Cerebral blood flow and structural connectivity after working memory or physical training in paediatric cancer survivors – Exploratory findings

Figures & data

Figure 1. Design of the Brainfit study.

Figure 1 shows a schematic representation of the Brainfit study design. The study was initiated with a baseline assessment (T1) where cognitive performance was assessed and MRI scans were conducted. Following the baseline assessment, patients were randomized into either one of the intervention groups (Group A: Cogmed and Group B: Exergame) or the waiting control group (Group C). There were two additional assessments, identical to the baseline, one immediately after an eight-week training or waiting period (T2) and again at a three-month follow-up (T3). The three assessments and the training or waiting period are visually arranged in chronological order from left to right.

Table 1. Demographics, medical characteristics, and training data at baseline (T1).

	Waiting (n = 13) M (SD) Range	Cogmed (n = 10) M (SD) Range	Exergame (n = 11) M (SD) Range	H/χ^2/U	p
Demographic data
Age at T1^a	10.75 (2.38)	10.81 (2.38)	11.62 (2.36)	0.952	.621
	7.28–15.56	7.46–14.85	7.97–14.98
Sex (m/f)	9/4	5/5	5/6	1.565	.457
Handedness (r/l)	12/1	10/0	11/0	1.664	.435
BMI	18.50 (2.19)	19.37 (4.17)	17.74 (2.62)	1.124	.570
	15.75–21.07	14.81–26.22	13.05–21.64
SES	6.69 (1.44)	6.10 (1.20)	6.60 (1.43)	0.960	.619
	5–9	4–8	5–9
Nonverbal IQ	105.54 (10.24)	109.00 (13.92)	107.82 (11.24)	0.914	.633
	91–126	82–126	94–129
Medical data
Age at diagnosis^a	5.68 (3.56)	5.25 (3.64)	5.41 (3.47)	0.057	.972
	1.25–12.74	0.67–11.39	1.60–12.03
Treatment duration^a	1.57 (0.89)	1.55 (0.91)	1.52 (0.81)	0.054	.973
	0.30–3.17	0.33–3.18	0.35–3.01
Time since treatment^a	3.50 (1.67)	4.01 (1.97)	4.68 (1.97)	2.424	.298
	1.13–7.25	1.73–6.68	1.90–7.80
Training data
Time between T1 and T2^b	13.92 (2.06)	13.10 (2.60)	13.09 (1.81)	1.331	.514
	11–17	10–18	10–16
Time between T1 and T3^b	27.42 (3.26)	24.78 (3.87)	26.22 (1.48)	3.223	.200
	22–32	20–30	24–29
Training sessions	n.a.	18.30 (5.46)	18.73 (9.24)	48	.621
		9–25	5–30

Note: BMI = body mass index; SES = socioeconomic status ranging from 1 to 9, with higher scores representing higher SES; M = mean; SD = standard deviation; n = sample size; m/f = male/female; r/l = right/left; U = Mann–Whitney U test; H = Kruskal–Wallis H test; χ² = chi-square test; p = level of statistical significance.

^a Time in years.

^b Time in weeks.

Figure 2. Short- and long-term effects depicted as a series of boxplots (with interquartile range and minimum and maximum value) in (a) CBF within the working memory ROI and (b) structural connectivity (number of tracts [k]) presented for the three groups. The lines connect the mean values. Depending on comparison (T1–T2, T1–T3), sample sizes for cerebral blood flow analyses differed. Waiting control group: n = 8 to 10; Cogmed group: n = 7 to 9; Exergame group: n = 7 to 10; see Table S2. Depending on comparison (T1–T2, T1–T3), sample sizes for structural connectivity analyses differed. Waiting control group: n = 10 to 13; Cogmed group: n = 8 to 10; Exergame group: n = 7 to 10; see Table S3. *p < 0.05.

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Fig. 2 comprises two subfigures depicting a series of boxplots (with interquartile range and minimum and maximum value), (a) showing changes in cerebral blood flow within the working memory (ml/100 g/min) and (b) showing changes in structural connectivity (number of tracts [k]) on the y-axis. Both subfigures present boxplots with individual patient scatterplots for the three distinct groups: the waiting control group, the Cogmed group, and the Exergame group. Further, each boxplot shows a time point on the x-axis (T1: baseline, T2: post-intervention, and T3: follow-up). The boxplots have overlaid lines connecting the mean values at each time point. Notably, in subfigure (a), a significant reduction of cerebral blood flow is depicted post-intervention (T2) compared to the baseline (T1) in the Cogmed group. In subfigure (b), a significant increase in structural connectivity (number of tracts [k]) within the Cogmed group at follow-up (T3) compared to baseline (T1) as well as compared to post-intervention (T2) is illustrated. All significant changes are marked with horizontal lines and asterisks.

Figure 3. (a) Correlation between short-term changes in CBF within the working memory ROI and short-term changes in cognitive flexibility (n = 9) and (b) Correlation between long-term changes in structural connectivity and long-term changes in visuospatial working memory (n = 8). The solid line represents the linear regression fit. The shaded area around the line indicates the 95% confidence interval.

Read the detailed description of this figure

Fig. 3 consists of two subfigures, (a) showing a scatterplot between short-term changes in the cerebral blood flow within the working memory network (ml/100 g/min) on the x-axis and short-term changes in the cognitive flexibility on the y-axis and (b) showing a scatterplot between long-term changes in structural connectivity (median of the connectivity matrix) on the x-axis and long-term changes in the visuospatial working memory on the y-axis. The trend line in subfigure (a) depicts a negative correlation, signifying that a short-term decrease in cerebral blood flow is associated with a short-term increase in cognitive flexibility. The trend line in subfigure (b) indicates a positive correlation, implying that a long-term increase in structural connectivity correlated with a long-term increase in visuospatial working memory. In both subfigures, a solid line represents the linear regression fit. A shaded area around the line indicates the 95% confidence interval.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [RE], upon reasonable request.