Memory fMRI in left hippocampal sclerosis: optimizing the approach to predicting postsurgical memory

Abstract

Background: An optimal technique for clinical memory fMRI is not established. Previous studies suggest activity in right parahippocampal gyrus and right hippocampus shows the strongest difference between left hippocampal sclerosis (HS) patients and normal control subjects and that the difference in activity between left and right hippocampus predicts postoperative memory change.

Methods: The authors studied 30 patients with mesial temporal lobe epilepsy (mTLE) and left HS, 12 of whom subsequently underwent surgery, and 13 normal control subjects. The patients who had surgery underwent neuropsychometric evaluation pre- and postoperatively. All subjects underwent a verbal memory encoding event-related fMRI study. Activation maps were assessed visually. Subsequently, the brain regions involved in the memory task were revealed by group averaging; these regions were used to determine regions of interest (ROIs) for subsequent analysis. By use of stepwise discriminant function and stepwise multiple regression, the ROIs that optimally discriminated between patients and normal control subjects and that optimally predicted postoperative verbal memory outcome were determined.

Results: Visual inspection of individual patient activation statistic maps revealed noisy data that did not afford visual interpretation. Stepwise discriminant function revealed the difference between left and right hippocampal activity best discriminated between patients and normal control subjects. Stepwise multiple regression revealed left hippocampal activity was the strongest predictor of postoperative verbal memory outcome; greater left hippocampal activity predicted a greater postoperative decline in memory.

Conclusions: Patients with left hippocampal sclerosis (HS) differ from normal control subjects in the distribution of memory-encoding activity between left and right hippocampus. Functional adequacy of left hippocampus best predicts postoperative memory outcome in left HS.

Figure 1

Categorization of hippocampal activity by visual inspection: The upper panel shows the relationship between visually determined hippocampal activity and left hippocampal volume (mm³, corrected for total intracranial volume); the lower panel shows the relationship between these categories and postoperative change in delayed recall of previously learned word lists. The visually determined categories are as follows: strong L (R) = strongly left (right) predominant activity; slight L (R) = slightly predominant activity on the left (right); equal activity on the two sides; no activity evident at p = 0.05. The asterisk shows a significant difference in left hippocampal volume for the strongly left and right lateral ized groups at p = 0.05. n = number of patients in each category.

Figure 2

Group analysis: mesial temporal lobe regions showing significant activation at p <0.005 in the analysis of the whole group. Brain left is on the figure left. (Top left) left hippocampus; (top right) right hippocampus; (bottom left) right amygdale; (bottom right) right para-hippocampal gyrus. Coordinates and Z scores for these regions are given in table 1.

Figure 3

Preoperative measurement of verbal memory-encoding fMRI activity in left and right hippocampal regions of interest correlated with postoperative change in delayed recall of previously learned word lists. Memory-encoding fMRI activity is expressed as effect size in arbitrary units (13 parameters), relative to the mean 13 parameter across the entire image, which was set as 0. A positive 13 parameter is therefore a brain voxel with an effect size for the (R - K) contrast greater than the mean value across the whole brain; a negative 13 parameter is a