Mismatch Negativity as an Indicator of Cognitive Sub-Domain Dysfunction in Amyotrophic Lateral Sclerosis

作者：Iyer Parameswaran Mahadeva^*; Mohr Kieran; Broderick Michael; Gavin Brighid; Burke Tom; Bede Peter; Pinto Grau Marta; Pender Niall P; McLaughlin Russell; Vajda Alice; Heverin Mark; Lalor Edmund C; Hardiman Orla; Nasseroleslami Bahman

来源：Frontiers in Neurology, 2017, 8: 395.

DOI：10.3389/fneur.2017.00395

• amyotrophic lateral sclerosis
• auditory mismatch negativity
• neuronal networks
• EEG
• cognition
• phenotyping

Objective: To evaluate the utility of mismatch negativity (MMN), a neurophysiologic marker of non-motor cognitive processing, in amyotrophic lateral sclerosis (ALS).
Methods: 89 patients, stratified into 4 different phenotypic presentations of ALS (67 spinal-onset, 15 bulbar-onset, 7 ALS-FTD, 7 C9ORF72 gene careers), and 19 matched controls underwent 128-channel EEG data recording. Subjects were presented with standard auditory tones interleaved with pitch-deviant tones in three recording blocks. The MMN response was quantified by peak amplitude, peak delay, average amplitude, and average delay, 100-300 ms after stimuli. 64 patients underwent cognitive screening using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), and 38 participants underwent contemporaneous cognitive assessment using the Stroop Color-Word Interference test (CWIT), which measures attention shift, inhibitory control, and error monitoring.
Results: The MMN response was observed in frontal and frontocentral regions of patient and control groups. Compared to controls, waveforms were attenuated in early onset, and the average delay was significantly increased in all of the ALS subgroups, with no significant difference between subgroups. Comparing with the control response, the ALS MMN response clustered into four new subgroups characterized by differences in response latency. The increased average delay correlated with changes in the Stroop CWIT; however, it did not show a direct relationship with age, gender, traditional phenotypes, revised ALS Functional Rating Scale, or ECAS scores.
Conclusion and significance: The MMN response in ALS patients reflects the cognitive dysfunction in specific sub-domains, as the new patient subgroups, identified by cluster analysis, do not segregate with existing clinical or cognitive classifications. Event-related potentials can provide additional quantitative neurophysiologic measures of impairment in specific cognitive sub-domains from which it may be possible to generate novel biologically relevant subgroups of ALS.

• 出版日期2017-8-15