Nicole Wenderoth

The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism

Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)—a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7–64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.

Neural Basis of Aging: The Penetration of Cognition into Action Control

Although functional imaging studies have frequently examined age-related changes in neural recruitment during cognitive tasks, much less is known about such changes during motor performance. In the present study, we used functional magnetic resonance imaging to investigate age-related changes in cyclical hand and/or foot movements across different degrees of complexity. Right-handed volunteers (11 young, 10 old) were scanned while performing isolated flexion-extension movements of the right wrist and foot as well as their coordination, according to the “easy” isodirectional and “difficult” nonisodirectional mode. Findings revealed activation of a typical motor network in both age groups, but several additional brain areas were involved in the elderly. Regardless of the performed motor task, the elderly exhibited additional activation in areas involved in sensory processing and integration, such as contralateral anterior insula, frontal operculum, superior temporal gyrus, supramarginal gyrus, secondary somatosensory area, and ipsilateral precuneus. Age-related activation differences during coordination of both segments were additionally observed in areas reflecting increased cognitive monitoring of motor performance, such as the pre-supplementary motor area, pre-dorsal premotor area, rostral cingulate, and prefrontal cortex. In the most complex coordination task, the elderly exhibited additional activation in anterior rostral cingulate and dorsolateral prefrontal cortex, known to be involved in suppression of prepotent response tendencies and inhibitory cognitive control. Overall, these findings are indicative of an age-related shift along the continuum from automatic to more controlled processing of movement. This increased cognitive monitoring of movement refers to enhanced attentional deployment, more pronounced processing of sensory information, and intersensory integration.

Systems Neuroplasticity in the Aging Brain: Recruiting Additional Neural Resources for Successful Motor Performance in Elderly Persons

Functional imaging studies have shown that seniors exhibit more elaborate brain activation than younger controls while performing motor tasks. Here, we investigated whether this age-related overactivation reflects compensation or dedifferentiation mechanisms. “Compensation” refers to additional activation that counteracts age-related decline of brain function and supports successful performance, whereas “dedifferentiation” reflects age-related difficulties in recruiting specialized neural mechanisms and is not relevant to task performance. To test these predictions, performance on a complex interlimb coordination task was correlated with brain activation. Findings revealed that coordination resulted in activation of classical motor coordination regions, but also higher-level sensorimotor regions, and frontal regions in the elderly. Interestingly, a positive correlation between activation level in these latter regions and motor performance was observed in the elderly. This performance enhancing additional recruitment is consistent with the compensation hypothesis and characterizes neuroplasticity at the systems level in the aging brain.

Internal vs external generation of movements: differential neural pathways involved in bimanual coordination performed in the presence or absence of augmented visual feedback.

It is commonly agreed that a functional dissociation with respect to the internal vs external control of movements exists for several brain regions. This has, however, only been tested in relation to the timing and preparation of motor responses, but not to ongoing movement control. Using functional magnetic resonance imaging (fMRI), the present study addressed the neuroanatomical substrate of the internal-external control hypothesis by comparing regional brain activation for cyclical bimanual movements performed in the presence or absence of augmented visual feedback. Subjects performed a bimanual movement pattern, either with the help of on-line visual feedback of the movements (externally guided coordination) or with the eyes closed on the basis of an internal representation of the movement pattern (internally generated coordination). Visual control and baseline rest conditions were also added. Results showed a clear functional dissociation within the network involved in movement coordination. The hMT/V5+, the superior parietal cortex, the premotor cortex, the thalamus, and cerebellar lobule VI showed higher activation levels when movements were guided by visual feedback. Conversely, the basal ganglia, the supplementary motor area, cingulate motor cortex, the inferior parietal, frontal operculum, and cerebellar lobule IV-V/dentate nucleus showed higher involvement when movements were internally generated. Consequently, the present findings suggest the existence of distinct cortico-cortical and subcortico-cortical neural pathways for externally (augmented feedback) and internally guided cyclical bimanual movements. This provides a neurophysiological account for the beneficial effect of providing augmented visual feedback to optimize movements in normal and motor disordered patients.

Proprioceptive sensibility in the elderly: Degeneration, functional consequences and plastic-adaptive processes

As the percentage of individuals over the age of 60 years continues to rise, determining the extent and functional significance of age-related declines in sensorimotor performance is of increasing importance. This review examines the specific contribution of proprioceptive feedback to sensorimotor performance in older adults. First, a global perspective of proprioceptive acuity is provided assimilating information from studies where only one of several aspects of proprioceptive function (e.g. sense of position, motion or dynamic position) was quantified, and/or a single joint or limb segment tested. Second, the consequences of proprioceptive deficits are established with particular emphasis placed on postural control. Lastly, the potential for plastic changes in the aging proprioceptive system is highlighted, including studies which relate physical activity to enhanced proprioceptive abilities in older adults. Overall, this review provides a foundation for future studies regarding the proprioceptive feedback abilities of elderly individuals. Such studies may lead to greater advances in the treatment and prevention of the sensorimotor deficits typically associated with the aging process.

A technical guide to tDCS, and related non-invasive brain stimulation tools.

Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain.

Changes in brain activation during the acquisition of a new bimanual coordination task

Motor skill acquisition is associated with the development of automaticity and induces neuroplastic changes in the brain. Using functional magnetic resonance imaging (fMRI), the present study traced learning-related activation changes during the acquisition of a new complex bimanual skill, requiring a difficult spatio-temporal relationship between the limbs, i.e., cyclical flexion-extension movements of both hands with a phase offset of 90 degrees. Subjects were scanned during initial learning and after the coordination pattern was established. Kinematics of the movements were accurately registered and showed that the new skill was acquired well. Learning-related decreases in activation were found in right dorsolateral prefrontal cortex (DLPFC), right premotor, bilateral superior parietal cortex, and left cerebellar lobule VI. Conversely, learning-related increases in activation were observed in bilateral primary motor cortex, bilateral superior temporal gyrus, bilateral cingulate motor cortex (CMC), left premotor cortex, cerebellar dentate nuclei/lobule III/IV/Crus I, putamen/globus pallidus and thalamus. Accordingly, bimanual skill learning was associated with a shift in activation among cortico-subcortical regions, providing further evidence for the existence of differential cortico-subcortical circuits preferentially involved during the early and advanced stages of learning. The observed activation changes account for the transition from highly attention-demanding task performance, involving processing of sensory information and corrective action planning, to automatic performance based on memory representations and forward control.

Changes in brain activation during the acquisition of a multifrequency bimanual coordination task: from the cognitive stage to advanced levels of automaticity.

Little is known about activation changes reflecting overlearning, i.e., extensive motor training beyond asymptotic performance. Here we used functional magnetic resonance imaging to trace the neural shifts from an initial to a skilled (learning) and finally overlearned stage (automatization). Scanning occurred before training (PRE) and after 1 (MID) and 2 weeks (POST) of intensive practice on a new bimanual coordination task (>10,500 cycles). Kinematics revealed major improvements between PRE and MID sessions, whereas MID to POST session performance leveled off, indicative of learning and automatization, respectively. Imaging findings showed that activation decreased in bilateral opercular areas, bilateral ventrolateral prefrontal cortex, the right ventral premotor and supramarginal gyrus, and the anterior cingulate sulcus during the learning stage and in the supplementary motor area during the automatization stage. These changes are hypothesized to reflect decreases in attention-demanding sensory processing, as well as suppression of preferred coordination tendencies as a prelude to acquiring new coordination modes. Conversely, learning-related increases were observed in the primary motor cortex (M1), posterior cingulate zone (PCZ), putamen, and right anterior cerebellum. Importantly, both M1 and PCZ activation decreased again to initial level (PRE) during automated performance (POST). Only the putamen and anterior cerebellum remained more activated across both learning and automatization stages, supporting their crucial role in long-term motor memory formation for coordination tasks.

The role of anterior cingulate cortex and precuneus in the coordination of motor behaviour

Behavioral studies in humans have shown that bimanual coordination imposes specific demands on the central nervous system that exceed unimanual task control. In the present study we used functional magnetic resonance imaging to investigate the neural correlate of this additional coordination effort, i.e. regions responding more strongly to bimanual movements than inferred from summing up the responses to the unimanual subtasks. Subjects were scanned while performing movements along different directions, either uni‐ or bimanually. During the bimanual condition, trajectories of movement of the left and right hand were spatially incompatible, such that additional effort was required to break away from intrinsically favored mirror‐movements and to integrate movements of both limbs into a new spatial pattern. Our main finding was that the execution of spatially complex bimanual coordination as compared with the unimanual subtasks activated the anterior cingulate cortex (posterior part) as well as the dorso‐anterior precuneus. We hypothesize that the anterior cingulate exerts its modulatory effect on other motor areas, such as the primary motor cortex and the supplementary motor area, in order to suppress intrinsically favored coordination tendencies. Conversely, the precuneus is likely to be involved in shifting attention between different locations in space, which was necessary for monitoring the trajectories of the left and right wrist when both limbs moved in parallel. Our findings suggest that the coordination effort during bimanual and perhaps other modes of coordinated behavior is mediated by regions contributing to higher order functions, which form an interface between cognition and action.

Cerebellar and premotor function in bimanual coordination: parametric neural responses to spatiotemporal complexity and cycling frequency.

In the present functional magnetic resonance imaging (fMRI) study, we assessed the neural network governing bimanual coordination during manipulations of spatiotemporal complexity and cycling frequency. A parametric analysis was applied to determine the effects of each of both factors as well as their interaction. Subjects performed four different cyclical movement tasks of increasing spatiotemporal complexity (i.e., unimanual left-right hand movements, bimanual in-phase movements, bimanual anti-phase movements, and bimanual 90 degrees out-of-phase movements) across four frequency levels (0.9, 1.2, 1.5, and 1.8 Hz). Results showed that, within the network involved in bimanual coordination, functional subcircuits could be distinguished: Activation in the supplementary motor area, superior parietal cortex (SPS), and thalamic VPL Nc was mainly correlated with increasing spatiotemporal complexity of the limb movements, suggesting that these areas are involved in higher-order movement control. By contrast, activation within the primary motor cortex, cingulate motor cortex (CMC), globus pallidus, and thalamic VLo Nc correlated mainly with movement frequency, indicating that these areas play an important role during movement execution. Interestingly, the cerebellum and the dorsal premotor cortex were identified as the principal regions responding to manipulation of both parameters and exhibiting clear interaction effects. Therefore, it is concluded that both areas represent critical sites for the control of bimanual coordination.