Effects of the cardiac cycle on auditory processing: A preregistered study on mismatch negativity.

The systolic and diastolic phases of the cardiac cycle are known to affect perception and cognition differently. Higher order processing tends to be facilitated at systole, whereas sensory processing of external stimuli tends to be impaired at systole compared to diastole. The current study aims to examine whether the cardiac cycle affects auditory deviance detection, as reflected in the mismatch negativity (MMN) of the event-related brain potential (ERP). We recorded the intensity deviance response to deviant tones (70 dB) presented among standard tones (60 or 80 dB, depending on blocks) and calculated the MMN by subtracting standard ERP waveforms from deviant ERP waveforms. We also assessed intensity-dependent N1 and P2 amplitude changes by subtracting ERPs elicited by soft standard tones (60 dB) from ERPs elicited by loud standard tones (80 dB). These subtraction methods were used to eliminate phase-locked cardiac-related electric artifacts that overlap auditory ERPs. The endogenous MMN was expected to be larger at systole, reflecting the facilitation of memory-based auditory deviance detection, whereas the exogenous N1 and P2 would be smaller at systole, reflecting impaired exteroceptive sensory processing. However, after the elimination of cardiac-related artifacts, there were no significant differences between systole and diastole in any ERP components. The intensity-dependent N1 and P2 amplitude changes were not obvious in either cardiac phase, probably because of the short interstimulus intervals. The lack of a cardiac phase effect on MMN amplitude suggests that preattentive auditory processing may not be affected by bodily signals from the heart.

An 8-channel Tx dipole and 20-channel Rx loop coil array for MRI of the cervical spinal cord at 7 Tesla.

The quality of cervical spinal cord images can be improved by the use of tailored radiofrequency (RF) coil solutions for ultrahigh field imaging; however, very few commercial and research 7-T RF coils currently exist for the spinal cord, and in particular, those with parallel transmission (pTx) capabilities. This work presents the design, testing, and validation of a pTx/Rx coil for the human neck and cervical/upper thoracic spinal cord. The pTx portion is composed of eight dipoles to ensure high homogeneity over this large region of the spinal cord. The Rx portion is made up of twenty semiadaptable overlapping loops to produce high signal-to-noise ratio (SNR) across the patient population. The coil housing is designed to facilitate patient positioning and comfort, while also being tight fitting to ensure high sensitivity. We demonstrate RF shimming capabilities to optimize B1 + uniformity, power efficiency, and/or specific absorption rate efficiency. B1 + homogeneity, SNR, and g-factor were evaluated in adult volunteers and demonstrated excellent performance from the occipital lobe down to the T4-T5 level. We compared the proposed coil with two state-of-the-art head and head/neck coils, confirming its superiority in the cervical and upper thoracic regions of the spinal cord. This coil solution therefore provides a convincing platform for producing the high image quality necessary for clinical and research scanning of the upper spinal cord.

Establishing the validity of a diagnostic questionnaire for childbirth-related posttraumatic stress disorder.

BACKGROUND: Labor and delivery can entail complications and severe maternal morbidities that threaten a woman's life or cause her to believe that her life is in danger. Women with these experiences are at risk for developing posttraumatic stress disorder. Postpartum posttraumatic stress disorder, or childbirth-related posttraumatic stress disorder, can become an enduring and debilitating condition. At present, validated tools for a rapid and efficient screen for childbirth-related posttraumatic stress disorder are lacking. OBJECTIVE: We examined the diagnostic validity of the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, for detecting posttraumatic stress disorder among women who have had a traumatic childbirth. This Checklist assesses the 20 Diagnostic and Statistical Manual of Mental Disorders, posttraumatic stress disorder symptoms and is a commonly used patient-administrated screening instrument. Its diagnostic accuracy for detecting childbirth-related posttraumatic stress disorder is unknown. STUDY DESIGN: The sample included 59 patients who reported a traumatic childbirth experience determined in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, posttraumatic stress disorder criterion A for exposure involving a threat or potential threat to the life of the mother or infant, experienced or perceived, or physical injury. The majority (66%) of the participants were less than 1 year postpartum (for full sample: median, 4.67 months; mean, 1.5 years) and were recruited via the Mass General Brigham's online platform, during the postpartum unit hospitalization or after discharge. Patients were instructed to complete the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, concerning posttraumatic stress disorder symptoms related to childbirth. Other comorbid conditions (ie, depression and anxiety) were also assessed. They also underwent a clinician interview for posttraumatic stress disorder using the gold-standard Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. A second administration of the checklist was performed in a subgroup (n=43), altogether allowing an assessment of internal consistency, test-retest reliability, and convergent and diagnostic validity of the Checklist. The diagnostic accuracy of the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, in reference to the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, was determined using the area under the receiver operating characteristic curve; an optimal cutoff score was identified using the Youden's J index. RESULTS: One-third of the sample (35.59%) met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for a posttraumatic stress disorder diagnosis stemming from childbirth. The Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, symptom severity score was strongly correlated with the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, total score (ρ=0.82; P<.001). The area under the receiver operating characteristic curve was 0.93 (95% confidence interval, 0.87-0.99), indicating excellent diagnostic performance of the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. A cutoff value of 28 maximized the sensitivity (0.81) and specificity (0.90) and correctly diagnosed 86% of women. A higher value (32) identified individuals with more severe posttraumatic stress disorder symptoms (specificity, 0.95), but with lower sensitivity (0.62). Checklist scores were also stable over time (intraclass correlation coefficient, 0.73), indicating good test-retest reliability. Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, scores were moderately correlated with the depression and anxiety symptom scores (Edinburgh Postnatal Depression Scale: ρ=0.58; P<.001 and the Brief Symptom Inventory, anxiety subscale: ρ=0.51; P<.001). CONCLUSION: This study demonstrates the validity of the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, as a screening tool for posttraumatic stress disorder among women who had a traumatic childbirth experience. The instrument may facilitate screening for childbirth-related posttraumatic stress disorder on a large scale and help identify women who might benefit from further diagnostics and services. Replication of the findings in larger, postpartum samples is needed.

A patient-friendly 16-channel transmit/64-channel receive coil array for combined head-neck MRI at 7 Tesla.

PURPOSE: To extend the coverage of brain coil arrays to the neck and cervical-spine region to enable combined head and neck imaging at 7 Tesla (T) ultra-high field MRI. METHODS: The coil array structures of a 64-channel receive coil and a 16-channel transmit coil were merged into one anatomically shaped close-fitting housing. Transmit characteristics were evaluated in a B1+ -field mapping study and an electromagnetic model. Receive SNR and the encoding capability for accelerated imaging were evaluated and compared with a commercially available 7 T brain array coil. The performance of the head-neck array coil was demonstrated in human volunteers using high-resolution accelerated imaging. RESULTS: In the brain, the SNR matches the commercially available 32-channel brain array and showed improvements in accelerated imaging capabilities. More importantly, the constructed coil array improved the SNR in the face area, neck area, and cervical spine by a factor of 1.5, 3.4, and 5.2, respectively, in regions not covered by 32-channel brain arrays at 7 T. The interelement coupling of the 16-channel transmit coil ranged from -14 to -44 dB (mean = -19 dB, adjacent elements <-18 dB). The parallel 16-channel transmit coil greatly facilitates B1+ field shaping required for large FOV neuroimaging at 7 T. CONCLUSION: This new head-neck array coil is the first demonstration of a device of this nature used for combined full-brain, head-neck, and cervical-spine imaging at 7 T. The array coil is well suited to provide large FOV images, which potentially improves ultrahigh field neuroimaging applications for clinical settings.

Feasibility of simultaneous high-resolution anatomical and quantitative magnetic resonance imaging of sciatic nerves in patients with Charcot-Marie-Tooth type 1A (CMT1A) at 7T.

INTRODUCTION/AIMS: Magnetic resonance imaging (MRI) of peripheral nerves can provide image-based anatomical information and quantitative measurement. The aim of this pilot study was to investigate the feasibility of high-resolution anatomical and quantitative MRI assessment of sciatic nerve fascicles in patients with Charcot-Marie-Tooth (CMT) 1A using 7T field strength. METHODS: Six patients with CMT1A underwent imaging on a high-gradient 7T MRI scanner using a 28-channel knee coil. Two high-resolution axial images were simultaneously acquired using a quantitative double-echo in steady-state (DESS) sequence. By comparing the two DESS echoes, T2 and apparent diffusion coefficient (ADC) maps were calculated. The cross-sectional areas and mean T2 and ADC were measured in individual fascicles of the tibial and fibular (peroneal) portions of the sciatic nerve at its bifurcation and 10 mm distally. Disease severity was measured using Charcot-Marie-Tooth Examination Score (CMTES) version 2 and compared to imaging findings. RESULTS: We demonstrated the feasibility of 7T MRI of the proximal sciatic nerve in patients with CMT1A. Using the higher field, it was possible to measure individual bundles in the tibial and fibular divisions of the sciatic nerve. There was no apparent correlation between diffusion measures and disease severity in this small cohort. DISCUSSION: This pilot study indicated that high-resolution MRI that allows for combined anatomical and quantitative imaging in one scan is feasible at 7T field strengths and can be used to investigate the microstructure of individual nerve fascicles.

Structural and resting state functional connectivity beyond the cortex.

Mapping the structural and functional connectivity of the central nervous system has become a key area within neuroimaging research. While detailed network structures across the entire brain have been probed using animal models, non-invasive neuroimaging in humans has thus far been dominated by cortical investigations. Beyond the cortex, subcortical nuclei have traditionally been less accessible due to their smaller size and greater distance from radio frequency coils. However, major neuroimaging developments now provide improved signal and the resolution required to study these structures. Here, we present an overview of the connectivity between the amygdala, brainstem, cerebellum, spinal cord and the rest of the brain. While limitations to their imaging and analyses remain, we also provide some recommendations and considerations for mapping brain connectivity beyond the cortex.

Multi-shot acquisitions for stimulus-evoked spinal cord BOLD fMRI.

PURPOSE: To demonstrate the feasibility of 3D multi-shot magnetic resonance imaging acquisitions for stimulus-evoked blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in the human spinal cord in vivo. METHODS: Two fMRI studies were performed at 3T. The first study was a hypercapnic gas challenge where data were acquired from healthy volunteers using a multi-shot 3D fast field echo (FFE) sequence as well as single-shot multi-slice echo-planar imaging (EPI). In the second study, another cohort of healthy volunteers performed an upper extremity motor task while fMRI data were acquired using a 3D multi-shot acquisition. RESULTS: Both 2D-EPI and 3D-FFE were shown to be sensitive to BOLD signal changes in the cervical spinal cord, and had comparable contrast-to-noise ratios in gray matter. FFE exhibited much less signal drop-out and weaker geometric distortions compared to EPI. In the motor paradigm study, the mean number of active voxels was highest in the ventral gray matter horns ipsilateral to the side of the task and at the spinal level associated with innervation of finger extensors. CONCLUSIONS: Highly multi-shot acquisition sequences such as 3D-FFE are well suited for stimulus-evoked spinal cord BOLD fMRI.

Magnetic resonance imaging and spectroscopy in late-onset GM2-gangliosidosis.

OBJECTIVE: Our study aimed to quantify structural changes in relation to metabolic abnormalities in the cerebellum, thalamus, and parietal cortex of patients with late-onset GM2-gangliosidosis (LOGG), which encompasses late-onset Tay-Sachs disease (LOTS) and Sandhoff disease (LOSD). METHODS: We enrolled 10 patients with LOGG (7 LOTS, 3 LOSD) who underwent a neurological assessment battery and 7 age-matched controls. Structural MRI and MRS were performed on a 3 T scanner. Structural volumes were obtained from FreeSurfer and normalized by total intracranial volume. Quantified metabolites included N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cr), and combined glutamate-glutamine (Glx). Metabolic concentrations were corrected for partial volume effects. RESULTS: Structural analyses revealed significant cerebellar atrophy in the LOGG cohort, which was primarily driven by LOTS patients. NAA was lower and mI higher in LOGG, but this was also significantly driven by the LOTS patients. Clinical ataxia deficits (via the Scale for the Assessment and Rating of Ataxia) were associated with neuronal injury (via NAA), neuroinflammation (via mI), and volumetric atrophy in the cerebellum. INTERPRETATION: The decrease of NAA in the cerebellum suggests that, in addition to cerebellar atrophy, there is ongoing impaired neuronal function and/or loss, while an increase in mI indicates possible neuroinflammation in LOGG (more so within the LOTS subvariant). Quantifying cerebellar atrophy in relation to neurometabolic differences in LOGG may lead to improvements in assessing disease severity, progression, and pharmacological efficacy. Lastly, additional neuroimaging studies in LOGG are required to contrast LOTS and LOSD more accurately.

Feed Intake as an Estimation of Attractability in Pacific White Shrimp Litopenaeus vannamei.

A simple bioassay that quantifies feed intake as an estimation of relative attractability of feeds containing different ingredients in the Pacific white shrimp Litopenaeus vannamei is described. Fish meal (FM), fish protein hydrolysate (FPH), squid meal (SqM) and casein (CN) were assessed at the same dietary level for their relative influence on feed intake rates of Litopenaeus vannamei. A bland diet containing 92% whole wheat grain meal, 6% diatomaceous earth and 2% alginate with a known low attractability was used as the standard control or base diet. Ingredients were added to the bland base control diet at a level of 3% as fed. Shrimp were stocked into 80 L glass tanks (n= 20 per tank) in a recirculating aquaculture system. Tanks were randomly assigned to one of five diet treatments (3tanks/treatment). Experiments measuring the attractability of each feed were conducted twice daily at 0900 hours and 1330 hours over a five day period. For each experiment, 40 feed pellets (ca. 1 g) corresponding to the assigned treatment were provided to each tank. To calculate the rate of feed intake, pellets remaining in each tank were counted at six minute intervals for a seventy-two minute period. Differences in rate of feed intake among diets were evaluated using Cox Regression Analysis. This attractability assay required only small amounts of ingredients and incorporated ingredients into a bland feed, which significantly reduces the influence from other ingredients or compound in the pellets. All of the test protein ingredients, especially SqM, in the feeds significantly increased the feed consumption rate. The diet containing SqM was consumed at a significantly higher rate than those containing casein and FM but not FPH. FPH and CN containing diets were not significantly different but consumed at a higher rate than the diet containing FM. Results of these trials indicate that the presence of certain ingredients can increase feed intake, thereby increasing nutrient availability of the diets. This reported method to determine consumption of diets containing certain ingredients can be considered as a valid method to estimate attractability.

DSM-5 Adult Attention-Deficit/Hyperactivity Disorder: Sex Differences in EEG Activity.

This study examined sex differences in the EEG of adults diagnosed with Attention-Deficit/Hyperactivity Disorder (AD/HD) according to DSM-5 criteria. Sixteen females and 16 males with AD/HD, and age- and sex-matched control groups, had an eyes-closed resting EEG recorded from 19 electrode sites. EEGs were Fast Fourier transformed and estimates for total power, absolute and relative power in the delta, theta, alpha, beta and gamma bands, and the theta/beta ratio, were analysed across nine cortical regions. Males with AD/HD, compared with male controls, had globally reduced absolute beta, globally elevated relative theta, and a larger theta/beta ratio. In contrast, no global effects emerged between females with and without AD/HD. Significant group interactions indicated that globally elevated relative theta and elevated frontal-midline theta/beta ratio noted in males with AD/HD differed significantly from results in females. There are statistically significant EEG differences in relative theta and the theta/beta ratio between males and females with and without AD/HD. These results indicate that AD/HD affects the EEG activity of males and females differently. This study helps confirm the need for further independent examination of AD/HD within female populations.

Interrogating the Relationship Between Schizotypy, the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism, and Neuronal Oscillatory Activity.

The COMT Val158Met polymorphism affects the availability of synaptic dopamine in the prefrontal cortex and has been widely studied as a genetic risk factor for psychosis. Schizotypy is associated with an increased risk of psychosis, with some studies implicating similar neurobiological mechanisms to schizophrenia. The present study sought to interrogate the link between the COMT Val158Met polymorphism and schizotypy using electroencephalogram (EEG) to identify neurophysiological mechanisms underpinning psychosis risk. Neurotypical (N = 91) adults were genotyped for the COMT Val158Met polymorphism, completed the Schizotypal Personality Questionnaire (SPQ), and had eyes open resting-state EEG recorded for 4 min. SPQ suspiciousness subscale scores were higher for individuals homozygous for Val/Val and Met/Met versus Val/Met genotypes. Delta, theta, alpha-2, beta-1, and beta-2 amplitudes were lower for Val/Val than Met/Met individuals. Lower theta amplitudes were correlated with higher total SPQ scores (P = 0.050), and multiple regression revealed that higher delta, and lower theta and beta-2 amplitudes (but not COMT genotype) best predicted total SPQ scores (P = 0.014). This study demonstrates the importance of COMT genotype in determining trait suspiciousness and EEG oscillatory activity. It also highlights relationships between dopaminergic alterations, EEG and schizotypy that are dissimilar to those observed in schizophrenia.

Dietary antioxidant vitamin C influences the evolutionary path of insecticide resistance in Drosophila melanogaster.

Herbivorous insects encounter a variety of toxic environmental substances ranging from ingested plant defensive compounds to human-introduced insecticidal agents. Dietary antioxidants are known to reduce the negative physiological impacts of toxins in mammalian systems through amelioration of reactive oxygen-related cellular damage. The analogous impacts to insects caused by multigenerational exposure to pesticides and the effects on adaptive responses within insect populations, however, are currently unknown. To address these research gaps, we used Drosophila as a model system to explore adaptive phenotypic responses to acute dichlorodiphenyltrichloroethane (DDT) exposure in the presence of the dietary antioxidant vitamin C and to examine the structural genomic consequences of this exposure. DDT resistance increased significantly among four replicates exposed to a low concentration of DDT for 10 generations. In contrast, dietary intake of vitamin C significantly reduced DDT resistance after mutigenerational exposure to the same concentration of DDT. As to the genomic consequences, no significant differences were predicted in overall nucleotide substitution rates across the genome between any of the treatments. Despite this, replicates exposed to a low concentration of DDT without vitamin C showed the highest number of synonymous and non-synonymous variants (3196 in total), followed by the DDT plus vitamin C (1174 in total), and vitamin C alone (728 in total) treatments. This study demonstrates the potential role of diet (specifically, antioxidant intake) on adaptive genome responses, and thus on the evolution of pesticide resistance within insect populations.

Measurement of T2* in the human spinal cord at 3T.

PURPOSE: To measure the transverse relaxation time T2* in healthy human cervical spinal cord gray matter (GM) and white matter (WM) at 3T. METHODS: Thirty healthy volunteers were recruited. Axial images were acquired using an averaged multi-echo gradient-echo (mFFE) T2*-weighted sequence with 5 echoes. We used the signal equation for an mFFE sequence with constant dephasing gradients after each echo to jointly estimate the spin density and T2* for each voxel. RESULTS: No global difference in T2* was observed between all GM (41.3 ± 5.6 ms) and all WM (39.8 ± 5.4 ms). No significant differences were observed between left (43.2 ± 6.8 ms) and right (43.4 ± 5.5 ms) ventral GM, left (38.3 ± 6.1 ms) and right (38.6 ± 6.5 ms) dorsal GM, and left (39.4 ± 5.8 ms) and right (40.3 ± 5.8 ms) lateral WM. However, significant regional differences were observed between ventral (43.4 ± 5.7 ms) and dorsal (38.4 ± 6.0 ms) GM (p < 0.05), as well as between ventral (42.9 ± 6.5 ms) and dorsal (37.9 ± 6.2 ms) WM (p < 0.05). In analyses across slices, inferior T2* was longer than superior T2* in GM (44.7 ms vs. 40.1 ms; p < 0.01) and in WM (41.8 ms vs. 35.9 ms; p < 0.01). CONCLUSIONS: Significant differences in T2* are observed between ventral and dorsal GM, ventral and dorsal WM, and superior and inferior GM and WM. There is no evidence for bilateral asymmetry in T2* in the healthy cord. These values of T2* in the spinal cord are notably lower than most reported values of T2* in the cortex.

A pilot trial of RNS60 in amyotrophic lateral sclerosis.

INTRODUCTION: RNS60 is a novel immune-modulatory agent that has shown neuroprotective effects in amytrophic lateral sclerosis (ALS) preclinical models. RNS60 is administered by weekly intravenous infusion and daily nebulization. The objective of this pilot open-label trial was to test the feasibility, safety, and tolerability of long-term RNS60 administration in ALS patients. METHODS: The planned treatment duration was 23 weeks and the primary outcomes were safety and tolerability. Secondary outcomes included PBR28 positron emission tomography (PET) imaging and plasma biomarkers of inflammation. RESULTS: Sixteen participants with ALS received RNS60 and 13 (81%) completed 23 weeks of RNS60 treatment. There were no serious adverse events and no participants withdrew from the trial due to drug-related adverse events. There were no significant changes in the biomarkers. DISCUSSION: Long-term RNS60 administration was safe and well-tolerated. A large, multicenter, phase II trial of RNS60 is currently enrolling participants to test the effects of RNS60 on ALS biomarkers and disease progression. Muscle Nerve 59:303-308, 2019.

Multiple sclerosis lesions affect intrinsic functional connectivity of the spinal cord.

Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.

Time Effects on Resting EEG in Children With/Without AD/HD.

In this study we extend on behavioural evidence to examine the effect of time on EEG measures related to arousal and emotion/motivation in children with/without AD/HD. Thirty children with AD/HD and 30 age- and sex-matched controls participated. EEG was recorded during an eyes-closed resting condition and divided into three 2.5 min blocks after pre-processing. Time effects for absolute and relative alpha activity were found in healthy controls; these effects did not interact with AD/HD status. Interactions between time and AD/HD status were found for absolute theta, relative theta, and theta/beta ratio (TBR), with these EEG indices increasing over time in children with AD/HD. Moreover, IQ played a role in the interaction between time and AD/HD status. These results are consistent with predictions from both the optimal stimulation model and the delay aversion model, and suggest important methodological considerations for future EEG research in children with/without AD/HD.

The EEG Theta/Beta Ratio: A marker of Arousal or Cognitive Processing Capacity?

Attention-Deficit/Hyperactivity Disorder (AD/HD) is the most common psychiatric disorder of childhood and has been extensively researched using EEG technology. Within this literature, one of the most widely examined measures has been the theta/beta ratio. The theta/beta ratio was initially hypothesised to represent the arousal mechanism. However, subsequent research has shown this to be inaccurate and it was hypothesised that the ratio represents cognitive processing capacity. To examine that hypothesis, this study aimed to test the relationship between the P300 and the theta/beta ratio. The P300, absolute alpha and the theta/beta ratio were measured at Fz, Cz and Pz, and correlated in a group of 47 normal adults. A significant positive correlation was found between P300 latency and the theta/beta ratio. No relationship was found between P300 amplitude and the theta/beta ratio. P300 amplitude, but not latency, significantly correlated with alpha power. These results support the hypothesis that the theta/beta ratio is a marker of cognitive processing capacity.

Spinal cord MRI at 7T.

Magnetic resonance imaging (MRI) of the human spinal cord at 7T has been demonstrated by a handful of research sites worldwide, and the spinal cord remains one of the areas in which higher fields and resolution could have high impact. The small diameter of the cord (∼1 cm) necessitates high spatial resolution to minimize partial volume effects between gray and white matter, and so MRI of the cord can greatly benefit from increased signal-to-noise ratio and contrasts at ultra-high field (UHF). Herein we review the current state of UHF spinal cord imaging. Technical challenges to successful UHF spinal cord MRI include radiofrequency (B1) nonuniformities and a general lack of optimized radiofrequency coils, amplified physiological noise, and an absence of methods for robust B0 shimming along the cord to mitigate image distortions and signal losses. Numerous solutions to address these challenges have been and are continuing to be explored, and include novel approaches for signal excitation and acquisition, dynamic shimming and specialized shim coils, and acquisitions with increased coverage or optimal slice angulations.

Amide proton transfer CEST of the cervical spinal cord in multiple sclerosis patients at 3T.

PURPOSE: The ability to evaluate pathological changes in the spinal cord in multiple sclerosis (MS) is limited because T1 - and T2 -w MRI imaging are not sensitive to biochemical changes in vivo. Amide proton transfer (APT) chemical exchange saturation transfer (CEST) can indirectly detect amide protons associated with proteins and peptides, potentially providing more pathological specificity. Here, we implement APT CEST in the cervical spinal cord of healthy and MS cohorts at 3T. METHODS: APT CEST of the cervical spinal cord was obtained in a cohort of 10 controls and 10 MS patients using a novel respiratory correction methodology. APT was quantified using two methods: 1) APTw , based off the conventional magnetization transfer ratio asymmetry, and 2) ΔAPT, a spatial characterization of APT changes in MS patients relative to the controls. RESULTS: Respiratory correction yielded highly reproducible z-spectra in white matter (intraclass correlation coefficient = 0.82). APTw signals in normal-appearing white matter (NAWM) of MS patients were significantly different from healthy controls (P = 0.04), whereas ΔAPT of MS patients highlighted large APT differences in NAWM. CONCLUSION: Respiration correction in the spinal cord is necessary to accurately quantify APT CEST, which can provide unique biochemical information regarding disease processes within the spinal cord. Magn Reson Med 79:806-814, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Anti-tumour necrosis factor biological therapies for the treatment of uveitic macular oedema (UMO) for non-infectious uveitis.

BACKGROUND: Non-infectious uveitis describes a heterogenous group of ocular disorders characterised by intraocular inflammation in the absence of infection. Uveitis is a leading cause of visual loss, most commonly due to uveitic macular oedema (UMO). Treatment is aimed at reducing disease activity by suppression of the intraocular inflammatory response. In the case of macular oedema, the aim is to restore macular architecture as quickly as possible, in order to prevent irreversible photoreceptor damage in this area. Acute exacerbations are typically managed with corticosteroids, which may be administered topically, locally or systemically. Whilst these are often rapidly effective in achieving disease control, long-term use is associated with significant local and systemic side effects, and 'steroid sparing agents' are typically used to achieve prolonged control in severe or recalcitrant disease. Anti-tumour necrosis factor (TNF) drugs block a critical cytokine in the inflammatory signalling process, and have emerged as effective steroid-sparing immunomodulatory agents in a wide range of non-ocular conditions. There is mechanistic data to suggest that they may provide a more targeted approach to disease control in UMO than other agents, but to date, these agents have predominantly been used 'off label' as the majority are not licensed for ocular use. This review aims to summarise the available literature reporting the use of anti-TNF therapy in UMO, thus developing the evidence-base on which to make future treatment decisions and develop clinical guidelines in this area. OBJECTIVES: To assess the efficacy of anti-TNF therapy in treatment of UMO. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), which contains the Cochrane Eyes and Vision Trials Register; Ovid MEDLINE; Ovid Embase; LILACS; Web of Science Conference Proceedings Citation Index- Science (CPCI-S); System for Information on Grey Literature in Europe (OpenGrey); the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 29 March 2018. SELECTION CRITERIA: We planned to include all relevant randomised controlled trials assessing the use of anti-TNF agents in treatment of UMO. No limits were applied to participant age, gender or ethnicity. The primary comparisons of this review were: anti-TNF versus no treatment or placebo; anti-TNF versus another pharmacological agent; comparison of different anti-TNF drugs; comparison of different doses and routes of administration of the same anti-TNF drug. The primary outcome measure that we assessed for this review was best-corrected visual acuity (BCVA) in the treated eye. Secondary outcome measures were anatomical macular change, clinical estimation of vitreous haze and health-related quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts retrieved through the database searches. We retrieved full-text reports of studies categorised as 'unsure' or 'include' after we had reviewed the abstracts. Two review authors independently reviewed each full-text report for eligibility. We resolved discrepancies through discussion. MAIN RESULTS: We identified no completed or ongoing trial that was eligible for this Cochrane Review. AUTHORS' CONCLUSIONS: Our review did not identify any evidence from randomised controlled trials for or against the role of anti-TNF agents in the management of UMO. Although there are a number of high-quality randomised controlled trials that demonstrate the efficacy of anti-TNF agents in preventing recurrence of inflammation in uveitis, the reported study outcomes do not include changes in UMO. As a result, there were insufficient data to conclude whether there was a significant treatment effect specifically for UMO. Future trials should be designed to include quantitative measures of UMO as primary study outcomes, for example by reporting the presence or absence of UMO, or by measuring central macular thickness for study participants. Furthermore, whilst UMO is an important complication of uveitis, we acknowledge that uveitis is associated with many significant structural and functional complications. It is not possible to determine treatment efficacy based on a single outcome measure. We recommend that future reviews of therapeutic interventions in uveitis should use composite measures of treatment response comprising a range of potential complications of disease.