Computerized Cognitive Training for Amelioration of Cognitive Late Effects Among Childhood Cancer Survivors: A Randomized Controlled Trial

Heather M Conklin, Robert J Ogg, Jason M Ashford, Matthew A Scoggins, Ping Zou, Kellie N Clark, Karen Martin-Elbahesh, Kristina K Hardy, Thomas E Merchant, Sima Jeha, Lu Huang, Hui Zhang, Heather M Conklin, Robert J Ogg, Jason M Ashford, Matthew A Scoggins, Ping Zou, Kellie N Clark, Karen Martin-Elbahesh, Kristina K Hardy, Thomas E Merchant, Sima Jeha, Lu Huang, Hui Zhang

Abstract

Purpose: Children receiving CNS-directed therapy for cancer are at risk for cognitive problems, with few available empirically supported interventions. Cognitive problems indicate neurodevelopmental disruption that may be modifiable with intervention. This study evaluated short-term efficacy of a computerized cognitive training program and neural correlates of cognitive change.

Patient and methods: A total of 68 survivors of childhood acute lymphoblastic leukemia (ALL) or brain tumor (BT) with identified cognitive deficits were randomly assigned to computerized cognitive intervention (male, n = 18; female, n = 16; ALL, n = 23; BT, n = 11; mean age ± standard deviation, 12.21 ± 2.47 years) or waitlist (male, n = 18; female, n = 16; ALL, n = 24; BT, n = 10; median age ± standard deviation, 11.82 ± 2.42 years). Intervention participants were asked to complete 25 training sessions at home with weekly, telephone-based coaching. Cognitive assessments and functional magnetic resonance imaging scans (intervention group) were completed pre- and postintervention, with immediate change in spatial span backward as the primary outcome.

Results: Survivors completing the intervention (n = 30; 88%) demonstrated greater improvement than controls on measures of working memory (mean ± SEM; eg, Wechsler Intelligence Scale for Children [fourth edition; WISC-IV] spatial span backward, 3.13 ± 0.58 v 0.75 ± 0.43; P = .002; effect size [ES], 0.84), attention (eg, WISC-IV spatial span forward, 3.30 ± 0.71 v 1.25 ± 0.39; P = .01; ES, 0.65), and processing speed (eg, Conners' Continuous Performance Test hit reaction time, -2.10 ± 1.47 v 2.54 ± 1.25; P = .02; ES, .61) and showed greater reductions in reported executive dysfunction (eg, Conners' Parent Rating Scale III, -6.73 ± 1.51 v 0.41 ± 1.53; P = .002; ES, 0.84). Functional magnetic resonance imaging revealed significant pre- to post-training reduction in activation of left lateral prefrontal and bilateral medial frontal areas.

Conclusion: Study findings show computerized cognitive training is feasible and efficacious for childhood cancer survivors, with evidence for training-related neuroplasticity.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2015 by American Society of Clinical Oncology.

Figures

Fig 1.
Fig 1.
CONSORT diagram. WM, working memory. (*) Completed visit one functional magnetic resonance imaging (fMRI; n = 31); one participant supplied partial preintervention fMRI data because of fatigue. (†) Completed visit two fMRI (n = 28).
Fig 2.
Fig 2.
Pre- to post-training cognitive scores. (A) Wechsler Intelligence Scale for Children (fourth edition; WISC-IV) spatial span backward; (B) WISC-IV digit span backward; (C) Conners' Parent Rating Scale III (CPRS-3) executive function; (D) CPRS-3 inattention. (*) P < .05 group × time interaction on repeated-measures analysis of variance.
Fig 3.
Fig 3.
Functional neuroimaging. (A) Preintervention activation during Olesen working memory (WM) task (contrast: WM trials > control trials in random-effects group analysis; t test P < .05 with family wise error [FWE] correction). (B) Neural correlates of WM ability and training. Green denotes areas of decreased activation after WM intervention (contrast: WM trials > control trials in random-effects group analysis; paired t test P < .05 with FWE correction). Yellow denotes areas where activity was positively associated with Wechsler Intelligence Scale for Children–Fourth Edition (WISC-IV) WM index (regression: WM trials > control trials v WM index in random-effects analysis; P < .05 with FWE correction). Purple denotes area where low preintervention activity (contrast: WM trials > control trials) predicted good response to intervention (median split on spatial span backward change; P < .05 with cluster correction). (C) Activity (fixed-effects parameter estimate for each participant) of green left middle frontal gyrus cluster in (B) showing significant groupwise decrease in activation after intervention. (D) Activity of yellow right postcentral gyrus cluster in (B) versus WM index scores. Blue symbols identify patients who responded to intervention (median split on WM index change). SS, standard score (mean = 100, standard deviation = 15). Gold symbols identify nonresponders. (E) Change in spatial span backward score versus preintervention activity for purple right frontal cluster in (B). ScS, scaled score (mean = 10, standard deviation = 3). Dots are colored as in (D).
Fig A1.
Fig A1.
Block-design spatial working memory task designed by Olesen et al. ISI, interstimulus interval.
Fig A2.
Fig A2.
Working memory task (designed by Olesen et al) performance. (A) Trial time versus trial type; (B) accuracy versus load; (C) high-load performance (order).

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