test meal (P < .05) and peak levels were significantly greater after 7 days of HGI dietary intervention compared with those at the beginning of the intervention (P < .05). Liver fat fractions increased significantly after the HGI dietary intervention compared with the LGI dietary intervention (two-way repeated-measures analysis of variance P ≤ .05). Conclusions: Compared with an LGI diet, a 1-week HGI diet increased hepatic fat and glycogen stores. This may have important clinical relevance for dietary interventions in the prevention and management of non-alcoholic fatty liver disease

Exploring the relative efficacy of motion artefact correction techniques for EEG data acquired during simultaneous fMRI

Simultaneous EEG-fMRI allows multi-parametric characterisation of brain function, in principle enabling a more complete understanding of brain responses; unfortunately the hostile MRI environment severely reduces EEG data quality. Simply eliminating data segments containing gross motion artefacts [MAs] (generated by movement of the EEG system and head in the MRI scanner’s static magnetic field) was previously believed sufficient. However recently the importance of removal of all MAs has been highlighted and new methods developed.A systematic comparison of the ability to remove MAs and retain underlying neuronal activity using different methods of MA detection and post-processing algorithms is needed to guide the neuroscience community. Using a head phantom, we recorded MAs while simultaneously monitoring the motion using three different approaches: Reference Layer Artefact Subtraction (RLAS), Moire Phase Tracker (MPT) markers, and Wire Loop Motion Sensors (WLMS). These EEG recordings were combined with EEG responses to simple visual tasks acquired on a subject outside the MRI environment. MAs were then corrected using the motion information collected with each of the methods combined with different analysis pipelines.All tested methods retained the neuronal signal. However, often the MA was not removed sufficiently to allow accurate detection of the underlying neuronal signal. We show that the MA is best corrected using the RLAS combined with post-processing using a multi-channel, recursive least squares (M-RLS) algorithm. This method needs to be developed further to enable practical utility; thus, WLMS combined with M-RLS currently provides the best compromise between EEG data quality and practicalities of motion detection

Using OPM-MEG in contrasting magnetic environments

Magnetoencephalography (MEG) has been revolutionised by optically pumped magnetometers (OPMs). “OPM-MEG ” offers higher sensitivity, better spatial resolution, and lower cost than conventional instrumentation based on superconducting quantum interference devices (SQUIDs). Moreover, because OPMs are small, lightweight, and portable they offer the possibility of lifespan compliance and (with control of background field) motion robustness, dramatically expanding the range of MEG applications. However, OPM-MEG remains nascent technology; it places stringent requirements on magnetic shielding, and whilst a number of viable systems exist, most are custom made and there have been no cross-site investigations showing the reliability of data. In this paper, we undertake the first cross-site OPM-MEG comparison, using near identical commercial systems scanning the same participant. The two sites are deliberately contrasting, with different magnetic environments: a “green field ” campus university site with an OPM-optimised shielded room (low interference) and a city centre hospital site with a “standard ” (non-optimised) MSR (higher interference). We show that despite a 20-fold difference in background field, and a 30-fold difference in low frequency interference, using dynamic field control and software-based suppression of interference we can generate comparable noise floors at both sites. In human data recorded during a visuo-motor task and a face processing paradigm, we were able to generate similar data, with source localisation showing that brain regions could be pinpointed with just ~10 mm spatial discrepancy and temporal correlations of > 80%. Overall, our study demonstrates that, with appropriate field control, OPM-MEG systems can be sited even in city centre hospital locations. The methods presented pave the way for wider deployment of OPM-MEG

Gastrointestinal peptides and small bowel hypomotility are possible causes for fasting and postprandial symptoms in active Crohn’s disease

BackgroundCrohn's disease (CD) patients suffer postprandial aversive symptoms, which can lead to anorexia and malnutrition. Changes in the regulation of gut hormones and gut dysmotility are believed to play a role.ObjectivesThis study aimed to investigate small-bowel motility and gut peptide responses to a standard test meal in CD by using MRI.MethodsWe studied 15 CD patients with active disease (age 36 ± 3 y; BMI 26 ± 1 kg/m 2) and 20 healthy volunteers (HVs; age 31 ± 3 years; BMI 24 ± 1 kg/m 2). They underwent baseline and postprandial MRI scans, symptom questionnaires, and blood sampling following a 400-g soup meal (204 kcal). Small-bowel motility, other MRI parameters, and glucagon-like peptide-1 (GLP-1), polypeptide YY (PYY), and cholecystokinin peptides were measured. Data are presented as means ± SEMs.ResultsHVs had significantly higher fasting motility indexes [106 ± 13 arbitrary units (a.u.)], compared with CD participants (70 ± 8 a.u.; P ≤ 0.05). Postprandial small-bowel water content showed a significant time by group interaction (P < 0.05), with CD participants showing higher levels from 210 min postprandially. Fasting concentrations of GLP-1 and PYY were significantly greater in CD participants, compared with HVs [GLP-1, CD 50 ± 8 µg/mL versus HV 13 ± 3 µg/mL (P ≤ 0.0001); PYY, CD 236 ± 16 pg/mL versus HV 118 ± 12 pg/mL (P ≤ 0.0001)]. The meal challenge induced a significant postprandial increase in aversive symptom scores (fullness, distention, bloating, abdominal pain, and sickness) in CD participants compared with HVs (P ≤ 0.05).ConclusionsThe decrease in fasting small-bowel motility noted in CD participants can be ascribed to the increased fasting gut peptides. A better understanding of the etiology of aversive symptoms in CD will facilitate identification of better therapeutic targets to improve nutritional status. This trial was registered at clinicaltrials.gov as NCT03052465

Implementation of 23Na MRI

Sodium magnetic resonance imaging (23Na MRI) has the potential to provide insight into cellular, tissue and organ health. Proton (1H) MRI is well established, but 23Na MRI faces several challenges, principally due to the low inherent 23Na signal from the body and the need for specialist hardware. The aim of this thesis was to lay the groundwork for carrying out 23Na MRI in humans on a clinical MRI scanner, to determine quantitative 23Na measures in the kidneys, muscle and skin. Firstly, work was carried out to install the 23Na RF coils to allow for the study of the 23Na distribution in the leg, muscle and skin, and abdomen. This required modelling of the specific absorption rate (SAR), phantom construction, temperature testing, coupling checks, power calibration and measurement of the coil's transmit/receive switching time. Secondly, the implementation and assessment of scanning techniques and calibration methods for the measurement of tissue sodium concentration (TSC) in the calf is described. This work includes 3D gradient recalled echo (GRE) imaging and sequence optimisation and the development of improved B1 mapping for correction of sodium images to more accurately compute TSC. Comparisons of measures using 3D GRE and ultrashort echo time (UTE) schemes are made, and measurement of the bi-exponential 23Na transverse relaxation time performed. An optimised 1 hour scan protocol for future studies is outlined. Thirdly, 23Na imaging of the abdomen, specifically of the kidney, is outlined. Results of initial scans performed in vivo using the dual loops coil to assess TSC in the kidney are shown. The limitations of such methods in terms of image homogeneity are described. This is followed by the assessment of a 6-channel body coil for improved homogeneity of sodium measures, and the evaluation of receive sensitivity correction. Finally, work on proton (1H) imaging using a skin coil to assess changes in skin hydration, lays the ground work for future studies combining 1H measurement of skin water content with 23Na imaging of the skin

The MRI colonic function test: Reproducibility of the Macrogol stimulus challenge

Background Magnetic resonance imaging (MRI) of the colonic response to a macrogol challenge drink can be used to assess the mechanisms underlying severe constipation. We measured the intra-subject reproducibility of MRI measures of colonic function to aid their implementation as a possible clinical test. Methods Healthy participants attended for MRI on two occasions (identical protocols, minimum 1 week apart). They underwent a fasted scan then consumed the macrogol drink. Subjects were scanned at 60 and 120 minutes, with maximum value reached used for comparison. The colonic volume, water content, mixing of colonic content and the movement of the colon walls were measured. Coefficients of variation and intraclass correlation coefficients (ICC) were calculated. Results 12 participants completed the study: 9 female, mean age 26 years (SD 5) and body mass index 24.8kg/m2 (SD 3.2). All measures consistently increased above baseline following provocation with macrogol. The volume, water content and content mixing had good intra-subject reproducibility (ICC volume=0.84, water content=0.93, mixing=0.79,

MRI assessment of the postprandial gastrointestinal motility and peptide response in healthy humans

Background: Feeding triggers inter-related gastrointestinal (GI) motor, peptide and appetite responses. These are rarely studied together due to methodological limitations. Recent MRI advances allow pan-intestinal, non-invasive assessment of motility in the undisturbed gut. This study aimed to develop a methodology to assess pan-intestinal motility and transit in a single session using MRI and compare imaging findings to GI peptide responses to a test meal and symptoms in a healthy volunteer cohort. Methods: Fifteen healthy volunteers (29.3±2.7years and BMI 20.1±1.2Kg/m2) underwent baseline and postprandial MRI scans, symptom questionnaires and blood sampling (for subsequent GI peptide analysis, Glucagon-like peptide-1 (GLP-1), Polypeptide YY (PYY), Cholecystokinin (CCK)) at intervals for 270min following a 400g soup meal (204kcal, Heinz, UK). Gastric volume, gall bladder volume, small bowel water content, small bowel motility and whole gut transit were measured from the MRI scans. Key Results: (mean±SEM) Small bowel motility index increased from fasting 39±3 arbitrary units (a.u.) to a maximum of 87±7a.u. immediately after feeding. PYY increased from fasting 98±10pg/ml to 149±14pg/ml at 30min and GLP-1 from fasting 15±3µg/ml to 22±4µg/ml. CCK increased from fasting 0.40±0.06pmol/ml to 0.94±0.1pmol/ml. Gastric volumes declined with a T1/2 of 46±5min and the gallbladder contracted from a fasting volume of 19±2ml to 12±2ml. Small bowel water content increased from 39±2ml to 51±2ml postprandial. Fullness VAS score increased from 9±5mm to 41±6mm at 30min postprandial. Conclusions and Inferences: The test meal challenge was effective in inducing a change in MRI motility end-points which will improve understanding of the pathophysiological postprandial GI response