Processing of auditory novelty in human cortex during a semantic categorization task.

Auditory semantic novelty - a new meaningful sound in the context of a predictable acoustical environment - can probe neural circuits involved in language processing. Aberrant novelty detection is a feature of many neuropsychiatric disorders. This large-scale human intracranial electrophysiology study examined the spatial distribution of gamma and alpha power and auditory evoked potentials (AEP) associated with responses to unexpected words during performance of semantic categorization tasks. Participants were neurosurgical patients undergoing monitoring for medically intractable epilepsy. Each task included repeatedly presented monosyllabic words from different talkers ("common") and ten words presented only once ("novel"). Targets were words belonging to a specific semantic category. Novelty effects were defined as differences between neural responses to novel and common words. Novelty increased task difficulty and was associated with augmented gamma, suppressed alpha power, and AEP differences broadly distributed across the cortex. Gamma novelty effect had the highest prevalence in planum temporale, posterior superior temporal gyrus (STG) and pars triangularis of the inferior frontal gyrus; alpha in anterolateral Heschl's gyrus (HG), anterior STG and middle anterior cingulate cortex; AEP in posteromedial HG, lower bank of the superior temporal sulcus, and planum polare. Gamma novelty effect had a higher prevalence in dorsal than ventral auditory-related areas. Novelty effects were more pronounced in the left hemisphere. Better novel target detection was associated with reduced gamma novelty effect within auditory cortex and enhanced gamma effect within prefrontal and sensorimotor cortex. Alpha and AEP novelty effects were generally more prevalent in better performing participants. Multiple areas, including auditory cortex on the superior temporal plane, featured AEP novelty effect within the time frame of P3a and N400 scalp-recorded novelty-related potentials. This work provides a detailed account of auditory novelty in a paradigm that directly examined brain regions associated with semantic processing. Future studies may aid in the development of objective measures to assess the integrity of semantic novelty processing in clinical populations.

Activity-induced gene expression in the human brain.

Activity-induced gene expression underlies synaptic plasticity and brain function. Here, using molecular sequencing techniques, we define activity-dependent transcriptomic and epigenomic changes at the tissue and single-cell level in the human brain following direct electrical stimulation of the anterior temporal lobe in patients undergoing neurosurgery. Genes related to transcriptional regulation and microglia-specific cytokine activity displayed the greatest induction pattern, revealing a precise molecular signature of neuronal activation in the human brain.

Functional geometry of auditory cortical resting state networks derived from intracranial electrophysiology.

Understanding central auditory processing critically depends on defining underlying auditory cortical networks and their relationship to the rest of the brain. We addressed these questions using resting state functional connectivity derived from human intracranial electroencephalography. Mapping recording sites into a low-dimensional space where proximity represents functional similarity revealed a hierarchical organization. At a fine scale, a group of auditory cortical regions excluded several higher-order auditory areas and segregated maximally from the prefrontal cortex. On mesoscale, the proximity of limbic structures to the auditory cortex suggested a limbic stream that parallels the classically described ventral and dorsal auditory processing streams. Identities of global hubs in anterior temporal and cingulate cortex depended on frequency band, consistent with diverse roles in semantic and cognitive processing. On a macroscale, observed hemispheric asymmetries were not specific for speech and language networks. This approach can be applied to multivariate brain data with respect to development, behavior, and disorders.

Sensory processing of native and non-native phonotactic patterns in the alpha and beta frequency bands.

The phonotactic patterns of one's native language are established within cortical network processing during development. Sensory processing of native language phonotactic patterns established in memory may be modulated by top-down signals within the alpha and beta frequency bands. To explore sensory processing of phonotactic patterns in the alpha and beta frequency bands, electroencephalograms (EEGs) were recorded from native Polish and native English-speaking adults as they listened to spoken nonwords within same and different nonword pairs. The nonwords contained three phonological sequence onsets that occur in the Polish and English languages (/pət/, /st/, /sət/) and one onset sequence /pt/, which occurs in Polish but not in English onsets. Source localization modeling was used to transform 64-channel EEGs into brain source-level channels. Spectral power values in the low frequencies (2-29 Hz) were analyzed in response to the first nonword in nonword pairs within the context of counterbalanced listening-task conditions, which were presented on separate testing days. For the with-task listening condition, participants performed a behavioral task to the second nonword in the pairs. For the without-task condition participants were only instructed to listen to the stimuli. Thus, in the with-task condition, the first nonword served as a cue for the second nonword, the target stimulus. The results revealed decreased spectral power in the beta frequency band for the with-task condition compared to the without-task condition in response to native language phonotactic patterns. In contrast, the task-related suppression effects in response to the non-native phonotactic pattern /pt/ for the English listeners extended into the alpha frequency band. These effects were localized to source channels in left auditory cortex, the left anterior temporal cortex and the occipital pole. This exploratory study revealed a pattern of results that, if replicated, suggests that native language speech perception is supported by modulations in the alpha and beta frequency bands.

Analogous cortical reorganization accompanies entry into states of reduced consciousness during anesthesia and sleep.

Theories of consciousness suggest that brain mechanisms underlying transitions into and out of unconsciousness are conserved no matter the context or precipitating conditions. We compared signatures of these mechanisms using intracranial electroencephalography in neurosurgical patients during propofol anesthesia and overnight sleep and found strikingly similar reorganization of human cortical networks. We computed the "effective dimensionality" of the normalized resting state functional connectivity matrix to quantify network complexity. Effective dimensionality decreased during stages of reduced consciousness (anesthesia unresponsiveness, N2 and N3 sleep). These changes were not region-specific, suggesting global network reorganization. When connectivity data were embedded into a low-dimensional space in which proximity represents functional similarity, we observed greater distances between brain regions during stages of reduced consciousness, and individual recording sites became closer to their nearest neighbors. These changes corresponded to decreased differentiation and functional integration and correlated with decreases in effective dimensionality. This network reorganization constitutes a neural signature of states of reduced consciousness that is common to anesthesia and sleep. These results establish a framework for understanding the neural correlates of consciousness and for practical evaluation of loss and recovery of consciousness.

Surgical outcomes and risk factors for recurrence of myxopapillary ependymoma: a single-center experience.

OBJECTIVE: Myxopapillary ependymomas (MPEs) are low-grade, well-circumscribed tumors that often involve the conus medullaris, cauda equina, or filum terminale. They account for up to 5% of all tumors of the spine and 13% of spinal ependymomas, with a peak incidence between 30 and 50 years of age. Because of the rarity of MPEs, their clinical course and optimal management strategy are not well defined, and long-term outcomes remain difficult to predict. The objective of this study was to review long-term clinical outcomes of spinal MPEs and identify factors that may predict tumor resectability and recurrence. METHODS: Pathologically confirmed cases of MPE at the authors' institution were identified and medical records were reviewed. Demographics, clinical presentation, imaging characteristics, surgical technique, follow-up, and outcome data were noted. Two groups of patients-those who underwent gross-total resection (GTR) and those who underwent subtotal resection (STR)-were compared using the Mann-Whitney U-test for continuous and ordinal variables and the Fisher exact test for categorical variables. Differences were considered statistically significant at p ≤ 0.05. RESULTS: Twenty-eight patients were identified, with a median age of 43 years at the index surgery. The median postoperative follow-up duration was 107 months (range 5-372 months). All patients presented with pain. Other common presenting symptoms were weakness (25.0%), sphincter disturbance (21.4%), and numbness (14.3%). GTR was achieved in 19 patients (68%) and STR in 9 (32%). Preoperative weakness and involvement of the sacral spinal canal were more common in the STR group. Tumors were larger and spanned more spinal levels in the STR group compared with the GTR cohort. Postoperative modified McCormick Scale grades were significantly higher in the STR cohort compared with the GTR group (p = 0.00175). Seven of the 9 STR patients (77.8%) underwent reoperation for recurrence at a median of 32 months from the index operation, while no patients required reoperation after GTR, for an overall reoperation rate of 25%. CONCLUSIONS: Findings of this study emphasize the importance of tumor size and location-particularly involvement of the sacral canal-in determining resectability. Reoperation for recurrence was necessary in 78% of patients with subtotally resected tumors; none of the patients who underwent GTR required reoperation. Most patients had stable neurological status postoperatively.

High-dimensional multivariate autoregressive model estimation of human electrophysiological data using fMRI priors.

Multivariate autoregressive (MVAR) model estimation enables assessment of causal interactions in brain networks. However, accurately estimating MVAR models for high-dimensional electrophysiological recordings is challenging due to the extensive data requirements. Hence, the applicability of MVAR models for study of brain behavior over hundreds of recording sites has been very limited. Prior work has focused on different strategies for selecting a subset of important MVAR coefficients in the model to reduce the data requirements of conventional least-squares estimation algorithms. Here we propose incorporating prior information, such as resting state functional connectivity derived from functional magnetic resonance imaging, into MVAR model estimation using a weighted group least absolute shrinkage and selection operator (LASSO) regularization strategy. The proposed approach is shown to reduce data requirements by a factor of two relative to the recently proposed group LASSO method of Endemann et al (Neuroimage 254:119057, 2022) while resulting in models that are both more parsimonious and more accurate. The effectiveness of the method is demonstrated using simulation studies of physiologically realistic MVAR models derived from intracranial electroencephalography (iEEG) data. The robustness of the approach to deviations between the conditions under which the prior information and iEEG data is obtained is illustrated using models from data collected in different sleep stages. This approach allows accurate effective connectivity analyses over short time scales, facilitating investigations of causal interactions in the brain underlying perception and cognition during rapid transitions in behavioral state.

Intracranial electrophysiology of spectrally degraded speech in the human cortex.

Introduction: Cochlear implants (CIs) are the treatment of choice for severe to profound hearing loss. Variability in CI outcomes remains despite advances in technology and is attributed in part to differences in cortical processing. Studying these differences in CI users is technically challenging. Spectrally degraded stimuli presented to normal-hearing individuals approximate input to the central auditory system in CI users. This study used intracranial electroencephalography (iEEG) to investigate cortical processing of spectrally degraded speech. Methods: Participants were adult neurosurgical epilepsy patients. Stimuli were utterances /aba/ and /ada/, spectrally degraded using a noise vocoder (1-4 bands) or presented without vocoding. The stimuli were presented in a two-alternative forced choice task. Cortical activity was recorded using depth and subdural iEEG electrodes. Electrode coverage included auditory core in posteromedial Heschl's gyrus (HGPM), superior temporal gyrus (STG), ventral and dorsal auditory-related areas, and prefrontal and sensorimotor cortex. Analysis focused on high gamma (70-150 Hz) power augmentation and alpha (8-14 Hz) suppression. Results: Chance task performance occurred with 1-2 spectral bands and was near-ceiling for clear stimuli. Performance was variable with 3-4 bands, permitting identification of good and poor performers. There was no relationship between task performance and participants demographic, audiometric, neuropsychological, or clinical profiles. Several response patterns were identified based on magnitude and differences between stimulus conditions. HGPM responded strongly to all stimuli. A preference for clear speech emerged within non-core auditory cortex. Good performers typically had strong responses to all stimuli along the dorsal stream, including posterior STG, supramarginal, and precentral gyrus; a minority of sites in STG and supramarginal gyrus had a preference for vocoded stimuli. In poor performers, responses were typically restricted to clear speech. Alpha suppression was more pronounced in good performers. In contrast, poor performers exhibited a greater involvement of posterior middle temporal gyrus when listening to clear speech. Discussion: Responses to noise-vocoded speech provide insights into potential factors underlying CI outcome variability. The results emphasize differences in the balance of neural processing along the dorsal and ventral stream between good and poor performers, identify specific cortical regions that may have diagnostic and prognostic utility, and suggest potential targets for neuromodulation-based CI rehabilitation strategies.

Spinal Nerve Sheath Tumors: Factors Associated with Postoperative Residual and Recurrent Tumors: A Single-Center Experience.

BACKGROUND: Spinal schwannomas (SSs) are usually benign tumors with a good prognosis when treated by surgical excision. However, complete resection can be complicated by factors such as the tumor location and configuration. In the present study, we sought to identify the factors associated with incomplete surgical resection (residual) and the factors associated with tumor recurrence. METHODS: We performed a retrospective review of 113 cases of SSs treated surgically from 2008 to 2021. RESULTS: Of the 113 SSs, 102 were benign and 2 were malignant nerve sheath tumors. Of the 102 benign SSs, gross total resection (GTR) was performed for 87, with 8 displaying residual and 7, recurrent tumor. We found a significantly higher ratio of cervical and sacral tumors (P = 0.008 and P = 0.004, respectively), dumbbell and foraminal configurations (P < 0.0001 and P = 0.0006, respectively), and larger tumor volumes (P = 0.003) in the residual and recurrent cohorts compared with the GTR cohort. A second operation was performed for 2 patients in the residual and 4 patients in the recurrent cohorts. The total complication rate was 6%. CONCLUSIONS: We found that most benign SSs will be amenable to GTR (85% of cases), with an excellent prognosis. The patients with residual or recurrent tumor were more likely to have had a cervical or sacral location, a dumbbell or foraminal configuration, and a larger tumor volume. Except for 1 new SS and 1 recurrent tumor that had necessitated a lateral approach, the remainder had been treated using a posterior approach. At surgery, ultrasonography of the canal is advisable to ensure that the intra- and extraspinal components of dumbbell lesions have both been entirely removed.

Biomechanical assessment of the effect of sublaminar band tensioning on lumbar motion.

OBJECTIVE: Adjacent-segment disease (ASD) proximal to lumbosacral fusion is assumed to result from increased stress and motion that extends above or below the fusion construct. Sublaminar bands (SBs) have been shown to potentially mitigate stresses in deformity constructs. A similar application of SBs in lumbar fusions is not well described yet may potentially mitigate against ASD. METHODS: Eight fresh-frozen human cadaveric spine specimens were instrumented with transforaminal lumbar interbody fusion (TLIF) cages at L3-4 and L4-5, and pedicle screws from L3 to S1. Bilateral SBs were applied at L2 and tightened around the rods extending above the L3 pedicle screws. After being mounted on a testing frame, the spines were loaded at L1 to 6 Nm in all 3 planes, i.e., flexion/extension, right and left lateral bending, and right and left axial rotation. Motion and intradiscal pressures (IDPs) at L2-3 were measured for 5 conditions: intact, instrumentation (L3-S1), band tension (BT) 30%, BT 50%, and BT 100%. RESULTS: There was significant increase in motion at L2-3 with L3-S1 instrumentation compared with the intact spine in flexion/extension (median 8.78°, range 4.07°-10.81°, vs median 7.27°, range 1.63°-9.66°; p = 0.016). When compared with instrumentation, BT 100% reduced motion at L2-3 in flexion/extension (median 8.78°, range 4.07°-10.81°, vs median 3.61°, range 1.11°-9.39°; p < 0.001) and lateral bending (median 6.58°, range 3.67°-8.59°, vs median 5.62°, range 3.28°-6.74°; p = 0.001). BT 50% reduced motion at L2-3 only in flexion/extension when compared with instrumentation (median 8.78°, range 4.07°-10.81°, vs median 5.91°, range 2.54°-10.59°; p = 0.027). There was no significant increase of motion at L1-2 with banding when compared with instrumentation, although an increase was seen from the intact spine with BT 100% in flexion/extension (median 5.14°, range 2.47°-9.73°, vs median 7.34°, range 4.22°-9.89°; p = 0.005). BT 100% significantly reduced IDP at L2-3 from 25.07 psi (range 2.41-48.08 psi) before tensioning to 19.46 psi (range -2.35 to 29.55 psi) after tensioning (p = 0.016). CONCLUSIONS: In this model, the addition of L2 SBs reduced motion and IDP at L2-3 after the L3-S1 instrumentation. There was no significant increase in motion at L1-2 in response to band tensioning compared with instrumentation alone. The application of SBs may have a clinical application in reducing the incidence of ASD.

Spinal Meningioma in Adults: Imaging Characteristics, Surgical Outcomes, and Risk Factors for Recurrence.

OBJECTIVE: Although spinal meningiomas (SMs) are associated with overall long tumor-free survival, SMs can recur. This study analyzed factors associated with complications, misdiagnosis, and recurrence of SMs. METHODS: We reviewed patient demographics; radiographic characteristics of patients with SMs, including level, location within the canal, and size; surgical resection; pathology; and recurrence. RESULTS: The study included 64 women and 10 men (74 SMs). Of patients, 64 showed no recurrence after surgery with a median (range) follow-up of 17 (1-99) months. Recurrence was identified in 10 patients (13.5%) during a median (range) follow-up of 66 (25-230) months. There was no significant difference in sex between the recurrence and no recurrence cohorts. Patients in the recurrence cohort were significantly younger (median [range] age 58 [35-70] years) than patients in the no recurrence cohort (median [range] age 69 [18-93] years; P = 0.0091). There was significant predilection for foraminal locations in the recurrence cohort (P < 0.001) compared with the no recurrence cohort. SM was correctly identified on preoperative magnetic resonance imaging or computed tomography myelography in 62 of 64 tumors (96.9%) in the no recurrence cohort, but in only 6 of 10 tumors (60%) in the recurrence cohort (P < 0.001). CONCLUSIONS: In 74 patients with SMs, a preponderance of female patients and a predilection of tumors for the thoracic spine were shown. Recurrence was significantly more common in younger than older patients. Risk factors for recurrence included larger tumors, foraminal location, and en plaque lesions. Patients who developed recurrence were significantly more likely to have been misdiagnosed on preoperative imaging with nerve sheath tumors or lymphoma.

Gamma Activation and Alpha Suppression within Human Auditory Cortex during a Speech Classification Task.

The dynamics of information flow within the auditory cortical hierarchy associated with speech processing and the emergence of hemispheric specialization remain incompletely understood. To study these questions with high spatiotemporal resolution, intracranial recordings in 29 human neurosurgical patients of both sexes were obtained while subjects performed a semantic classification task. Neural activity was recorded from posteromedial portion of Heschl's gyrus (HGPM) and anterolateral portion of Heschl's gyrus (HGAL), planum temporale (PT), planum polare, insula, and superior temporal gyrus (STG). Responses to monosyllabic words exhibited early gamma power increases and a later suppression of alpha power, envisioned to represent feedforward activity and decreased feedback signaling, respectively. Gamma activation and alpha suppression had distinct magnitude and latency profiles. HGPM and PT had the strongest gamma responses with shortest onset latencies, indicating that they are the earliest auditory cortical processing stages. The origin of attenuated top-down influences in auditory cortex, as indexed by alpha suppression, was in STG and HGAL. Gamma responses and alpha suppression were typically larger to nontarget words than tones. Alpha suppression was uniformly greater to target versus nontarget stimuli. Hemispheric bias for words versus tones and for target versus nontarget words, when present, was left lateralized. Better task performance was associated with increased gamma activity in the left PT and greater alpha suppression in HGPM and HGAL bilaterally. The prominence of alpha suppression during semantic classification and its accessibility for noninvasive electrophysiologic studies suggests that this measure is a promising index of auditory cortical speech processing.SIGNIFICANCE STATEMENT Understanding the dynamics of cortical speech processing requires the use of active tasks. This is the first comprehensive intracranial electroencephalography study to examine cortical activity within the superior temporal plane, lateral superior temporal gyrus, and the insula during a semantic classification task. Distinct gamma activation and alpha suppression profiles clarify the functional organization of feedforward and feedback processing within the auditory cortical hierarchy. Asymmetries in cortical speech processing emerge at early processing stages. Relationships between cortical activity and task performance are interpreted in the context of current models of speech processing. Results lay the groundwork for iEEG studies using connectivity measures of the bidirectional information flow within the auditory processing hierarchy.

Multivariate autoregressive model estimation for high-dimensional intracranial electrophysiological data.

Fundamental to elucidating the functional organization of the brain is the assessment of causal interactions between different brain regions. Multivariate autoregressive (MVAR) modeling techniques applied to multisite electrophysiological recordings are a promising avenue for identifying such causal links. They estimate the degree to which past activity in one or more brain regions is predictive of another region's present activity, while simultaneously accounting for the mediating effects of other regions. Including as many mediating variables as possible in the model has the benefit of drastically reducing the odds of detecting spurious causal connectivity. However, effective bounds on the number of MVAR model coefficients that can be estimated reliably from limited data make exploiting the potential of MVAR models challenging for even modest numbers of recording sites. Here, we utilize well-established dimensionality-reduction techniques to fit MVAR models to human intracranial data from ∼100 - 200 recording sites spanning dozens of anatomically and functionally distinct cortical regions. First, we show that high-dimensional MVAR models can be successfully estimated from long segments of data and yield plausible connectivity profiles. Next, we use these models to generate synthetic data with known ground-truth connectivity to explore the utility of applying principal component analysis and group least absolute shrinkage and selection operator (gLASSO) to reduce the number of parameters (connections) during model fitting to shorter data segments. We show that gLASSO is highly effective for recovering ground-truth connectivity in the limited data regime, capturing important features of connectivity for high-dimensional models with as little as 10 seconds of data. The methods presented here have broad applicability to the analysis of high-dimensional time series data in neuroscience, facilitating the elucidation of the neural basis of sensation, cognition, and arousal.

Human intracranial recordings reveal distinct cortical activity patterns during invasive and non-invasive vagus nerve stimulation.

Vagus nerve stimulation (VNS) is being used increasingly to treat a wide array of diseases and disorders. This growth is driven in part by the putative ability to stimulate the nerve non-invasively. Despite decades of use and a rapidly expanding application space, we lack a complete understanding of the acute effects of VNS on human cortical neurophysiology. Here, we investigated cortical responses to sub-perceptual threshold cervical implanted (iVNS) and transcutaneous auricular (taVNS) vagus nerve stimulation using intracranial neurophysiological recordings in human epilepsy patients. To understand the areas that are modulated by VNS and how they differ depending on invasiveness and stimulation parameters, we compared VNS-evoked neural activity across a range of stimulation modalities, frequencies, and amplitudes. Using comparable stimulation parameters, both iVNS and taVNS caused subtle changes in low-frequency power across broad cortical networks, which were not the same across modalities and were highly variable across participants. However, within at least some individuals, it may be possible to elicit similar responses across modalities using distinct sets of stimulation parameters. These results demonstrate that both invasive and non-invasive VNS cause evoked changes in activity across a set of highly distributed cortical networks that are relevant to a diverse array of clinical, rehabilitative, and enhancement applications.

Arousal State-Dependence of Interactions Between Short- and Long-Term Auditory Novelty Responses in Human Subjects.

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.

Learning nonnative speech sounds changes local encoding in the adult human cortex.

Adults can learn to identify nonnative speech sounds with training, albeit with substantial variability in learning behavior. Increases in behavioral accuracy are associated with increased separability for sound representations in cortical speech areas. However, it remains unclear whether individual auditory neural populations all show the same types of changes with learning, or whether there are heterogeneous encoding patterns. Here, we used high-resolution direct neural recordings to examine local population response patterns, while native English listeners learned to recognize unfamiliar vocal pitch patterns in Mandarin Chinese tones. We found a distributed set of neural populations in bilateral superior temporal gyrus and ventrolateral frontal cortex, where the encoding of Mandarin tones changed throughout training as a function of trial-by-trial accuracy ("learning effect"), including both increases and decreases in the separability of tones. These populations were distinct from populations that showed changes as a function of exposure to the stimuli regardless of trial-by-trial accuracy. These learning effects were driven in part by more variable neural responses to repeated presentations of acoustically identical stimuli. Finally, learning effects could be predicted from speech-evoked activity even before training, suggesting that intrinsic properties of these populations make them amenable to behavior-related changes. Together, these results demonstrate that nonnative speech sound learning involves a wide array of changes in neural representations across a distributed set of brain regions.

Cortical Responses to Vowel Sequences in Awake and Anesthetized States: A Human Intracranial Electrophysiology 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.

Common fronto-temporal effective connectivity in humans and monkeys.

Human brain pathways supporting language and declarative memory are thought to have differentiated substantially during evolution. However, cross-species comparisons are missing on site-specific effective connectivity between regions important for cognition. We harnessed functional imaging to visualize the effects of direct electrical brain stimulation in macaque monkeys and human neurosurgery patients. We discovered comparable effective connectivity between caudal auditory cortex and both ventro-lateral prefrontal cortex (VLPFC, including area 44) and parahippocampal cortex in both species. Human-specific differences were clearest in the form of stronger hemispheric lateralization effects. In humans, electrical tractography revealed remarkably rapid evoked potentials in VLPFC following auditory cortex stimulation and speech sounds drove VLPFC, consistent with prior evidence in monkeys of direct auditory cortex projections to homologous vocalization-responsive regions. The results identify a common effective connectivity signature in human and nonhuman primates, which from auditory cortex appears equally direct to VLPFC and indirect to the hippocampus. VIDEO ABSTRACT.