Current Research in Neurobiology

Dietary iron deficiency in the absence of anemia (IDNA) affects numerous people worldwide, with a wide range of negative effects on brain functioning and cognition. Although studies employing electroencephalography (EEG) have revealed a number of negative effects of IDNA in both the time- and frequency domains, to date there have been no attempts to characterize the effects of IDNA on the temporal dynamics of whole brain interactions. To address this issue, we applied multiscale entropy (MSE) analysis to resting-state EEG data collected from IDNA (n = 21) and iron sufficient (IS, n = 21) women. The MSE analysis on this data revealed that entropy was higher overall for the IS than the IDNA group, with significant differences appearing primarily at longer time scales and under right frontal and left and right parietal electrodes. These results suggest that IDNA may negatively affect long-distance interactions among brain regions and that this could conceivably be a source of diminished cognitive function and neural resilience in IDNA.

In this paper, we address the problem of quantifying similarity between planar 2D shapes, which is relevant to studies of internal representations in cognitive, developmental, and neurological research. We designed a set of test shapes arranged along a visually defined perceptual similarity gradient and used them to evaluate classical geometric methods for shape comparison, including Procrustes and Chamfer distance, as well as a convolutional neural network (CNN)-inspired feature-based method. Based on the limitations identified for these individual methods, we developed a hybrid Geometric-Feature Similarity (GFS) algorithm that combines geometric alignment, global contour properties, and convolutional feature-based descriptors into a unified weighted similarity score. By combining global geometric information with local structural features, the GFS algorithm more accurately reproduces human perceptual judgments of shape similarity than either geometric or feature-based methods alone. Requiring neither network training nor large labelled datasets, the proposed algorithm provides an efficient and interpretable tool for a broad range of studies involving quantitative shape comparison.

Volitional intention can bias perception in cases where two or more interpretations of a stimulus are available to us. The neural mechanisms whereby such an intention influences perception are poorly understood. Here we investigated whether intending to see horizontal versus vertical motion in a subsequently presented instantaneous position shift of a quartet apparent motion stimulus establishes decodable sensory representations prior to both the position shift and the perception of motion. Twelve participants underwent fMRI scanning under three conditions: (1) while passively viewing either continuously or (2) discretely moving quartet stimuli, or (3) while actively intending to see a subsequent single-shot apparent motion as either a vertical or horizontal motion. Multivariate decoding analyses revealed that activity patterns during the intention period of (3) generalized to patterns evoked by both (1) physical and (2) ambiguous motion perception. Cross-decoding was strongest within dorsal/lateral visual regions, including hMT+, V3AB, and the intraparietal sulcus (IPS), but was largely absent from ventral visual cortex. Widespread overlap was also observed between intention-related and perceptual motion representations throughout the dorsal/lateral visual cortex. Our findings suggest that volitional intention establishes prospective sensory representations before perceptual experience emerges and that these representations closely resemble those associated with illusory motion perception. The predominance of intention-related representations within dorsal/lateral visual regions is consistent with top-down influences from attentional control systems. More broadly, the results demonstrate that internally generated cognitive states can shape sensory representations, constraining subsequent perceptual experience.

Background: Neuropathic pain (NP) remains a therapeutic challenge, with conventional repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) yielding a response rate of approximately 40%. Personalised targeting based on dysfunctional neurocircuitry offers a promising strategy to enhance efficacy, yet its application in NP is unexplored. This open-label trial investigated a novel targeting approach guided by the recently described cingulo-opercular and somato-cognitive action (CON-SCAN) network, a circuit integrating cognitive and affective dimensions of pain. Methods: Twenty patients with NP received 10 sessions of M1-rTMS over two weeks, with the stimulation site individually localised based on maximal functional connectivity to a CON template. Results: Increased CON-SCAN connectivity from baseline to post-treatment was associated with reduction in pain interference, anxiety and depression scores. The response rate was 50% post-treatment, which was maintained at the 1-month follow-up. Improvements were also observed in neuropathic pain symptoms, negative affect, and overall health. Conclusions: As the first connectivity-guided rTMS trial for NP, this study provides preliminary evidence that personalised targeting of the CON-SCAN network is feasible and associated with the analgesic effects of M1-rTMS, supporting further investigation in randomised controlled trials. Trial registration: Chinese Clinical Trial Registry, ChiCTR2500104679. Registered 20 June 2025, http://www.chictr.org.cn. Chinese Clinical Trial Registry, ChiCTR2400094568. Registered 24 December 2024, http://www.chictr.org.cn. Keywords: Personalised TMS; Pain; M1; CON; SCAN

Sensory systems share common circuit organization motifs across mammalian species, however, anatomical subdivisions show varying degrees of complexity depending on ecological niche and species-specific sensory requirements. While coarse neuroanatomical connections seem preserved within the visual system, it remains unknown if molecularly defined cell-types share a similar degree of conservation, regarding not only their functional properties but also connectivity. Here we analyze the organization, molecular marker expression, and connections between two prominent visual centers, the superior colliculus (SC) and the dorsal lateral geniculate nucleus of the thalamus (dLGN), in the mouse and the tree shrew, a highly visual, diurnal species closely related to primates. Previous attempts to link molecular markers to subdivisions and connectivity of the dLGN have shown lack of conservation across species, thus preventing the systematic investigation of brain-wide interactions involved in vision. Leveraging recent single-cell and single-nucleus RNA sequencing studies, our results unravel a conserved molecular marker that shows spatial restriction in the dLGN and correlates with the location of connections from the SC in both the mouse and the tree shrew. We extend our findings by confirming the presence of this molecular marker in the human dLGN. These results provide a molecular definition and genetic access point for SC to dLGN connections in the mouse and tree shrew, enabling cell-type specific studies of the parallel processing of visual information.

Understanding how neural circuits transform sensory and bodily signals into motivational states and adaptive behavior is a central problem in neuroscience. In teleost fish, the dorsomedial telencephalon (Dm) is a key pallial region implicated in both sensory processing and aversive behavior, yet whether these functions arise from a functionally uniform region or from interactions among specialized pallial domains has remained unknown. Here we show that the teleost dorsomedial telencephalon exhibits a previously unrecognized functional organization in which distinct but interconnected pallial domains perform complementary computations that progressively transform multimodal sensory and bodily representations into aversive motivational value and adaptive behavioral control. Wide-field voltage-sensitive dye imaging revealed that tactile, auditory, and gustatory stimuli evoke spatially organized, modality-specific activity exclusively within the caudal subdivision of Dm (Dmc), whereas the rostral subdivision (Dmr) showed little or no sensory responsiveness. In contrast, focal intracerebral microstimulation demonstrated that activation of Dmr, but not Dmc, is sufficient to generate robust, flexible, and reversible conditioned place avoidance, identifying Dmr as a pallial node causally involved in the assignment of negative motivational value. Anatomical tracing revealed a circuit in which sensory and bodily-related inputs converge onto Dmc, are relayed intrapallially to Dmr, where they are transformed into an aversive motivational signal before being conveyed to hypothalamic and brainstem centers involved in autonomic and behavioral regulation. Immunohistochemical analyses confirmed the pallial identity of both subdivisions and their distinct rostrocaudal organization, while providing no evidence that Dm corresponds to a classical pallial amygdaloid territory. This functional architecture more closely resembles the distributed organization of mammalian corticolimbic networks than either a unitary pallial amygdala or a neocortical sensory hierarchy, suggesting that the transformation of sensory and bodily representations into motivational control may represent a conserved organizational feature of the pallium that emerged early during vertebrate evolution. Short abstract / Significance statementThis study shows that the teleost dorsomedial pallium is organized into complementary functional domains that dissociate multimodal sensory representation from negative motivational processing while forming an interconnected pallial circuit associated with adaptive behavioral control. Our findings reveal a distributed pallial organization resembling mammalian corticolimbic architectures and provide a new framework for understanding the evolution of vertebrate pallial function.

PurposeThe neural representation of pitch and timbre in complex sounds has previously been studied using synthetic, controlled stimuli to investigate underlying encoding mechanisms. These studies provide information about how single attributes of sound are represented in the inferior colliculus (IC), a critical hub of the auditory pathway where neurons are sensitive to stimulus periodicity and spectral shape, giving rise to representations of pitch and timbre, respectively. However, there is a gap in understanding how natural sounds with both pitch and timbre attributes, such as instrument sounds, are represented in the IC. MethodsIn this study, extracellular recordings were made in the IC of awake rabbits in response to natural instrument stimuli varying in fundamental frequency (F0) to determine how instrument identity (timbre) and F0 (pitch) are represented in IC neurons. ResultsUsing decoding models for instrument identification, we found that instrument identity was redundantly encoded in a population of neurons with diverse rate and timing characteristics. F0 identification using decoding models trained on single-neuron rate responses was poor, but the population of rate responses contained enough information to identify F0 reliably. F0 information was also encoded in single-neuron temporal responses up to 196 Hz. F0 identification from a population of temporal responses was accurate up to approximately 900 Hz, but accuracy decreased at high F0s. For the task in which F0 was identified based on responses to both oboe and bassoon stimuli that had overlapping F0s, performance decreased compared to F0 identification based on responses to a single instrument. ConclusionThis result supports the hypothesis that pitch and timbre information are encoded jointly in the IC.

Congenital sensory loss reveals how experience shapes the brain organization, yet most accounts of such plasticity have focused on cortex rather than the thalamic systems that link sensory input, cortical development, and distributed networks. Here, we tested whether primary and higher-order thalamic nuclei show distinct relationships with thalamocortical organization after early sensory loss. In congenital blindness, structural differences were focal to the lateral geniculate nucleus (LGN), the primary thalamic nucleus of the visual system, with individual differences in LGN volume associated with areal features of primary visual cortex morphology. Functional differences, by contrast, involved altered relationships between visual cortex and higher-order cortical and thalamic systems, including stronger functional similarity between visual cortex and control-related networks at rest and during active nonvisual cognition. A parallel analysis of congenital deafness showed no detectable volumetric difference in the medial geniculate nucleus, the primary thalamic nucleus of the auditory system, but revealed altered functional relationships between auditory cortex and higher-order cortical and thalamic systems. These findings suggest that primary thalamic pathways are associated with modality-specific structural consequences of early sensory loss, whereas higher-order thalamocortical systems contribute to convergent functional reorganization of affected sensory cortices across sensory modalities.

Visual recall is classically thought to depend on reinstatement: areas engaged when encoding a visual input are similarly reactivated when remembering it. Here we investigated if reinstatement might be differently implemented across the diverse category-selective systems of visual cortex. Using fMRI in 25 participants, we assessed possible reinstatement organizations across scene-, face-, and body-selective cortex. We asked whether memory reactivates the same category-selective areas engaged during perception, whether it engages same or distinct vertices, and whether perceptual-mnemonic distinctions were topographically organized. All regions were selectively engaged during both perception and memory, though memory activity was weaker overall. At the vertex-level, most regions--including body-selective LOS, ITG, MTG; face-selective FFA1, FFA2; and scene-selective PPA--showed classic reinstatement, with memory enriched in the most perceptually selective vertices. In contrast, OFA and OPA showed separable perception-and memory-biased vertices. Critically, only scene-selective areas showed topographic distinction: in both PPA and OPA, mnemonic activity was located consistently anterior to perceptual activity, whereas no face-or body-selective areas showed such a distinction. Thus, while all category-selective areas are reactivated during memory, scene-selective cortex topographically separates memory from perception, suggesting different sensory reinstatement implementations across high-level visual cortex, possibly reflecting the distinct computational demands.

The cerebellar nuclei (CN) has demonstrated its influence on cognitive behavior via the cerebello-cortico circuit, yet the role of CN critical period mechanisms and how they may influence cognitive behavior, such as parvalbumin (PV) expressing interneurons enwrapped by perineuronal nets (PNNs), is still unclear. Therefore, we investigated the role of the lateral CN (LCN) PV cell calcium activity while animals performed a visual discrimination touchscreen cognitive task. All animals received the PV cell calcium indicator GCaMP6f at postnatal day 21 (P21). We targeted the LCN critical period by manipulating neural activity in male mice using the inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) from postnatal day 21 to 35 or by injecting an Hapln1-AAV vector to selectively target LCN PNN development. After animals completed the visual discrimination task, cerebellar tissue was collected for viral recovery and antibody staining for PNN components, Hapln1 and aggrecan. Results revealed DREADD animals showed improved reversal learning, an increase in calcium response to learning-related activity and altered PNN expression (Hapln1 and aggrecan). Hapln1 treated animals displayed a decrease in final day acquisition performance, lower reversal performance compared to DREADD groups, a decrease in reversal calcium learning-related activity, and an increase in PNN expression (Hapln1). Together, these data provide further evidence of LCN mechanisms associated with learning as well as the importance of understanding region-specific critical periods of plasticity.

Abstract Introduction: Despite advances in pain management, effective analgesics in pain situations remain elusive. Opioids and non-opioids carry risks of neurotoxic and psychedelic effects with adverse physiological outcomes. Indian instrumental music (IIM) mitigates subacute pain by rewiring neurochemical synergy as an evidence-based, non-invasive, non-pharmacological system to mitigate pain. Objective: Investigating therapeutic efficacy of IIM in mitigating subacute pain by analyzing behavioral, peripheral, and central neurochemical re-tuning. Methods: Mice were divided into Control, Pain, Pain+Music, and Music groups. Pre-treatment behavioral parameters were compared with those observed after 14 days IIM exposure. Evaluations included nociceptive latencies (hot-plate/tail-flick), locomotion (Open Field Test), and anxiety (Elevated Plus Maze). Molecular analyses quantified peripheral neuropeptides (SP, NK-1R, CGRP), serum cortisol, spinal neurotrophic factor, neurotransmitters (glutamate, GABA, dopamine (DA), 5-HT), BDNF, and mRNA expression of BDNF, Ntrk1R/2R, and D1R in cortex, thalamus, hippocampus and hypothalamus. All procedures adhered to IAEC guidelines. Results: IIM yielded 3.9-4.4-fold antinociceptive improvements, 3.3-fold locomotor restoration, and 3.6-4.9-fold anxiolysis. 14 days IIM exposure reduced peripheral nociceptive-neuropeptides 1.3-2.0-fold (SP, NK-1R, CGRP), serum cortisol 1.3-fold, and spinal glutamate, serotonin levels 1.5- and 1.3-fold. An enhanced expression of spinal GABA, DA about 1.5-fold, and BDNF by 1.3-fold was observed after music listening. Brain-region-specific differential mRNA-expression at cortex, thalamus, hypothalamus and hippocampus revealed the neuromodulatory impact of rhythmic music in a formalin-induced murine pain-model. Conclusion: Gross reduction of pain parameters demonstrates therapeutic potential of IIM as multilevel neuromodulator to suppress the multidimensional stressor, pain, via peripheral desensitization, spinal E-I balance, and differential calibration of BDNF/Trk/D1R plasticity at specific brain-regions. Keywords: Pain, Non-Pharmacological Method, Indian Instrumental Music (IIM), Behavior, Neurotransmitters, Neuroplasticity, mRNA Expression.

Background: Transcranial low-intensity focused ultrasound (LIFU) neuromodulation can alter human task performance depending on target and acoustic configurations. However, single behavioral endpoints cannot locate effects within multistep tasks, and predefined target labels ignore acoustic variations. Objective: To determine whether thalamic LIFU affects visual categorization or subsequent subjective report latency and whether the effects vary with target, acoustic parameter, and beam location. Methods: Sixty healthy adults were randomized to 70% or 5% duty cycle (DC70 or DC5) and received sonication on four left thalamic targets with matched pulse repetition frequency (10 Hz) and temporal-average intensity (0.72 W/cm2). Behavioral models tested target-by-DC interactions in categorization (RT1) and subjective report (RT2) latencies. Spatial analyses correlated focal spot coordinates and voxel-wise intensity from 179 acoustic simulations to baseline-adjusted RT2. Results: The target-by-DC interaction was detected for RT2 but not RT1. At the ventroposterior thalamic target, adjusted RT2 was 55.9 ms longer under DC70 than DC5. More anterior focal spots shortened RT2 under DC70 but increased RT2 under DC5. Correlation between intensity and adjusted RT2 significantly differed between DC70 and DC5 in 18.8% of thalamic voxels. These voxels formed an anterior mediodorsal-motor set and a posterior pulvinar-dominant set. Conclusions: The latency of reporting conscious visual experience, but not categorization latency, was affected by thalamic LIFU. This effect varied jointly with anterior-posterior target engagement and acoustic configuration. Analyzing sequential reaction times separately and treating field variation as an anatomical variable revealed associations not fully captured by a single endpoint or predefined target labels.

BackgroundHearing aids and cochlear implants (CIs) are the primary interventions for sensorineural hearing loss, restoring auditory function through amplification and intracochlear electrical stimulation, respectively. For those with residual low-frequency hearing, the combined electric-acoustic stimulation (EAS) has demonstrated superior speech perception, particularly in noisy environments, compared to either modality. However, CI surgery carries inherent risks, including postoperative hearing loss, which undermines EAS benefits and limits future rehabilitation options. To overcome these limitations, we propose a non-invasive alternative: extracochlear electric and acoustic stimulation (EEAS), delivering electrical stimulation via transcutaneous electrodes without surgery. Here, we present a first systematic investigation of non-invasive extracochlear electrical stimulation using ear canal electrode montages, evaluating its feasibility, perceptual effects, and key parameters across diverse hearing statuses. MethodsWe conducted a controlled, within-subject study with 15 participants: 5 with normal hearing (NH), 5 with high-frequency hearing loss (HI), and 5 with severe-to-profound deafness (PL). We used charge-balanced sinusoidal stimuli (125-4000 Hz) applied via an ear canal electrode and four return electrode montages, including contralateral ear canal, contralateral mastoid, ipsilateral mastoid, and forehead electrodes. Participants rated auditory sensations, including loudness, sound quality, and lateralization, as well as side effects on separate 0-10 scales, with current intensity increased up to 2 mA/cm{superscript 2}. Thresholds and perceptual responses were analyzed across frequencies, electrode configurations, and hearing groups. ResultsReliable auditory percepts were elicited across all groups. NH participants reported pure-tone sensations, whereas HI and PL participants perceived broadband, noise-like sounds. Loudness decreased with increasing frequency, particularly for HI and PL, with minimal responses in the high-frequency range. The current threshold increased with stimulation frequency, whereas the threshold expressed as charge per phase remained constant, suggesting that charge per phase primarily determines neural activation, whereas current amplitude is more closely associated with the intensity of auditory and side effect perception. Contralateral montages produced significantly higher loudness ratings than ipsilateral or forehead configurations. The forehead montage was poorly tolerated, leading to early termination due to discomforting side effects. Sound lateralization was predominantly central or bilateral with contralateral setups, while ipsilateral and forehead configurations yielded ipsilateral perceptions. ConclusionsNon-invasive extracochlear electrical stimulation via ear canal electrodes is feasible and perceptually effective across a spectrum of hearing statuses. Perceptive outcomes are strongly influenced by electrode montage and residual hearing, with evidence of electrophonic excitation in NH individuals and electroneural activation in HI and PL participants. Contralateral mastoid electrode configurations offer the optimal balance of perceptual strength, tolerability, and spatial localization. These findings establish a critical foundation for the development of EEAS devices, demonstrating that non-invasive electrical stimulation can generate meaningful auditory percepts, paving the way for safe, accessible, and integrated hearing rehabilitation solutions. This work informs future EEAS developments and advances the path toward clinically viable, non-invasive cochlear stimulation.

BackgroundBrain regions integrate neural information arriving from several convergent projection sources. At the mesoscale level, neural projections can potentially span both hemispheres and extend along the entire rostrocaudal axis, which complicates efforts to map their full extent. To address this issue, we describe a novel method for mapping such mesoscale connectivity in vivo and ex vivo. Our neurotomographic approach utilizes micro-computed tomography (micro-CT) to image the spatial distribution of neural tracers bound to high Z-elements, e.g, gold. MethodsIn this study, we conjugated colloidal gold to a retrograde tracer wheat-germ agglutinin apo-horseradish peroxidase (WGA-HRP) and then stereotactically injected the gold-bound tracer (WAHG) into the mouse forebrain. Micro-CT was then used to image the brain in vivo and ex vivo, followed by three-dimensional reconstruction of tracer distribution. We then validated our approach by histologically processing the brains using silver enhancement to label gold particles; this enabled a direct comparison of histological labeling with the neurotomographic images. ResultsWe found that micro-CT imaging could reveal the major spatial distributions of the gold-bound tracer, which was consistent across in vivo and ex vivo imaging conditions. Moreover, the neurotomographically determined patterns corresponded with the labeling observed in histologically processed tissue, with the major sites of labeling reliably detected in reconstructed neurotomographic images. ConclusionsOverall, our findings demonstrate a potential novel method for non-destructive, three-dimensional mapping of neural tracers in vivo. This novel approach can potentially guide targeted multi-site recordings, enable validation of injection site placement, and facilitate rapid longitudinal connectomic analyses in vivo.

Understanding cortical function in large, gyrencephalic brains requires following the same tissue over time and interrogating it through complementary methods - yet in practice each recording modality is run on its own preparation, across separate animals and sessions that cannot be quantitatively related, while the recorded cortex can rarely be revisited. Functional ultrasound (fUS), widefield optical imaging, and electrocorticography (ECoG) are individually mature and strongly complementary, but no single preparation has combined all three within the same chronically accessible tissue in a gyrencephalic brain. Here we present a modular chronic cranial platform, validated in three cats with implants remaining functional for up to 3.3 years that unites these modalities in one customized chamber built around fUS as an anchor modality. The platform also supports fUS imaging in awake, head-unrestrained animals, with activation maps remaining spatially consistent across imaging days. By providing stable, quantitatively reproducible access to the same cortical region over time, this platform enables longitudinal, multimodal characterization of cortical function within individual subjects.

Noise exposure can produce lasting auditory dysfunction in the absence of permanent threshold shifts or hair cell loss, yet the functional consequences of temporary threshold shift (TTS) remain poorly defined in translational models. We assessed auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) in rhesus macaques (n = 13) at 2 and 9-10 months following a single moderate noise exposure that induced TTS. Previous histological analyses of these macaques showed no significant loss of hair cells or ribbon synapses but revealed persistent broadening of inner and outer hair cell ribbon-volume distributions. After exposure, DPOAE amplitudes and thresholds and ABR thresholds returned to pre-exposure values and showed low-frequency enhancement at later time points. Suprathreshold click- and tone-evoked ABR amplitudes were largely preserved or enhanced after exposure, consistent with compensatory gain. In contrast, macaque-specific chirp-evoked ABRs showed modest amplitude reductions and latency prolongation across waves, indicating altered neural synchrony at standard stimulus presentation rates, but with variable time courses. More temporally demanding paradigms revealed persistent impairments. ABRs to faster click rates and shorter paired-click intervals showed reduced adaptability in response amplitude and timing after normalization, with deficits persisting through 9-10 months. Increased inner hair cell ribbon-volume variability was more consistently associated with temporal response measures, including latency, paired-click recovery, and rate adaptation, than with amplitude-based ABR measures. Together, these findings reveal a lasting dissociation between response magnitude and fidelity after TTS: suprathreshold responses may be preserved or enhanced, while neural synchrony and temporal adaptability remain impaired. Increased presynaptic ribbon volume variability may serve as a structural marker of synaptic remodeling accompanying hidden auditory dysfunction, rather than as a direct determinant of suprathreshold response magnitude. Temporally demanding ABR paradigms may supplement threshold-based diagnostics for detecting persistent noise-induced auditory dysfunction.

Language comprehension requires the continuous transformation of speech into a hierarchy of linguistic units, from phonemes to syllables to words. Because speech unfolds rapidly, listeners are thought to predict upcoming content to keep pace. Previous research has provided empirical evidence for predictive processes operating at multiple linguistic levels during naturalistic listening, including words and phonemes. However, it remains unclear whether prediction also operates concurrently at other levels, such as syllabic and phrasal representation. Here we use Mandarin Chinese to examine the neural signatures of predictive processing across multiple levels of linguistic granularity during natural speech comprehension. Mandarin comprises four representational levels: phoneme, sub-syllabic, character and word, and its lexical identity is largely constrained at the sub-syllabic level, potentially redistributing predictive weight across linguistic representations. We recorded magnetoencephalography (MEG) data while 34 native Mandarin speakers (21 females) listened to a naturalistic audiobook and applied linear regression modeling to examine how linguistic features modulated neural activity. We found that the brain activity of listeners segmented speech into hierarchical units, and that surprisal modulated responses simultaneously across sub-syllabic, character and word levels. In contrast to findings from Indo-European languages, however, we did not observe unique surprisal effects at the lowest, phonemic level. Furthermore, the surprisal of lexical tone in Mandarin modulated brain activity only when integrated with its phonological components. These findings suggest that predictive processing during Mandarin speech comprehension operates concurrently across multiple (though not necessarily all) levels of linguistic granularity, with its implementation shaped by language-specific structural properties. Significance statementLanguage comprehension involves segmenting a continuous acoustic stream into multiple linguistic units, from phonemes to words, and generating predictions at these levels. However, direct neural evidence remains limited regarding how segmentation and prediction operate simultaneously across levels of linguistic granularity, particularly outside Indo-European languages. Using temporal response function analysis of magnetoencephalography data recorded during naturalistic Mandarin listening, we show that predictive processing occurs across multiple levels of linguistic granularity. Specifically, we find evidence for prediction-related neural responses at sub-syllabic, character, and word levels, but not a reliable unique effect at the phonemic level. These results indicate that predictive processing also operates during Mandarin speech comprehension, and its neural implementation is shaped by language-specific structural properties.

Recent work has revealed two food-selective areas in the lateral and ventromedial occipitotemporal cortex (OTC). These studies have shown that food selectivity in these regions cannot be explained by mid-level features like shape, texture, or colour but differences in their representational content remain unclear. Across two fMRI experiments conducted in the same group of participants, we characterized the dimensions underlying food representations in lateral and ventral OTC by examining the contribution of action-related object properties, such as manipulability, relevant to object interaction, and visual features, such as colour and ensemble statistics, relevant to object recognition. Our results reveal a clear dissociation between lateral and ventral OTC, indicating that food representations in these regions reflect distinct computational constraints. In lateral OTC, food representations were primarily associated with action-related properties shared between food and other graspable objects, whereas in ventral OTC, food representations were sensitive to surface object properties, such as colour and ensemble configuration. Consistent with this distinction, lateral OTC showed greater sensitivity to individual objects against distinctive background and responded equally to colour and greyscale stimuli, while ventral OTC exhibited greater sensitivity to coloured stimuli and ensembles with no distinctive background. Finally, topographic artificial neural networks implementing architectural constraints meant to capture OTC spatial organization similarly exhibited two dissociable clusters of food-selective units based on sensitivity to ensemble statistics. Together, these findings suggest that lateral food representations reflect action-relevant properties shared with other manipulable objects, whereas ventral food representations arise from surface-based visual features critical for food identification.

IntroductionThe insula is an increasingly important target for functional neurosurgery given its involvement in a range of neurological and neuropsychiatric disorders, including epilepsy and chronic pain. As this practice evolves, optimal targeting will require standardized outcome measures that relate electrode or laser trajectory to postprocedural outcome. Traditional whole- brain registration approaches fail to capture the substantial person-to-person variability in insular gyral configuration, including the relative internal rotation of the insular gyri with respect to standard stereotactic space. ObjectiveWe propose and validate a stereotactic coordinate system based on local anatomical landmarks to facilitate surgical planning and standardized outcome assessment within the insular cortex. MethodsOur approach transforms brain MRI first into standard AC-PC space, and then into an insular-specific space defined by five anatomical landmarks: four points along the central sulcus of the insula and one point at the middle cerebral artery (MCA) bifurcation (at the limen insulae). The system calculates two angles - {theta} (axial) and {varphi} (sagittal) - between the AC-PC line and the insular axis, and the brain volume undergoes sequential rotation through these angles followed by translation to place the coordinate systems origin along the insular axis. ResultsIn a sample of 32 patients, the angle between the AC-PC line and the insular axis ranged from -17{degrees} to 17{degrees} in the axial plane ({theta}) and 31{degrees} to 69{degrees} in the sagittal plane ({varphi}). In the resulting coordinate system, the insular axis defines z = 0 and the MCA turning point defines y = 0. We developed a custom, open-access MATLAB graphical interface that allows intuitive implementation of this system for both surgical planning and postoperative analysis; implanted electrodes, laser fiber position, and ablation geometry can each be localized within this common space. As a demonstration of its utility for pooling data across subjects, we applied the transformation to a previously acquired intracranial electrophysiology dataset and found that anatomically consistent, effector-specific motor representations emerged across 18 subjects once electrode positions were expressed in insular-specific coordinates. ConclusionAs stereotactic surgery for insular targets becomes more common with expanding scientific inquiry, an insular-specific coordinate system may facilitate operative planning and functional mapping, and may help standardize outcome assessment across patients and institutions. SIGNIFICANCE STATEMENTThe insular cortex represents an increasingly important surgical target for therapeutic interventions, yet substantial person-to-person anatomical variability hampers standardized targeting and outcome comparison. The insula is simultaneously the subject of expanding scientific inquiry -- into interoception, pain, autonomic regulation, salience processing, and sensorimotor representation -- much of it now pursued through intracranial recording and stimulation in humans, where cohorts are small, electrode sampling is idiosyncratic, and progress therefore depends on pooling data across patients in a frame that respects insular gyral architecture. We present "Insulotaxy," a stereotactic coordinate system built from consistent, easily identifiable local anatomical landmarks that accounts for the insulas unique rotational relationship to standard brain coordinates. An open-source MATLAB tool transforms imaging into insular-specific coordinates, facilitating surgical planning for ablation and electrode placement while enabling standardized outcome reporting across institutions. By providing locally anchored, anatomically aligned coordinates rather than relying on whole-brain registration, this framework addresses a practical gap in functional neurosurgery and lays a foundation for pooling clinical and electrophysiological data as insular interventions become more prevalent.

Objective: This study investigated whether plosive consonants carry a perceptual loudness weighting that significantly exceeds that of non-plosive consonants when judged by hearing-impaired listeners. Design: A prospective loudness matching experiment utilizing the method of adjustment. Study Sample: 19 consenting native English speakers (Mean age: 61.4, SD: 16.4) with bilateral mild to moderate high-frequency sensorineural hearing loss, indicative of presbycusis. Stimuli: 13 vowel-consonant-vowel (VCV) nonsense syllables, exclusively utilizing the flanking vowel /u/. Results: Descriptive analysis revealed a strong time-order effect influencing loudness judgments for 7 of the 13 VCV test stimuli. Statistical testing showed no significant didference (P = 0.94) between the relative amplitudes corresponding to the point of equal loudness for plosive-containing versus non-plosive-containing VCV stimuli. However, 6 individual VCV stimuli, containing consonants from 4 separate manners of articulation, produced significant loudness matching data (P < 0.01). Conclusions: The results falsify the hypothesis that plosives, analyzed collectively as a class, possess a heavier perceptual loudness weighting than non-plosive consonants. While 6 individual VCV stimuli indicated potential individual consonantal loudness weightings, these findings must be interpreted cautiously due to the restriction to a single vowel context and the presence of procedural time-order biases.