We evaluate a fully automatic technique for labeling hippocampal subfields and cortical subregions in the medial temporal lobe (MTL) in in vivo 3 Tesla MRI. The method performs segmentation on a T2-weighted MRI scan with 0.4 × 0.4 × 2.0 mm3 resolution, partial brain coverage, and oblique orientation. Hippocampal subfields, entorhinal cortex, and perirhinal cortex are labeled using a pipeline that combines multi-atlas label fusion and learning-based error correction. In contrast to earlier work on automatic subfield segmentation in T2-weighted MRI (Yushkevich et al., 2010), our approach requires no manual initialization, labels hippocampal subfields over a greater anterior-posterior extent, and labels the perirhinal cortex, which is further subdivided into Brodmann areas 35 and 36. The accuracy of the automatic segmentation relative to manual segmentation is measured using cross-validation in 29 subjects from a study of amnestic Mild Cognitive Impairment (aMCI), and is highest for the dentate gyrus (Dice coefficient is 0.823), CA1 (0.803), perirhinal cortex (0.797) and entorhinal cortex (0.786) labels. A larger cohort of 83 subjects is used to examine the effects of aMCI in the hippocampal region using both subfield volume and regional subfield thickness maps. Most significant differences between aMCI and healthy aging are observed bilaterally in the CA1 subfield and in the left Brodmann area 35. Thickness analysis results are consistent with volumetry, but provide additional regional specificity and suggest non-uniformity in the effects of aMCI on hippocampal subfields and MTL cortical subregions.

Transcranial direct current stimulation (tDCS) has been reported to improve working memory (WM) performance in healthy individuals, suggesting its value as a means of cognitive enhancement. However, recent meta-analyses concluded that tDCS has little or no effect on WM in healthy participants. In this article, we review reasons why these meta-analyses may have underestimated the effect of tDCS on WM and report a more comprehensive and arguably more sensitive meta-analysis. Consistent with our interest in enhancement, we focused on anodal stimulation. Thirty-one articles matched inclusion criteria and were included in four primary meta-analyses assessing the WM effects of anodal stimulation over the left and right dorsolateral pFC (DLPFC) and right parietal lobe as well as left DLPFC stimulation coupled with WM training. These analyses revealed a small but significant effect of left DLPFC stimulation coupled with WM training. Left DLPFC stimulation alone also enhanced WM performance, but the effect was reduced to nonsignificance after correction for publication bias. No other effects were significant, including a variety of tested moderators. Additional meta-analyses were undertaken with study selection criteria based on previous meta-analyses, to reassess the findings from these studies using the analytic methods of this study. These analyses revealed a mix of significant and nonsignificant small effects. We conclude that the primary WM enhancement potential of tDCS probably lies in its use during training. However, recent meta-analyses concluded that tDCS has little or no effect on WM in healthy participants.In this article, we review reasons why these meta-analyses may have underestimated the effect of tDCS on WM and report a more comprehensive and arguably more sensitive metaanalysis. Consistent with our interest in enhancement, we focused on anodal stimulation. Thirty-one articles matched inclusion criteria and were included in four primary meta-analyses assessing the WM effects of anodal stimulation over the left and right dorsolateral pFC (DLPFC) and right parietal lobe as well as left DLPFC stimulation coupled with WM training. These analyses revealed a small but significant effect of left DLPFC stimulation coupled with WM training. Left DLPFC stimulation alone also enhanced WM performance, but the effect was reduced to nonsignificance after correction for publication bias. No other effects were significant, including a variety of tested moderators. Additional meta-analyses were undertaken with study selection criteria based on previous meta-analyses, to reassess the findings from these studies using the analytic methods of this study. These analyses revealed a mix of significant and nonsignificant small effects. We conclude that the primary WM enhancement potential of tDCS probably lies in its use during training. ■

There is great interest in the development of cognitive markers that differentiate “normal” age-associated cognitive change from that of Alzheimer's disease (AD) in its prodromal (i.e., mild cognitive impairment; MCI) or even preclinical stages. Dual process models posit that recognition memory is supported by the dissociable processes of recollection and familiarity. Familiarity-based memory has generally been considered to be spared during normal aging, but it remains controversial whether this type of memory is impaired in early AD. Here, we describe findings of estimates of recollection and familiarity in young adults (YA), cognitively normal older adults (CN), and patients with amnestic-MCI (a-MCI). These measures in the CN and a-MCI patients were then related to a structural imaging biomarker of AD that has previously been demonstrated to be sensitive to preclinical and prodromal AD, the Cortical Signature of AD (ADsig). Consistent with much work in the literature, recollection, but not familiarity, was impaired in CN versus YA. Replicating our prior findings, a-MCI patients displayed impairment in both familiarity and recollection. Finally, the familiarity measure was correlated with the ADsig biomarker across the CN and a-MCI group, as well as within the CN adults alone. No other standard psychometric measure was as highly associated with the ADsig, suggesting that familiarity may be a sensitive biomarker of AD-specific brain changes in preclinical and prodromal AD and that it may offer a qualitatively distinct measure of early AD memory impairment relative to normal age-associated change.

Pathology at preclinical and prodromal stages of Alzheimer's disease (AD) may manifest itself as measurable functional change in neuronal networks earlier than detectable structural change. Functional connectivity as measured using resting-state fMRI (functional Magnetic Resonance Imaging) has emerged as a useful tool for studying disease effects on baseline states of neuronal networks. In this study, we use high resolution MRI to label subregions within the medial temporal lobe (MTL), a site of early pathology in AD, and report an increase in functional connectivity in amnesic MCI (aMCI) between entorhinal cortex and subregions of the MTL, with the strongest effect in the anterior hippocampus. However, our data also replicated the effects of decreased connectivity of the MTL to other nodes of the default mode network reported by other researchers. This dissociation of changes in functional connectivity within the MTL versus the MTL’s connection with other neocortical structures can help enrich the characterization of early stages of disease progression in AD.