Neurophysiologic and Cognitive Changes Arising from Cognitive Training Interventions in Persons with Mild Cognitive Impairment: A Systematic Review

Table 3

COT BOLD activations and connectivity.

Study	Design	Sample	Intervention conditions	fMRI protocol cognitive measure	Post-intervention fMRI comparisons	Direction of FMRI	fMRI results after intervention	fMRI and cognitive tasks
Rosen et al. [14]	RCT double-blind	12 MCIs	Auditory processing training Computer-based activities	Auditory verbal task RBANS	COT MCI	Increasing	L hippocampus	L hippocampus activation correlated with changes in memory performance on RBANS ()
					CCI MCI	Decreased	L hippocampus
Belleville et al. [17]	CGT single-blind	15 HC 15 MCI	Mnemonic strategy training	Word list memory encoding and retrieval and word list recall test	ENCODING HC	Decreased	R/L basal ganglia, R/L cingulate gyrus, R inferior frontal gyrus, R inferior and superior parietal cortex, R inferior, medial and superior frontal gyrus, L prefrontal cortex, L precentral gyrus, and R hippocampus	HC performance on immediate word recall was correlated with activation in L inferior frontal gyrus during retrieval ()
					MCI	Increased	L superior temporal gyrus, L thalamus, putamen and globus pallidus, R inferior parietal cortex, R superior frontal gyrus, and R cerebellum
					RETRIEVAL HC	Increased	R middle temporal gyrus, thalamus, R superior temporal gyrus, R putamen, R/L precuneus, L superior temporal gyrus, L inferior frontal gyrus, and R hippocampus
					MCI	Increased	L postcentral gyrus, L inferior parietal lobule, L inferior and supramarginal gyrus, R/L posterior cingulate, R/L superior temporal gyrus, R insula, and L middle frontal gyrus	MCI performance on delayed word recall was correlated with activation in R inferior parietal lobule during encoding ()
					COT MCI post > pre encoding		Cingulate and medial frontal gyri () and R inferior parietal lobule ()
					Retrieval		L middle frontal gyrus () R superior Parietal lobule ()
Hampstead et al. [18]	Case control	6 MCI	Face name associative training	Face name Associative encoding and off-scan recognition task	TS > US	Increased	R/L medial frontal cortex; medial parietal cortex, precuneus, medial occipital cortex, L frontal operculum, L temporoparietal junction, and L temporal cortex
					U S > TS	Increased	L middle occipital gyrus
					U S > RS	Increased	L occipital cortex, L inferior frontal cortex and R/L inferior parietal cortex. The activations on inferior frontal gyrus, inferior frontal sulcus, superior middle occipital gyrus and fusiform area could be related to attempts to generalize the trained strategies
					Connectivity analysis		Effective connectivity on L middle temporal gyrus
Hampstead et al. [20]	RCT single-blind	16 HC 18 MCI	Object location Associative training; Stimuli exposition	Object location associative encoding and retrieval task	ENCODING COT MCI	Increased	L hippocampal body (TS + US)
					RETRIEVAL COT HC	Increased	L hippocampal tail and R hippocampal head (US)
					COT MCI	Increased	R/L hippocampal body and tail (TS)
						Increased	L hippocampal body and tail (US)
					COT HC + CCI MCI	Decreased	R hippocampal body (TS)
					COT MCI > CCI MCI	Increased	L hippocampal body and R hippocampus (TS)
						Increased	R hippocampal body (US)
Balardin et al. [21]	CGT Single Blind	17 MCI 18 HC	Semantic encoding strategy orientation	SR and UR Word Lists memory encoding with off-scan free recall	HC	Increased	L middle frontal gyrus, inferior frontal gyrus, dorsal premotor cortex, posterior parietal cortex, angular gyrus within intraparietal sulcus borders	Performance on encoding the SR list was correlated with activations in orbitofrontal cortex, medial prefrontal cortex, and anterior cingulate HC - higher performance correlated with greater decrease on activations () MCI - higher performance correlated with greater increase on activations ()
						Decreased	R superior frontal gyrus, vmPFC, L inferior Parietal Cortex, infero-lateral Temporal cortex, posterior cingulate and precuneus
					MCI	Increased	L middle frontal gyrus, inferior frontal gyrus, dorsal premotor cortex, posterior parietal cortex, angular gyrus within intraparietal sulcus borders
						Decreased	Parietooccipital cortex
					Changes on activations HC	Decreased	L middle frontal gyrus
						Decreased	R superior frontal gyrus
					MCI	Increased	R superior frontal gyrus
Lin et al. [15]	RCT	21 MCI	Visual	Resting	Connectivity		Improvement
	Single-blind		Speed of processing and attention training; Computer-based activities	State	Analysis COT MCI		of connectivity on CEN ()
					CCI MCI		Trend to poor connectivity strength in DMN ()
					COT MCI > CCI MCI		COT MCI showed increased connectivity in DMN compared to CCI MCI (, )
De Marco et al. [16]	RCT single-blind	23 MCI	Cognitive training Social engagement	Resting state and CCRI	DMN connectivity analysis COT MCI		Increased in DMN connectivity on precuneus - cuneus and increased connectivity on R/L parietal cortices	Connectivity on parietal DMN were associated with the CCRI ()
					CCI MCI		Decreased connectivity in R/L parietal cortices

RCT: randomized controlled trial; CGT: controlled group trial; COT: cognitive oriented treatment; CCI: control condition intervention; MCI: mild cognitive impairment; HC: healthy controls; fMRI: functional magnetic resonance imaging; TS: trained stimulus; US: untrained stimulus; SR: semantic related; UR: unrelated; R: right; L: left; vmPFC: ventromedial prefrontal cortex; r: Pearson correlation coefficient; CCRI: cognitive change ratio index; DMN: default mode network.