Cognitive network hyperactivation and motor cortex decline correlate with ALS prognosis

• Published in: Neurobiology of aging 2021-08, Vol.104, p.57-70
• Main Authors: McMackin, Roisin, Dukic, Stefan, Costello, Emmet, Pinto-Grau, Marta, McManus, Lara, Broderick, Michael, Chipika, Rangariroyashe, Iyer, Parameswaran M, Heverin, Mark, Bede, Peter, Muthuraman, Muthuraman, Pender, Niall, Hardiman, Orla, Nasseroleslami, Bahman
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - physiopathology; Amyotrophic Lateral Sclerosis - psychology; Attention; Cognition; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - physiopathology; Cognitive Dysfunction - psychology; Cross-Sectional Studies; Electroencephalography; Electroencephalography - methods; Female; Humans; Hyperexcitability; Longitudinal; Male; Middle Aged; Motor Cortex - physiopathology; Network; Prefrontal Cortex - physiopathology; Prognosis; Temporal Lobe - physiopathology
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2021.03.002

•Early dorsolateral prefrontal and motor hyperactivity decline to inactivity in ALS.•Inferior frontal and superior temporal cortices become hyperactive over time in ALS.•Early and longitudinal EEG measures predict motor and cognitive-behavioural decline. We aimed to quantitatively characterize progressive brain network disruption in Amyotrophic Lateral Sclerosis (ALS) during cognition using the mismatch negativity (MMN), an electrophysiological index of attention switching. We measured the MMN using 128-channel EEG longitudinally (2–5 timepoints) in 60 ALS patients and cross-sectionally in 62 healthy controls. Using dipole fitting and linearly constrained minimum variance beamforming we investigated cortical source activity changes over time. In ALS, the inferior frontal gyri (IFG) show significantly lower baseline activity compared to controls. The right IFG and both superior temporal gyri (STG) become progressively hyperactive longitudinally. By contrast, the left motor and dorsolateral prefrontal cortices are initially hyperactive, declining progressively. Baseline motor hyperactivity correlates with cognitive disinhibition, and lower baseline IFG activities correlate with motor decline rate, while left dorsolateral prefrontal activity predicted cognitive and behavioural impairment. Shorter survival correlates with reduced baseline IFG and STG activity and later STG hyperactivation. Source-resolved EEG facilitates quantitative characterization of symptom-associated and symptom-preceding motor and cognitive-behavioral cortical network decline in ALS.