ASYMMETRIES IN rsFMRI INTRINSIC BRAIN ACTIVITY MEASURES AS A PREDICTOR OF EPILEPSY SURGERY SUCCESS Carly M. Rosen, David M. Groppe, Ashesh D. Mehta Laboratory of Multimodal Brain Mapping Feinstein Institute for Medical Research

Introduction Epilepsy is a neurological disorder that characterized by recurrent seizures. It is estimated to affect over 70 million people worldwide. Surgical resection of the epileptogenic zone (EZ) is considered a standard of care for patients with seizures that cannot be controlled with antiepileptic drugs. This condition is known as intractable epilepsy. The success of this epilepsy surgery is highly variable (30-80%). Question Background Can rs-fMRI analysis be used to determine the degree of seizure freedom after epilepsy surgery?

Methods Prior to implantation of intracranial electrodes, structural and functional MRIs were acquired from 13 intractable epilepsy patients Implantation of intracranial grid and strip electrodes is used to determine EZ and vital brain areas prior to resection surgery After implantation, the EZ is determined through electrocorticography (ECoG) analysis and is targeted for resection. The preoperative structural MRI is compared to the postoperative MRI to determine the resected area.

The blood-oxygenation level dependent (BOLD) response, used in fMRI analysis, is a correlate of brain activity. Resting-state functional Magnetic Resonance Imaging (rsfMRI) may be used to identify the extent of epileptogenic tissue as well as predict cognitive changes after resection. Measures of intrinsic brain activity such as regional homogeneity (ReHo), amplitude of low frequency fluctuations (ALFF), and fractional amplitude of low frequency fluctuations (fALFF) can be obtained from rsfMRI data. – In this presentation these measures are obtained for the areas outside of the resected zone. The measure is considered significant when the value of a region on the resected hemisphere differ from the identical contralateral region by |Z|>1.65 (p<0.05) Resting-state fMRI and its Measures

Defining the Resection Zone Fig. 1: Resection mask on pre- operative MRI Fig. 2: Resection mask on post- operative MRI Engel Epilepsy Surgery Outcome Scale Class 1: free of disabling seizures Class 2: rare disabling seizures Class 3: worthwhile improvement Class 4: no worthwhile improvement

Patient Data Right Resections RO: 1 R Occipital (3) RT: 0 R Temporal RF: 0 R Frontal Left Resections LF: 3 L Frontal (1,1,1) LT: 8 L Temporal (4,3,3,2,2,1,1,1) LO: 1 L Occipital (2)

Predictions Worse surgery outcome correlates with a greater number of brain regions of: – high ReHo outside the resection zone A previous study (Zeng et al. 2013) proposed that increased ReHo regions compose a network that is responsible for seizure propagation and generation. – low ALFF/fALFF outside the resection zone Previous PET studies (Friedman et al. 1993) have determined that areas of hypometabolism, which is correlated with decreases ALFF, may indicate epileptogenic regions.

Regional Homogeneity (ReHo) Resection zone Engel 2 Engel 1 Measures the synchronization in local brain regions. Increased ReHo regions may compose a network of seizure generation and propagation Warm areas represent the regions of which the ReHo is greater relative to the contralateral side.

Amplitude of Low Frequency Fluctuations (ALFF) Reflects the intensity of fluctuations of regional spontaneous brain activity. Thought to correlate with brain metabolism. Low values of ALFF (blue-colored regions) may predict seizure areas. Engel 2 Engel 3

fALFF is the ALFF adjusted for artifacts, such as signals in the cerebral-spinal fluid where no such signal should exist. Low values of fALFF (blue regions) may predict seizure propagation areas. Fractional Amplitude of Low Frequency Fluctuations (fALFF) Engel 4 Engel 1

Results

ReHo and fALFF relationships to Engel are the opposite of the predicted relationships – Suggests that a priori hypotheses were incorrect ALFF trendline slope is very minimal – Suggests that there is no clear relationship between epilepsy surgery success (Engel Outcome) and the ALFF hypometabolism measure Results Summary

Conclusions Insignificant results may be due to – Arbitrary threshold (|z|>1.65; p<0.05 ) – Relatively small sample size Engel outcome may not rely purely on the number of ReHo or ALFF/fALFF areas outside of the resection zone that remain after surgery – The size of the resting-state abnormality within the resected region may be important