Authors :
Presenting Author: Priyanka Shah-Basak, PhD – Medical College of Wisconsin
Vahab Youssofzadeh, PhD – Assistant Professor, Neurology, Medical College of Wisconsin; Candida Ustine, M.Eng – MEG Engineer, Neurology, Medical College of Wisconsin; Christopher Anderson, MD – Associate Professor, Neurology, Medical College of Wisconsin; Chad Carlson, MD – Professor, Neurology, Medical College of Wisconsin; William Gross, MD, PhD – Assistant Professor, Anesthesiology, Medical College of Wisconsin; Colin Humphries, PhD – Assistant Professor, Neurology, Medical College of Wisconsin; Jeffrey Stout, PhD – Computer systems analyst, National Institute of Health; Mary Meyerand, PhD – Professor, Medical Physics, University of Wisconsin-Madison; Bruce Hermann, PhD – Professor, Neurology, University of Wisconsin-Madison; Lisa Conant, PhD – Associate Professor, Neurology, Medical College of Wisconsin; Jeffrey Binder, MD – Professor, Neurology, Medical College of Wisconsin; Manoj Raghavan, MD, PhD – Professor, Neurology, Medical College of Wisconsin
Rationale:
Cognitive impairment is common in temporal lobe epilepsy (TLE), with neuropsychological testing typically showing diminished performance across multiple cognitive domains. The physiological basis of these impairments remains unclear. Inter-regional communication facilitated by neural oscillations, particularly in the theta frequency range, has been proposed as an important mechanism underlying information processing in the brain. We examined the relationship between theta-band (4-7 Hz) connectivity derived from resting-state magnetoencephalography (MEG) and cognition across multiple domains in people with left TLE.
Methods:
We studied 52 individuals with left TLE and 30 age-matched healthy controls from the Epilepsy Connectome Project, who completed a neuropsychological test battery and MEG recordings. The severity of epilepsy was estimated from the number of current anti-seizure medications (ASMs) and the frequency and number of different seizure types. Test scores from the neuropsychological battery were subjected to principal axis factor extraction and reduced to six factors related to language, episodic memory, motor speed, visuomotor executive function, verbal executive function, and visuospatial processing. Three five minute runs of eyes-open resting-state MEG were recorded. Cortical source time series were computed within 360 Human Connectome Project atlas parcels. Weighted phase lag index (wPLI), a phase-based measure of connectivity, and absolute theta-band power estimates were computed. Thresholded wPLI estimates (the top 20% of connection weights) and averaged theta-band power at the nodes linked by these high-strength connections were subjected to nonparametric Kruskal-Wallis tests or Spearman correlations for comparisons with measures of epilepsy severity and cognition.Results:
Theta-band connectivity was related to the lifetime count of generalized tonic-clonic seizure events (p=0.035); connectivity was increased in individuals with more than six events. Theta power showed no such relationship (Figure 1). Increased theta connectivity was also predictive of poorer scores across all domains identified in the factor analysis (Figure 2). Mean theta power across the nodes linked by high-strength connections was, however, not correlated with any factor scores (all p >0.05). While neither theta connectivity nor power was related to ASM count, neuropsychological performance was worse in patients on more ASMs (p=0.017). After controlling for ASM counts, the relationship between theta connectivity and factor scores remained significant (p=0.002), ruling out the possibility that these relationships were a by-product of ASM use.
Conclusions:
Our findings suggest that in people with left TLE, there is an increase in theta-band connectivity that is correlated with the estimated number of lifetime tonic-clonic seizures. Theta-band hyperconnectivity in the brain appears detrimental to cognition across multiple domains. This relationship was not explained by the number of ASMs. More research is needed to understand the mechanisms driving theta hyperconnectivity and its impact on cognition.
Funding:
This study was supported by the Epilepsy Connectome Project (U01NS093650; NIH).