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Working Memory Network Changes in ALS: An fMRI Study.

Vellage AK, Veit M, Kobeleva X, Petri S, Vielhaber S, Müller NG - Front Neurosci (2016)

Bottom Line: 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.This hyperactivation might reflect a possible compensational mechanism for the prefrontal degeneration found in ALS.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.

View Article: PubMed Central - PubMed

Affiliation: Neuroprotection Group, German Centre of Neurodegenerative DiseasesMagdeburg, Germany; Berlin School of Mind and Brain, Humboldt-UniversityBerlin, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration of the experimental design.
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Figure 1: Schematic illustration of the experimental design.

Mentions: The fMRI experiment (Figure 1) included three conditions with the following demands: high memory storage (high load, HL), low memory storage (low load, LL) and low memory but high filtering (low load + distractors, LLDIS). Participants were instructed to memorize the vertical rectangles only. The HL condition consisted of a memory array with four vertical rectangles, whereas the LL condition consisted of two vertical rectangles only. In the LLDIS condition two vertical rectangles were presented alongside two horizontal rectangles which served as distractors. All stimuli had the same color (red) and were presented within 14 placeholder squares that were arranged in a circle. The memory array was followed by a delay and then by a probe stimulus (gray dot) to which subjects had to decide by button press with the index or middle finger of their right hand whether the probe location had been occupied by a target stimulus in the preceding memory array or not. When the probe stimulus was not in the position of a target, it was either on a position adjacent to the target that was formerly an empty placeholder square or, in case distractors had been presented, with equal probability on a distractor position. The required responses (yes or no) were distributed evenly across all trials. Subjects completed six runs à 60 trials (360 trials in total) with one run lasting 8 min. Conditions were presented in a randomized order.


Working Memory Network Changes in ALS: An fMRI Study.

Vellage AK, Veit M, Kobeleva X, Petri S, Vielhaber S, Müller NG - Front Neurosci (2016)

Schematic illustration of the experimental design.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835479&req=5

Figure 1: Schematic illustration of the experimental design.
Mentions: The fMRI experiment (Figure 1) included three conditions with the following demands: high memory storage (high load, HL), low memory storage (low load, LL) and low memory but high filtering (low load + distractors, LLDIS). Participants were instructed to memorize the vertical rectangles only. The HL condition consisted of a memory array with four vertical rectangles, whereas the LL condition consisted of two vertical rectangles only. In the LLDIS condition two vertical rectangles were presented alongside two horizontal rectangles which served as distractors. All stimuli had the same color (red) and were presented within 14 placeholder squares that were arranged in a circle. The memory array was followed by a delay and then by a probe stimulus (gray dot) to which subjects had to decide by button press with the index or middle finger of their right hand whether the probe location had been occupied by a target stimulus in the preceding memory array or not. When the probe stimulus was not in the position of a target, it was either on a position adjacent to the target that was formerly an empty placeholder square or, in case distractors had been presented, with equal probability on a distractor position. The required responses (yes or no) were distributed evenly across all trials. Subjects completed six runs à 60 trials (360 trials in total) with one run lasting 8 min. Conditions were presented in a randomized order.

Bottom Line: 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.This hyperactivation might reflect a possible compensational mechanism for the prefrontal degeneration found in ALS.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.

View Article: PubMed Central - PubMed

Affiliation: Neuroprotection Group, German Centre of Neurodegenerative DiseasesMagdeburg, Germany; Berlin School of Mind and Brain, Humboldt-UniversityBerlin, Germany.

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.

No MeSH data available.


Related in: MedlinePlus