Hippocampal Atrophy Confounds Template-Based Functional MR Imaging Measures of Hippocampal Activation in Patients with Mild Cognitive Impairment

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Fig 1.
A, Hippocampal ROI (from WFU PickAtlas^31–33) on the MNI template.¹¹
B, Seventy-five-year-old man with MCI, with hippocampal ROI drawn manually on image.
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Fig 2.
Correlation of right hippocampal activation in a template-space-based ROI with right hippocampal volume in subjects with MCI and control subjects during retrieval. Hippocampal volumes have been normalized by single-section intracranial area and hippocampal activation has been adjusted for subject age. Units of activation are represented as proportion of ROI activated. The line demonstrates a significant negative correlation between hippocampal volume and activation in the subjects with MCI.
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Fig 3.
Correlation of right hippocampal activation in a native-space-based manual ROI with right hippocampal volume in subjects with MCI and control subjects during retrieval. Hippocampal volumes have been normalized by single-section intracranial area and hippocampal activation has been adjusted for subject age. Units of activation are represented as proportion of ROI activated.

Table 1:

Demographic and clinical characteristics

Note:—Values shown are means (SD) unless otherwise noted. CVLT indicates delayed recall score on the California Verbal Learning Test-II; MMSE, Mini Mental State Examination; LHV, left hippocampal volume; RHV, right hippocampal volume; ICA, intracranial area.
* P < .05.

Table 2:

Results from ANCOVA (with P values for independent variables included in the model)

ANCOVA Model	Template-Based Analysis	Native Subject Space with Manual ROI
LH, encoding
Group	.699	.617
Age	.616	.017
LHV/ICA	.428	.490
Group X LHV/ICA	.789	.700
LH, retrieval
Group	.591	.542
Age	.271	.181
LHV/ICA	.496	.619
Group X LHV/ICA	.620	.593
RH, encoding
Group	.909	.724
Age	.148	.070
RHV/ICA	.731	.943
Group X RHV/ICA	.108	.897
RH, retrieval
Group	.030^*	.694
Age	.707	.828
RHV/ICA	.812	.121
Group X RHV/ICA	.020	.712

Note:—Dependent variable is proportion of activated voxels in hippocampal region of interest.
LH indicates left hippocampal activation; LHV/ICA, left hippocampal volume divided by single-section intracranial volume; RH, right hippocampal activation; RHV/ICA, right hippocampal volume divided by single-section intracranial volume; Group X LHV/ICA and Group X RHV/ICA, interaction term between group and hippocampal volume. Significant values of P are indicated in boldface type.
* Group term becomes nonsignificant (P = .314) when the interaction term, Group X RHV/ICA, is removed from the ANCOVA model.