Aging-Related Changes in Cortical Sources of Sleep Oscillatory Neural Activity Following Motor Learning Reflect Contributions of Cortical Thickness and Pre-sleep Functional Activity

Oscillatory neural activity during sleep, such as that in the delta and sigma bands, is important for motor learning consolidation. This activity is reduced with typical aging, and this reduction may contribute to aging-related declines in motor learning consolidation. Evidence suggests that brain regions involved in motor learning contribute to oscillatory neural activity during subsequent sleep. However, aging-related differences in regional contributions to sleep oscillatory activity following motor learning are unclear. To characterize these differences, we estimated the cortical sources of consolidation-related oscillatory activity using individual anatomical information in young and older adults during non-rapid eye movement sleep after motor learning and analyzed them in light of cortical thickness and pre-sleep functional brain activation. High-density electroencephalogram was recorded from young and older adults during a midday nap, following completion of a functional magnetic resonance imaged serial reaction time task as part of a larger experimental protocol. Sleep delta activity was reduced with age in a left-weighted motor cortical network, including premotor cortex, primary motor cortex, supplementary motor area, and pre-supplementary motor area, as well as non-motor regions in parietal, temporal, occipital, and cingulate cortices. Sleep theta activity was reduced with age in a similar left-weighted motor network, and in non-motor prefrontal and middle cingulate regions. Sleep sigma activity was reduced with age in left primary motor cortex, in a non-motor right-weighted prefrontal-temporal network, and in cingulate regions. Cortical thinning mediated aging-related sigma reductions in lateral orbitofrontal cortex and frontal pole, and partially mediated delta reductions in parahippocampal, fusiform, and lingual gyri. Putamen, caudate, and inferior parietal cortex activation prior to sleep predicted frontal and motor cortical contributions to sleep delta and theta activity in an age-moderated fashion, reflecting negative relationships in young adults and positive or absent relationships in older adults. Overall, these results support the local sleep hypothesis that brain regions active during learning contribute to consolidation-related neural activity during subsequent sleep and demonstrate that sleep oscillatory activity in these regions is reduced with aging.

Algebra dissociates from arithmetic in the brain semantic network

Background Mathematical expressions mainly include arithmetic (such as 8 − (1 + 3)) and algebra (such as a − (b + c)). Previous studies have shown that both algebraic processing and arithmetic involved the bilateral parietal brain regions. Although previous studies have revealed that algebra was dissociated from arithmetic, the neural bases of the dissociation between algebraic processing and arithmetic is still unclear. The present study uses functional magnetic resonance imaging (fMRI) to identify the specific brain networks for algebraic and arithmetic processing. Methods Using fMRI, this study scanned 30 undergraduates and directly compared the brain activation during algebra and arithmetic. Brain activations, single-trial (item-wise) interindividual correlation and mean-trial interindividual correlation related to algebra processing were compared with those related to arithmetic. The functional connectivity was analyzed by a seed-based region of interest (ROI)-to-ROI analysis. Results Brain activation analyses showed that algebra elicited greater activation in the angular gyrus and arithmetic elicited greater activation in the bilateral supplementary motor area, left insula, and left inferior parietal lobule. Interindividual single-trial brain-behavior correlation revealed significant brain-behavior correlations in the semantic network, including the middle temporal gyri, inferior frontal gyri, dorsomedial prefrontal cortices, and left angular gyrus, for algebra. For arithmetic, the significant brain-behavior correlations were located in the phonological network, including the precentral gyrus and supplementary motor area, and in the visuospatial network, including the bilateral superior parietal lobules. For algebra, significant positive functional connectivity was observed between the visuospatial network and semantic network, whereas for arithmetic, significant positive functional connectivity was observed only between the visuospatial network and phonological network. Conclusion These findings suggest that algebra relies on the semantic network and conversely, arithmetic relies on the phonological and visuospatial networks.

Examining the Neural Correlates of Error Awareness in a Large fMRI Study

Goal-directed behaviour is dependent upon the ability to detect errors and implement appropriate post-error adjustments. Accordingly, several studies have explored the neural activity underlying error-monitoring processes, identifying the insula cortex as crucial for error awareness and reporting mixed findings with respect to the anterior cingulate cortex. Variable patterns of activation have previously been attributed to insufficient statistical power. We therefore sought to clarify the neural correlates of error awareness in a large event-related functional magnetic resonance imaging (MRI) study. Four hundred and two healthy participants undertook the Error Awareness Task, a motor Go/No-Go response inhibition paradigm in which participants were required to indicate their awareness of commission errors. Compared to unaware errors, aware errors were accompanied by significantly greater activity in a network of regions including the insula cortex, supramarginal gyrus, and midline structures such as the anterior cingulate cortex and supplementary motor area. Error awareness activity was related to indices of task performance and dimensional measures of psychopathology in select regions including the insula, supramarginal gyrus and supplementary motor area. Taken together, we identified a robust and reliable neural network associated with error awareness.

Sex Differences in Brain Structure Account for the Sexual Distinction on Balanced Time Perspective

Sex differences in behaviour and cognition have been widely observed, however, little is known about such differences in maintaining a balanced time perspective or their potential underlying neural substrates. To answer the above questions, two studies were conducted. In Study 1, time perspective was assessed in 1,913 college students, including 771 males and 1,092 females, and demonstrated that females had a significantly more balanced time perspective than males. In Study 2, 58 males and 47 females underwent assessment of time perspective and structural brain imaging. Voxel-based morphometry analysis and cortical thickness analysis were used to analyse the structural imaging data. Results showed that compared with males, females demonstrated a more balanced time perspective, which primarily related to lower grey matter volume in left precuneus, right cerebellum, right putamen and left supplementary motor area. Analysis of cortical thickness failed to reveal any significant sex differences. Furthermore, the sex difference in grey matter volume of left precuneus, right cerebellum, right putamen and left supplementary motor area could account for the difference in balanced time perspective between males and females. The findings deepen our understanding of sex differences in human cognition and their potential neural signature, and may inform tailored interventions to support a balanced time perspective in daily life.

Prefrontal Cortex and Supplementary Motor Area Activation During Robot-Assisted Weight-Supported Over-Ground Walking in Young Neurological Patients: A Pilot fNIRS Study

Introduction: Rehabilitation therapy devices are designed for practicing intensively task-specific exercises inducing long-term neuroplastic changes underlying improved functional outcome. The Andago enables over-ground walking with bodyweight support requiring relatively high cognitive demands. In this study, we investigated whether we could identify children and adolescents with neurological gait impairments who show increased hemodynamic responses of the supplementary motor area (SMA) or prefrontal cortex (PFC) measured with functional near-infrared spectroscopy (fNIRS) when walking in Andago compared to walking on a treadmill. We further assessed the practicability and acceptability of fNIRS.Methods: Thirteen participants (two girls, 11 boys, age 8.0–15.7 years) with neurological impairments walked in the Andago and on a treadmill under comparable conditions. We measured hemodynamic responses over SMA and PFC during 10 walks (each lasting 20 s.) per condition and analyzed the data according to the latest recommendations. In addition, we listed technical issues, stopped the time needed to don fNIRS, and used a questionnaire to assess acceptability.Results: Hemodynamic responses varied largely between participants. Participants with a typical hemodynamic response (i.e., increased oxygenated hemoglobin concentration) showed large cortical activations during walking in Andago compared to treadmill walking (large effect sizes, i.e., for SMA: r = 0.91, n = 4; for PFC: r = 0.62, n = 3). Other participants showed atypical (SMA: n = 2; PFC: n = 4) or inconclusive hemodynamic responses (SMA: n = 5; PFC: n = 4). The median time for donning fNIRS was 28 min. The questionnaire indicated high acceptance of fNIRS, despite that single participants reported painful sensations.Discussion: Repetitive increased activation of cortical areas like the SMA and PFC might result in long-term neuroplastic changes underlying improved functional outcome. This cross-sectional pilot study provides first numbers on hemodynamic responses in SMA and PFC during walking in Andago in children with neurological impairments, reveals that only a small proportion of the participants shows typical hemodynamic responses, and reports that fNIRS requires considerable time for donning. This information is needed when designing future longitudinal studies to investigate whether increased brain activation of SMA and PFC during walking in Andago could serve as a biomarker to identify potential therapy responders among children and adolescents undergoing neurorehabilitation.

Targeted Interventions in Tourette’s using Advanced Neuroimaging and Stimulation (TITANS): study protocol for a double-blind, randomised controlled trial of transcranial magnetic stimulation (TMS) to the supplementary motor area in children with Tourette’s syndrome

IntroductionTourette’s syndrome (TS) affects approximately 1% of children. This study will determine the efficacy and safety of paired comprehensive behavioural intervention for tics (CBIT) plus repetitive transcranial magnetic stimulation (rTMS) treatment in children with Tourette’s syndrome. We hypothesise that CBIT and active rTMS to the supplementary motor area (SMA) will (1) decrease tic severity, and (2) be associated with changes indicative of enhanced neuroplasticity (eg, changes in in vivo metabolite concentrations and TMS neurophysiology measures).Methods and analysisThis study will recruit 50 youth with TS, aged 6–18 for a phase II, double-blind, block randomised, sham-controlled trial comparing active rTMS plus CBIT to sham rTMS plus CBIT in a 1:1 ratio. The CBIT protocol is eight sessions over 10 weeks, once a week for 6 weeks and then biweekly. The rTMS protocol is 20 sessions of functional MRI-guided, low-frequency (1 Hz) rTMS targeted to the bilateral SMA over 5 weeks (weeks 2–6). MRI, clinical and motor assessments and neurophysiological evaluations including motor mapping will be performed 1 week before CBIT start, 1 week after rTMS treatment and 1 week after CBIT completion. The primary outcome measure is Tourette’s symptom change from baseline to post-CBIT treatment, as measured by the Yale Global Tic Severity Scale. Secondary outcomes include changes in imaging, neurophysiological and behavioural markers.Ethics and disseminationEthical approval by the Conjoint Health Research Ethics Board (REB18-0220). The results of this study will be published in peer-reviewed scientific journals, on ClinicalTrials.gov and shared with the Tourette and OCD Alberta Network. The results will also be disseminated through the Alberta Addictions and Mental Health Research Hub.Trial registrationNCT03844919.

Altered functional connectivity relates to motor performance deficits in bipolar but not unipolar depression

Underpinnings of psychomotor deficits in bipolar and unipolar depression remain underexplored. Here, we hypothesize that motor performance deficits in patients may be partially explained by altered functional connectivities between hand primary motor cortex and posterior cingulate cortex with supplementary motor area. 95 participants between 18-65 years of age, including bipolar depressed, unipolar depressed, and sex-, age-, and education-matched healthy controls, participated in this observational study with two separate visits about five weeks apart, during which the patients received psychopharmacological treatment. Motor performance was measured with a finger-tapping-task and related to functional connectivity from individual seeds in hand primary motor cortex and posterior cingulate cortex as well as to the default mode and sensory motor networks from resting state functional MRI data. 79 participants (45.6% females, 21 bipolar depressed, 27 unipolar depressed and 31 healthy controls) were included in the analysis. Using a finger-tapping-task, the groups differed in motor performance (ANOVA factor group F(2,76) = 4.122; p = 0.020) and bipolar depressed but not unipolar depressed showed performance deficits compared to controls (post-hoc-test p = 0.023 and p = 0.158 respectively). Behavioral performance correlated with functional coupling of posterior cingulate cortex - supplementary motor area, but not with coupling of primary motor cortex - supplementary motor area at cluster-wise correction level p FWEc < 0.05. Correlation differences were seen in posterior cingulate cortex - supplementary motor area (healthy controls>bipolar depressed, unipolar depressed>bipolar depressed) at second visit and in primary motor cortex - supplementary motor area (bipolar depressed>unipolar depressed) at both visits at cluster-wise correction level p FWEc<0.05. Motor performance did not relate to functional coupling of sensory motor network - anterior (visit 1 p = 0.375, visit 2 p = 0.700) or - posterior (visit 1 p = 0.903, visit 2 p = 0.772) default mode network. Motor performance deficits were seen exclusively in bipolar depressed and related to reduced posterior cingulate cortex - supplementary motor area functional connectivity at rest. Our results shed new light on a possible disruption in the anticorrelation between these regions, which seems fundamental for the preservation of motor skills. Given that nuisance factors were controlled for in the study, it is unlikely that the main results are biased by lefthanders, medication load, seed volumes, or differences in movements during MRI scanning. If these findings are confirmed, new targeted non-invasive interventions, such as repetitive transcranial magnetic stimulation, may be more effective against psychomotor deficits in bipolar depression, when aimed at modulating the supplementary motor area.