Neural Activity Research Articles

Perceptual Learning of Fine Contrast Discrimination Under Non-roving, Roving-Without-Flanker, and Roving-with-Flanker Conditions and its Relation to Neuronal Activity in Macaque V1

AbstractPerceptual learning refers to an improvement in perceptual abilities with training. Neural signatures of visual perceptual learning have been demonstrated mostly in mid- and high-level cortical areas, while changes in early sensory cortex were often more limited. We recorded continuously from multiple neuronal clusters in area V1 while macaque monkeys learned a fine contrast categorization task. Monkeys performed the contrast discrimination task initially when a constant-contrast sample stimulus was followed by a test stimulus of variable contrast, whereby they had to indicate whether the test was of lower or higher contrast than the sample. This was followed by sessions where we employed stimulus roving; i.e. the contrast of the sample stimulus varied from trial to trial. Finally, we trained animals, under ‘stimulus roving-with-flanker’ conditions, where the test stimuli to be discriminated were flanked by ‘flanking stimuli’. Perceptual discrimination abilities improved under non-roving conditions and under roving-with-flanker conditions as training progressed. Neuronal discrimination abilities improved with training mostly under non-roving conditions, but the effect was modest and limited to the most difficult contrast. Choice probabilities, quantifying how well neural activity is correlated with choice, equally increased with training during non-roving, but not during either of the roving conditions (with and without flankers). Noise correlations changed with training in both monkeys, but the changes were not consistent between monkeys. In one monkey, noise correlations decreased with training for non-roving and both roving conditions. In the other monkey, noise correlations changed for some conditions, but lacked a systematic pattern. Thus, while perceptual learning occurred under non-roving and roving-with-flanker conditions, the changes in neural activity in V1 were overall modest and were essentially absent under the different roving conditions.

EEG entropy insights in the context of physiological aging and Alzheimer's and Parkinson's diseases: a comprehensive review.

In recent decades, entropy measures have gained prominence in neuroscience due to the nonlinear behaviour exhibited by neural systems. This rationale justifies the application of methods from the theory of nonlinear dynamics to cerebral activity, aiming to detect and quantify its variability more effectively. In the context of electroencephalogram (EEG) signals, entropy analysis offers valuable insights into the complexity and irregularity of electromagnetic brain activity. By moving beyond linear analyses, entropy measures provide a deeper understanding of neural dynamics, particularly pertinent in elucidating the mechanisms underlying brain aging and various acute/chronic-progressive neurological disorders. Indeed, various pathologies can disrupt nonlinear structuring in neural activity, which may remain undetected by linear methods such as power spectral analysis. Consequently, the utilization of nonlinear tools, including entropy analysis, becomes crucial for capturing these alterations. To establish the relevance of entropy analysis and its potential to discern between physiological and pathological conditions, this review discusses its diverse applications in studying healthy brain aging and neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Various entropy parameters, such as approximate entropy (ApEn), sample entropy (SampEn), multiscale entropy (MSE), and permutation entropy (PermEn), are analysed within this context. By quantifying the complexity and irregularity of EEG signals, entropy analysis may serve as a valuable biomarker for early diagnosis, treatment monitoring, and disease management. Such insights offer clinicians crucial information for devising personalized treatment and rehabilitation plans tailored to individual patients.

Complexity matters: Normalization to prototypical viewpoint induces memory distortion along the vertical axis of scenes.

Scene memory is prone to systematic distortions potentially arising from experience with the external world. Boundary transformation, a well-known memory distortion effect along the near-far axis of the three-dimensional space, represents the observer's erroneous recall of scenes' viewing distance. Researchers argued that normalization to the prototypical viewpoint with the high-probability viewing distance influenced this phenomenon. Herein, we hypothesized that the prototypical viewpoint also exists in the vertical Angle of View (AOV) dimension and could cause memory distortion along scenes' vertical axis. Human subjects of both sexes were recruited to test this hypothesis and two behavioral experiments were conducted, revealing a systematic memory distortion in the vertical AOV in both the forced choice (n = 79) and free adjustment (n = 30) tasks. Furthermore, the regression analysis implied that the complexity information asymmetry in scenes' vertical axis and the independent subjective AOV ratings from a large set of online participants (n = 1208) could jointly predict AOV biases. Furthermore, in a functional Magnetic Resonance Imaging (fMRI) experiment (n = 24), we demonstrated the involvement of areas in the ventral visual pathway (V3/V4, PPA, and OPA) in AOV bias judgment. Additionally, in a Magnetoencephalography (MEG) experiment (n = 20), we could significantly decode the subjects' AOV bias judgments ∼140 ms after scene onset and the low-level visual complexity information around the similar temporal interval. These findings suggest that AOV bias is driven by the normalization process and associated with the neural activities in the early stage of scene processing.Significance Statement Perceiving a scene with high precision is critical for our navigation and interaction with the surrounding environment. However, systematic memory distortion is quite common. Herein, we discovered that scene memory could be distorted to the upper or lower visual field. According to the behavioral results, multiple measures of scenes' complexity information were critically involved in the formation of this memory distortion. Furthermore, the results support the normalization theory regarding the existence of a high-probability prototypical viewpoint in scene processing. Our findings also suggested that the normalization process-induced scene memory distortion could be beneficial for the observer's future action selection. The identified complexity measures could be used in designing Artificial Intelligence (AI) systems with navigational functions.

Vertebrates on a Chip: Noninvasive Electrical and Optical Mapping of Whole Brain Activity Associated with Pharmacological Treatments.

Mapping brain activities is necessary for understanding brain physiology and discovering new treatments for neurological disorders. Such efforts have greatly benefited from the advancement in technologies for analyzing neural activity with improving temporal or spatial resolution. Here, we constructed a multielectrode array based brain activity mapping (BAM) system capable of stabilizing and orienting zebrafish larvae for recording electroencephalogram (EEG) like local field potential (LFP) signals and brain-wide calcium dynamics in awake zebrafish. Particularly, we designed a zebrafish trap chip that integrates with an eight-by-eight surface electrode array, so that brain electrophysiology can be noninvasively recorded in an agarose-free and anesthetic-free format with a high temporal resolution of 40 μs, matching the capability typically achieved by invasive LFP recording. Benefiting from the specially designed hybrid system, we can also conduct calcium imaging directly on immobilized awake larval zebrafish, which further supplies us with high spatial resolution brain-wide activity data. All of these innovations reconcile the limitations of sole LFP recording or calcium imaging, emphasizing a synergy of combining electrical and optical modalities within one unified device for activity mapping across a whole vertebrate brain with both improved spatial and temporal resolutions. The compatibility with in vivo drug treatment further makes it suitable for pharmacology studies based on multimodal measurement of brain-wide physiology.

Association Between Intracochlear Electrode Design and Electrically-Evoked Compound Action Potential Measures in Cochlear Implant Users.

Cochlear implant (CI) electrode design has changed over time. Changes in intracochlear electrode design might influence the spread of neural activation along the auditory nerve and the number of independent channels. This study aimed to investigate the impact of intracochlear electrode design on the electrode-neuron interface using electrophysiological measures. Prospective cohort study. A single tertiary hospital. Fifty-two ears who were implanted with CI divided into 3 groups based on the design of intracochlear electrode arrays. Twenty-three ears were implanted with lateral wall straight electrodes. Eighteen ears were implanted with the slim perimodiolar electrode, and 11 ears were implanted with the old perimodiolar electrode. Various electrically-evoked compound action potential (ECAP) metrics were measured to quantify spread of excitation and channel interaction. ECAP threshold and slope were not significantly different among groups. ECAP spread of excitation (SOE) half-width and channel interaction index (CII) were significantly larger in subjects implanted with the lateral wall straight electrodes, indicating a wider spread of excitation compared to those with perimodiolar electrodes. Electrode impedance was significantly lower in subjects implanted with perimodiolar electrodes than those with lateral wall electrodes. Perimodiolar electrode groups yielded significantly narrower SOE half-widths and smaller CII than the lateral wall straight electrode group. This may indicate that the electrode array that hugged the modiolus had less overlap in neural excitation between adjacent electrodes, resulting in reduced channel interaction and potentially better spectral resolution than the electrode array positioned more laterally.

Brain activity during reappraisal and associations with psychotherapy response in social anxiety and major depression: a randomized trial.

Cognitive behavioral therapy (CBT) is an effective treatment for patients with social anxiety disorder (SAD) or major depressive disorder (MDD), yet there is variability in clinical improvement. Though prior research suggests pre-treatment engagement of brain regions supporting cognitive reappraisal (e.g. dorsolateral prefrontal cortex [dlPFC]) foretells CBT response in SAD, it remains unknown if this extends to MDD or is specific to CBT. The current study examined associations between pre-treatment neural activity during reappraisal and clinical improvement in patients with SAD or MDD following a trial of CBT or supportive therapy (ST), a common-factors comparator arm. Participants were 75 treatment-seeking patients with SAD (n = 34) or MDD (n = 41) randomized to CBT (n = 40) or ST (n = 35). Before randomization, patients completed a cognitive reappraisal task during functional magnetic resonance imaging. Additionally, patients completed clinician-administered symptom measures and a self-report cognitive reappraisal measure before treatment and every 2 weeks throughout treatment. Results indicated that pre-treatment neural activity during reappraisal differentially predicted CBT and ST response. Specifically, greater trajectories of symptom improvement throughout treatment were associated with less ventrolateral prefrontal cortex (vlPFC) activity for CBT patients, but more vlPFC activity for ST patients. Also, less baseline dlPFC activity corresponded with greater trajectories of self-reported reappraisal improvement, regardless of treatment arm. If replicated, findings suggest individual differences in brain response during reappraisal may be transdiagnostically associated with treatment-dependent improvement in symptom severity, but improvement in subjective reappraisal following psychotherapy, more broadly.

EEG dynamic source imaging using a regularized optimization with spatio-temporal constraints.

One of the most important needs in neuroimaging is brain dynamic source imaging with high spatial and temporal resolution. EEG source imaging estimates the underlying sources from EEG recordings, which provides enhanced spatial resolution with intrinsically high temporal resolution. To ensure identifiability in the underdetermined source reconstruction problem, constraints on EEG sources are essential. This paper introduces a novel method for estimating source activities based on spatio-temporal constraints and a dynamic source imaging algorithm. The method enhances time resolution by incorporating temporal evolution of neural activity into a regularization function. Additionally, two spatial regularization constraints based on and norms are applied in the transformed domain to address both focal and spread neural activities, achieved through spatial gradient and Laplacian transform. Performance evaluation, conducted quantitatively using synthetic datasets, discusses the influence of parameters such as source extent, number of sources, correlation level, and SNR level on temporal and spatial metrics. Results demonstrate that the proposed method provides superior spatial and temporal reconstructions compared to state-of-the-art inverse solutions including STRAPS, sLORETA, SBL, dSPM, and MxNE. This improvement is attributed to the simultaneous integration of transformed spatial and temporal constraints. When applied to a real auditory ERP dataset, our algorithm accurately reconstructs brain source time series and locations, effectively identifying the origins of auditory evoked potentials. In conclusion, our proposed method with spatio-temporal constraints outperforms the state-of-the-art algorithms in estimating source distribution and time courses.

Single trial Bayesian inference by population vector readout in the barn owl's sound localization system.

Bayesian models have proven effective in characterizing perception, behavior, and neural encoding across diverse species and systems. The neural implementation of Bayesian inference in the barn owl's sound localization system and behavior has been previously explained by a non-uniform population code model. This model specifies the neural population activity pattern required for a population vector readout to match the optimal Bayesian estimate. While prior analyses focused on trial-averaged comparisons of model predictions with behavior and single-neuron responses, it remains unknown whether this model can accurately approximate Bayesian inference on single trials under varying sensory reliability, a fundamental condition for natural perception and behavior. In this study, we utilized mathematical analysis and simulations to demonstrate that decoding a non-uniform population code via a population vector readout approximates the Bayesian estimate on single trials for varying sensory reliabilities. Our findings provide additional support for the non-uniform population code model as a viable explanation for the barn owl's sound localization pathway and behavior.

Dissociable neuronal mechanism for different crossmodal correspondence effects in humans

Crossmodal correspondences (CMCs) refer to associations between seemingly arbitrary stimulus features in different sensory modalities. Pitch‑size correspondences refer to the strong association of e.g., small objects with high pitches. Pitch‑elevation correspondences refer to the strong association of e.g., visuospatial elevated objects with high pitches. We used functional magnetic resonance imaging (fMRI) to study the neural components, which underlie the CMCs in pitch‑size and spatial pitch‑elevation. This study focuses on answering the question of whether or not different CMCs are driven by similar neural mechanisms. The comparison of congruent against incongruent trials allows the estimation of CMC effects across different CMCs. The analysis of the measured neural activity in different CMCs strongly pointed toward different mechanisms which are involved in the processing of pitch‑size and pitch‑elevation correspondences. Differential, whole brain effects were observed within the superior parietal lobule (SPL), cerebellum and Heschls’ gyrus (HG). Further, the angular gyrus (AnG), the intraparietal sulcus (IPS) and anterior cingulate cortex (ACC) were engaged in processing the CMCs but showed different effects for processing congruent compared to incongruent stimulus presentations. Within pitch‑size significant effects in the AnG and ACC were found for congruent stimulus presentations whereas for pitch‑elevation, significant effects in the ACC and IPS were found for incongruent stimulus presentations. In summary, the present results indicated differential neural processing in different simple audio‑visual CMCs.

Is a wandering mind a novelty-seeking mind? The curious case of incubation.

The Novelty-Seeking Model can explain incubation's effect on creativity by assuming an adaptive decision threshold. During an impasse, the threshold for novelty becomes too high and biased to previous neural activity, hindering progress. Incubation "resets" this threshold through attentional decoupling, allowing for spontaneous ideas to emerge from subsequent mind wandering or other activities that attract attention, facilitating progress.

A novel CNN-based image segmentation pipeline for individualized feline spinal cord stimulation modeling.

Spinal cord stimulation (SCS) is a well-established treatment for the management of certain chronic pain conditions. More recently, it has also garnered attention as a means of modulating neural activity with the goal of restoring lost autonomic or sensory-motor function. Personalized modeling and treatment planning are critical aspects of safe and effective SCS [46, 60]. However, the generation of spine models at the required level of detail and accuracy requires time and labor intensive manual image segmentation by human experts. Hence, there is a need for maximally automated segmentation routines capable of producing high-quality anatomical models that can be used even in cases where available data is limited. To this end, we developed an automated image segmentation and model generation pipeline based on a novel Convolutional Neural Network (CNN) architecture trained on feline spinal cord magnetic resonance imaging (MRI) data. The pipeline includes steps for image preprocessing, data augmentation, transfer learning and cleanup. To assess the relative importance of each step in the pipeline and of our choice of CNN architecture, we systematically dropped steps or substituted architectures, quantifying the downstream effects in terms of tissue segmentation quality (Jaccard index and Hausdorff distance) and predicted nerve recruitment (estimated axonal depolarization). This leaveone-out analysis demonstrated that each pipeline step contributed a small but measurable increment to mean segmentation quality. Surprisingly, minor differences in segmentation accuracy translated to significant deviations (ranging between 4% and 13% for each pipeline step) in predicted nerve recruitment, highlighting the importance of careful workflow design. To our knowledge, this is the first analysis to also assess the downstream impact of segmentation quality differences on neurostimulation predictions. Furthermore, transfer learning techniques enhanced segmentation metric consistency and allowed generalization to a completely different spine region with minimal additional training data. This work helps pave the way towards fully automated, personalized SCS treatment planning in clinical settings.

Self-organization of modular activity in immature cortical networks

During development, cortical activity is organized into distributed modular patterns that are a precursor of the mature columnar functional architecture. Theoretically, such structured neural activity can emerge dynamically from local synaptic interactions through a recurrent network with effective local excitation with lateral inhibition (LE/LI) connectivity. Utilizing simultaneous widefield calcium imaging and optogenetics in juvenile ferret cortex prior to eye opening, we directly test several critical predictions of an LE/LI mechanism. We show that cortical networks transform uniform stimulations into diverse modular patterns exhibiting a characteristic spatial wavelength. Moreover, patterned optogenetic stimulation matching this wavelength selectively biases evoked activity patterns, while stimulation with varying wavelengths transforms activity towards this characteristic wavelength, revealing a dynamic compromise between input drive and the network’s intrinsic tendency to organize activity. Furthermore, the structure of early spontaneous cortical activity – which is reflected in the developing representations of visual orientation – strongly overlaps that of uniform opto-evoked activity, suggesting a common underlying mechanism as a basis for the formation of orderly columnar maps underlying sensory representations in the brain.

Social context modulates multibrain broadband dynamics and functional brain-to-brain coupling in the group of mice

Although mice are social, multiple animals’ neural activities are rarely explored. To characterise the neural activities during multi-brain interaction, we simultaneously recorded local field potentials (LFP) in the prefrontal cortex of four mice. The social context and locomotive states predominately modulated the entire LFP structure. The power of lower frequency bands—delta to alpha—were correlated with each other and anti-correlated with gamma power. The high-to-low-power ratio (HLR) provided a useful measure to understand LFP changes along the change of behavioural and locomotive states. The HLR during huddled conditions was lower than that during non-huddled conditions, dividing the social context into two. Multi-brain analyses of HLR indicated that the mice in the group displayed high cross-correlation. The mice in the group often showed unilateral precedence of HLR by Granger causality analysis, possibly comprising a hierarchical social structure. Overall, this study shows the importance of the social environment in brain dynamics and emphasises the simultaneous multi-brain recordings in social neuroscience.

A Multimodal Fitting Approach to Construct Single-Neuron Models with Patch Clamp and High-Density Microelectrode Arrays.

In computational neuroscience, multicompartment models are among the most biophysically realistic representations of single neurons. Constructing such models usually involves the use of the patch-clamp technique to record somatic voltage signals under different experimental conditions. The experimental data are then used to fit the many parameters of the model. While patching of the soma is currently the gold-standard approach to build multicompartment models, several studies have also evidenced a richness of dynamics in dendritic and axonal sections. Recording from the soma alone makes it hard to observe and correctly parameterize the activity of nonsomatic compartments. In order to provide a richer set of data as input to multicompartment models, we here investigate the combination of somatic patch-clamp recordings with recordings of high-density microelectrode arrays (HD-MEAs). HD-MEAs enable the observation of extracellular potentials and neural activity of neuronal compartments at subcellular resolution. In this work, we introduce a novel framework to combine patch-clamp and HD-MEA data to construct multicompartment models. We first validate our method on a ground-truth model with known parameters and show that the use of features extracted from extracellular signals, in addition to intracellular ones, yields models enabling better fits than using intracellular features alone. We also demonstrate our procedure using experimental data by constructing cell models from in vitro cell cultures. The proposed multimodal fitting procedure has the potential to augment the modeling efforts of the computational neuroscience community and provide the field with neuronal models that are more realistic and can be better validated.

Idiosyncratic patterns of interhemispheric connectivity in the face and scene networks of the human brain

Abstract Neuroimaging studies have revealed a network of regions in both hemispheres of the human brain that respond selectively to faces. Neural models of face processing have typically focused on functional connectivity between regions in the same hemisphere (intrahemispheric), with a particular bias toward the right hemisphere. Here, we explored the role of interhemispheric connectivity using fMRI. We used three datasets to compare functional connectivity, as shown by correlations between the time-courses of neural activity of face regions during different natural viewing paradigms. We found higher correlations of neural activity between corresponding interhemispheric regions (e.g., rFFA–lFFA) than between intrahemispheric regions (e.g., rFFA–rOFA), indicating a bias towards higher interhemispheric than intrahemispheric connectivity. A similar interhemispheric bias was evident in scene-selective regions. In contrast, we did not find an interhemispheric bias in early visual regions (V1–V3), where intrahemispheric connectivity between corresponding regions was generally higher than interhemispheric connectivity. Next, we asked whether the higher interhemispheric connectivity in the face and scene networks between corresponding regions was consistent across participants. We found that the interhemispheric bias was significantly attenuated when we compared the time-course of response across participants. This shows that interhemispheric bias in connectivity between corresponding regions in the face and scene networks is specific to the individual. These findings raise the possibility that idiosyncratic variation in interhemispheric connectivity may explain individual differences in perception.

Cortical networks relating to arousal are differentially coupled to neural activity and hemodynamics.

Even in the absence of specific sensory input or a behavioral task, the brain produces structured patterns of activity. This organized activity is modulated by changes in arousal. Here, we use wide-field voltage imaging to establish how arousal relates to cortical network voltage and hemodynamic activity in spontaneously behaving head-fixed male and female mice expressing the voltage-sensitive fluorescent FRET sensor Butterfly 1.2. We find that global voltage and hemodynamic signals are both positively correlated with changes in arousal with a maximum correlation of 0.5 and 0.25 respectively at a time lag of 0 seconds. We next show that arousal influences distinct cortical regions for both voltage and hemodynamic signals. These include a broad positive correlation across most sensory-motor cortices extending posteriorly to the primary visual cortex observed in both signals. In contrast, activity in prefrontal cortex is positively correlated to changes in arousal for the voltage signal while it is a slight net negative correlation observed in the hemodynamic signal. Additionally, we show that coherence between voltage and hemodynamic signals relative to arousal is strongest for slow frequencies below 0.15 Hz and is near zero for frequencies greater than 1Hz. We finally show that coupling patterns are dependent on the behavioral state of the animal with correlations being driven by periods of increased orofacial movement. Our results indicate that while hemodynamic signals show strong relations to behavior and arousal, these relations are distinct from those observed by voltage activity.Significance Statement We leverage wide-field voltage imaging to examine the relation between cortical changes in membrane potential dynamics and hemodynamics. These two signals are then examined with respect to changes in arousal, as measured by pupil diameter, in awake head fixed mice. Our results show similarities as well as important differences in the correlation of arousal with neuronal population activity dynamics and the hemodynamic signal. Further, the spatial activity correlation maps with arousal depended differentially on the behavioral state of the animal in a frequency dependent manner. Our results indicate that the modulation of brain networks by arousal is dynamically regulated, and only partly overlap between functional networks determined from hemodynamic or voltage activity.

Parvalbumin Interneuron Dysfunction in Neurological Disorders: Focus on Epilepsy and Alzheimer’s Disease

Parvalbumin expressing (PV+) GABAergic interneurons are fast spiking neurons that provide powerful but relatively short-lived inhibition to principal excitatory cells in the brain. They play a vital role in feedforward and feedback synaptic inhibition, preventing run away excitation in neural networks. Hence, their dysfunction can lead to hyperexcitability and increased susceptibility to seizures. PV+ interneurons are also key players in generating gamma oscillations, which are synchronized neural oscillations associated with various cognitive functions. PV+ interneuron are particularly vulnerable to aging and their degeneration has been associated with cognitive decline and memory impairment in dementia and Alzheimer’s disease (AD). Overall, dysfunction of PV+ interneurons disrupts the normal excitatory/inhibitory balance within specific neurocircuits in the brain and thus has been linked to a wide range of neurodevelopmental and neuropsychiatric disorders. This review focuses on the role of dysfunctional PV+ inhibitory interneurons in the generation of epileptic seizures and cognitive impairment and their potential as targets in the design of future therapeutic strategies to treat these disorders. Recent research using cutting-edge optogenetic and chemogenetic technologies has demonstrated that they can be selectively manipulated to control seizures and restore the balance of neural activity in the brains of animal models. This suggests that PV+ interneurons could be important targets in developing future treatments for patients with epilepsy and comorbid disorders, such as AD, where seizures and cognitive decline are directly linked to specific PV+ interneuron deficits.

Elucidating the underlying components of metacognitive systematic bias in the human dorsolateral prefrontal cortex and inferior parietal cortex

Metacognitive systematic bias impairs human learning efficiency, which is characterized by the inconsistency between predicted and actual memory performance. However, the underlying mechanism of metacognitive systematic bias remains unclear in existing studies. In this study, we utilized judgments of learning task in human participants to compare the neural mechanism difference in metacognitive systematic bias. Participants encoded words in fMRI sessions that would be tested later. Immediately after encoding each item, participants predicted how likely they would remember it. Multivariate analyses on fMRI data demonstrated that working memory and uncertainty decisions are represented in patterns of neural activity in metacognitive systematic bias. The available information participants used led to overestimated bias and underestimated bias. Effective connectivity analyses further indicate that information about the metacognitive systematic bias is represented in the dorsolateral prefrontal cortex and inferior parietal cortex. Different neural patterns were found underlying overestimated bias and underestimated bias. Specifically, connectivity regions with the dorsolateral prefrontal cortex, anterior cingulate cortex, and supramarginal gyrus form overestimated bias, while less regional connectivity forms underestimated bias. These findings provide a mechanistic account for the construction of metacognitive systematic bias.

MAPPING THYROID HORMONE ACTION IN THE HUMAN BRAIN.

Normal brain development, mood, and cognitive functions depend on thyroid hormone (TH) action. However, little is known about how TH mediates its actions in the human brain. This is because of limited access to human brains deprived of TH during fetal and early postnatal life, as well as from adults with altered thyroid status. One way to partially bypass these limitations is by using magnetic resonance imaging and spectroscopy, two neuroimaging techniques that provide detailed, non-invasive information on human brain structure and function. Another way is using human-induced pluripotent stem cells (hiPSCs)-derived three-dimensional in vitro systems, known as brain organoids, which allow for studying fundamental aspects of the early stages of human brain development. This narrative review focuses on neuroimaging and brain organoid studies. Neuroimaging of human brains performed in individuals with different thyroid conditions provides information on the volume, myelination, blood flow, neural activity, and connectivity of different areas. Such studies show that a suboptimal thyroid status can impact human brain development and its normal function throughout life. This is true not only for patients with sporadic congenital hypothyroidism, during pregnancy or early after birth, but also for adult patients with hypo- or hyperthyroidism and for patients carrying mutations that manifest as impaired sensitivity to TH-and even for normal individuals during aging. Studies using brain organoids generated from iPSCs of healthy individuals or patients with thyroid genetic conditions provide insights into how TH can impact the early development of the human cerebral cortex. The developmental alterations in children born to mothers with different degrees of gestational hypothyroidism or who developed hypothyroidism early in life are remarkable, affecting multiple brain regions and pathways, including the cerebral cortex, hippocampus, cerebellum, interhemispheric and corticospinal tracts, and associative nuclei. The data connecting such changes to poor neurological outcomes in adult patients with hypothyroidism represent an objective link between thyroid-specific functional brain alterations and behavior. Growing brain organoids require TH, proving critical for human neuro- and oligodendrogenesis. These models proved useful in screening drugs with potential therapeutics for patients with genetic thyroid diseases.

Suspending the embodied self in meditation attenuates beta oscillations in posterior medial cortex.

Human experience is imbued by the sense of being an embodied agent. The investigation of such basic self-consciousness has been hampered by the difficulty of comprehensively modulating it in the laboratory while reliably capturing ensuing subjective changes. The present preregistered study fills this gap by combining advanced meditative states with principled phenomenological interviews: Forty-six long-term meditators (19 female, 27 male) were instructed to modulate and attenuate their embodied self-experience during magnetoencephalographic monitoring. Results showed frequency specific (high beta band) activity reductions in frontoparietal and posterior medial cortices (PMC). Importantly, PMC reductions were driven by a subgroup describing radical embodied self disruptions, including suspension of agency and dissolution of a localised first-person perspective. Neural changes were correlated with lifetime meditation and interview-derived experiential changes, but not with classical self-reports. The results demonstrate the potential of integrating in-depth first-person methods into neuroscientific experiments. Furthermore, they highlight neural oscillations in the PMC as a central process supporting the embodied sense of self.Significance statement Human consciousness is not only characterised by the contents of experience, but also by an implicit sense of subjectivity, delineating the perceiving, embodied agent from her environment. The current study addressed this basic sense of self by scrutinising meditation-induced states of self-boundary dissolution using a neurophenomenological approach: In-depth phenomenological interviews assessed core dimensions of self-experience during such states (agency, self-location, first-person perspective), while magnetoencephalography monitored neural oscillatory activity. Full-blown suspension of self-experience was associated with robust reductions of beta-band power in the posterior medial cortex. These results pinpoint a neural candidate mediating our embodied perspective on the world and highlight the unique potential of integrating rigorous phenomenological methods with neuroscientific experiments for the study of consciousness.