Intraoperative thalamocortical tract monitoring via direct cortical recordings during craniotomy.

OBJECTIVE: Neuromonitoring of primary motor regions allows preservation of motor strength and is frequently employed during cranial procedures. Less is known about protection of sensory function and ability to modulate movements, both of which rely on integrity of thalamocortical afferents (TCA) to fronto-parietal regions. We describe our experience with TCA monitoring and their cortical relays during brain tumor surgery. METHODOLOGY: To study its feasibility and usefulness, continuous somatosensory evoked potentials (SSEP) recording via a subdural electrode was attempted in 32 consecutive patients. RESULTS: Median and posterior tibial SSEP were successfully monitored in 31 and 17 patients respectively. SSEP improved lesion localization and prevented unnecessary cortical stimulation in 9 and 16 cases respectively. A threshold of ≥30% SSEP amplitude decrease influenced management in 10 patients while a decrement of ≥50 % had a sensitivity of 0.89 and specificity of 1 in detecting worsening of sensory function. Simultaneous motor evoked potentials (MEP) and SSEP monitoring were performed in 10 cases, 9 of which showed short-lived fluctuations of the former. CONCLUSION: Direct cortical SSEP monitoring is feasible, informs management and predicts outcome. SIGNIFICANCE: Early intervention prevents sensory deficit. Concomitant MEP fluctuations may reflect modulation of motor activity by TCA.

Microscale Physiological Events on the Human Cortical Surface.

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.

Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma.

IDH1 mutations are common in low-grade gliomas and secondary glioblastomas and cause overproduction of (R)-2HG. (R)-2HG modulates the activity of many enzymes, including some that are linked to transformation and some that are probably bystanders. Although prior work on (R)-2HG targets focused on 2OG-dependent dioxygenases, we found that (R)-2HG potently inhibits the 2OG-dependent transaminases BCAT1 and BCAT2, likely as a bystander effect, thereby decreasing glutamate levels and increasing dependence on glutaminase for the biosynthesis of glutamate and one of its products, glutathione. Inhibiting glutaminase specifically sensitized IDH mutant glioma cells to oxidative stress in vitro and to radiation in vitro and in vivo. These findings highlight the complementary roles for BCATs and glutaminase in glutamate biosynthesis, explain the sensitivity of IDH mutant cells to glutaminase inhibitors, and suggest a strategy for maximizing the effectiveness of such inhibitors against IDH mutant gliomas.