Authors :
First Author: KLEVEST GJINI, MD, PHD – University of Wisconsin-Madison
Presenting Author: Aaron Struck, MD – University of Wisconsin School of Medicine and Public Health
AARON STRUCK, MD – Neurology – University of Wisconsin-Madison
Rationale:
As part of the Juvenile Myoclonic Epilepsy Connectome Project (JME-CP), this study aims to assess differences in mismatch negativity (MMN) between a group of JME patients (N=50) and a group of healthy controls (N=24). In addition, we investigated potential differences in the elicited responses between two subgroups of JME patients with or without presence of generalized epileptiform discharges (GEDs) in the resting-state EEG data recorded during the same session. Thirdly, we aimed to use dynamic causal modeling (DCM) to estimate effective connectivity between brain regions involved in generation of auditory MMN and test the effect of experimental perturbations on coupling among the involved sources generating the acquired ERP signals.
Methods:
256-channel hdEEG data were recorded with a bandwidth of DC-400 Hz and a sampling rate of 1000 Hz. The auditory roving oddball paradigm consisted in the presentation of a sequence of pure sinusoidal tones belonging to seven frequencies with a roving, or sporadically changing frequency. The oddball was the first tone in a train of a different frequency from preceding train, and the standard stimulus was the sixth tone in the same frequency train. MMN is an event-related potential (ERP) elicited by deviant tones following the presentation of repeated tones. Nonparametric permutation-based statistics were used to compare the MMN amplitudes between the two main groups or patient subgroups. DCM and Parametric Empirical Bayes (PEB) were used to model experimental perturbations in cortical connectivity during the oddball sequence and assess between-group differences.
Results:
Scalp MMN amplitudes were smaller in the JME patients group compared to controls (quantified both as negative potential in the mid-frontocentral sites, as well as positivity in the mastoid location sites). Although no clear difference was seen between the overall regional sensor-level MMN amplitudes in JME patients w/ or w/o GEDs, the spatial location of the maximal MMN response was noticed to be different in the expected mid-frontocentral region.
DCM and PEB analyses revealed group-level differences in cortical connectivity as the result of experimental effects (i.e., differential response to the deviant stimuli in relation to the standard ones): (1) Differences in extrinsic (between regions) and intrinsic (within a region) connectivity between right inferior frontal gyrus (r-IFG) and right superior temporal gyrus (r-STG) for JME patients versus controls, and (2) Differences in extrinsic and intrinsic (within a region) connectivity between the two temporal sources modeled (primary auditory (A1) cortex and STG).
Conclusions:
We found reduced MMN amplitudes in our JME patient cohort with underlying cortical connectivity changes compared to controls. Evaluation of relationships between the obtained differential neurophysiological responses with neuropsychological assessment scores is warranted to further clarify the clinical significance of these findings.
Funding:
R01 NS111022