Biology subjects

Dugan, P.

Publications and source records attributed to Dugan, P..

3 recordsLinked to original sources

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

Hippocampal signature of associative memory measured by chronic ambulatory intracranial EEG

Some patients with medically refractory focal epilepsy are chronically implanted with a brain-responsive neurostimulation device (the RNS(R) System), permitting neurophysiological measurements at millisecond resolution. This clinical device can be adapted to measure hippocampal dynamics time-locked to cognitive tasks. We illustrate the technique with a proof of concept in three patients previously implanted with the RNS System as they engage in an associative memory task, measured months apart. Hippocampal activity measured in successful encoding in RNS System patients mirrors that in surgical patients during intracranial electroencephalography (iEEG), suggesting that chronic iEEG allows sensitive measurements of hippocampal physiology over prolonged timescales.

neuroscience↗

bioRxiv2017

Replay of large-scale spatio-temporal patterns from waking during subsequent slow-wave sleep in human cortex

Animal studies support the hypothesis that in slow-wave sleep, replay of waking neocortical activity under hippocampal guidance leads to memory consolidation. However, no intracranial electrophysiological evidence for replay exists in humans. We identified consistent sequences of population firing peaks across widespread cortical regions during complete waking periods. The occurrence of these Motifs were compared between sleeps preceding the waking period (Sleep-Pre) when the Motifs were identified, and those following (Sleep-Post). In all subjects, the majority of waking Motifs (most of which were novel) had more matches in Sleep-Post than in Sleep-Pre. In rodents, hippocampal replay occurs during local sharp-wave ripples, and the associated neocortical replay tends to occur during local sleep spindles and down-to-up transitions. These waves may facilitate consolidation by sequencing cell-firing and encouraging plasticity. Similarly, we found that Motifs were coupled to neocortical spindles, down-to-up transitions, theta bursts, and hippocampal sharp-wave ripples. While Motifs occurring during cognitive task performance were more likely to have more matches in subsequent sleep, our studies provide no direct demonstration that the replay of Motifs contributes to consolidation. Nonetheless, these results confirm a core prediction of the dominant neurobiological theory of human memory consolidation.

neuroscience↗