ABSTRACT
Central pain disorders, such as central post-stroke pain, remain clinically challenging to treat, despite many decades of pharmacological advances and the evolution of neuromodulation. For treatment refractory cases, previous studies have highlighted some benefits of cortical stimulation. Recent advances in new targets for pain and the optimization of neuromodulation encouraged our group to develop a dual cortical target approach paired with Bayesian optimization to provide a personalized treatment. Here, we present a case report of a woman who developed left-sided facial pain after multiple thalamic strokes. All previous pharmacologic and interventional treatments failed to mitigate the pain, leaving her incapacitated due to pain and medication side effects. She subsequently underwent a single burr hole for placement of motor cortex (M1) and dorsolateral prefrontal cortex (dlPFC) paddles for stimulation with externalization. By using Bayesian optimization to find optimal stimulation parameters and stimulation sites, we were able to reduce pain from an 8.5/10 to a 0/10 during a 5-day inpatient stay, with pain staying at or below a 2/10 one-month post-procedure. We found optimal treatment to be simultaneous stimulation of M1 and dlPFC without any evidence of seizure induction. In addition, we found no worsening in cognitive performance during a working memory task with dlPFC stimulation. This personalized approach using Bayesian optimization may provide a new foundation for treating central pain and other functional disorders through systematic evaluation of stimulation parameters.
ABSTRACT
Here we describe a novel mouse model of temporal lobe epilepsy (TLE) that moves the site of kainate injection from the rodent dorsal hippocampus (corresponding to the human posterior hippocampus) to the ventral hippocampus (corresponding to the human anterior hippocampus). We compare the phenotypes of this new model-with respect to seizures, cognitive impairment, affective deficits, and histopathology-to the standard dorsal intrahippocampal kainate model. Our results demonstrate that histopathological measures of granule cell dispersion and mossy fiber sprouting maximize near the site of kainate injection. Somewhat surprisingly, both the dorsal and ventral models exhibit similar spatial memory impairments in addition to similar electrographic and behavioral seizure burdens. In contrast, we find a more pronounced affective (anhedonic) phenotype specifically in the ventral model. These results demonstrate that the ventral intrahippocampal kainic acid model recapitulates critical pathologies of the dorsal model while providing a means to further study affective phenotypes such as depression in TLE.
