Working memory in ALS patients: preserved performance but marked changes in underlying neuronal networks

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease which affects the motor system but also other frontal brain regions. In this study we investigated changes in functional neuronal networks including posterior brain regions that are not directly affected by the neurodegenerative process. To this end, we analyzed the contralateral delay activity (CDA), an ERP component considered an online marker of memory storage in posterior cortex, while 23 ALS patients and their controls performed a delayed-matching-to-sample working memory (WM) task. The task required encoding of stimuli in the cued hemifield whilst ignoring stimuli in the other hemifield. Despite their unimpaired behavioral performance patients displayed several changes in the neuronal markers of the memory processes. Their CDA amplitude was smaller; it showed less load-dependent modulation and lacked the reduction observed when controls performed the same task three months later. The smaller CDA in the patients could be attributed to more ipsilateral cortical activity which may indicate that ALS patients unnecessarily processed the irrelevant stimuli as well. The latter is presumably related to deterioration of the frontal cortex in the patient group which was indicated by slight deficits in tests of their executive functions that increased over time. The frontal pathology presumably affected their top-down control of memory storage in remote regions in the posterior brain. In sum, the present results demonstrate functional changes in neuronal networks, i.e. neuroplasticity, in ALS that go well beyond the known structural changes. They also show that at least in WM tasks, in which strategic top-down control demands are relatively low, the frontal deficit can be compensated for by intact low level processes in posterior brain regions.