a new locus of dysfunction in adult attention-deficit/hyperactivity

73 Moment-to-moment reaction time variability on tasks of attention, often quantified by intra-individual response variability (IRV), provides a good indication of the degree to which an individual is vulnerable to lapses in sustained attention. Increased IRV is a hallmark of several disorders of attention, including Attention-Deficit/Hyperactivity Disorder (ADHD). 76 Here, task-based fMRI was used to provide the first examination of how average brain activation and functional connectivity 77 patterns in adolescents are related to individual differences in sustained attention as measured by IRV. We computed IRV 78 in a large sample of adolescents (n=758) across 'Go' trials of a Stop Signal Task (SST). A data-driven, multi-step analysis 79 approach was used to identify networks associated with low IRV (i.e., good sustained attention) and high IRV (i.e., poorer 80 sustained attention). Low IRV was associated with greater functional segregation (i.e., stronger negative connectivity) 81 amongst an array of brain networks, particularly between cerebellum and motor, cerebellum and prefrontal, and occipital 82 and motor networks. In contrast, high IRV was associated with stronger positive connectivity within the motor network 83 bilaterally and between motor and parietal, prefrontal, and limbic networks. Consistent with these observations, a separate 84 sample of adolescents exhibiting elevated ADHD symptoms had increased fMRI activation and stronger positive 85 connectivity within the same motor network denoting poorer sustained attention, compared to a matched asymptomatic 86 control sample. With respect to the functional connectivity signature of low IRV, there were no statistically significant 87 differences in networks denoting good sustained attention between the ADHD symptom group and asymptomatic control 88 group. We propose that sustained attentional processes are facilitated by an array of neural networks working together, and 89 provide an empirical account of how the functional role of the cerebellum extends to cognition in adolescents. This work highlights the involvement of motor cortex in the integrity of sustained attention, and suggests that atypically strong connectivity within motor networks characterizes poor attentional capacity in both typically developing and ADHD symptomatic adolescents. normative .235, (786)= -3.216, p .001), difference in IRV between the normative sample control group -1.026, p = .305). with IRV for the normative sample ( r = .06, p = .09), the ADHD sample ( r = .24, p = .19), the control group ( r = -.08, p = .66).