Feasibility and Challenges of Performing Magnetoencephalography Experiments in Children With Arthrogryposis Multiplex Congenita.

Arthrogryposis multiplex congenita (AMC) has recently drawn substantial attention from researchers and clinicians. New effective surgical and physiotherapeutic methods have been developed to improve the quality of life of patients with AMC. While it is clear that all these interventions should strongly rely on the plastic reorganization of the central nervous system, almost no studies have investigated this topic. The present study demonstrates the feasibility of using magnetoencephalography (MEG) to investigate brain activity in young AMC patients. We also outlined the general challenges and limitations of electrophysiological investigations on patients with arthrogryposis. We conducted MEG recordings using a 306-channel Elekta Neuromag VectorView system during a cued motor task performance in four patients with arthrogryposis, five normally developed children, and five control adults. Following the voice command of the experimenter, each subject was asked to bring their hand toward their mouth to imitate the self-feeding process. Two patients had latissimus dorsi transferred to the biceps brachii position, one patient had a pectoralis major transferred to the biceps brachii position, and one patient had no elbow flexion restoration surgery before the MEG investigation. Three patients who had undergone autotransplantation prior to the MEG investigation demonstrated activation in the sensorimotor area contralateral to the elbow flexion movement similar to the healthy controls. One patient who was recorded before the surgery demonstrated subjectively weak distributed bilateral activation during both left and right elbow flexion. Visual inspection of MEG data suggested that neural activity associated with motor performance was less pronounced and more widely distributed across the cortical areas of patients than of healthy control subjects. In general, our results could serve as a proof of principle in terms of the application of MEG in studies on cortical activity in patients with AMC. Reported trends might be consistent with the idea that prolonged motor deficits are associated with more difficult neuronal recruitment and the spatial heterogeneity of neuronal sources, most likely reflecting compensatory neuronal mechanisms. On the practical side, MEG could be a valuable technique for investigating the neurodynamics of patients with AMC as a function of postoperative abilitation.

Test-Retest Reliability of Neural Correlates of Response Inhibition and Error Monitoring: An fMRI Study of a Stop-Signal Task.

Response inhibition (RI) and error monitoring (EM) are important processes of adaptive goal-directed behavior, and neural correlates of these processes are being increasingly used as transdiagnostic biomarkers of risk for a range of neuropsychiatric disorders. Potential utility of these purported biomarkers relies on the assumption that individual differences in brain activation are reproducible over time; however, available data on test-retest reliability (TRR) of task-fMRI are very mixed. This study examined TRR of RI and EM-related activations using a stop signal task in young adults (n = 56, including 27 pairs of monozygotic (MZ) twins) in order to identify brain regions with high TRR and familial influences (as indicated by MZ twin correlations) and to examine factors potentially affecting reliability. We identified brain regions with good TRR of activations related to RI (inferior/middle frontal, superior parietal, and precentral gyri) and EM (insula, medial superior frontal and dorsolateral prefrontal cortex). No subcortical regions showed significant TRR. Regions with higher group-level activation showed higher TRR; increasing task duration improved TRR; within-session reliability was weakly related to the long-term TRR; motion negatively affected TRR, but this effect was abolished after the application of ICA-FIX, a data-driven noise removal method.

Test-retest reliability of fMRI-measured brain activity during decision making under risk.

Neural correlates of decision making under risk are being increasingly utilized as biomarkers of risk for substance abuse and other psychiatric disorders, treatment outcomes, and brain development. This research relies on the basic assumption that fMRI measures of decision making represent stable, trait-like individual differences. However, reliability needs to be established for each individual construct. Here we assessed long-term test-retest reliability (TRR) of regional brain activations related to decision making under risk using the Balloon Analogue Risk Taking task (BART) and identified regions with good TRRs and familial influences, an important prerequisite for the use of fMRI measures in genetic studies. A secondary goal was to examine the factors potentially affecting fMRI TRRs in one particular risk task, including the magnitude of neural activation, data analytical approaches, different methods of defining boundaries of a region, and participant motion. For the average BOLD response, reliabilities ranged across brain regions from poor to good (ICCs of 0 to 0.8, with a mean ICC of 0.17) and highest reliabilities were observed for parietal, occipital, and temporal regions. Among the regions that were of a priori theoretical importance due to their reported associations with decision making, the activation of left anterior insula and right caudate during the decision period showed the highest reliabilities (ICCs of 0.54 and 0.63, respectively). Among the regions with highest reliabilities, the right fusiform, right rostral anterior cingulate and left superior parietal regions also showed high familiality as indicated by intrapair monozygotic twin correlations (ranging from 0.66 to 0.69). Overall, regions identified by modeling the average BOLD response to a specific event type (rather than its modulation by a parametric regressor), regions including significantly activated vertices (compared to a whole parcel), and regions with greater magnitude of task-related activations showed greater reliabilities. Participant motion had a moderate negative effect on TRR. Regions activated during decision period rather than outcome period of risky decisions showed the greatest TRR and familiality. Regions with reliable activations can be utilized as neural markers of individual differences or endophenotypes in future clinical neuroscience and genetic studies of risk-taking.

Adolescent Decision-Making Under Risk: Neural Correlates and Sex Differences.

An increased propensity for risk taking is a hallmark of adolescent behavior with significant health and social consequences. Here, we elucidated cortical and subcortical regions associated with risky and risk-averse decisions and outcome evaluation using the Balloon Analog Risk Task in a large sample of adolescents (n = 256, 56% female, age 14 ± 0.6), including the level of risk as a parametric modulator. We also identified sex differences in neural activity. Risky decisions engaged regions that are parts of the salience, dorsal attention, and frontoparietal networks, but only the insula was sensitive to increasing risks in parametric analyses. During risk-averse decisions, the same networks covaried with parametric levels of risk. The dorsal striatum was engaged by both risky and risk-averse decisions, but was not sensitive to escalating risk. Negative-outcome processing showed greater activations than positive-outcome processing. Insula, lateral orbitofrontal cortex, middle, rostral, and superior frontal areas, rostral and caudal anterior cingulate cortex were activated only by negative outcomes, with a subset of regions associated with negative outcomes showing greater activation in females. Taken together, these results suggest that safe decisions are predicted by more accurate neural representation of increasing risk levels, whereas reward-related processes play a relatively minor role.

Shared genetic influences on adolescent body mass index and brain structure: A voxel-based morphometry study in twins.

BACKGROUND: Previous research has demonstrated significant relationships between obesity and brain structure. Both phenotypes are heritable, but it is not known whether they are influenced by common genetic factors. We investigated the genetic etiology of the relationship between individual variability in brain morphology and BMIz using structural MRI in adolescent twins. METHOD: The sample (n = 258) consisted of 54 monozygotic and 75 dizygotic twin pairs (mean(SD) age = 13.61(0.505), BMIz = 0.608(1.013). Brain structure (volume and density of gray and white matter) was assessed using VBM. Significant voxelwise heritability of brain structure was established using the Accelerated Permutation inference for ACE models (APACE) program, with structural heritability varying from 15 to 97%, depending on region. Bivariate heritability analyses were carried out comparing additive genetic and unique environment models with and without shared genetics on BMIz and the voxels showing significant heritability in the APACE analyses. RESULTS: BMIz was positively related to gray matter volume in the brainstem and thalamus and negatively related to gray matter volume in the bilateral uncus and medial orbitofrontal cortex, gray matter density in the cerebellum, prefrontal lobe, temporal lobe, and limbic system, and white matter density in the brainstem. Bivariate heritability analyses showed that BMIz and brain structure share ∼1/3 of their genes and that ∼95% of the phenotypic correlation between BMIz and brain structure is due to shared additive genetic influences. These regions included areas related to decision-making, motivation, liking vs. wanting, taste, interoception, reward processing/learning, caloric evaluation, and inhibition. CONCLUSION: These results suggested genetic factors are responsible for the relationship between BMIz and heritable BMIz related brain structure in areas related to eating behavior.