A game-based neurofeedback training system to enhance cognitive performance in healthy elderly subjects and in patients with amnestic mild cognitive impairment

Figures & data

Figure 1 The experiment protocol, CONSORT flow diagram.

Abbreviations: aMCI, patients with amnestic mild cognitive impairment; CANTAB, Cambridge Neuropsychological Test Automated Battery; CAU, care as usual; HC, healthy controls; NFT, neurofeedback training; ITT, intention-to-treat analysis.

Figure 2 NFT system process flow.

Notes: NFT processing pipeline starts with a four-channel raw EEG signal acquisition, and then artifact removal system provides clean EEG signals before computing power spectrum for each band using FFT. The system examines brain activity changes to determine attention state. Then, subjects can recognize their own cognitive state of attention through games on the display.
Abbreviations: EEG, electroencephalogram; FFT, Fast Fourier Transform; NFT, neurofeedback training.

Figure 3 Neurofeedback intervention sessions.

Notes: (A) NFT intervention session. (B) NFT tutorial session.
Abbreviation: NFT, neurofeedback training.

Figure 4 Neurofeedback games.

Note: (A) Run Run, (B) Sun Shine Day, (C) Cast Away, (D) Paper Plane, and (E) Shoot Shoot.

Figure 5 Exergame games.

Note: (A) Dogsperate, (B) Penguin, (C) Both Hands Draw, (D) Recall Mem, and (E) Math.

Figure 6 Exergame intervention sessions.

Note: (A) Dogsperate and (B) Penguin.

Table 1 Baseline CANTAB measurements in women allocated to three treatment groups

Variables	CAUa	CAU + Exergameb	CAU + NFTc	F	df	P-valued
Age (years)	70.9 (5.1)	73.9 (6.2)	71.7 (6.5)	1.39	2/116	0.576
TMSE	27.9 (1.8)	27.5 (2.1)	27.3 (2.1)	0.69	2/116	0.732
MOCA	23.6 (0.38)	22.8 (4.4)	22.4 (4.3)	0.68	2/116	0.732
Education (years)	11.4 (4.5)	9.4 (6.0)	9.0 (5.7)	1.73	2/116	0.576
SWM_BER	52.8 (11.2)	57.6 (15.1)	58.3 (13.8)	0.74	2/114	0.732
SWM_STR	39.0 (3.5)	39.6 (3.2)	39.3 (3.0)	0.09	2/114	0.916
PRM_COR	84.8 (7.9)	78.5 (13.0)	77.5 (14.2)	1.54	2/114	0.576
DMS_COR	78.1 (9.0)	75.7 (13.2)	75.9 (12.1)	0.11	2/114	0.916
DMS_MdCOR	3,684 (823)	4,131 (1,199)	4,278 (1,430)	1.96	2/114	0.576
DMS_PER	0.193 (0.147)	0.204 (0.186)	0.219 (0.178)	0.41	2/114	0.888
RVP_A′	0.856 (0.611)	0.821 (0.695)	0.837 (0.055)	1.54	2/114	0.576
RVP_MdL	507.6 (137.1)	5522 (142.1)	5,38.3 (157.5)	0.17	2/144	0.916
SSP_SPAN	5.16 (0.62)	4.44 (0.94)	4.88 (1.06)	3.16	2/144	0.576

Notes:

a No intervention group (only CAU).

b CAU + Exergame training intervention group.

c CAU + Neurofeedback cognitive training intervention group.

d P-value corrected for false discovery rate.

Abbreviations: CANTAB, Cambridge Neuropsychological Test Automated Battery; CAU, care as usual; DMS_COR, Delayed Matching to Sample Total Correct; DMS_MdCOR, Delayed Matching to Sample Median Correct Latency (ms); DMS_PER, Matching to Sample Percent Correct; MOCA, Montreal Cognitive Assessment; NFT, neurofeedback training; PRM_COR, Pattern Recognition Memory Number Correct; RVP_A′, Rapid Visual Information Processing A prime; RVP_MdL, Rapid Visual Information Processing Median Correct Latency (ms); SSP_SPAN, Spatial Span Length; SWM_BER, Spatial Working Memory Between Error; SWM_STR, Spatial Working Memory Strategy; TMSE, Thai Mental State Examination.

Table 2 Results of generalized estimating equation analysis, repeated measurements, with the CANTAB tests scores as dependent variables

Variables	Time			Time × treatment			HC vs aMCI
	W	df	P-valuea	W	df	P-valuea	W	df	P-valuea
SWM_BER	0.12	1	0.963	18.68	2	0.002	12.27	1	0.002
SWM_STR	0.34	1	0.963	15.16	2	0.002	11.02	1	0.002
PRM_COR	1.39	1	0.717	1.12	2	0.642	15.61	1	0.002
DMS_COR	0.06	1	0.963	1.15	2	0.642	29.57	1	0.002
DMS_MdCOR	4.14	1	0.189	1.99	2	0.642	3.25	1	0.093
DMS_PER	0.03	1	0.963	0.04	2	0.979	10.75	1	0.004
RVP_A′	4.85	1	0.189	31.66	2	0.002	2.34	1	0.142
RVP_MdL	0.00	1	0.989	1.46	2	0.642	2.07	1	0.150
SSP_SPAN	0.56	1	0.963	16.03	2	0.002	3.28	1	0.093

Notes: This table examines the effects of CAU + neurofeedback vs CAU + exergame vs CAU alone (No active intervention).

a After P-value correction for false discovery rate.

Abbreviations: aMCI, amnestic mild cognitive impairment; CANTAB, Cambridge Neuropsychological Test Automated Battery; CAU, care as usual; DMS_COR, Delayed Matching to Sample Total Correct; DMS_MdCOR, Delayed Matching to Sample Median Correct Latency (ms); DMS_PER, Matching to Sample Percent Correct; HC, healthy controls; PRM_COR, Pattern Recognition Memory Number Correct; RVP_A′, Rapid Visual Information Processing A prime; RVP_MdL, Rapid Visual Information Processing Median Correct Latency (ms); SSP_SPAN, Spatial Span Length; SWM_BER, Spatial Working Memory Between Error; SWM_STR, Spatial Working Memory Strategy; Time, differences in pretreatment vs posttreatment CANTAB scores; Time × Treatment, interaction time × three treatment groups.

Figure 7 The effects of neurofeedback treatment.

Notes: Shown are the results of the CANTAB tests both before (1) and after (2) treatment. Results are shown as mean (SE) values of the z transformations of the CANTAB test scores.
Abbreviations: CANTAB, Cambridge Neuropsychological Test Automated Battery; DMS_COR, Delayed Matching to Sample Total Correct; DMS_MdCOR, Delayed Matching to Sample Median Correct Latency (ms); DMS_PER, Matching to Sample Percent Correct; PRM_COR, Pattern Recognition Memory Number Correct; RVP_A′, Rapid Visual Information Processing A prime; RVP_MdL, Rapid Visual Information Processing Median Correct Latency (ms); SE, standard error; SSP_SPAN, Spatial Span Length; SWM_BER, Spatial Working Memory Between Error; SWM_STR, Spatial Working Memory Strategy.

Table 3 Results of generalized estimating equation analysis, repeated measurements, with the CANTAB tests as dependent variables

CANTAB tests	Time × treatment			NFT vs no-NFT
	W	df	P-valuea	W	df	P-valuea
SWM_BER	15.56	1	0.002	0.61	1	0.435
SWM_STR	9.87	1	0.003	5.59	1	0.036
RVP_A′	28.17	1	0.002	18.08	1	0.004
SSP_SPAN	6.01	1	0.014	0.94	1	0.435

Notes: This table examines the effects of CAU + NFT vs the other two treatments, namely CAU + exergame and CAU alone (no-NFT).

a After P correction for false discovery rate.

Abbreviations: CANTAB, Cambridge Neuropsychological Test Automated Battery; CAU, care as usual; NFT, neurofeedback training; NFT vs No-NFT, differences in cognitive tests scores between subjects treated with NFT versus those not treated with NFT; RVP_A′, Rapid Visual Information Processing A prime; SSP_ SPAN, Spatial Span Length; SWM_BER, Spatial Working Memory Between Error; SWM_STR, Spatial Working Memory Strategy; Time, differences in pretreatment vs posttreatment CANTAB scores.

Figure 8 CANTAB test results in both healthy elderly subjects (0) and patients with aMCI (1).

Note: Results are shown as mean (SE) values of the z transformations of the CANTAB test scores.
Abbreviations: aMCI, amnestic mild cognitive impairment; CANTAB, Cambridge Neuropsychological Test Automated Battery; SE, standard error.