Large-scale Brain Organization During Cognitive Control in ADHD

Assessment of how changes in brain network topology relate to improvements in behavioral performance on the GNG regular and reward tasks, in which subjects respond to go stimuli and withhold responses to no-go stimuli. GNG tasks are identical, except subjects are rewarded for good performance on the reward task. Brain measures include change in modularity during rest, GNG regular, and GNG reward (Outcome Measures 1, 2); behavioral measures include change in commission rate, omission rate, and coefficient of variation of response time during GNG tasks (Outcome Measures 5-7). Pearson correlations are used to relate change in brain measures with change in behavioral measures from the placebo to the methylphenidate scans. Positive correlations indicate that subjects with greater change in the brain measure had greater change in the behavioral measure. Negative correlations indicate that subjects with less change in the brain measure had greater change in the behavioral measure.

Time frame: 1 to 3 hours after administration of intervention

Population: Participants excluded due to excessive head motion (mean framewise displacement \[FD\] \> 0.5 mm or fewer than 150 timepoints remaining after scrubbing all timepoints with FD \> 0.2 mm), incomplete brain coverage, or poor-quality fMRI data. Participants excluded if incomplete behavioral GNG data. Must have good data from both scan days to be included.

Assessment of network topology during a resting state using functional connectivity estimates. Modularity will be determined by applying graph theoretical methods to functional connectivity estimates acquired during functional magnetic resonance imaging (fMRI) scans. Modularity is measured on a -1 to 1 scale, with higher scores indicating stronger community structure, or a stronger tendency of clusters of brain regions to separate into distinct, highly interconnected networks with sparse connections across networks. The optimal modularity value depends on the context. For example, during complex tasks lower modularity is better, while during basic, automatic tasks higher modularity is better.

Time frame: 1 to 3 hours after administration of intervention

Population: Participants excluded due to excessive head motion (mean framewise displacement (FD) \> 0.5mm or fewer than 150 timepoints remaining after scrubbing all timepoints with FD \> 0.2mm), incomplete brain coverage, or poor-quality fMRI data. Participants must have good data from both methylphenidate and placebo scan days to be included in this analysis.

Assessment of reconfiguration of network topology between the GNG regular task and the resting state and GNG reward task and resting state. In the GNG tasks, subjects see a series of sports balls and are told to respond to most of the balls (go trials), but not to some specific balls (no-go trials). GNG tasks are identical, except in the rewarded task, correct fast go responses and correct withholding on no-go trials are rewarded with 1 cent and 5 cents respectively. Normalized mutual information will be determined by applying the same graph theoretical methods to functional connectivity estimates acquired during fMRI scans for each rest-task pair. Normalized mutual information is measured on a 0 to 1 scale, with higher scores indicating more similarity in network structure across task and rest conditions.

Time frame: 1 to 3 hours after administration of intervention

Population: Participants excluded due to excessive head motion (mean framewise displacement \[FD\] \> 0.5mm or fewer than 150 timepoints remaining after scrubbing all timepoints with FD \> 0.2mm), incomplete brain coverage, or poor-quality fMRI data. Participants must have good data from both scan days and all tasks being compared to be included in this analysis.

Assessment of network topology during the Go/No-go (GNG) regular and GNG reward tasks. Subjects see a series of sports balls and are told to respond to most balls (go trials), but not to some specific balls (no-go trials). GNG tasks are identical, except in the rewarded task, correct fast go responses and correct withholding on no-go trials are rewarded with 1 cent and 5 cents respectively. Graph theoretical methods are applied to functional connectivity estimates from fMRI scans to determine modularity during each task. Modularity (-1 to 1 scale) measures the degree to which the whole-brain system separates into distinct communities, such that greater modularity reflects stronger community structure, or stronger tendency of brain regions to separate into distinct, highly interconnected networks with few connections across networks. Optimal modularity value depends on context. During complex tasks lower modularity is better, while higher modularity is better for basic tasks.

Time frame: 1 to 3 hours after administration of intervention

Population: Participants excluded due to excessive head motion (mean framewise displacement \[FD\] \> 0.5mm or fewer than 150 timepoints remaining after scrubbing all timepoints with FD \> 0.2mm), incomplete brain coverage, or poor-quality fMRI data. Participants must have good data from both methylphenidate and placebo scan days to be included in this analysis.

Evaluation of commission errors assessed during the GNG regular and GNG reward tasks. In the GNG tasks, subjects see a series of sports balls and are told to respond to most of the balls (go trials), but not to some specific balls (no-go trials). GNG tasks are identical, except in the rewarded task, correct fast go responses and correct withholding on no-go trials are rewarded with 1 cent and 5 cents respectively. In both tasks, commission errors occur on trials on which participants respond to a stimulus (go response) when they are supposed to withhold a response (no-go trial). Commission errors are scored from 0 (no commission errors) to 1 (100% commission errors), with lower values indicating better performance.

Time frame: 1 to 3 hours after administration of intervention

Population: Participants must have good data from both methylphenidate and placebo scan days to be included in this analysis. Participants included if they completed at least one task.

Evaluation of omission errors assessed during the GNG regular and GNG reward tasks. In the GNG tasks, subjects see a series of sports balls and are told to respond to most of the balls (go trials), but not to some specific balls (no-go trials). GNG tasks are identical, except in the rewarded task, correct fast go responses and correct withholding on no-go trials are rewarded with 1 cent and 5 cents respectively. In both tasks, omission errors occur on trials on which participants do not respond to a go stimulus to which they are supposed to respond. Omission errors are scored from 0 (no omission errors) to 1 (100% omission errors), with lower values indicating better performance.

Time frame: 1 to 3 hours after administration of intervention

Population: Participants must have good data from both methylphenidate and placebo scan days to be included in this analysis. Participants included if they completed at least one task.

Evaluation of response time variability assessed during the GNG regular and GNG reward tasks. In the GNG tasks, subjects see a series of sports balls and are told to respond to most of the balls (go trials), but not to some specific balls (no-go trials). GNG tasks are identical, except in the rewarded task, correct fast go responses and correct withholding on no-go trials are rewarded with 1 cent and 5 cents respectively. Coefficient of variation (standard deviation / mean) will be calculated for response time in GNG regular and GNG reward tasks separately to account for group differences in mean response time.

Time frame: 1 to 3 hours after administration of intervention

Population: Participants must have good data from both methylphenidate and placebo scan days to be included in this analysis. Participants included if they completed at least one task.