The functional organization of human auditory cortex remains incompletely characterized. While the posteromedial two thirds of Heschl’s gyrus (HG) is generally considered to be part of core auditory cortex, additional subdivisions of HG remain speculative. To further delineate the hierarchical organization of human auditory cortex, we investigated regional heterogeneity in the modulation of auditory cortical responses under varying depths of anesthesia induced by propofol. Non-invasive studies have shown that propofol differentially affects auditory cortical activity, with a greater impact on non-core areas. Subjects were neurosurgical patients undergoing removal of intracranial electrodes placed to identify epileptic foci. Stimuli were 50 Hz click trains, presented continuously during an awake baseline period, and subsequently, while propofol infusion was incrementally titrated to induce general anesthesia. Electrocorticographic recordings were made with depth electrodes implanted in HG and subdural grid electrodes implanted over superior temporal gyrus (STG). Depth of anesthesia was monitored using spectral entropy. Averaged evoked potentials (AEPs), frequency-following responses (FFRs) and high gamma (70–150 Hz) event-related band power (ERBP) were used to characterize auditory cortical activity. Based on the changes in AEPs and FFRs during the induction of anesthesia, posteromedial HG could be divided into two subdivisions. In the most posteromedial aspect of the gyrus, the earliest AEP deflections were preserved and FFRs increased during induction. In contrast, the remainder of the posteromedial HG exhibited attenuation of both the AEP and the FFR. The anterolateral HG exhibited weaker activation characterized by broad, low-voltage AEPs and the absence of FFRs. Lateral STG exhibited limited activation by click trains, and FFRs there diminished during induction. Sustained high gamma activity was attenuated in the most posteromedial portion of HG, and was absent in all other regions. These differential patterns of auditory cortical activity during the induction of anesthesia may serve as useful physiological markers for field delineation. In this study, the posteromedial HG could be parcellated into at least two subdivisions. Preservation of the earliest AEP deflections and FFRs in the posteromedial HG likely reflects the persistence of feedforward synaptic activity generated by inputs from subcortical auditory pathways, including the medial geniculate nucleus.

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In everyday life, predictable sensory stimuli are generally not ecologically informative. By contrast, novel or unexpected stimuli signal ecologically salient changes in the environment. This idea forms the basis of the predictive coding hypothesis: efficient sensory encoding minimizes neural activity associated with predictable backgrounds and emphasizes detection of changes in the environment. In real life, the brain must resolve multiple unexpected sensory events occurring over different time scales. The local/global deviant experimental paradigm examines auditory predictive coding over multiple time scales. For short-term novelty [hundreds of milliseconds; local deviance (LD)], sequences of identical sounds (/xxxxx/) are interspersed with sequences that contain deviants (/xxxxy/). Long-term novelty [several seconds; global deviance (GD)] is created using either (a) frequent /xxxxx/ and infrequent /xxxxy/ sequences, or (b) frequent /xxxxy/ and infrequent /xxxxx/ sequences. In scenario (a), there is both an LD and a GD effect (LDGD, “double surprise”). In (b), the global deviant is a local standard, i.e., sequence of identical sounds (LSGD). Cortical responses reflecting LD and GD originate in different brain areas, have a different time course, and are differentially sensitive to general anesthesia. Neural processes underlying LD and GD have been shown to interact, reflecting overlapping networks subserving the detection of novel auditory stimuli. This study examined these interactions using intracranial electroencephalography in neurosurgical patients. Subjects performed a GD target detection task before and during induction of anesthesia with propofol. Recordings were made from the auditory cortex, surrounding auditory-related and prefrontal cortex in awake, sedated, and unresponsive states. High gamma activity was used to measure the neural basis of local-by-global novelty interactions. Positive interaction was defined as a greater response to the double surprise LDGD condition compared to LSGD. Negative interaction was defined as a weaker response to LDGD. Positive interaction was more frequent than negative interaction and was primarily found in auditory cortex. Negative interaction typically occurred in prefrontal cortex and was more sensitive to general anesthesia. Temporo-parietal auditory-related areas exhibited both types of interaction. These interactions may have relevance in a clinical setting as biomarkers of conscious perception in the assessment of depth of anesthesia and disorders of consciousness.

General anesthesia or monitored anesthesia care sometimes is provided in nonoperating room (OR) locations during nights and weekends (e.g., for magnetic resonance imaging [MRI] or computerized tomography [CT]). Rational and consistent scheduling and sequencing decisions for these diagnostic imaging procedures, including coordination with OR cases, cannot be done without knowing how long each case can wait to be started without risking a worsening of the patient's condition. We reviewed the medical records of the 81 patients who underwent diagnostic imaging procedures (78 = MRI, 3 = CT scan) under general anesthesia or monitored anesthesia care either on weekends or between 6 pm and 6 am at the University of Iowa Hospitals between March 2012 and February 2014. For 77.8% of patients, the indications could have changed clinical management within 4 hours (N = 63/81). Among the 63 imaging studies with potential immediate impact, there was documentation of results having been communicated to the treating team within 4 hours of the completion of imaging for 39 of the patients. Among the 39 patients, 15 promptly received medications or underwent procedures based on the imaging results. Thus, 15 of the 81 patients had a change in care (18.5%, 95% lower confidence limit = 11.2%). Our results are important since we showed previously that it is not possible to make rational and consistent decisions in case sequencing without knowing how long each case (including diagnostic imaging procedures) can wait to be started without a change in the patient's risk. The scheduled surgical procedure itself provides sufficient information to assess safe waiting times to start add-on cases (e.g., appendectomy). In contrast, MRI provides no context as to how potential findings will influence treatment. Our results show that the assumption cannot reasonably be made when sequencing cases that all imaging studies can or cannot wait longer than pending surgical procedures. Our results show that, for evidence-based OR management decision-making, information to decide appropriate waiting should be obtained electronically or verbally for each imaging study.

Elucidating neural signatures of sensory processing across consciousness states is a major focus in neuroscience. Noninvasive human studies using the general anesthetic propofol reveal differential effects on auditory cortical activity, with a greater impact on nonprimary and auditory-related areas than primary auditory cortex. This study used intracranial electroencephalography to examine cortical responses to vowel sequences during induction of general anesthesia with propofol. Subjects were adult neurosurgical patients with intracranial electrodes placed to identify epileptic foci. Data were collected before electrode removal surgery. Stimuli were vowel sequences presented in a target detection task during awake, sedated, and unresponsive states. Averaged evoked potentials (AEPs) and high gamma (70–150 Hz) power were measured in auditory, auditory-related, and prefrontal cortex. In the awake state, AEPs were found throughout studied brain areas; high gamma activity was limited to canonical auditory cortex. Sedation led to a decrease in AEP magnitude. Upon LOC, there was a decrease in the superior temporal gyrus and adjacent auditory-related cortex and a further decrease in AEP magnitude in core auditory cortex, changes in the temporal structure and increased trial-to-trial variability of responses. The findings identify putative biomarkers of LOC and serve as a foundation for future investigations of altered sensory processing.

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Lubeluzole [S-4-(2-benzothiazolylmethylamino)-alpha-((3,4-difluorophenoxy)methyl)-1-piperidineethanol] reduces the severity of cerebral injury in animal models of brain ischemia. Its beneficial effects may include decreased concentration of extracellular glutamate, blockade of sodium and calcium channels, and attenuation of nitric oxide-mediated neuronal death. Previous studies have shown that global cerebral ischemia in rabbits impaired the subsequent acquisition of a trace-conditioned eyeblink reflex. Here, we examined the effect of preischemic treatment with lubeluzole on the acquisition of a trace-conditioned eyeblink response after 6.5 min of global cerebral ischemia. Three groups of rabbits underwent cerebral ischemia: one group underwent ischemia alone (I) and two groups underwent ischemia and also received lubeluzole (L(1), 1.25 mg/kg, and L(2), 2.5 mg/kg). All animals were subsequently trained using classical trace conditioning. Each training session consisted of the presentation of the conditioned stimulus (an 85-dB, 6-kHz auditory tone lasting for 100 ms) followed by a trace interval (a period of 300 ms during which no external stimulus was delivered) followed finally by the delivery of the unconditioned stimulus (a 150-ms puff of air directed at the cornea). We found that animals receiving preischemic administration of 1.25 mg/kg of lubeluzole demonstrated a significantly improved acquisition of the trace-conditioned reflex as compared to animals that did not receive lubeluzole. This finding demonstrates improved long-term neurobehavioral outcome with preischemic administration of 1.25 mg/kg of lubeluzole.