The Role of Anatomic Connectivity in Inhibitory Control Revealed by Combining Connectome-based Lesion-symptom Mapping with Event-related Potentials.

Inhibitory control refers to the ability to suppress cognitive or motor processes. Current neurocognitive models indicate that this function mainly involves the anterior cingulate cortex and the inferior frontal cortex. However, how the communication between these areas influence inhibitory control performance and their functional response remains unknown. We addressed this question by injecting behavioral and electrophysiological markers of inhibitory control recorded during a Go/NoGo task as the 'symptoms' in a connectome-based lesion-symptom mapping approach in a sample of 96 first unilateral stroke patients. This approach enables us to identify the white matter tracts whose disruption by the lesions causally influences brain functional activity during inhibitory control. We found a central role of left frontotemporal and frontobasal intrahemispheric connections, as well as of the connections between the left temporoparietal and right temporal areas in inhibitory control performance. We also found that connections between the left temporal and right superior parietal areas modulate the conflict-related N2 event-related potential component and between the left temporal parietal area and right temporal and occipital areas for the inhibition P3 component. Our study supports the role of a distributed bilateral network in inhibitory control and reveals that combining lesion-symptom mapping approaches with functional indices of cognitive processes could shed new light on post-stroke functional reorganization. It may further help to refine the interpretation of classical electrophysiological markers of executive control in stroke patients.

Mental flexibility depends on a largely distributed white matter network: Causal evidence from connectome-based lesion-symptom mapping.

Mental flexibility (MF) refers to the capacity to dynamically switch from one task to another. Current neurocognitive models suggest that since this function requires interactions between multiple remote brain areas, the integrity of the anatomic tracts connecting these brain areas is necessary to maintain performance. We tested this hypothesis by assessing with a connectome-based lesion-symptom mapping approach the effects of white matter lesions on the brain's structural connectome and their association with performance on the trail making test, a neuropsychological test of MF, in a sample of 167 first unilateral stroke patients. We found associations between MF deficits and damage of i) left lateralized fronto-temporo-parietal connections and interhemispheric connections between left temporo-parietal and right parietal areas; ii) left cortico-basal connections; and iii) left cortico-pontine connections. We further identified a relationship between MF and white matter disconnections within cortical areas composing the cognitive control, default mode and attention functional networks. These results for a central role of white matter integrity in MF extend current literature by providing causal evidence for a functional interdependence among the regional cortical and subcortical structures composing the MF network. Our results further emphasize the necessity to consider connectomics in lesion-symptom mapping analyses to establish comprehensive neurocognitive models of high-order cognitive functions.

Aging Modulates Prefrontal Plasticity Induced by Executive Control Training.

While declines in inhibitory control, the capacity to suppress unwanted neurocognitive processes, represent a hallmark of healthy aging, whether this function is susceptible to training-induced plasticity in older populations remains largely unresolved. We addressed this question with a randomized controlled trial investigating the changes in behavior and electrical neuroimaging activity induced by a 3-week adaptive gamified Go/NoGo inhibitory control training (ICT). Performance improvements were accompanied by the development of more impulsive response strategies, but did not generalize to impulsivity traits nor quality of life. As compared with a 2-back working-memory training, the ICT in the older adults resulted in a purely quantitative reduction in the strength of the activity in a medial and ventrolateral prefrontal network over the 400 ms P3 inhibition-related event-related potentials component. However, as compared with young adults, the ICT induced distinct configurational modifications in older adults' 200 ms N2 conflict monitoring medial-frontal functional network. Hence, while older populations show preserved capacities for training-induced plasticity in executive control, aging interacts with the underlying plastic brain mechanisms. Training improves the efficiency of the inhibition process in older adults, but its effects differ from those in young adults at the level of the coping with inhibition demands.

Sexual dimorphism in growth and insulin-like growth factor-I in children with type 1 diabetes mellitus.

OBJECTIVE: Impaired linear growth and reduced IGF-I levels in children with type 1 diabetes (T1DM) have been related to poor metabolic control. The aim of this study was to identify additional factors which may negatively affect growth and IGF system in patients with T1DM. DESIGN: Ninety-one T1DM children (54 males, age=: 11.73±3years, disease duration=5.6±2.1years) were studied. All children were on intensive insulin therapy: 62 children were on multiple injection therapy (MI) and 29 children on continuous subcutaneous insulin infusion (CSII). RESULTS: Height velocity (HV) SDS and IGF-I levels were higher in females and in pubertal children [HV SDS: females=0.6±2.4 vs males=-0.45±2.3 (p=0.04); IGF-I SDS: females=-1.09±0.58 vs males=-1.4±0.6 (p=0.02); IGF-I/IGFBP-3 molar ratio: females=0.25±0.1 vs males=0.21±0.08 (p=0.04); IGF-I SDS: pre-pubertal=-1.58±0.46 vs pubertal=-1.15±0.65 (p<0.001); IGF-I/IGFBP-3 molar ratio: pre-pubertal=0.16±0.08 vs pubertal=0.26±0.09 (p<0.001)]. No differences between children on CSII or MI therapy were found. IGF-I SDS was positively related to C peptide level (p<0.001), puberty (p<0.001) and female gender (p=0.02) and negatively related to HbA1c (p=0.04). IGF-I/IGFBP-3 molar ratio was positively affected by C peptide level (p<0.001), puberty (p<0.001) and daily insulin dose (p<0.001). CONCLUSIONS: Our results indicate that despite intensive insulin therapy, T1DM still negatively affects IGF-I secretion and linear growth. Growth impairment is more severe in males and primarily related to poor glycemic control and loss of the residual beta cell mass.