Decoding reveals the neural representation of perceived and imagined musical sounds.

Vividly imagining a song or a melody is a skill that many people accomplish with relatively little effort. However, we are only beginning to understand how the brain represents, holds, and manipulates these musical "thoughts." Here, we decoded perceived and imagined melodies from magnetoencephalography (MEG) brain data (N = 71) to characterize their neural representation. We found that, during perception, auditory regions represent the sensory properties of individual sounds. In contrast, a widespread network including fronto-parietal cortex, hippocampus, basal nuclei, and sensorimotor regions hold the melody as an abstract unit during both perception and imagination. Furthermore, the mental manipulation of a melody systematically changes its neural representation, reflecting volitional control of auditory images. Our work sheds light on the nature and dynamics of auditory representations, informing future research on neural decoding of auditory imagination.

Differential neural mechanisms underlie cortical gating of visual spatial attention mediated by alpha-band oscillations.

Selective attention relies on neural mechanisms that facilitate processing of behaviorally relevant sensory information while suppressing irrelevant information, consistently linked to alpha-band oscillations in human M/EEG studies. We analyzed cortical alpha responses from intracranial electrodes implanted in eight epilepsy patients, who performed a visual spatial attention task. Electrocorticographic data revealed a spatiotemporal dissociation between attention-modulated alpha desynchronization, associated with the enhancement of sensory processing, and alpha synchronization, associated with the suppression of sensory processing, during the cue-target interval. Dorsal intraparietal areas contralateral to the attended hemifield primarily exhibited a delayed and sustained alpha desynchronization, while ventrolateral extrastriatal areas ipsilateral to the attended hemifield primarily exhibited an earlier and sustained alpha synchronization. Analyses of cross-frequency coupling between alpha phase and broadband high-frequency activity (HFA) further revealed cross-frequency interactions along the visual hierarchy contralateral to the attended locations. Directionality analyses indicate that alpha phase in early and extrastriatal visual areas modulated HFA power in downstream visual areas, thus potentially facilitating the feedforward processing of an upcoming, spatially predictable target. In contrast, in areas ipsilateral to the attended locations, HFA power modulated local alpha phase in early and extrastriatal visual areas, with suppressed interareal interactions, potentially attenuating the processing of distractors. Our findings reveal divergent alpha-mediated neural mechanisms underlying target enhancement and distractor suppression during the deployment of spatial attention, reflecting enhanced functional connectivity at attended locations, while suppressed functional connectivity at unattended locations. The collective dynamics of these alpha-mediated neural mechanisms play complementary roles in the efficient gating of sensory information.

Music can be reconstructed from human auditory cortex activity using nonlinear decoding models.

Music is core to human experience, yet the precise neural dynamics underlying music perception remain unknown. We analyzed a unique intracranial electroencephalography (iEEG) dataset of 29 patients who listened to a Pink Floyd song and applied a stimulus reconstruction approach previously used in the speech domain. We successfully reconstructed a recognizable song from direct neural recordings and quantified the impact of different factors on decoding accuracy. Combining encoding and decoding analyses, we found a right-hemisphere dominance for music perception with a primary role of the superior temporal gyrus (STG), evidenced a new STG subregion tuned to musical rhythm, and defined an anterior-posterior STG organization exhibiting sustained and onset responses to musical elements. Our findings show the feasibility of applying predictive modeling on short datasets acquired in single patients, paving the way for adding musical elements to brain-computer interface (BCI) applications.

Subspace partitioning in the human prefrontal cortex resolves cognitive interference.

The human prefrontal cortex (PFC) constitutes the structural basis underlying flexible cognitive control, where mixed-selective neural populations encode multiple task features to guide subsequent behavior. The mechanisms by which the brain simultaneously encodes multiple task-relevant variables while minimizing interference from task-irrelevant features remain unknown. Leveraging intracranial recordings from the human PFC, we first demonstrate that competition between coexisting representations of past and present task variables incurs a behavioral switch cost. Our results reveal that this interference between past and present states in the PFC is resolved through coding partitioning into distinct low-dimensional neural states; thereby strongly attenuating behavioral switch costs. In sum, these findings uncover a fundamental coding mechanism that constitutes a central building block of flexible cognitive control.

Low-Frequency Oscillations in Mid-rostral Dorsolateral Prefrontal Cortex Support Response Inhibition.

Executive control of movement enables inhibiting impulsive responses critical for successful navigation of the environment. Circuits mediating stop commands involve prefrontal and basal ganglia structures with fMRI evidence demonstrating increased activity during response inhibition in the dorsolateral prefrontal cortex (dlPFC)-often ascribed to maintaining task attentional demands. Using direct intraoperative cortical recordings in male and female human subjects, we investigated oscillatory dynamics along the rostral-caudal axis of dlPFC during a modified Go/No-go task, probing components of both proactive and reactive motor control. We assessed whether cognitive control is topographically organized along this axis and observed that low-frequency power increased prominently in mid-rostral dlPFC when inhibiting and delaying responses. These findings provide evidence for a key role for mid-rostral dlPFC low-frequency oscillations in sculpting motor control.

A Comparison of Rapid Rule-Learning Strategies in Humans and Monkeys.

Interspecies comparisons are key to deriving an understanding of the behavioral and neural correlates of human cognition from animal models. We perform a detailed comparison of the strategies of female macaque monkeys to male and female humans on a variant of the Wisconsin Card Sorting Test (WCST), a widely studied and applied task that provides a multiattribute measure of cognitive function and depends on the frontal lobe. WCST performance requires the inference of a rule change given ambiguous feedback. We found that well-trained monkeys infer new rules three times more slowly than minimally instructed humans. Input-dependent hidden Markov model-generalized linear models were fit to their choices, revealing hidden states akin to feature-based attention in both species. Decision processes resembled a win-stay, lose-shift strategy with interspecies similarities as well as key differences. Monkeys and humans both test multiple rule hypotheses over a series of rule-search trials and perform inference-like computations to exclude candidate choice options. We quantitatively show that perseveration, random exploration, and poor sensitivity to negative feedback account for the slower task-switching performance in monkeys.

Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease. METHODS: We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function. RESULTS: Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = -2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged. INTERPRETATION: Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205-1219.

Predictable and unpredictable deviance detection in the human hippocampus and amygdala.

Our brains extract structure from the environment and form predictions given past experience. Predictive circuits have been identified in wide-spread cortical regions. However, the contribution of medial temporal structures in predictions remains under-explored. The hippocampus underlies sequence detection and is sensitive to novel stimuli, sufficient to gain access to memory, while the amygdala to novelty. Yet, their electrophysiological profiles in detecting predictable and unpredictable deviant auditory events remain unknown. Here, we hypothesized that the hippocampus would be sensitive to predictability, while the amygdala to unexpected deviance. We presented epileptic patients undergoing presurgical monitoring with standard and deviant sounds, in predictable or unpredictable contexts. Onsets of auditory responses and unpredictable deviance effects were detected earlier in the temporal cortex compared with the amygdala and hippocampus. Deviance effects in 1-20 Hz local field potentials were detected in the lateral temporal cortex, irrespective of predictability. The amygdala showed stronger deviance in the unpredictable context. Low-frequency deviance responses in the hippocampus (1-8 Hz) were observed in the predictable but not in the unpredictable context. Our results reveal a distributed network underlying the generation of auditory predictions and suggest that the neural basis of sensory predictions and prediction error signals needs to be extended.

Differential contribution of sensorimotor cortex and subthalamic nucleus to unimanual and bimanual hand movements.

Why does unilateral deep brain stimulation improve motor function bilaterally? To address this clinical observation, we collected parallel neural recordings from sensorimotor cortex (SMC) and the subthalamic nucleus (STN) during repetitive ipsilateral, contralateral, and bilateral hand movements in patients with Parkinson's disease. We used a cross-validated electrode-wise encoding model to map electromyography data to the neural signals. Electrodes in the STN encoded movement at a comparable level for both hands, whereas SMC electrodes displayed a strong contralateral bias. To examine representational overlap across the two hands, we trained the model with data from one condition (contralateral hand) and used the trained weights to predict neural activity for movements produced with the other hand (ipsilateral hand). Overall, between-hand generalization was poor, and this limitation was evident in both regions. A similar method was used to probe representational overlap across different task contexts (unimanual vs. bimanual). Task context was more important for the STN compared to the SMC indicating that neural activity in the STN showed greater divergence between the unimanual and bimanual conditions. These results indicate that SMC activity is strongly lateralized and relatively context-free, whereas the STN integrates contextual information with the ongoing behavior.

Consciousness is supported by near-critical slow cortical electrodynamics.

Mounting evidence suggests that during conscious states, the electrodynamics of the cortex are poised near a critical point or phase transition and that this near-critical behavior supports the vast flow of information through cortical networks during conscious states. Here, we empirically identify a mathematically specific critical point near which waking cortical oscillatory dynamics operate, which is known as the edge-of-chaos critical point, or the boundary between stability and chaos. We do so by applying the recently developed modified 0-1 chaos test to electrocorticography (ECoG) and magnetoencephalography (MEG) recordings from the cortices of humans and macaques across normal waking, generalized seizure, anesthesia, and psychedelic states. Our evidence suggests that cortical information processing is disrupted during unconscious states because of a transition of low-frequency cortical electric oscillations away from this critical point; conversely, we show that psychedelics may increase the information richness of cortical activity by tuning low-frequency cortical oscillations closer to this critical point. Finally, we analyze clinical electroencephalography (EEG) recordings from patients with disorders of consciousness (DOC) and show that assessing the proximity of slow cortical oscillatory electrodynamics to the edge-of-chaos critical point may be useful as an index of consciousness in the clinical setting.

Electrocorticographic Activation Patterns of Electroencephalographic Microstates.

Electroencephalography (EEG) microstates are short successive periods of stable scalp field potentials representing spontaneous activation of brain resting-state networks. EEG microstates are assumed to mediate local activity patterns. To test this hypothesis, we correlated momentary global EEG microstate dynamics with the local temporo-spectral evolution of electrocorticography (ECoG) and stereotactic EEG (SEEG) depth electrode recordings. We hypothesized that these correlations involve the gamma band. We also hypothesized that the anatomical locations of these correlations would converge with those of previous studies using either combined functional magnetic resonance imaging (fMRI)-EEG or EEG source localization. We analyzed resting-state data (5 min) of simultaneous noninvasive scalp EEG and invasive ECoG and SEEG recordings of two participants. Data were recorded during the presurgical evaluation of pharmacoresistant epilepsy using subdural and intracranial electrodes. After standard preprocessing, we fitted a set of normative microstate template maps to the scalp EEG data. Using covariance mapping with EEG microstate timelines and ECoG/SEEG temporo-spectral evolutions as inputs, we identified systematic changes in the activation of ECoG/SEEG local field potentials in different frequency bands (theta, alpha, beta, and high-gamma) based on the presence of particular microstate classes. We found significant covariation of ECoG/SEEG spectral amplitudes with microstate timelines in all four frequency bands (p = 0.001, permutation test). The covariance patterns of the ECoG/SEEG electrodes during the different microstates of both participants were similar. To our knowledge, this is the first study to demonstrate distinct activation/deactivation patterns of frequency-domain ECoG local field potentials associated with simultaneous EEG microstates.

Grasp-specific high-frequency broadband mirror neuron activity during reach-and-grasp movements in humans.

Broadly congruent mirror neurons, responding to any grasp movement, and strictly congruent mirror neurons, responding only to specific grasp movements, have been reported in single-cell studies with primates. Delineating grasp properties in humans is essential to understand the human mirror neuron system with implications for behavior and social cognition. We analyzed electrocorticography data from a natural reach-and-grasp movement observation and delayed imitation task with 3 different natural grasp types of everyday objects. We focused on the classification of grasp types from high-frequency broadband mirror activation patterns found in classic mirror system areas, including sensorimotor, supplementary motor, inferior frontal, and parietal cortices. Classification of grasp types was successful during movement observation and execution intervals but not during movement retention. Our grasp type classification from combined and single mirror electrodes provides evidence for grasp-congruent activity in the human mirror neuron system potentially arising from strictly congruent mirror neurons.

Unexpected sound omissions are signaled in human posterior superior temporal gyrus: an intracranial study.

Context modulates sensory neural activations enhancing perceptual and behavioral performance and reducing prediction errors. However, the mechanism of when and where these high-level expectations act on sensory processing is unclear. Here, we isolate the effect of expectation absent of any auditory evoked activity by assessing the response to omitted expected sounds. Electrocorticographic signals were recorded directly from subdural electrode grids placed over the superior temporal gyrus (STG). Subjects listened to a predictable sequence of syllables, with some infrequently omitted. We found high-frequency band activity (HFA, 70-170 Hz) in response to omissions, which overlapped with a posterior subset of auditory-active electrodes in STG. Heard syllables could be distinguishable reliably from STG, but not the identity of the omitted stimulus. Both omission- and target-detection responses were also observed in the prefrontal cortex. We propose that the posterior STG is central for implementing predictions in the auditory environment. HFA omission responses in this region appear to index mismatch-signaling or salience detection processes.

Distinct electrophysiological signatures of task-unrelated and dynamic thoughts.

Humans spend much of their lives engaging with their internal train of thoughts. Traditionally, research focused on whether or not these thoughts are related to ongoing tasks, and has identified reliable and distinct behavioral and neural correlates of task-unrelated and task-related thought. A recent theoretical framework highlighted a different aspect of thinking-how it dynamically moves between topics. However, the neural correlates of such thought dynamics are unknown. The current study aimed to determine the electrophysiological signatures of these dynamics by recording electroencephalogram (EEG) while participants performed an attention task and periodically answered thought-sampling questions about whether their thoughts were 1) task-unrelated, 2) freely moving, 3) deliberately constrained, and 4) automatically constrained. We examined three EEG measures across different time windows as a function of each thought type: stimulus-evoked P3 event-related potentials and non-stimulus-evoked alpha power and variability. Parietal P3 was larger for task-related relative to task-unrelated thoughts, whereas frontal P3 was increased for deliberately constrained compared with unconstrained thoughts. Frontal electrodes showed enhanced alpha power for freely moving thoughts relative to non-freely moving thoughts. Alpha-power variability was increased for task-unrelated, freely moving, and unconstrained thoughts. Our findings indicate distinct electrophysiological patterns associated with task-unrelated and dynamic thoughts, suggesting these neural measures capture the heterogeneity of our ongoing thoughts.

Coupling between slow waves and sharp-wave ripples engages distributed neural activity during sleep in humans.

Hippocampal-dependent memory consolidation during sleep is hypothesized to depend on the synchronization of distributed neuronal ensembles, organized by the hippocampal sharp-wave ripples (SWRs, 80 to 150 Hz), subcortical/cortical slow-wave activity (SWA, 0.5 to 4 Hz), and sleep spindles (SP, 7 to 15 Hz). However, the precise role of these interactions in synchronizing subcortical/cortical neuronal activity is unclear. Here, we leverage intracranial electrophysiological recordings from the human hippocampus, amygdala, and temporal and frontal cortices to examine activity modulation and cross-regional coordination during SWRs. Hippocampal SWRs are associated with widespread modulation of high-frequency activity (HFA, 70 to 200 Hz), a measure of local neuronal activation. This peri-SWR HFA modulation is predicted by the coupling between hippocampal SWRs and local subcortical/cortical SWA or SP. Finally, local cortical SWA phase offsets and SWR amplitudes predicted functional connectivity between the frontal and temporal cortex during individual SWRs. These findings suggest a selection mechanism wherein hippocampal SWR and cortical slow-wave synchronization governs the transient engagement of distributed neuronal populations supporting hippocampal-dependent memory consolidation.

Multiple memory systems for efficient temporal order memory.

We report distinct contributions of multiple memory systems to the retrieval of the temporal order of events. The neural dynamics related to the retrieval of movie scenes revealed that recalling the temporal order of close events elevates hippocampal theta power, like that observed for recalling close spatial relationships. In contrast, recalling far events increases beta power in the orbitofrontal cortex, reflecting recall based on the overall movie structure.

Enhancer trap lines with GFP driven by smad6b and frizzled1 regulatory sequences for the study of epithelial morphogenesis in the developing zebrafish inner ear.

Live imaging in the zebrafish embryo using tissue-specific expression of fluorescent proteins can yield important insights into the mechanisms that drive sensory organ morphogenesis and cell differentiation. Morphogenesis of the semicircular canal ducts of the vertebrate inner ear requires a complex rearrangement of epithelial cells, including outgrowth, adhesion, fusion and perforation of epithelial projections to generate pillars of tissue that form the hubs of each canal. We report the insertion sites and expression patterns of two enhancer trap lines in the developing zebrafish embryo, each of which highlight different aspects of epithelial cell morphogenesis in the inner ear. A membrane-linked EGFP driven by smad6b regulatory sequences is expressed throughout the otic epithelium, most strongly on the lateral side of the ear and in the sensory cristae. A second enhancer trap line, with cytoplasmic EGFP driven by frizzled1 (fzd1) regulatory sequences, specifically marks cells of the ventral projection and pillar in the developing ear, and marginal cells in the sensory cristae, together with variable expression in the retina and epiphysis, and neurons elsewhere in the developing central nervous system. We have used a combination of methods to identify the insertion sites of these two transgenes, which were generated through random insertion, and show that Targeted Locus Amplification is a rapid and reliable method for the identification of insertion sites of randomly inserted transgenes.

Future regenerative therapies for corneal disease.

PURPOSE OF REVIEW: To highlight the progress and future direction of stem-cell based regenerative therapies for the treatment of corneal disease. RECENT FINDINGS: Corneal stem cell-based therapies, such as limbal stem cell transplantation, corneal stromal stem cell transplantation, endothelial stem cell transplantation, and stem cell-derived extracellular vesicles have demonstrated promising results in the laboratory. Although most are still in preclinical development or early phase clinical trials, these stem cell-based therapies hold potential to facilitate tissue regeneration, restore native function, and inhibit pathologic disease processes such as fibrosis, inflammation, and neovascularization. SUMMARY: Stem cell-based therapy offers a promising therapeutic option that can circumvent several of the challenges and limitations of traditional surgical treatment. This concise review summarizes the progress in stem-cell based therapies for corneal diseases along with their history, underlying mechanisms, limitations, and future areas for development.

Contemporary Trends in Antiseptic Pocket Rinse in Primary Breast Implant Surgery.

BACKGROUND: Broad evidence supports the use of antiseptic pocket rinse in breast implant surgery to minimize the risk of capsular contracture or other complications. However, there is limited consensus or standardization of antiseptic rinse in practice. OBJECTIVES: In this preliminary study, we sought to determine contemporary trends in antiseptic rinse use in primary breast implant surgery based on Australian Breast Device Registry (ABDR) data, and whether these trends align with the suggestions of the 14-point plan.2 This further served as a feasibility study for subsequent comparison of antiseptic rinse effects on clinical outcomes. METHODS: Institutional ethics approval was obtained and national ABDR data for primary breast implant surgery from 2015-2020 was analysed for the use, and type, of antiseptic rinse. The surgeon-reported data was homogenized for terminology and categorized into major trends, and the literature reviewed. RESULTS: We analysed data for 37,143 patients, totalling 73,935 primary implants. Antiseptic rinse included Povidone-Iodine (PVP-I) in 35,859 (48.5%), no antiseptic use in 24,216 (32.8%), other concentrations of PVP-I in 4,200 (5.7%), and 'Betadine® triple antibiotic'1 in 1,831 implants (2.5%). Multiple other antiseptic permutations were noted in 7,004 implants (9.5%). CONCLUSIONS: The majority (56.7%) of Australian practitioners utilise previously-described antiseptic pocket irrigation solutions which align with the 14-point plan. A third (32.8%), however, do not record any antiseptic pocket irrigation use. These findings will permit a subsequent (ongoing) study of outcomes comparing PVP-I to no antiseptic pocket rinse that will likely constitute the largest study of its kind.

Frontotemporal Regulation of Subjective Value to Suppress Impulsivity in Intertemporal Choices.

Impulsive decisions arise from preferring smaller but sooner rewards compared with larger but later rewards. How neural activity and attention to choice alternatives contribute to reward decisions during temporal discounting is not clear. Here we probed (1) attention to and (2) neural representation of delay and reward information in humans (both sexes) engaged in choices. We studied behavioral and frequency-specific dynamics supporting impulsive decisions on a fine-grained temporal scale using eye tracking and MEG recordings. In one condition, participants had to decide for themselves but pretended to decide for their best friend in a second prosocial condition, which required perspective taking. Hence, conditions varied in the value for themselves versus that pretending to choose for another person. Stronger impulsivity was reliably found across three independent groups for prosocial decisions. Eye tracking revealed a systematic shift of attention from the delay to the reward information and differences in eye tracking between conditions predicted differences in discounting. High-frequency activity (175-250 Hz) distributed over right frontotemporal sensors correlated with delay and reward information in consecutive temporal intervals for high value decisions for oneself but not the friend. Collectively, the results imply that the high-frequency activity recorded over frontotemporal MEG sensors plays a critical role in choice option integration.SIGNIFICANCE STATEMENT Humans face decisions between sooner smaller rewards and larger later rewards daily. An objective benefit of losing weight over a longer time might be devalued in face of ice cream because they prefer currently available options because of insufficiently considering long-term alternatives. The degree of contribution of neural representation and attention to choice alternatives is not clear. We investigated correlates of such decisions in participants deciding for themselves or pretending to choose for a friend. Behaviorally participants discounted less in self-choices compared with the prosocial condition. Eye movement and MEG recordings revealed how participants represent choice options most evident for options with high subjective value. These results advance our understanding of neural mechanisms underlying decision-making in humans.