MEG Working Memory N-Back Task Revealed Functional Deficits in Children with Mild Traumatic Brain Injury.

Abstract

Mild traumatic brain injury (mTBI) is a leading cause of sustained cognitive complaints in children. However, the TBI-related mechanisms underlying persistent cognitive symptoms including working memory (WM) dysfunction are not fully understood. Few pediatric studies of WM deficits in mTBI have taken advantage of the temporal and frequency resolution afforded by electromagnetic measurements. Using magnetoencephalography (MEG) and an N-back WM task, we investigated functional abnormalities in children with mTBI within a 3-week post-injury period. Children aged 8-15 years with mTBI (n = 60) and orthopedic injury (OI) controls (n = 37) from consecutive admissions to an emergency department were studied prospectively. MEG source-magnitude images were obtained for alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), theta (4-7 Hz), and delta (1-4 Hz) frequency bands. Compared with OI controls, children with mTBI showed decreased MEG signals (hypoactivity) across frequency bands in the proper WM network including dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex, and supramarginal gyrus (SMG), but over-recruitment with increased MEG signals (hyperactivity) in the frontal pole and ventromedial prefrontal cortex. The MEG activity from dlPFC and SMG regions also correlated with changes in symptom scores between 3-week and 3-month behavioral exams. This is the first pediatric study showing MEG hypoactivity from the WM proper network and over recruitment outside the WM network. One mechanism that may explain these novel findings could be the gamma-aminobutyric acid (GABA)-ergic inhibitory interneuron injury, which may cause disinhibition in the WM neural network, directly eliminating synchronized signals that are normally evoked by stimuli. This MEG study of abnormal MEG responses evoked by WM N-back stimuli provides a new functional imaging marker for pediatric mTBI.