Learning Impairments Among Survivors of Childhood Cancer

To compare the white matter volume of patients with those of sibling controls using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

Time frame: Enrollment to evaluation of MRI, on average 12.8 months.

Population: Of the 505 patients enrolled, 106 did not have MRI acquired to measure brain volume, 16 were not evaluable: 6 had metal artifacts, 3 had motion artifacts, 1 had an acquisition error in MRI image, 4 had tumor on exam, and 2 had ischemic insults. 383 patients had evaluable MRI images. 67 of the 91 sibling controls had evaluable MRI images.

To compare the white matter volume of Acute Lymphoblastic Leukemia (ALL) patients with those of patients with malignant brain tumors using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

Time frame: Enrollment to evaluation of MRI, on average 12.8 months.

Population: Of the 505 patients enrolled, 106 did not have MRI acquired to measure brain volume, 16 were not evaluable: 6 had metal artifacts, 3 had motion artifacts, 1 had an acquisition error in MRI image, 4 had tumor on exam, and 2 had ischemic insults. 383 patients had evaluable MRI images.

To compare the white matter volume of patients by treatment intensity groups (mild, moderate, and high) and sibling controls using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

Time frame: Enrollment to evaluation of MRI, on average 12.8 months.

Population: Of the 505 patients enrolled, 106 did not have MRI acquired to measure brain volume, 16 were not evaluable: 6 had metal artifacts, 3 had motion artifacts, 1 had an acquisition error in MRI image, 4 had tumor on exam, and 2 had ischemic insults. 383 patients had evaluable MRI images. 67 of the 91 sibling controls had an evaluable MRI image.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 and 24.36 months.

Time frame: From beginning and at completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the CPRS: ADHD T Score Questionnaire and 68 were screen at completion. 68 patients were analyzed.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

Time frame: From beginning and at completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the CPRS: Cognitive Problem T Score Questionnaire and 68 were screened at completion. 68 patients were analyzed.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-eight questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

Time frame: From beginning and at completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 55 were screened at the beginning of the trial using the CTRS: ADHD T Score Questionnaire and 59 were screened at completion. 47 patients were analyzed.

The Social Skills Rating System- Parent Version (SSRS-P) is a parent rating scale of social behaviors in reference to typically developing children. Thirty eight questions are rated 0 (Never) to 3 (very often). The social skills score is norm-referenced with a mean of 100±15 where a higher score is indicative of better skills. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

Time frame: From beginning and at completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Social Skills Rating System (SSRS-P) and 68 were screened at completion. 68 patients were analyzed.

The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Math Composite score assesses the child's ability to solve calculation problems (Numerical Operations) and solve applied, word problems (Math Reasoning). Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

Time frame: From beginning and after completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Wechsler Individual Achievement Test (WIAT) Math: Composite Standard Score System. 68 were screened at completion. 68 patients were analyzed.

The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Reading Composite consists of Basic Reading (single word reading) and Reading Comprehension. Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

Time frame: From beginning and at completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Wechsler Individual Achievement Test (WIAT) REading: Composite Standard Score questionnaire and 68 were screened at completion. 68 patients were analyzed.

The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Spelling score assesses the child's ability to spell words to dictation. Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

Time frame: From beginning and after completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Wechsler Individual Achievement Test (WIAT) Spelling: Standard Score System and 68 were screened at completion. 68 patients were analyzed.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-eight questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Methylphenidate (MPH) Home Maintenance Phase(baseline) and upon completion of the phase. Phase completion ranged between 11.44 and 24.36 months.

Time frame: From beginning and at completion of Methylphenidate (MPH) Home Maintenance Phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 55 were screened at the beginning of the trial using the CTRS: ADHD T Score Questionnaire and 59 were screen at completion. 47 patients were analyzed.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were done weekly during the 3-week Home Crossover Period with the best response being used as the measurement for the test.

Time frame: weekly during 3-week home crossover phase

Population: There were 122 patients treated in the home crossover period. Some patients had missing treatments and outcome assessments. A crossover design was used for better efficiency of test and better precision of estimation.

The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

Time frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

Time frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

Time frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

Time frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The Conners' Parent Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Time frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The Conners' Parent Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Time frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The Conners' Parent Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Time frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The Conners' Teacher Rating Scale-Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Time frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The Conners' Teacher Rating Scale-Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Time frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The Conners' Teacher Rating Scale-Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Time frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Color Naming Time have a mean of 50 and a standard deviation of 10.

Time frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Ink Color Naming Time have a mean of 50 and a standard deviation of 10.

Time frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Interference Score have a mean of 50 and a standard deviation of 10.

Time frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Word Naming Time have a mean of 50 and a standard deviation of 10.

Time frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the California Verbal Learning Test (CVLT) to estimate the effectiveness of MPH on laboratory measures of learning and recall. CVLT Z Score for Long Delay Free Recall has a mean of 0 and a standard deviation of 1.

Time frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the California Verbal Learning Test (CVLT) to estimate the effectiveness of MPH on laboratory measures of learning and recall. CVLT Z Score for Short Delay Free Recall has a mean of 0 and a standard deviation of 1.

Time frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the California Verbal Learning Test (CVLT) to estimate the effectiveness of MPH on laboratory measures of learning and recall. CVLT Trials 1-5 have a mean T Score of 50 and Standard Deviation of 10.

Time frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. D' and β are derived variables from signal detection theory. β is a measure of response tendency; higher scores indicate a more conservative response pattern. β was calculated using the formula = -d'\*.5\*(NORMSINV(hits)-NORMSINV(false alarms)). In the case where the false alarm rate = 0 or the hit rate = 1.0, we used the standard correction of 1/2N and 1- 1/2N, respectively.

Time frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. Commission errors are the raw score for the numbers of nontargets presented where the subject incorrectly responded. Accordingly, the range for this variable is 0-6 with a higher score indicative of worse performance or impulsivity.

Time frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. D' and β are derived variables from signal detection theory. D' is a measure of sensitivity of a person to the signal or target; a higher score is indicative of better performance or better sustained attention. D' was calculated as z(hit) - z(commission). Z-scores were calculated using the NORMSINV function in Microsoft Excel.

Time frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. Hit reaction time is average reaction time in milliseconds for all correct responses when targets were presented. There is no pre-defined range for reaction time; higher score is indicative of slower processing speed.

Time frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. Omission errors are the raw score for the number of targets presented where the subject did not respond. Accordingly, the range for this variable is 0-54 with a higher score indicative of worse performance or problems with sustained attention.

Time frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.