Table 3: COT BOLD activations and connectivity.

StudyDesignSampleIntervention conditionsfMRI protocol cognitive measurePost-intervention fMRI comparisonsDirection of FMRIfMRI results after interventionfMRI and cognitive tasks

Rosen et al. [14]RCT double-blind12 MCIsAuditory processing training Computer-based activitiesAuditory verbal task RBANSCOT MCIIncreasingL hippocampusL hippocampus activation correlated with changes in memory performance on RBANS ()
CCI MCIDecreasedL hippocampus

Belleville et al. [17]CGT single-blind15 HC 15 MCIMnemonic strategy trainingWord list memory encoding and retrieval and word list recall testENCODING HCDecreasedR/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 hippocampusHC performance on immediate word recall was correlated with activation in L inferior frontal gyrus during retrieval ()
MCIIncreasedL superior temporal gyrus, L thalamus, putamen and globus pallidus, R inferior parietal cortex, R superior frontal gyrus, and R cerebellum
RETRIEVAL HCIncreasedR middle temporal gyrus, thalamus, R superior temporal gyrus, R putamen, R/L precuneus, L superior temporal gyrus, L inferior frontal gyrus, and R hippocampus
MCIIncreasedL 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 gyrusMCI performance on delayed word recall was correlated with activation in R inferior parietal lobule during encoding ()
COT MCI post > pre encodingCingulate and medial frontal gyri () and R inferior parietal lobule ()
RetrievalL middle frontal gyrus () R superior Parietal lobule ()

Hampstead et al. [18]Case control6 MCIFace name associative trainingFace name Associative encoding and off-scan recognition taskTS > USIncreasedR/L medial frontal cortex; medial parietal cortex, precuneus, medial occipital cortex, L frontal operculum, L temporoparietal junction, and L temporal cortex
U S > TSIncreasedL middle occipital gyrus
U S > RSIncreasedL 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 analysisEffective connectivity on L middle temporal gyrus

Hampstead et al. [20]RCT single-blind16 HC 18 MCIObject location Associative training
Stimuli exposition
Object location associative encoding and retrieval taskENCODING COT MCIIncreasedL hippocampal body (TS + US)
RETRIEVAL COT HCIncreasedL hippocampal tail and R hippocampal head (US)
COT MCIIncreasedR/L hippocampal body and tail (TS)
IncreasedL hippocampal body and tail (US)
COT HC + CCI MCIDecreasedR hippocampal body (TS)
COT MCI > CCI MCIIncreasedL hippocampal body and R hippocampus (TS)
IncreasedR hippocampal body (US)

Balardin et al. [21]CGT Single Blind17 MCI 18 HCSemantic encoding strategy orientationSR and UR Word Lists memory encoding with off-scan free recallHCIncreasedL middle frontal gyrus, inferior frontal gyrus, dorsal premotor cortex, posterior parietal cortex, angular gyrus within intraparietal sulcus bordersPerformance 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 ()
DecreasedR superior frontal gyrus, vmPFC, L inferior Parietal Cortex, infero-lateral Temporal cortex, posterior cingulate and precuneus
MCIIncreasedL middle frontal gyrus, inferior frontal gyrus, dorsal premotor cortex, posterior parietal cortex, angular gyrus within intraparietal sulcus borders
DecreasedParietooccipital cortex
Changes on activations HCDecreasedL middle frontal gyrus
DecreasedR superior frontal gyrus
MCIIncreasedR superior frontal gyrus

Lin et al. [15]RCT21 MCIVisualRestingConnectivityImprovement
Single-blindSpeed of processing and attention training
Computer-based activities
StateAnalysis COT MCIof connectivity on CEN ()
CCI MCITrend to poor connectivity strength in DMN ()
COT MCI > CCI MCICOT MCI showed increased connectivity in DMN compared to CCI MCI (, )

De Marco et al. [16]RCT single-blind23 MCICognitive training Social engagementResting state and CCRIDMN connectivity analysis COT MCIIncreased in DMN connectivity on precuneus - cuneus and increased connectivity on R/L parietal corticesConnectivity on parietal DMN were associated with the CCRI ()
CCI MCIDecreased 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.