Decreased Thalamocortical Connectivity in Resolved Rolandic Epilepsy

Pediatrics Neurology Biophysics Medical Imaging Life Sciences Immunology Medicine
Rolandic epilepsy thalamocortical connectivity pediatric epilepsy neural conduction central nervous system

Research Illustration

Thalamocortical Connectivity Reduction in Rolandic Epilepsy

Rolandic Epilepsy (RE), also known as self-limited epilepsy with centrotemporal spikes (SELECTS), is the most common localized developmental epileptic encephalopathy. This type of epilepsy is typically accompanied by transient mild to severe cognitive symptoms, sleep-related rolandic spikes, and seizures originating from the sensorimotor cortex. Although most children with RE exhibit cognitive deficits detectable through formal testing during the active phase, these seizures and cognitive issues eventually become self-limiting and disappear. However, many questions remain unanswered, such as the specific neural mechanisms involved, the factors determining symptom resolution, and the long-term impacts of this epilepsy. In this context, the aim of this study is to explore the changes in neural connectivity that resolve Rolandic epilepsy symptoms.

Study Origin

This study is a collaborative effort among several institutions in Boston, including the Neurology Department at Massachusetts General Hospital, the Neuroscience Graduate Program at Boston University, the Department of Mathematics and Statistics at Boston University, the Center for Systems Neuroscience, and Harvard Medical School. The research article was published in the May 2023 issue of the journal Clinical Neurophysiology.

Research Process

Experimental Design and Procedures

The study included the following main experimental steps: 1. Subject Selection: The study enrolled 22 children diagnosed with RE according to the 1989 International League Against Epilepsy classification (10 in the active phase and 12 with resolved symptoms), as well as 13 age-matched healthy controls without a history of epilepsy or known neurological diseases. All participants were aged between 4 and 15. 2. Data Collection: MEG (magnetoencephalography) recordings were conducted, including left and right median nerve stimulation evoked field measurements and structural and diffusion MRI (magnetic resonance imaging) recordings. MEG data were recorded using a 306-sensor system with a sampling rate of 2035 Hz. 3. Data Processing and Analysis: MEG data were analyzed using the minimum norm estimate (MNE) method to assess cortical current distribution. N20 evoked responses were identified in the contralateral somatosensory cortex, and conduction times were recorded. 4. Subsequent Analysis: FreeSurfer software was used to perform volumetric estimation of thalamic volumes from T1-MPRAGE and T2-FLAIR MRI data, and probabilistic tractography was applied to assess thalamocortical structural connectivity.

Detailed Experimental Procedures

MEG Recording and Processing: During the MEG experiments, data for evoked fields induced by median nerve and visual stimuli were collected. Head position was recorded approximately every four minutes to ensure quality through appropriate head-to-helmet distance values. Participants were asked to stay awake and were monitored via video during data collection.

MRI Recording: All participants underwent structural and diffusion MRI scans, scheduled as close to the MEG recordings as possible (median 0.0 days). Imaging results were visually inspected by a neuroradiologist to confirm the absence of obvious structural abnormalities.

Data Analysis: First, MEG and MRI data were extracted and processed, with mean evoked fields detected and measured in the cortical source space. Subsequently, the relationship between thalamic volume and conduction times in the ventral thalamic region was assessed. Finally, probabilistic tractography was used to evaluate thalamocortical structural connectivity.

Main Findings

Changes in Conduction Time

  • Somatosensory Evoked Field (SEF) Conduction Time Differences: Compared to the control group, RE children, particularly those with resolved symptoms, exhibited significantly prolonged N20 conduction times in median nerve SEFs (P=0.042, effect size 0.6 ms).
  • No Differences in Visual Evoked Fields (VEFs): There were no significant differences in P100 conduction times of visual evoked fields between RE children and controls (P=0.83). This suggests that conduction delays are primarily associated with the Rolandic cortical sensory aspect.

Relationship Between Thalamic Volume and Conduction Time

  • Thalamic Volume Prediction: Overall thalamic volume was not significantly predictive of SEF conduction times (P=0.11), but the ventral thalamic region was notably larger in RE children (P=0.037) and positively correlated with conduction times (P=0.023).
  • White Matter Structural Connectivity and Conduction Time: White matter structural connectivity was not significantly related to SEF conduction times (P>0.3).

Conclusions and Implications

This study demonstrates that the prolonged conduction time of median nerve SEFs in RE children reflects localized connectivity abnormalities in the Rolandic thalamocortical circuits, persisting even after symptom resolution. This finding further supports the crucial role of thalamocortical circuits in the expression and resolution of RE symptoms, suggesting that enduring structural and functional abnormalities in these circuits may provide compensatory mechanisms for symptom resolution.

Highlights and Significance of the Study

  • Novel Biomarkers: By measuring median nerve SEF conduction times, the research team provided a new biomarker for RE, helping to identify anatomical disruption points.
  • Further Pathophysiological Understanding: The study results contribute new insights into the pathophysiology mechanisms of symptom resolution in this common childhood epilepsy. Furthermore, the identified relationship between thalamic volume and conduction times may reflect increased inhibitory processing strategies at the thalamic level, offering direction for future mechanistic research.

The findings of this study not only provide new diagnostic tools for RE but also offer significant references for the field of neurophysiology in exploring disease mechanisms and resolution strategies.