A new semantic list learning task to probe functioning of the Papez circuit

Abstract

Introduction: List learning tasks are powerful clinical tools for studying memory, yet have been relatively underutilized within the functional imaging literature. This limits understanding of regions such as the Papez circuit that support memory performance in healthy, nondemented adults.

Method: The current study characterized list learning performance in 40 adults who completed a semantic list learning task (SLLT) with a Brown-Peterson manipulation during functional magnetic resonance imaging (fMRI). Cued recall with semantic cues and recognition memory were assessed after imaging. Internal reliability, convergent, and discriminant validity were evaluated.

Results: Subjects averaged 38% accuracy in recall (62% for recognition), with primacy but no recency effects observed. Validity and reliability were demonstrated by showing that the SLLT was correlated with the California Verbal Learning Test (CVLT), but not with executive functioning tests, and by high intraclass correlation coefficient across lists for recall (.91). fMRI measurements during encoding (vs. silent rehearsal) revealed significant activation in bilateral hippocampus, parahippocampus, and bilateral anterior and posterior cingulate cortex. Post hoc analyses showed increased activation in anterior and middle hippocampus, subgenual cingulate, and mammillary bodies specific to encoding. In addition, increasing age was positively associated with increased activation in a diffuse network, particularly frontal cortex and specific Papez regions for correctly recalled words. Gender differences were specific to left inferior and superior frontal cortex.

Conclusions: This is a clinically relevant list learning task that can be used in studies of groups for which the Papez circuit is damaged or disrupted, in mixed or crossover studies at imaging and clinical sites.

Keywords: Functional magnetic resonance imaging; Hippocampus; Imaging; List learning; Memory; Papez circuit.

Figure 1

Semantic List Learning Task (SLLT) design.

Figure 2

Phases of Memory Recall for the SLLT and CVLT-II. Panel A includes the serial position curve modified by the SLLT with Brown-Peterson adjustment to the curve, removing the recency effect. Panel B includes the immediate recall for the CVLT-II. Panel C shows the correlation between SLLT Primacy Recall and CVLT-II Long Delay Free Recall Z scores.

Figure 3

Encoding-Silent Rehearsal Whole Brain Activation. Activation in orange indicates significant foci of activation in the Encoding-Silent Rehearsal contrast. The areas of greater activation in the Silent Rehearsal block relative to the Encoding block are illustrated in blue. Images are whole brain, AlphaSim corrected at p < 0.05.

Figure 4

Activation analysis of Encoding-Distraction. Activation in orange indicates significant foci of activation in the Encoding-Distraction contrast. The areas of greater activation in the Distraction block relative to the Encoding block are illustrated in blue. Images are whole brain, AlphaSim corrected at p < 0.05.

Figure 5

Activation in Papez Circuit Sub-regions by SLLT Condition. Regions used to extract activation, overlaid onto the MNI template. Signal change to illustrate differences between Encoding and Silent Rehearsal in the Papez circuit regions. Abbreviations: rostral anterior cingulate (RAC), subgenual anterior cingulate (SGAC), mammillary bodies (MB), posterior cingulate (PC), retrosplenial cingulate (RSC), insula (Ins), anterior hippocampus (AH), middle hippocampus (MH), posterior hippocampus (PH).