Working Memory Network Changes in ALS: An fMRI Study

Abstract

We used amyotrophic lateral sclerosis (ALS) as a model of prefrontal dysfunction in order to re-assess the potential neuronal substrates of two sub processes of working memory, namely information storage and filtering. To date it is unclear which exact neuronal networks sustain these two processes and the prefrontal cortex was suggested to play a crucial role both for filtering out of irrelevant information and for the storage of relevant information in memory. Other research has attributed information storage to more posterior brain regions, including the parietal cortex and stressed the role of subcortical areas in information filtering. We studied 14 patients suffering from ALS and the same number of healthy controls in an fMRI-task that allowed calculating separate storage and filtering scores. A brain volume analysis confirmed prefrontal atrophy in the patient group. Regarding their performance in the working memory task, we observed a trend toward slightly impaired storage capabilities whereas filtering appeared completely intact. Despite the rather subtle behavioral deficits we observed marked changes in neuronal activity associated with ALS: Compared to healthy controls patients showed significantly reduced hemodynamic responses in the left occipital cortex and right prefrontal cortex in the storage contrast. The filter contrast on the other hand revealed a relative hyperactivation in the superior frontal gyrus of the ALS patients. This hyperactivation might reflect a possible compensational mechanism for the prefrontal degeneration found in ALS. The reduced hemodynamic responses in the storage contrast might reflect a disruption of prefrontal top-down control of posterior brain regions, a process which was especially relevant in the most difficult high load memory task. Taken together, the present study demonstrates marked neurophysiological changes in ALS patients compared to healthy controls during the filtering and storage of information in spite of largely intact behavior. With respect to the neuronal substrates of the two working memory processes under investigation here, the results suggest that it is rather the degree to which top-down control is required for task completion that determines prefrontal cortex involvement than the specific nature of the process, i.e., storage vs. filtering.

Keywords: ALS; fMRI; prefrontal cortex; selective attention; working memory.

Figure 1

Schematic illustration of the experimental design.

Figure 2

Mean difference in accuracy (Δp correct) reflecting storage and filter score. Error bars indicate the standard error of the mean.

Figure 3

Difference in corrected frontal lobe volume between ALS patients and healthy controls.

Figure 4

Task-related changes in BOLD signal during encoding: The color bar indicates the T-value; (A) Control group activation map for the storage contrast (HL > LL); (B) ALS group activation map for the storage contrast (HL > LL); (C) Group activation map for the difference in storage contrast between ALS and control group (red/yellow: Controls > ALS, blue/green: ALS > Controls).

Figure 5

Task-related changes in BOLD signal during encoding: The color bar indicates the T-value; (A) Control group activation map for the filter contrast (LLDIS > LL); (B) ALS group activation map for the filter contrast (LLDIS > LL); (C) Group activation map for the difference in filter contrast between ALS and control group (red/yellow: Controls > ALS, blue/green: ALS > Controls).