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Is motor response inhibition supported by a specialised neuronal inhibitory control mechanism, or by a more general system of action updating? This pre-registered study employed a context-cueing paradigm requiring both inhibitory and non-inhibitory action updating in combination with functional magnetic resonance imaging to test the specificity of responses under different updating conditions, including the cancellation of actions. Cortical regions of activity were found to be common to multiple forms of action updating. However, functional specificity during response inhibition was observed in the anterior right inferior frontal gyrus. In addition, fronto-subcortical activity was explored using a novel contrast method. These exploratory results indicate that the specificity for response inhibition observed in right prefrontal cortex continued downstream and was observed in right hemisphere subcortical activity, while left hemisphere activity was associated with right-hand response execution. Overall, our findings reveal both common and distinct correlates of response inhibition in prefrontal cortex, with exploratory analyses supporting putative models of subcortical pathways and extending them through the demonstration of lateralisation., Highlights • Anterior specificity in cortical activity to response inhibition was identified. • Methodological development of a compound contrast methodology optimising data usage. • Exploratory demonstration of lateralised subcortical action control pathways.

Understanding brain reserve in preclinical stages of neurodegenerative disorders allows determination of which brain regions contribute to normal functioning despite accelerated neuronal loss. Besides the recruitment of additional regions, a reorganisation and shift of relevance between normally engaged regions are a suggested key mechanism. Thus, network analysis methods seem critical for investigation of changes in directed causal interactions between such candidate brain regions. To identify core compensatory regions, fifteen preclinical patients carrying the genetic mutation leading to Huntington's disease and twelve controls underwent fMRI scanning. They accomplished an auditory paced finger sequence tapping task, which challenged cognitive as well as executive aspects of motor functioning by varying speed and complexity of movements. To investigate causal interactions among brain regions a single Dynamic Causal Model (DCM) was constructed and fitted to the data from each subject. The DCM parameters were analysed using statistical methods to assess group differences in connectivity, and the relationship between connectivity patterns and predicted years to clinical onset was assessed in gene carriers. In preclinical patients, we found indications for neural reserve mechanisms predominantly driven by bilateral dorsal premotor cortex, which increasingly activated superior parietal cortices the closer individuals were to estimated clinical onset. This compensatory mechanism was restricted to complex movements characterised by high cognitive demand. Additionally, we identified task-induced connectivity changes in both groups of subjects towards pre- and caudal supplementary motor areas, which were linked to either faster or more complex task conditions. Interestingly, coupling of dorsal premotor cortex and supplementary motor area was more negative in controls compared to gene mutation carriers. Furthermore, changes in the connectivity pattern of gene carriers allowed prediction of the years to estimated disease onset in individuals. Our study characterises the connectivity pattern of core cortical regions maintaining motor function in relation to varying task demand. We identified connections of bilateral dorsal premotor cortex as critical for compensation as well as task-dependent recruitment of pre- and caudal supplementary motor area. The latter finding nicely mirrors a previously published general linear model-based analysis of the same data. Such knowledge about disease specific inter-regional effective connectivity may help identify foci for interventions based on transcranial magnetic stimulation designed to stimulate functioning and also to predict their impact on other regions in motor-associated networks., Highlights • Connectivity of a motor network is altered in preclinical neurodegeneration. • Dynamic Causal Modelling reveals task-dependent recruitment of pre- and caudal SMA. • Connectivity of the dorsal premotor cortex reveals compensatory mechanisms. • DCM allows prediction of years to clinical onset in preclinical patients.

The purpose of the present study was to detail the childhood developmental course of different white matter (WM) characteristics. In a longitudinal diffusion tensor imaging (DTI) study of 159 healthy children between 4 and 11 years scanned twice, we used tract-based spatial statistics as well as delineation of 15 major WM tracts to characterize the regional pattern of change in fractional anisotropy (FA), mean (MD), radial (RD) and axial diffusivity (AD). We tested whether there were decelerations of change with increasing age globally and tract-wise, and also illustrated change along medial-to-lateral, posterior-to-anterior and inferior-to-superior gradients. We found a significant linear increase in global FA, and decrease in MD and RD over time. For mean AD, a weak decrease was observed. The developmental changes in specific WM tracts showed regional differences. Eight WM tracts showed non-linear development patterns for one or several DTI metrics, with a deceleration in change with age. Sex did not affect change in any DTI metric. Overall, greater rate of change was found in the left hemisphere. Spatially, there was a posterior-to-anterior gradient of change with greater change in frontal regions for all metrics. The current study provides a comprehensive characterization of the regional patters of change in WM microstructure across pre-adolescence childhood., Highlights • We explore longitudinal change in white matter (WM) microstructure in children. • Using TBSS to delineate 15 WM tracts and several gradients in the brain • Global WM change show linear developmental patterns from age 4 to 11 years. • Greater WM change in the anterior compared to the posterior brain region. • The developmental patterns for WM tracts show regional differences.