Segmentation of the thalamus based on BOLD frequencies affected in temporal lobe epilepsy

Abstract

Objective: Temporal lobe epilepsy is associated with functional changes throughout the brain, particularly including a putative seizure propagation network involving the hippocampus, insula, and thalamus. We identified a specified frequency range where functional connectivity in this network was related to duration of disease. Then, to identify specific thalamic nuclei involved in seizure propagation, we determined the subregions of the thalamus that have increased resting functional oscillations in this frequency range.

Methods: Resting-state functional magnetic resonance imaging (fMRI) was acquired from 20 patients with unilateral temporal lobe epilepsy (TLE; 14 right and 6 left) and 20 healthy controls who were each age and gender matched to a specific patient. Wavelet-based fMRI connectivity mapping across the network was computed at each frequency to determine those frequencies where connectivity significantly decreases with duration of disease consistent with impairment due to repeated seizures. The voxel-wise power of the spontaneous blood oxygenation fluctuations of this frequency band was computed in the thalamus of each subject.

Results: Functional connectivity was impaired in the proposed seizure propagation network over a specific range (0.0067-0.013 Hz and 0.024-0.032 Hz) of blood oxygenation oscillations. Increased power in this frequency band (<0.032 Hz) was detected bilaterally in the pulvinar and anterior nucleus of the thalamus of healthy controls, and was increased over the ipsilateral thalamus compared to the contralateral thalamus in TLE.

Significance: This study identified frequencies of impaired connectivity in a TLE seizure propagation network and used them to localize the anterior nucleus and pulvinar of the thalamus as subregions most susceptible to TLE seizures. Further examinations of these frequencies in healthy and TLE subjects may provide unique information relating to the mechanism of seizure propagation and potential treatment using electrical stimulation.

Keywords: Functional neuroimaging; Temporal lobe epilepsy; Thalamus; fMRI.

Figure 1

Example of a cross wavelet transform (CWT) plot for INSI and THALI of a TLE patient using the Morlet wavelet. The R² is denoted by color (0–1) and the θ is indicated by the direction of the arrow. The white shading represents frequencies temporally filtered in the preprocessing for functional connectivity. The horizontal axis is the time during the scan. The vertical axis represents frequency of BOLD oscillations. This example shows that in the first 200 seconds of the scan, the highest connectivity between the two regions occurs at a frequency of approximately 0.01 Hz (A); while later in the last 400 seconds of the scan, the highest correlation occurs at a frequency of about 0.007 Hz (B).

Figure 2

Validation of IWFC(f,t) measure. (A) Frequency and time averaged IWFC vs. traditional FC. (B) Frequency and time averaged IWFC vs. duration of disease. Solid line represents linear trendline. Each point in (B) represents the IWFC of each patient minus the age and gender matched healthy control (pat-con).

Figure 3

IWFC(f) frequency analysis. (A) Correlation between IWFC(f) (pat-con) vs. duration of disease at each frequency. Dotted black line indicates r² value over which p < 0.05. Shaded black areas show frequencies for which this correlation is statistically significant. The blue line represents the frequency band of interest (F_i), while the red line denotes the other frequencies (F_o) used for thalamus segmentation. (B) IWFC averaged only for significant frequencies shown in A (0.0067–0.013 Hz and 0.024–0.032 Hz). Correlation to duration of disease is higher than that of all frequencies shown in Figure 2B (r = −0.505 for all frequencies vs. r = −0.683 for significant frequencies only). Solid line represents linear trendline. Each point in (B) represents the IWFC of each patient minus the age and gender matched healthy control (pat-con).

Figure 4

Frequency segmentation of the thalamus in healthy controls. Average of Fi/Fo power across 20 healthy control subjects. (A) Axial slice showing increased power in bilateral anterior nucleus and pulvinar regions. Increased power in the anterior nucleus region is shown in a sagittal (B) and coronal (C) section. Increased power in the pulvinar region is shown in a sagittal (D) and coronal (E) section. Left (L) or posterior (P) side of the image is indicated in each. MNI template slice location is given in the bottom right corner in mm.

Figure 5

Frequency segmentation of the thalamus in TLE. Average of Fi/Fo power across 6 left TLE patients (left) and 14 right TLE patients (right). MNI template slice location is given in the bottom right corner in mm.