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Unifying integration and segregation in the brain has been a fundamental puzzle in neuroscience ever since the conception of the "binding problem." Here, we introduce a framework that places integration and segregation within a continuum based on a fundamental property of the brain-its structural connectivity graph Laplacian harmonics and a new feature we term the gap-spectrum. This framework organizes harmonics into three regimes-integrative, segregative, and degenerate-that together account for various group-level properties. Integrative and segregative harmonics occupy the ends of the continuum, and they share properties such as reproducibility across individuals, stability to perturbation, and involve "bottom-up" sensory networks. Degenerate harmonics are in the middle of the continuum, and they are subject-specific, flexible, and involve "top-down" networks. The proposed framework accommodates inter-subject variation, sensitivity to changes, and structure-function coupling in ways that offer promising avenues for studying cognition and consciousness in the brain.
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Encéfalo , Conectoma , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Humanos , Red Nerviosa/fisiología , Red Nerviosa/diagnóstico por imagen , Modelos NeurológicosRESUMEN
The spectral content of macroscopic neural activity evolves throughout development, yet how this maturation relates to underlying brain network formation and dynamics remains unknown. Here, we assess the developmental maturation of electroencephalogram spectra via Bayesian model inversion of the spectral graph model, a parsimonious whole-brain model of spatiospectral neural activity derived from linearized neural field models coupled by the structural connectome. Simulation-based inference was used to estimate age-varying spectral graph model parameter posterior distributions from electroencephalogram spectra spanning the developmental period. This model-fitting approach accurately captures observed developmental electroencephalogram spectral maturation via a neurobiologically consistent progression of key neural parameters: long-range coupling, axonal conduction speed, and excitatory:inhibitory balance. These results suggest that the spectral maturation of macroscopic neural activity observed during typical development is supported by age-dependent functional adaptations in localized neural dynamics and their long-range coupling across the macroscopic structural network.
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Resting state functional MRI (rs-fMRI) is a popular and widely used technique to explore the brain's functional organization and to examine if it is altered in neurological or mental disorders. The most common approach for its analysis targets the measurement of the synchronized fluctuations between brain regions, characterized as functional connectivity (FC), typically relying on pairwise correlations in activity across different brain regions. While hugely successful in exploring state- and disease-dependent network alterations, these statistical graph theory tools suffer from two key limitations. First, they discard useful information about the rich frequency content of the fMRI signal. The rich spectral information now achievable from advances in fast multiband acquisitions is consequently being under-utilized. Second, the analyzed FCs are phenomenological without a direct neurobiological underpinning in the underlying structures and processes in the brain. There does not currently exist a complete generative model framework for whole brain resting fMRI that is informed by its underlying biological basis in the structural connectome. Here we propose that a different approach can solve both challenges at once: the use of an appropriately realistic yet parsimonious biophysical signal generation model followed by graph spectral (i.e. eigen) decomposition. We call this model a Spectral Graph Model (SGM) for fMRI, using which we can not only quantify the structure-function relationship in individual subjects, but also condense the variable and individual-specific repertoire of fMRI signal's spectral and spatial features into a small number of biophysically-interpretable parameters. We expect this model-based inference of rs-fMRI that seamlessly integrates with structure can be used to examine state and trait characteristics of structure-function relations in a variety of brain disorders.
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While animal models of Alzheimer's disease (AD) have shown altered gamma oscillations (â¼40â Hz) in local neural circuits, the low signal-to-noise ratio of gamma in the resting human brain precludes its quantification via conventional spectral estimates. Phase-amplitude coupling (PAC) indicating the dynamic integration between the gamma amplitude and the phase of low-frequency (4-12â Hz) oscillations is a useful alternative to capture local gamma activity. In addition, PAC is also an index of neuronal excitability as the phase of low-frequency oscillations that modulate gamma amplitude, effectively regulates the excitability of local neuronal firing. In this study, we sought to examine the local neuronal activity and excitability using gamma PAC, within brain regions vulnerable to early AD pathophysiology-entorhinal cortex and parahippocampus, in a clinical population of patients with AD and age-matched controls. Our clinical cohorts consisted of a well-characterized cohort of AD patients (n = 50; age, 60 ± 8 years) with positive AD biomarkers, and age-matched, cognitively unimpaired controls (n = 35; age, 63 ± 5.8 years). We identified the presence or the absence of epileptiform activity in AD patients (AD patients with epileptiform activity, AD-EPI+, n = 20; AD patients without epileptiform activity, AD-EPI-, n = 30) using long-term electroencephalography (LTM-EEG) and 1-hour long magnetoencephalography (MEG) with simultaneous EEG. Using the source reconstructed MEG data, we computed gamma PAC as the coupling between amplitude of the gamma frequency (30-40â Hz) with phase of the theta (4-8â Hz) and alpha (8-12â Hz) frequency oscillations, within entorhinal and parahippocampal cortices. We found that patients with AD have reduced gamma PAC in the left parahippocampal cortex, compared to age-matched controls. Furthermore, AD-EPI+ patients showed greater reductions in gamma PAC than AD-EPI- in bilateral parahippocampal cortices. In contrast, entorhinal cortices did not show gamma PAC abnormalities in patients with AD. Our findings demonstrate the spatial patterns of altered gamma oscillations indicating possible region-specific manifestations of network hyperexcitability within medial temporal lobe regions vulnerable to AD pathophysiology. Greater deficits in AD-EPI+ suggests that reduced gamma PAC is a sensitive index of network hyperexcitability in AD patients. Collectively, the current results emphasize the importance of investigating the role of neural circuit hyperexcitability in early AD pathophysiology and explore its potential as a modifiable contributor to AD pathobiology.
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BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia, progressively impairing cognitive abilities. While neuroimaging studies have revealed functional abnormalities in AD, how these relate to aberrant neuronal circuit mechanisms remains unclear. Using magnetoencephalography imaging we documented abnormal local neural synchrony patterns in patients with AD. To identify global abnormal biophysical mechanisms underlying the spatial and spectral electrophysiological patterns in AD, we estimated the parameters of a biophysical spectral graph model (SGM). METHODS: SGM is an analytic neural mass model that describes how long-range fiber projections in the brain mediate the excitatory and inhibitory activity of local neuronal subpopulations. Unlike other coupled neuronal mass models, the SGM is linear, available in closed-form, and parameterized by a small set of biophysical interpretable global parameters. This facilitates their rapid and unambiguous inference which we performed here on a well-characterized clinical population of patients with AD (N = 88, age = 62.73 +/- 8.64 years) and a cohort of age-matched controls (N = 88, age = 65.07 +/- 9.92 years). RESULTS: Patients with AD showed significantly elevated long-range excitatory neuronal time scales, local excitatory neuronal time scales and local inhibitory neural synaptic strength. The long-range excitatory time scale had a larger effect size, compared to local excitatory time scale and inhibitory synaptic strength and contributed highest for the accurate classification of patients with AD from controls. Furthermore, increased long-range time scale was associated with greater deficits in global cognition. CONCLUSIONS: These results demonstrate that long-range excitatory time scale of neuronal activity, despite being a global measure, is a key determinant in the local spectral signatures and cognition in the human brain, and how it might be a parsimonious factor underlying altered neuronal activity in AD. Our findings provide new insights into mechanistic links between abnormal local spectral signatures and global connectivity measures in AD.
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Enfermedad de Alzheimer , Trastornos del Conocimiento , Disfunción Cognitiva , Humanos , Persona de Mediana Edad , Anciano , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , CogniciónRESUMEN
Self-agency is the awareness of being the agent of one's own thoughts and actions. Self-agency is essential for interacting with the outside world (reality-monitoring). The medial prefrontal cortex (mPFC) is thought to be one neural correlate of self-agency. We investigated whether mPFC activity can causally modulate self-agency on two different tasks of speech-monitoring and reality-monitoring. The experience of self-agency is thought to result from making reliable predictions about the expected outcomes of one's own actions. This self-prediction ability is necessary for the encoding and memory retrieval of one's own thoughts during reality-monitoring to enable accurate judgments of self-agency. This self-prediction ability is also necessary for speech-monitoring where speakers consistently compare auditory feedback (what we hear ourselves say) with what we expect to hear while speaking. In this study, 30 healthy participants are assigned to either 10 Hz repetitive transcranial magnetic stimulation (rTMS) to enhance mPFC excitability (N = 15) or 10 Hz rTMS targeting a distal temporoparietal site (N = 15). High-frequency rTMS to mPFC enhanced self-predictions during speech-monitoring that predicted improved self-agency judgments during reality-monitoring. This is the first study to provide robust evidence for mPFC underlying a causal role in self-agency, that results from the fundamental ability of improving self-predictions across two different tasks.
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Memoria , Habla , Humanos , Memoria/fisiología , Estimulación Magnética Transcraneal/métodos , Corteza Prefrontal/fisiología , JuicioRESUMEN
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-ß and misfolded tau proteins causing synaptic dysfunction, and progressive neurodegeneration and cognitive decline. Altered neural oscillations have been consistently demonstrated in AD. However, the trajectories of abnormal neural oscillations in AD progression and their relationship to neurodegeneration and cognitive decline are unknown. Here, we deployed robust event-based sequencing models (EBMs) to investigate the trajectories of long-range and local neural synchrony across AD stages, estimated from resting-state magnetoencephalography. The increases in neural synchrony in the delta-theta band and the decreases in the alpha and beta bands showed progressive changes throughout the stages of the EBM. Decreases in alpha and beta band synchrony preceded both neurodegeneration and cognitive decline, indicating that frequency-specific neuronal synchrony abnormalities are early manifestations of AD pathophysiology. The long-range synchrony effects were greater than the local synchrony, indicating a greater sensitivity of connectivity metrics involving multiple regions of the brain. These results demonstrate the evolution of functional neuronal deficits along the sequence of AD progression.
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Enfermedad de Alzheimer , Humanos , Péptidos beta-Amiloides , Proteínas tau , Benchmarking , EncéfaloRESUMEN
Magnetic resonance imaging is subject to slow acquisition times due to the inherent limitations in data sampling. Recently, supervised deep learning has emerged as a promising technique for reconstructing sub-sampled MRI. However, supervised deep learning requires a large dataset of fully-sampled data. Although unsupervised or self-supervised deep learning methods have emerged to address the limitations of supervised deep learning approaches, they still require a database of images. In contrast, scan-specific deep learning methods learn and reconstruct using only the sub-sampled data from a single scan. Here, we introduce Scan-Specific Self-Supervised Bayesian Deep Non-Linear Inversion (DNLINV) that does not require an auto calibration scan region. DNLINV utilizes a Deep Image Prior-type generative modeling approach and relies on approximate Bayesian inference to regularize the deep convolutional neural network. We demonstrate our approach on several anatomies, contrasts, and sampling patterns and show improved performance over existing approaches in scan-specific calibrationless parallel imaging and compressed sensing.
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Teorema de Bayes , Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Encéfalo/diagnóstico por imagen , Algoritmos , Aprendizaje Automático SupervisadoRESUMEN
Self-agency is being aware of oneself as the agent of one's thoughts and actions. Self-agency is necessary for successful interactions with the outside world (reality-monitoring). Prior research has shown that the medial superior prefrontal gyri (mPFC/SFG) may represent one neural correlate underlying self-agency judgments. However, the causal relationship remains unknown. Here, we applied high-frequency 10Hz repetitive transcranial magnetic stimulation (rTMS) to modulate the excitability of the mPFC/SFG site that we have previously shown to mediate self-agency. For the first time, we delineate causal neural mechanisms, revealing precisely how rTMS modulates SFG excitability and impacts directional neural information flow in the self-agency network by implementing innovative magnetoencephalography (MEG) phase-transfer entropy (PTE) metrics, measured from pre-to-post rTMS. We found that, compared to control rTMS, enhancing SFG excitability by rTMS induced significant increases in information flow between SFG and specific cingulate and paracentral regions in the self-agency network in delta-theta, alpha, and gamma bands, which predicted improved self-agency judgments. This is the first multimodal imaging study in which we implement MEG PTE metrics of 5D imaging of space, frequency and time, to provide cutting-edge analyses of the causal neural mechanisms of how rTMS enhances SFG excitability and improves neural information flow between distinct regions in the self-agency network to potentiate improved self-agency judgments. Our findings provide a novel perspective for investigating causal neural mechanisms underlying self-agency and create a path towards developing novel neuromodulation interventions to improve self-agency that will be particularly useful for patients with psychosis who exhibit severe impairments in self-agency.
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Sensory processing dysfunction not only affects most individuals with autism spectrum disorder (ASD), but at least 5% of children without ASD also experience dysfunctional sensory processing. Our understanding of the relationship between sensory dysfunction and resting state brain activity is still emerging. This study compared long-range resting state functional connectivity of neural oscillatory behavior in children aged 8-12 years with autism spectrum disorder (ASD; N=18), those with sensory processing dysfunction (SPD; N=18) who do not meet ASD criteria, and typically developing control participants (TDC; N=24) using magnetoencephalography (MEG). Functional connectivity analyses were performed in the alpha and beta frequency bands, which are known to be implicated in sensory information processing. Group differences in functional connectivity and associations between sensory abilities and functional connectivity were examined. Distinct patterns of functional connectivity differences between ASD and SPD groups were found only in the beta band, but not in the alpha band. In both alpha and beta bands, ASD and SPD cohorts differed from the TDC cohort. Somatosensory cortical beta-band functional connectivity was associated with tactile processing abilities, while higher-order auditory cortical alpha-band functional connectivity was associated with auditory processing abilities. These findings demonstrate distinct long-range neural synchrony alterations in SPD and ASD that are associated with sensory processing abilities. Neural synchrony measures could serve as potential sensitive biomarkers for ASD and SPD.
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INTRODUCTION: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are the most common four-repeat tauopathies (4RT), and both frequently occur with varying degree of Alzheimer's disease (AD) copathology. Intriguingly, patients with 4RT and patients with AD are at opposite ends of the wakefulness spectrum-AD showing reduced wakefulness and excessive sleepiness whereas 4RT showing decreased homeostatic sleep. The neural mechanisms underlying these distinct phenotypes in the comorbid condition of 4RT and AD are unknown. The objective of the current study was to define the alpha oscillatory spectrum, which is prominent in the awake resting-state in the human brain, in patients with primary 4RT, and how it is modified in comorbid AD-pathology. METHOD: In an autopsy-confirmed case series of 4R-tauopathy patients (n = 10), whose primary neuropathological diagnosis was either PSP (n = 7) or CBD (n = 3), using high spatiotemporal resolution magnetoencephalography (MEG), we quantified the spectral power density within alpha-band (8-12 Hz) and examined how this pattern was modified in increasing AD-copathology. For each patient, their regional alpha power was compared to an age-matched normative control cohort (n = 35). RESULT: Patients with 4RT showed increased alpha power but in the presence of AD-copathology alpha power was reduced. CONCLUSIONS: Alpha power increase in PSP-tauopathy and reduction in the presence of AD-tauopathy is consistent with the observation that neurons activating wakefulness-promoting systems are preserved in PSP but degenerated in AD. These results highlight the selectively vulnerable impacts in 4RT versus AD-tauopathy that may have translational significance on disease-modifying therapies for specific proteinopathies.
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Enfermedad de Alzheimer , Parálisis Supranuclear Progresiva , Tauopatías , Humanos , Proteínas tau/metabolismo , Enfermedad de Alzheimer/patología , Parálisis Supranuclear Progresiva/diagnóstico , Encéfalo/patologíaRESUMEN
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-ß and misfolded tau proteins causing synaptic dysfunction, and progressive neurodegeneration and cognitive decline. Altered neural oscillations have been consistently demonstrated in AD. However, the trajectories of abnormal neural oscillations in AD progression and their relationship to neurodegeneration and cognitive decline are unknown. Here, we deployed robust event-based sequencing models (EBMs) to investigate the trajectories of long-range and local neural synchrony across AD stages, estimated from resting-state magnetoencephalography. The increases in neural synchrony in the delta-theta band and the decreases in the alpha and beta bands showed progressive changes throughout the stages of the EBM. Decreases in alpha and beta band synchrony preceded both neurodegeneration and cognitive decline, indicating that frequency-specific neuronal synchrony abnormalities are early manifestations of AD pathophysiology. The long-range synchrony effects were greater than the local synchrony, indicating a greater sensitivity of connectivity metrics involving multiple regions of the brain. These results demonstrate the evolution of functional neuronal deficits along the sequence of AD progression.
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The human sensorimotor system has a remarkable ability to quickly and efficiently learn movements from sensory experience. A prominent example is sensorimotor adaptation, learning that characterizes the sensorimotor system's response to persistent sensory errors by adjusting future movements to compensate for those errors. Despite being essential for maintaining and fine-tuning motor control, mechanisms underlying sensorimotor adaptation remain unclear. A component of sensorimotor adaptation is implicit (i.e., the learner is unaware of the learning process) which has been suggested to result from sensory prediction errors-the discrepancies between predicted sensory consequences of motor commands and actual sensory feedback. However, to date no direct neurophysiological evidence that sensory prediction errors drive adaptation has been demonstrated. Here, we examined prediction errors via magnetoencephalography (MEG) imaging of the auditory cortex during sensorimotor adaptation of speech to altered auditory feedback, an entirely implicit adaptation task. Specifically, we measured how speaking-induced suppression (SIS)--a neural representation of auditory prediction errors--changed over the trials of the adaptation experiment. SIS refers to the suppression of auditory cortical response to speech onset (in particular, the M100 response) to self-produced speech when compared to the response to passive listening to identical playback of that speech. SIS was reduced (reflecting larger prediction errors) during the early learning phase compared to the initial unaltered feedback phase. Furthermore, reduction in SIS positively correlated with behavioral adaptation extents, suggesting that larger prediction errors were associated with more learning. In contrast, such a reduction in SIS was not found in a control experiment in which participants heard unaltered feedback and thus did not adapt. In addition, in some participants who reached a plateau in the late learning phase, SIS increased (reflecting smaller prediction errors), demonstrating that prediction errors were minimal when there was no further adaptation. Together, these findings provide the first neurophysiological evidence for the hypothesis that prediction errors drive human sensorimotor adaptation.
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Self-agency is being aware of oneself as the agent of one's thoughts and actions. Self agency is necessary for successful interactions with the external world (reality-monitoring). The medial prefrontal cortex (mPFC) is considered to represent one neural correlate underlying self-agency. We investigated whether mPFC activity can causally modulate self-agency on two different tasks involving speech-monitoring and reality-monitoring. The experience of self-agency is thought to result from being able to reliably predict the sensory outcomes of one's own actions. This self-prediction ability is necessary for successfully encoding and recalling one's own thoughts to enable accurate self-agency judgments during reality-monitoring tasks. This self-prediction ability is also necessary during speech-monitoring tasks where speakers compare what we hear ourselves say in auditory feedback with what we predict we will hear while speaking. In this randomised-controlled study, heathy controls (HC) are assigned to either high-frequency transcranial magnetic stimulation (TMS) to enhance mPFC excitability or TMS targeting a control site. After TMS to mPFC, HC improved self-predictions during speech-monitoring tasks that predicted improved self-agency judgments during different reality-monitoring tasks. These first-in-kind findings demonstrate the mechanisms of how mPFC plays a causal role in self-agency that results from the fundamental ability of improving self-predictions across two different tasks.
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Sleep is a highly stereotyped phenomenon, requiring robust spatiotemporal coordination of neural activity. Understanding how the brain coordinates neural activity with sleep onset can provide insights into the physiological functions subserved by sleep and the pathologic phenomena associated with sleep onset. We quantified whole-brain network changes in synchrony and information flow during the transition from wakefulness to light non-rapid eye movement (NREM) sleep, using MEG imaging in a convenient sample of 14 healthy human participants (11 female; mean 63.4 years [SD 11.8 years]). We furthermore performed computational modeling to infer excitatory and inhibitory properties of local neural activity. The transition from wakefulness to light NREM was identified to be encoded in spatially and temporally specific patterns of long-range synchrony. Within the delta band, there was a global increase in connectivity from wakefulness to light NREM, which was highest in frontoparietal regions. Within the theta band, there was an increase in connectivity in fronto-parieto-occipital regions and a decrease in temporal regions from wakefulness to Stage 1 sleep. Patterns of information flow revealed that mesial frontal regions receive hierarchically organized inputs from broad cortical regions upon sleep onset, including direct inflow from occipital regions and indirect inflow via parieto-temporal regions within the delta frequency band. Finally, biophysical neural mass modeling demonstrated changes in the anterior-to-posterior distribution of cortical excitation-to-inhibition with increased excitation-to-inhibition model parameters in anterior regions in light NREM compared with wakefulness. Together, these findings uncover whole-brain corticocortical structure and the orchestration of local and long-range, frequency-specific cortical interactions in the sleep-wake transition.SIGNIFICANCE STATEMENT Our work uncovers spatiotemporal cortical structure of neural synchrony and information flow upon the transition from wakefulness to light non-rapid eye movement sleep. Mesial frontal regions were identified to receive hierarchically organized inputs from broad cortical regions, including both direct inputs from occipital regions and indirect inputs via the parieto-temporal regions within the delta frequency range. Biophysical neural mass modeling revealed a spatially heterogeneous, anterior-posterior distribution of cortical excitation-to-inhibition. Our findings shed light on the orchestration of local and long-range cortical neural structure that is fundamental to sleep onset, and support an emerging view of cortically driven regulation of sleep homeostasis.
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Electroencefalografía , Vigilia , Humanos , Femenino , Vigilia/fisiología , Electroencefalografía/métodos , Movimientos Oculares , Fases del Sueño/fisiología , Sueño/fisiologíaRESUMEN
Dynamic resting state functional connectivity (RSFC) characterizes time-varying fluctuations of functional brain network activity. While many studies have investigated static functional connectivity, it has been unclear whether features of dynamic functional connectivity are associated with neurodegenerative diseases. Popular sliding-window and clustering methods for extracting dynamic RSFC have various limitations that prevent extracting reliable features to address this question. Here, we use a novel and robust time-varying dynamic network (TVDN) approach to extract the dynamic RSFC features from high resolution magnetoencephalography (MEG) data of participants with Alzheimer's disease (AD) and matched controls. The TVDN algorithm automatically and adaptively learns the low-dimensional spatiotemporal manifold of dynamic RSFC and detects dynamic state transitions in data. We show that amongst all the functional features we investigated, the dynamic manifold features are the most predictive of AD. These include: the temporal complexity of the brain network, given by the number of state transitions and their dwell times, and the spatial complexity of the brain network, given by the number of eigenmodes. These dynamic features have higher sensitivity and specificity in distinguishing AD from healthy subjects than the existing benchmarks do. Intriguingly, we found that AD patients generally have higher spatial complexity but lower temporal complexity compared with healthy controls. We also show that graph theoretic metrics of dynamic component of TVDN are significantly different in AD versus controls, while static graph metrics are not statistically different. These results indicate that dynamic RSFC features are impacted in neurodegenerative disease like Alzheimer's disease, and may be crucial to understanding the pathophysiological trajectory of these diseases.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Humanos , Magnetoencefalografía/métodos , Imagen por Resonancia Magnética/métodos , EncéfaloRESUMEN
BACKGROUND: Caudate functional abnormalities have been identified as one critical neural substrate underlying sensory gating impairments that lead to auditory phantom hallucinations in both patients with schizophrenia (SZ) and tinnitus, characterized by the perception of internally generated sounds in the absence of external environmental auditory stimuli. In this study, we tested the hypothesis as to whether functional connectivity abnormalities in distinct caudate subdivisions implicated in sensory gating and auditory phantom percepts in tinnitus, which are currently being localized for neuromodulation targeting using deep brain stimulation techniques, would be associated with auditory phantom hallucination severity in SZ. METHODS: Twenty five SZ and twenty eight demographically-matched healthy control (HC) participants, completed this fMRI resting-state study and clinical assessments. RESULTS: Between-group seed-to-voxel analyses revealed only one region, the caudate anterior head, which showed reduced functional connectivity with the thalamus that survived whole-brain multiple comparison corrections. Importantly, connectivity between the caudate anterior head with thalamus negatively correlated with hallucination severity. CONCLUSIONS: In the present study, we deliver the first evidence of caudate subdivision specificity for the neural pathophysiology underlying hallucinations in schizophrenia within a sensory gating framework that has been developed for auditory phantoms in patients with tinnitus. Our findings provide transdiagnostic convergent evidence for the role of the caudate in the gating of auditory phantom hallucinations, observed across patients with SZ and tinnitus by specifying the anterior caudate division is key to mediation of hallucinations, and creating a path towards personalized treatment approaches to arrest auditory phantom hallucinations from reaching perceptual awareness.
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Esquizofrenia , Acúfeno , Humanos , Esquizofrenia/complicaciones , Esquizofrenia/diagnóstico por imagen , Acúfeno/complicaciones , Alucinaciones/etiología , Alucinaciones/complicaciones , Encéfalo , Mapeo Encefálico , Imagen por Resonancia MagnéticaRESUMEN
Upon perceiving sensory errors during movements, the human sensorimotor system updates future movements to compensate for the errors, a phenomenon called sensorimotor adaptation. One component of this adaptation is thought to be driven by sensory prediction errors-discrepancies between predicted and actual sensory feedback. However, the mechanisms by which prediction errors drive adaptation remain unclear. Here, auditory prediction error-based mechanisms involved in speech auditory-motor adaptation were examined via the feedback aware control of tasks in speech (FACTS) model. Consistent with theoretical perspectives in both non-speech and speech motor control, the hierarchical architecture of FACTS relies on both the higher-level task (vocal tract constrictions) as well as lower-level articulatory state representations. Importantly, FACTS also computes sensory prediction errors as a part of its state feedback control mechanism, a well-established framework in the field of motor control. We explored potential adaptation mechanisms and found that adaptive behavior was present only when prediction errors updated the articulatory-to-task state transformation. In contrast, designs in which prediction errors updated forward sensory prediction models alone did not generate adaptation. Thus, FACTS demonstrated that 1) prediction errors can drive adaptation through task-level updates, and 2) adaptation is likely driven by updates to task-level control rather than (only) to forward predictive models. Additionally, simulating adaptation with FACTS generated a number of important hypotheses regarding previously reported phenomena such as identifying the source(s) of incomplete adaptation and driving factor(s) for changes in the second formant frequency during adaptation to the first formant perturbation. The proposed model design paves the way for a hierarchical state feedback control framework to be examined in the context of sensorimotor adaptation in both speech and non-speech effector systems.
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Adaptación Fisiológica , Habla , Humanos , Retroalimentación , Retroalimentación Sensorial , MovimientoRESUMEN
The relationship between brain functional connectivity and structural connectivity has caught extensive attention of the neuroscience community, commonly inferred using mathematical modeling. Among many modeling approaches, spectral graph model (SGM) is distinctive as it has a closed-form solution of the wide-band frequency spectra of brain oscillations, requiring only global biophysically interpretable parameters. While SGM is parsimonious in parameters, the determination of SGM parameters is non-trivial. Prior works on SGM determine the parameters through a computational intensive annealing algorithm, which only provides a point estimate with no confidence intervals for parameter estimates. To fill this gap, we incorporate the simulation-based inference (SBI) algorithm and develop a Bayesian procedure for inferring the posterior distribution of the SGM parameters. Furthermore, using SBI dramatically reduces the computational burden for inferring the SGM parameters. We evaluate the proposed SBI-SGM framework on the resting-state magnetoencephalography recordings from healthy subjects and show that the proposed procedure has similar performance to the annealing algorithm in recovering power spectra and the spatial distribution of the alpha frequency band. In addition, we also analyze the correlations among the parameters and their uncertainty with the posterior distribution which cannot be done with annealing inference. These analyses provide a richer understanding of the interactions among biophysical parameters of the SGM. In general, the use of simulation-based Bayesian inference enables robust and efficient computations of generative model parameter uncertainties and may pave the way for the use of generative models in clinical translation applications.
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Encéfalo , Magnetoencefalografía , Humanos , Teorema de Bayes , Modelos Teóricos , Simulación por ComputadorRESUMEN
Overlapping clinical presentations in primary progressive aphasia (PPA) variants present challenges for diagnosis and understanding pathophysiology, particularly in the early stages of the disease when behavioral (speech) symptoms are not clearly evident. Divergent atrophy patterns (temporoparietal degeneration in logopenic variant lvPPA, frontal degeneration in nonfluent variant nfvPPA) can partially account for differential speech production errors in the two groups in the later stages of the disease. While the existing dogma states that neurodegeneration is the root cause of compromised behavior and cortical activity in PPA, the extent to which neurophysiological signatures of speech dysfunction manifest independent of their divergent atrophy patterns remain unknown. We test the hypothesis that nonword deficits in lvPPA and nfvPPA arise from distinct patterns of neural oscillations that are unrelated to atrophy. We use a novel structure-function imaging approach integrating magnetoencephalographic imaging of neural oscillations during a non-word repetition task with voxel-based morphometry-derived measures of gray matter volume to isolate neural oscillation abnormalities independent of atrophy. We find reduced beta band neural activity in left temporal regions associated with the late stages of auditory encoding unique to patients with lvPPA and reduced high-gamma neural activity over left frontal regions associated with the early stages of motor preparation in patients with nfvPPA. Neither of these patterns of reduced cortical oscillations was explained by cortical atrophy in our statistical model. These findings highlight the importance of structure-function imaging in revealing neurophysiological sequelae in early stages of dementia when neither structural atrophy nor behavioral deficits are clinically distinct.