Biology subjects

Blackmon, K.

Publications and source records attributed to Blackmon, K..

3 recordsLinked to original sources

bioRxiv2018

A systems-level analysis highlights microglial activation as a modifying factor in common forms of human epilepsy

The common human epilepsies are associated with distinct patterns of reduced cortical thickness, detectable on neuroimaging, with important clinical consequences. To explore underlying mechanisms, we layered MRI-based cortical structural maps from a large-scale epilepsy neuroimaging study onto highly spatially-resolved human brain gene expression data, identifying >2,500 genes overexpressed in regions of reduced cortical thickness, compared to relatively-protected regions. The resulting set of differentially-expressed genes shows enrichment for microglial markers, and in particular, activated microglial states. Parallel analyses of cell-specific eQTLs show enrichment in human genetic signatures of epilepsy severity, but not epilepsy causation. Post mortem brain tissue from humans with epilepsy shows excess activated microglia. In an experimental model, depletion of activated microglia prevents cortical thinning, but not the development of chronic seizures. These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

neuroscience↗

bioRxiv2018

Resting state functional connectivity patterns associated with pharmacological treatment resistance in temporal lobe epilepsy

There are no functional imaging based biomarkers for pharmacological treatment response in temporal lobe epilepsy (TLE). In this study, we investigated whether there is an association between resting state functional brain connectivity (RsFC) and seizure control in TLE. We screened a large database containing resting state functional magnetic resonance imaging (Rs-fMRI) data from 286 epilepsy patients. Patient medical records were screened for seizure characterization, EEG reports for lateralization and location of seizure foci to establish uniformity of seizure localization within patient groups. Rs-fMRI data from patients with well-controlled left TLE, patients with treatment-resistant left TLE, and healthy controls were analyzed. Healthy controls and cTLE showed similar functional connectivity patterns, whereas trTLE exhibited a significant bilateral decrease in thalamo-hippocampal functional connectivity. This work is the first to demonstrate differences in neural network connectivity between well-controlled and treatment-resistant TLE. These differences are spatially highly focused and suggest sites for the etiology and possibly treatment of TLE. Altered thalamo-hippocampal RsFC thus is a potential new biomarker for TLE treatment resistance.\n\nSummaryResting State functional magnetic resonance imaging (Rs-fMRI), previously utilized to predict lateralization of seizure foci in temporal lobe epilepsy (TLE), is utilized to determine potential mechanisms and biomarkers for treatment-resistant and well-controlled unilateral TLE. We found significant differences in thalamo-hippocampal functional connectivity between treatment-resistant and well-controlled TLE patients. Differences in functional connectivity were focused to thalamo-hippocampal connections and more pronounced in the hemisphere ipsilateral to seizure foci. Aberrant functional connectivity patterns as measured by Rs-fMRI could thus serve as biomarkers for treatment response in TLE.

neuroscience↗

bioRxiv2018

Two Sides of the Same Coin: The Hippocampus as a Common Neural Substrate for Model-Based Planning and Spatial Memory

Little is known about the neural mechanisms that allow humans and animals to plan actions using knowledge of task contingencies. Emerging theories hypothesize that it involves the same hippocampal mechanisms that support self-localization and memory for locations. Yet, there is limited direct evidence for the link between model-based planning and the hippocampal place map. We addressed this by investigating model-based planning and place memory in healthy controls and epilepsy patients treated using unilateral anterior temporal lobectomy with hippocampal resection. We found that both functions were impaired in the patient group. Specifically, the planning impairment was related to right hippocampal lesion size, controlling for overall lesion size. Furthermore, planning and place memory covaried with one another, but only in neurologically intact controls, consistent with both functions relying on the same structure in the healthy brain. These findings clarify the scope of hippocampal contributions to behavior and the neural mechanism of model-based planning.

neuroscience↗