Cognitive Deterioration and Functional Compensation in ALS Measured with fMRI Using an Inhibitory Task

Abstract

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons, resulting in progressive weakness and muscle atrophy. Recent studies suggest that nondemented ALS patients can show selective cognitive impairments, predominantly executive dysfunction, but little is known about the neural basis of these impairments. Oculomotor studies in ALS have described deficits in antisaccade execution, which requires the implementation of a task set that includes inhibition of automatic responses followed by generation of a voluntary action. It has been suggested that the dorsolateral prefrontal cortex (DLPFC) contributes in this process. Thus, we investigated whether deterioration of executive functions in ALS patients, such as the ability to implement flexible behavior during the antisaccade task, is related to DLPFC dysfunction. While undergoing an fMRI scan, 12 ALS patients and 12 age-matched controls performed an antisaccade task with concurrent eye tracking. We hypothesized that DLPFC deficits would appear during the antisaccade preparation stage, when the task set is being established. ALS patients made more antisaccade direction errors and showed significant reductions in DLPFC activation. In contrast, regions, such as supplementary eye fields and frontal eye fields, showed increased activation that was anticorrelated with the number of errors. The ALS group also showed reduced saccadic latencies that correlated with increased activation across the oculomotor saccade system. These findings suggest that ALS results in deficits in the inhibition of automatic responses that are related to impaired DLPFC activation. However, they also suggest that ALS patients undergo functional changes that partially compensate the neurological impairment.

Resting spontaneous activity in the default mode network predicts performance decline during prolonged attention workload

“…This explanation is further supported by the trend for a negative correlation between MFG activation increases and reaction time increases during the sustained attention task, which indicates that subjects with greater brain activation increases in the task-positive network were more resistant to the TOT effects. Increased brain activations from the first to last quintile of the PVT are also consistent with previous studies showing that enhanced brain activation or recruitment of additional neural resources may provide a compensatory mechanism to help people maintain normal cognition (Elman et al, 2014; Witiuk et al, 2014). …”

Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

“…Although cognitively impaired ALS patients are predictably under‐represented in demanding functional neuroimaging tasks, comparatively reduced activation in the dorsolateral prefrontal cortex has been demonstrated [Witiuk et al, 2014], while other frontal regions reveal increased activation during inhibition of prepared manual movements [Mohammadi et al, 2015]. The present finding of abnormal beta power in AGCs during successful inhibition was limited to posterior cortical regions in the context of task‐induced inferior and pre‐frontal activity.…”

Neuroimaging Endpoints in Amyotrophic Lateral Sclerosis

“…In addition to structural abnormalities, fMRI studies have demonstrated increased cortical activity in patients with ALS performing motor tasks [75, 76], as well as aberrations in the BOLD response to cognitive tasks, such as antisaccade [77] or phonemic fluency tasks [78]. A number of fMRI studies investigating differences between patients with ALS and controls at rest have furthermore revealed functional connectivity abnormalities within the sensorimotor network, although some studies reported reduced functional connectivity in ALS [79–81], others increased motor network coherence [71, 82], and others a mixed picture [83, 84].…”