Table 2.
Task-based fMRI correlates of episodic memory
| Author, year | Study groups | Episodic memory test | Imaging analysis method | Imaging correlates of episodic memory |
|---|---|---|---|---|
| Preclinical AD | ||||
| Han, et al 2007 [45] | 12 APOE ε4 carrier, 13 noncarrier CNC | Word pair association | Whole brain, ROI (HC)/HC volumetry | Increased R anterior cingulate, lingual, middle temporal, middle frontal gyri, PCG, precuneus and cerebellar tonsil activation in APOE ε4 carriers. |
| Quiroz, et al 2010 [46] | 20 Presenilin 1 mutation carriers, 19 noncarrier CNC | Face-name association | Whole brain, ROI (HC) | Increased right anterior HC activation during encoding in presenilin 1 mutation carriers. |
| Adamson, et al 2011 [47] | 10 APOE ε4 carrier, 11 noncarrier CNC | Spatial encoding | ROI (HC) | Reduced HC activation in APOE ε4 carriers. |
| Erk, et al 2011 [48] | 19 subjective memory impairment, 20 CNC | Face-profession association | ROI (HC, DLPFC) | Reduced right HC activation, increased right DLPFC activation in subjective memory impairment group. |
| Chen, et al 2017 [49] | 35 APOE ε4 carrier, 40 noncarrier CNC | Picture encoding | Seed ROI based on group cortical morphology differences and DMN/cortical thickness | Reduced precuneus deactivation, reduced postcentral, precentral, inferior occipital gyri, inferior parietal lobule activation in APOE ε4 carriers. |
| MCI | ||||
| Johnson, et al 2006 [50] | 14 MCI, 14 CNC | Picture encoding | Reference group activation | Reduced R HC head and body, L lateral frontal, R inferior temporal lobe activation in MCI during novel pictures. Reduced R PCG/precuneus activation during previously learned items in MCI. |
| Petrella, 2006 et al [51] | 20 aMCI, 20 CNC | Face-name association | Whole brain | Reduced frontal cortex, L cerebellum activation during encoding. Reduced frontal lobe, L HC; increased posterior frontal lobe activation during retrieval. |
| Heun, et al 2007 [52] | 21 MCI, 29 CNC | Verbal encoding | Whole brain | Increased R superior, inferior and L middle frontal gyri activation in MCI. |
| Kircher, et al 2007 [53] | 21 MCI, 29 CNC | Verbal encoding | Whole brain | Increased L HC, medial frontal, postcentral and cingulate gyri activation in MCI |
| Dannhauser, et al 2008 [54] | 10 aMCI, 10 CNC | Verbal encoding | Whole brain | Reduced L ventrolateral PFC activation stretching into premotor cortex in aMCI. |
| Trivedi, et al 2008 [55] | 16 aMCI, 23 CNC | Picture encoding | Whole brain, ROI (frontal cortex, MTL, PCG, inferior parietal cortex) | Reduced inferior frontal, R inferior parietal and parahippocampal cortex activation in aMCI during encoding. Reduced L inferior frontal cortex; increased R HC activation in aMCI during recognition. |
| Machulda, et al 2009 [56] | 19 aMCI, 12 naMCI, 29 CNC | Scene encoding | Whole brain | Reduced temporoparietal and frontal activation in MCI during encoding. Reduced temporoparietal activation in aMCI during recognition. |
| Mandzia, et al 2009 [57] | 14 MCI, 14 CNC | Object and animal encoding | ROI (HC and parahippocampal gyrus) | Reduced L superior and middle temporal, R middle temporal gyri, precuneus, L cuneus, anterior cingulate, R lentiform nucleus, caudate and putamen activation during deep encoding. Reduced L parahippocampal, fusiform, R middle temporal gyri, R inferior frontal, inferior parietal regions, caudate, L cerebellum, middle occipital gyrus and cuneus activation during shallow encoding. Reduced L HC, superior and middle frontal, R lateral inferior and medial frontal gyri, cingulate, L thalamus and middle occipital gyrus activation in during deeply encoded item recognition. Reduced L lentiform nucleus and putamen; increased L fusiform and superior frontal, R cingulate gyri activation during shallowly encoded item recognition. |
| Clement and Belleville, 2010 [58] | 28 MCI, 12 CNC | Word pair association | Whole brain, ROI (HC) | Increased R dorsolateral, ventrolateral PFC, premotor and motor area activation MCI with higher cognition scores. Reduced R occipital lobe and L inferior parietal lobule; increased dorsal L inferior parietal lobule activation in MCI with lower cognition scores. Increased L temporal regions, R precentral gyrus, dorsolateral PFC, L inferior and bilateral superior parietal lobules activation in the MCI with higher cognition scores compared with MCI with lower scores. |
| Clement, et al 2010 [59] | 12 MCI, 10 CNC | Verbal encoding | Whole brain, ROI (HC) | Reduced occipital lobe, R middle and superior temporal gyri, R thalamus, R anterior cingulate, R medial frontal lobe; increased L ventrolateral PFC activation during encoding. Reduced medial frontal lobe; increased premotor area activation during retrieval. |
| Yassa, et al 2010 [60] | 10 aMCI, 10 CNC | Picture encoding | ROI (L CA3/DG, CA1, subiculum, entorhinal cortex) | Increased CA3/DG and reduced entorhinal cortex activation. |
| Hampstead, et al 2011 [61] | 18 aMCI, 16 CNC | Object-location association | Whole brain, ROI (HC) | Reduced ventral and dorsal visual streams, frontal areas, dorsal precuneus, HC, perirhinal cortex, PCG, retrosplenial cortex, thalamus; increased mid-precuneus and L temporoparietal junction activation. |
| Hanseeuw, et al 2011 [62] | 16 aMCI, 16 CNC | Verbal encoding | Whole brain/HC volumetry | HC volume positively correlated with associative memory in aMCI. Reduced L anterior HC activation. |
| Lenzi, et al 2011 [83] | 15 aMCI, 14 CNC | Verbal encoding, Story Recall | Whole brain, ROI (HC, L inferior temporal, R superior temporal gyri)/VBM | Increased R superior temporal gyrus activation. This activation negatively correlated with Story Recall. |
| Giovanello, et al 2012 [63] | 12 aMCI, 12 CNC | Word pair association | Whole brain | Reduced R inferior and superior frontal gyri, increased anterior cingulate and inferior frontal gyrus activation. |
| Jin, et al 2012 [64] | 8 aMCI, 8 CNC | Scene encoding, face-occupation and object-location association | Whole brain, ROI (MTL) | Reduced MTL; increased medial PFC, L precentral and superior motor area activation during scene encoding. Increased L angular gyrus, R cuneus/precuneus activation during face-occupation task. Reduced R Rolandic operculum, insula; increased precentral and postcentral gyri activation during the object-location task. |
| ADD | ||||
| Rombouts, et al 2000 [65] | 12 ADD, 10 CNC | Picture encoding | Whole brain | Reduced activation in L HC and bilateral parahippocampal gyrus. |
| Kato, et al 2001 [66] | 7 ADD, 8 young CNC, 8 old CNC | Picture encoding | Whole brain/hippocampal formation and entorhinal cortex volumetry | Reduced R entorhinal cortex, supramarginal gyrus, prefrontal regions, L anterior inferior temporal lobe activation during encoding. Activations in these regions positively correlated with memory in the overall sample. |
| Gron, et al 2002 [67] | 12 ADD, 12 major depressive disorder patients, 12 CNC | Geometric pattern encoding | Whole brain | Reduced parahippocampal gyrus, HC, temporal cortex, R anterior caudate; increased L middle frontal, R inferior frontal gyri and inferior parietal cortex activation. |
| Lustig, et al 2003 [68] | 23 ADD, 32 young CNC, 27 old CNC | Verbal encoding | ROI (lateral parietotemporal, medial frontal, medial parietal/PCG, L frontal region) | Reduced medial parietal/PCG deactivation. |
| Sperling, et al 2003 [69] | 7 ADD, 10 young CNC, 10 old CNC | Face-name association | Whole brain/HC volumetry | Reduced hippocampal formation; increased medial parietal cortex, R PCG, superior frontal cortex activation during encoding. Increased superior frontal cortex activation during recall. |
| Golby, et al 2005 [70] | 7 ADD, 7 CNC | Scene encoding | Whole brain, ROI (hippocampal gyrus, parahippocampal gyrus, entorhinal cortex, subiculum, fusiform gyrus, calcarine cortex) | Reduced MTL, fusiform, lateral occipital activation. |
| Gould, et al 2005 [71] | 12 ADD, 12 CNC | Visuospatial paired association | Whole brain | No differences. |
| Pariente, et al 2005 [72] | 12 ADD, 17 CNC | Face-name association | Whole brain | Increased parietofrontal network activation during encoding. Reduced R HC, increased L parietal lobule and the L inferior frontal gyrus activation during recall. |
| Remy, et al 2005 [73] | 8 ADD, 11 CNC | Verbal encoding | Whole brain/VBM, HC volumetry | Reduced inferior parietal cortex, inferior frontal gyrus, L precentral gyrus, R temporal associative area, L PCG, L perirhinal cortex, and cerebellum; increased medial cerebellum and L middle frontal gyrus activation during encoding. Reduced L inferior frontal and precentral gyri, R lenticular nucleus, R HC and retrosplenial cortex, R inferior parietal cortex, superior temporal gyrus and cerebellum; increased inferior temporal gyrus, L lateral middle and superior frontal gyri activation during recognition. |
| Gould, et al 2006 [74] | 12 ADD, 12 CNC | Visuospatial paired association | Whole brain, ROI (bilateral inferior, middle, superior frontal gyri, medial prefrontal cortex) | Increased L medial and R lateral prefrontal cortex activation during encoding. |
| Pihlajamaki, et al 2008 [75] | 15 ADD, 29 CNC | Face-name association | Whole brain, ROI (HC and medial parietal regions) | Whole brain: Increased middle and inferior prefrontal gyri, L superior parietal lobule, intraparietal sulcus and supramarginal gyrus activation. ROI: Increased L MTL activation. Reduced precuneus, R PCG, L lateral parietal cortex deactivation. |
| Peters, et al 2009 [76] | 16 ADD, 16 CNC | Verbal encoding | Whole brain, ROI (inferior frontal, precentral, middle frontal gyri, insula, posterior parietal, caudate, cerebellum, inferior parietal sulcus, HC, parahippocampus) | Reduced middle frontal, L inferior frontal and transverse temporal gyri, R precuneus activation during encoding. Reduced supplementary motor area, superior frontal, precentral, supramarginal, L postcentral and R middle frontal gyri; increased fusiform gyrus activation during recognition. |
| MCI and ADD | ||||
| Machulda, et al 2003 [77] | 9 MCI, 9 ADD, 11 CNC | Picture encoding | ROI (HC, parahippocampal and fusiform gyri) | Reduced MTL activation in MCI and ADD. |
| Dickerson, et al 2005 [78] | 9 MCI, 10 ADD, 10 CNC | Face-name association | ROI (hippocampal formation, entorhinal cortex)/MTL volumetry | Increased HC activation in MCI. Reduced HC and entorhinal activation in ADD. |
| Celone, et al 2006 [79] | 15 low-CDR MCI, 12 high-CDR MCI, 10 ADD, 15 CNC | Face-name association | Whole brain, ROI (determined by regions contributing significantly to the independent components) | Increased HC and functionally connected neocortical regions activation, increased DMN deactivation in MCI group with low CDR. Reduced HC activation and DMN deactivation in MCI group with high CDR and ADD. |
| Hamalainen, et al 2007 [80] | 14 MCI, 15 ADD, 21 CNC | Picture-name association | Whole brain | Increased thalamus and L ventral visual stream extending to the posterior parahippocampal gyrus and HC activation in MCI. |
| Petrella, et al 2007 [81] | 34 aMCI, 13 ADD, 28 CNC | Face-name association, CVLT | Whole brain | Reduced MTL; increased the posteromedial cortex activation along the spectrum from CNC to ADD. Posteromedial cortex activation magnitude associated with CVLT. |
| Pihlajamaki and Sperling, 2009 [82] | 30 MCI (10 APOE ε4 carriers), 15 ADD (9 APOE ε4 carriers), 29 CNC (8 APOE ε4 carriers) | Face-name association | ROI (PCG, retrosplenial and precuneal regions) | Reduced L precuneus in MCI; bilateral PCG/precuneus deactivation in ADD. Reduced R PCG and bilateral precuneus deactivation in APOE ε4 carrier CNC compared to noncarrier CNC; reduced cuneus deactivation in APOE ε4 carrier ADD compared to noncarrier ADD. |
Abbreviations: APOE ε4, apolipoprotein E ε4; CNC, cognitively normal control; MCI, mild cognitive impairment; aMCI, amnestic mild cognitive impairment; naMCI, nonamnestic mild cognitive impairment; ADD, Alzheimer's disease dementia; CDR, Clinical Dementia Rating; CVLT, California Verbal Learning Test; ROI, region of interest; HC, hippocampus; DLPFC, dorsolateral prefrontal cortex; DMN, default mode network; MTL, medial temporal lobe; PCG, posterior cingulate gyrus; DG, dentate gyrus; L, left; R, right; VBM, voxel-based morphometry; PFC, prefrontal cortex.