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Delayed Diagnosis of Functional Seizures Associated With Abnormal Processing of Face Emotions

Increased posterior cingulate cortex activation to sad faces in the long-delay diagnostic group were associated with worse symptoms of depression, as expressed by Beck Depression Inventory scores.

By assessing emotion processing circuits, recently published findings in Epilepsy & Behavior showed that diagnostic delays for functional seizures (FS) are associated with functional MRI (fMRI) changes in the insula and cingulate regions of the brain. Both are implicated in mood control, self-referencing, and other emotion-relevant processes.1

In addition to completing several assessments related to symptoms of depression, anxiety, posttraumatic stress disorder (PTSD), and quality of life, patients also underwent fMRI at 3T with emotional faces task (EFT). Here, they indicated “male” or “female” via button press while implicitly processing happy, sad, fearful, and neutral faces. Findings showed that those with long-delay diagnosis (l-DD) had significantly greater fMRI activation than short-delay diagnosis (s-DD) to sad faces in the bilateral posterior cingulate cortex (PCC; 403 mm3; t = 4.66; peak MNI coordinates at x = –2, y = –43, z = 18) and to neutral faces in the right anterior insula (AI; 384 mm3; t = 5.04; peak MNI coordinates at x = 32, y = 20, z = –12).

Led by Jerzy P. Szaflarski, MD, PhD, Division Director of Epilepsy, The University of Alabama at Birmingham, the study included 52 adults who had a history of traumatic brain injury (TBI) prior to diagnosis of FS, which was confirmed on video EEG. Assessments such as the Global Assessment of Function (GAF), used to index individual differences in diseases severity; the Beck Depression Inventory (BDI-II), used to analyze symptoms of depression; the Beck Anxiety Inventory (BAI), which assessed symptoms of anxiety; and the PTSD checklist–stressor specific version (PCL-S), assessed post-traumatic stress disorder (PTSD) symptoms, were included in the analysis.

The event-related EFT, designed to assess response to basic emotional stimuli and programmed using E-Prime, was also presented during fMRI. As mentioned, the participants were presented with a series of faces with happy, fearful, sad, or neutral expressions in a pseudo-randomized order, and asked to identify the face as either male or female by pressing the left or right button with their pointer finger or middle finger, respectively, using the button box held in their right hand. After completing the MRI scan, participants identified emotional expression of each of the previously presented faces as happy, fearful, sad, neutral, or unknown.

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The median split (507 days) was used to define short and l-DD. Independent sample t-tests were used to examine differences between s-DD and l-DD groups for EFT in-scanner and post-scan performance. Between the groups, there were no differences in onset age of psychogenetic nonepileptic seizures, number of seizures in the past month, age at first TBI, number of TBIs, distribution of TBI severity, sex distribution, or years of education. Additionally, neither group differed on scores on the GAF, BDI-II, BAI, and PCL-S, or for EFT in-scanner and postscan performance; although, the s-DD group was younger (mean age, 32.6 vs 40.1; P = .022).

At the conclusion of the study, voxel wise regression analyses within the emotion network brain regions revealed significant linear relationship between DD and facial emotion processing. With increased DD, there was increased fMRI activation to sad faces in the bilateral PCC (520 mm3; t = 4.89; peak MNI coordinates at x = 44, y = 27, and z = –2). Between-group activation differences and within-group linear regressions with DD were corrected at P <.05 (voxelwise, P = .005; cluster > 306 mm3 for neutral faces; cluster > 292 mm3 for sad faces; cluster > 301 mm3 for happy faces) as determined by Monte Carlo simulations.

Findings also showed positive correlations between PCC response to sad faces and BDI-II scores in the l-DD group (ρ = 0.48; P = .012) and the combined sample (ρ = 0.30; P = .029), which was expected, according to study investigators. The s-DD group showed a nonsignificant trend for a negative correlation between PCC response to sad faces and PCL-S scores (ρ = 0.29; P = .15). There were no significant correlations between PCC response to sad faces and BAI or PCL-S scores in the combined sample, or the individual diagnostic groups. Furthermore, AI response to neutral faces showed no significant correlation to BDI-II, BAI, or PCL-S, in any of the groups.

1.Szaflarski JP, Allendorfer JB, Goodman AM, et al. Diagnostic delay in functional seizures is associated with abnormal processing of facial emotions. Epileps & Behav. 2022;131(A):108712. doi:10.1016/j.yebeh.2022.108712