Fundamental Neural Mechanisms Research Articles

Gray matter volumetric changes in tinnitus: The impact of hearing loss and severity

Tinnitus is a phantom auditory sensation that commonly co-occurs with hearing loss. Both tinnitus and hearing loss can impact the quality of life, emotional well-being, and cognitive functioning of the affected individuals. While previous studies have highlighted structural alterations in hearing loss and/or tinnitus, the fundamental neural mechanisms underpinning tinnitus severity remain poorly understood. In this study, we conducted a voxel-based morphometry to investigate gray matter (GM) volume differences among groups of participants with varying tinnitus severity and hearing status, and controls within a large sample. We observed reduced GM volume in the left anterior insula and right planum polare in participants with hearing loss, regardless of their tinnitus status, compared to normal hearing controls. We noted decreased GM volume in the bilateral anterior and posterior insula for those with tinnitus and normal hearing compared to a normal hearing control group. Further, the tinnitus with hearing loss group showed decreased GM volume in the left planum polare, left inferior temporal gyrus, bilateral anterior temporal gyri, and right superior frontal gyrus compared to the normal hearing control group, suggesting a combined effect of hearing loss and tinnitus. While tinnitus severity did not show a significant overall effect, there was a significant positive correlation between tinnitus distress and GM volume in bilateral planum polare. Our findings enhance the understanding of structural brain changes related to hearing loss and tinnitus, and advance the overall knowledge of tinnitus pathophysiology, which can contribute to the development of more effective treatments for tinnitus.

Cortical cognitive processing during reading captured using functional-near infrared spectroscopy

Neuroimaging studies using functional magnetic resonance imaging (fMRI) have provided unparalleled insights into the fundamental neural mechanisms underlying human cognitive processing, such as high-level linguistic processes during reading. Here, we build upon this prior work to capture sentence reading comprehension outside the MRI scanner using functional near infra-red spectroscopy (fNIRS) in a large sample of participants (n = 82). We observed increased task-related hemodynamic responses in prefrontal and temporal cortical regions during sentence-level reading relative to the control condition (a list of non-words), replicating prior fMRI work on cortical recruitment associated with high-level linguistic processing during reading comprehension. These results lay the groundwork towards developing adaptive systems to support novice readers and language learners by targeting the underlying cognitive processes. This work also contributes to bridging the gap between laboratory findings and more real-world applications in the realm of cognitive neuroscience.

Always expect the unexpected: eye position modulates visual cortex excitability in a stimulus-free environment.

Stimuli that potentially require a rapid defensive or avoidance action can appear from the periphery at any time in natural environments. de Wit et al. (Cortex 127: 120-130, 2020) recently reported novel evidence suggestive of a fundamental neural mechanism that allows organisms to effectively deal with such situations. In the absence of any task, motor cortex excitability was found to be greater whenever gaze was directed away from either hand. If modulation of cortical excitability as a function of gaze location is a fundamental principle of brain organization, then one would expect its operation to be present outside of motor cortex, including brain regions involved in perception. To test this hypothesis, we applied single-pulse transcranial magnetic stimulation (TMS) to the right lateral occipital lobe while participants directed their eyes to the left, straight-ahead, or to the right, and reported the presence or absence of a phosphene. No external stimuli were presented. Cortical excitability as reflected by the proportion of trials on which phosphenes were elicited from stimulation of the right visual cortex was greater with eyes deviated to the right as compared with the left. In conjunction with our previous findings of change in motor cortex excitability when gaze and effector are not aligned, this eye position-driven change in visual cortex excitability presumably serves to facilitate the detection of stimuli and subsequent readiness to act in nonfoveated regions of space. The existence of this brain-wide mechanism has clear adaptive value given the unpredictable nature of natural environments in which human beings are situated and have evolved.NEW & NOTEWORTHY For many complex tasks, humans focus attention on the site relevant to the task at hand. Humans evolved and live in dangerous environments, however, in which threats arise from outside the attended site; this fact necessitates a process by which the periphery is monitored. Using single-pulse transcranial magnetic stimulation (TMS), we demonstrated for the first time that eye position modulates visual cortex excitability. We argue that this underlies at least in part what we term "surveillance attention."

Diminished Repetition Suppression Reveals Selective and Systems-Level Face Processing Differences in ASD.

Repeated exposure to a stimulus results in reduced neural response, or repetition suppression, in brain regions responsible for processing that stimulus. This rapid accommodation to repetition is thought to underlie learning, stimulus selectivity, and strengthening of perceptual expectations. Importantly, reduced sensitivity to repetition has been identified in several neurodevelopmental, learning, and psychiatric disorders, including autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by challenges in social communication and repetitive behaviors and restricted interests. Reduced ability to exploit or learn from repetition in ASD is hypothesized to contribute to sensory hypersensitivities, and parallels several theoretical frameworks claiming that ASD individuals show difficulty using regularities in the environment to facilitate behavior. Using fMRI in autistic and neurotypical human adults (females and males), we assessed the status of repetition suppression across two modalities (vision, audition) and with four stimulus categories (faces, objects, printed words, and spoken words). ASD individuals showed domain-specific reductions in repetition suppression for face stimuli only, but not for objects, printed words, or spoken words. Reduced repetition suppression for faces was associated with greater challenges in social communication in ASD. We also found altered functional connectivity between atypically adapting cortical regions and higher-order face recognition regions, and microstructural differences in related white matter tracts in ASD. These results suggest that fundamental neural mechanisms and system-wide circuits are selectively altered for face processing in ASD and enhance our understanding of how disruptions in the formation of stable face representations may relate to higher-order social communication processes.SIGNIFICANCE STATEMENT A common finding in neuroscience is that repetition results in plasticity in stimulus-specific processing regions, reflecting selectivity and adaptation (repetition suppression [RS]). RS is reduced in several neurodevelopmental and psychiatric conditions including autism spectrum disorder (ASD). Theoretical frameworks of ASD posit that reduced adaptation may contribute to associated challenges in social communication and sensory processing. However, the scope of RS differences in ASD is unknown. We examined RS for multiple categories across visual and auditory domains (faces, objects, printed words, spoken words) in autistic and neurotypical individuals. We found reduced RS in ASD for face stimuli only and altered functional connectivity and white matter microstructure between cortical face-recognition areas. RS magnitude correlated with social communication challenges among autistic individuals.

Deeper Than You Think: Partisanship-Dependent Brain Responses in Early Sensory and Motor Brain Regions.

Recent political polarization has illustrated how individuals with opposing political views often experience ongoing events in markedly different ways. In this study, we explored the neural mechanisms underpinning this phenomenon. We conducted fMRI scanning of 34 right- and left-wing participants (45% females) watching political videos (e.g., campaign ads and political speeches) just before the elections in Israel. As expected, we observed significant differences between left- and right-wing participants in their interpretation of the videos' content. Furthermore, neuroimaging results revealed partisanship-dependent differences in activation and synchronization in higher-order regions. Surprisingly, such differences were also revealed in early sensory, motor, and somatosensory regions. We found that the political content synchronized the responses of primary visual and auditory cortices in a partisanship-dependent manner. Moreover, right-wing (and not left-wing) individuals' sensorimotor cortex was involved in processing right-wing (and not left-wing) political content. These differences were pronounced to the extent that we could predict political orientation from the early brain-response alone. Importantly, no such differences were found with respect to neutral content. Therefore, these results uncover more fundamental neural mechanisms underlying processes of political polarization.SIGNIFICANCE STATEMENT The political sphere has become highly polarized in recent years. Would it be possible to identify the neural mechanisms underpinning such processes? In our study, left- and right-wing participants were scanned in fMRI while watching political video clips just before the elections in Israel. We found that political content was potent in synchronizing the brain responses of individuals holding similar views. This was far more pronounced in individuals holding right-wing views. Moreover, partisan-dependent differences in neural responses were identified already in early sensory, somatosensory, and motor regions, and only for political content. These results suggest that individuals' political views shape their neural responses at a very basic level.

A visual sense of number emerges from divisive normalization in a simple center-surround convolutional network.

Many species of animals exhibit an intuitive sense of number, suggesting a fundamental neural mechanism for representing numerosity in a visual scene. Recent empirical studies demonstrate that early feedforward visual responses are sensitive to numerosity of a dot array but substantially less so to continuous dimensions orthogonal to numerosity, such as size and spacing of the dots. However, the mechanisms that extract numerosity are unknown. Here, we identified the core neurocomputational principles underlying these effects: (1) center-surround contrast filters; (2) at different spatial scales; with (3) divisive normalization across network units. In an untrained computational model, these principles eliminated sensitivity to size and spacing, making numerosity the main determinant of the neuronal response magnitude. Moreover, a model implementation of these principles explained both well-known and relatively novel illusions of numerosity perception across space and time. This supports the conclusion that the neural structures and feedforward processes that encode numerosity naturally produce visual illusions of numerosity. Taken together, these results identify a set of neurocomputational properties that gives rise to the ubiquity of the number sense in the animal kingdom.

Language acquisition and speech rhythm patterns: an auditory neuroscience perspective.

All human infants acquire language, but their brains do not know which language/s to prepare for. This observation suggests that there are fundamental components of the speech signal that contribute to building a language system, and fundamental neural processing mechanisms that use these components, which are shared across languages. Equally, disorders of language acquisition are found across all languages, with the most prevalent being developmental language disorder (approx. 7% prevalence), where oral language comprehension and production is atypical, and developmental dyslexia (approx. 7% prevalence), where written language acquisition is atypical. Recent advances in auditory neuroscience, along with advances in modelling the speech signal from an amplitude modulation (AM, intensity or energy change) perspective, have increased our understanding of both language acquisition and these developmental disorders. Speech rhythm patterns turn out to be fundamental to both sensory and neural linguistic processing. The rhythmic routines typical of childcare in many cultures, the parental practice of singing lullabies to infants, and the ubiquitous presence of BabyTalk (infant-directed speech) all enhance the fundamental AM components that contribute to building a linguistic brain.

High-Frequency Transcranial Magnetic Stimulation Combined With Functional Magnetic Resonance Imaging Reveals Distinct Activation Patterns Associated With Different Dorsolateral Prefrontal Cortex Stimulation Sites

ObjectivesTranscranial magnetic stimulation (TMS) has been extensively used for the treatment of depression, obsessive-compulsive disorder, and certain neurologic disorders. Despite having promising treatment efficacy, the fundamental neural mechanisms of TMS remain understudied. Materials and MethodsIn this study, 15 healthy adult participants received simultaneous TMS and functional magnetic resonance imaging to map the modulatory effect of TMS when it was applied over three different sites in the dorsolateral prefrontal cortex. Independent component analysis (ICA) was used to identify the networks affected by TMS when applied over the different sites. The standard general linear model (GLM) analysis was used for comparison. ResultsICA showed that TMS affected the stimulation sites as well as remote brain areas, some areas/networks common across all TMS sites, and other areas/networks specific to each TMS site. In particular, TMS site and laterality differences were observed at the left executive control network. In addition, laterality differences also were observed at the dorsal anterior cingulate cortex and dorsolateral/dorsomedial prefrontal cortex. In contrast with the ICA findings, the GLM-based results mainly showed activation of auditory cortices regardless of the TMS sites. ConclusionsOur findings support the notion that TMS could act through a top-down mechanism, indirectly modulating deep subcortical nodes by directly stimulating cortical regions. Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT03394066.

Alterations of dynamic functional connectivity between visual and executive-control networks in schizophrenia.

Schizophrenia is a chronic mental disorder characterized by continuous or relapsing episodes of psychosis. While previous studies have detected functional network connectivity alterations in patients with schizophrenia, and most have focused on static functional connectivity. However, brain activity is believed to change dynamically over time. Therefore, we computed dynamic functional network connectivity using the sliding window method in 38 patients with schizophrenia and 31 healthy controls. We found that patients with schizophrenia exhibited higher occurrences in the weakly and sparsely connected state (state 3) than healthy controls, positively correlated with negative symptoms. In addition, patients exhibited fewer occurrences in a strongly connected state (state 4) than healthy controls. Lastly, the dynamic functional network connectivity between the right executive-control network and the medial visual network was decreased in schizophrenia patients compared to healthy controls. Our results further prove that brain activity is dynamic, and that alterations of dynamic functional network connectivity features might be a fundamental neural mechanism in schizophrenia.

Arousal State-Dependent Alterations in Neural Activity in the Zebra Finch VTA/SNc.

Sleep-wake behaviors are important for survival and highly conserved among animal species. A growing body of evidence indicates that the midbrain dopaminergic system is associated with sleep-wake regulation in mammals. Songbirds exhibit mammalian-like sleep structures, and neurons in the midbrain ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) possess physiological properties similar to those in mammals. However, it remains uncertain whether the neurons in the songbird VTA/SNc are associated with sleep-wake regulation. Here, we show that VTA/SNc neurons in zebra finches exhibit arousal state-dependent alterations in spontaneous neural activity. By recording extracellular single-unit activity from anesthetized or freely behaving zebra finches, we found that VTA/SNc neurons exhibited increased firing rates during wakefulness, and the same population of neurons displayed reduced firing rates during anesthesia and slow-wave sleep. These results suggest that the songbird VTA/SNc is associated with the regulation of sleep and wakefulness along with other arousal regulatory systems. These findings raise the possibility that fundamental neural mechanisms of sleep-wake behaviors are evolutionarily conserved between birds and mammals.

Different strategies, distinguished cooperation efficiency, and brain synchronization for couples: An fNIRS-based hyperscanning study.

IntroductionIndividuals may employ different strategies when cooperating with others. For example, when two participants are asked to press buttons simultaneously, they may press the buttons as quickly as possible (immediate response strategy) or press them in a delayed pattern (delayed response strategy). Despite recognition of interpersonal brain synchronization (IBS) as a fundamental neural mechanism of cooperation, it remains unclear how various strategies influence cooperative behavior and its neural activities.MethodsTo address this issue, 43 married couples were recruited to complete a button‐press cooperative task, during which IBS was recorded by functional near‐infrared spectroscopy hyperscanning.ResultsBehavioral results showed that couples who adopted a delayed response strategy performed better than those who adopted an immediate response strategy and those without any obvious strategy, and a new measure (cooperation coefficient) was used to index the level of cooperation. In addition, stronger IBS in the right frontal cortex was observed in the delayed response condition. The greater couples’ perceived parenting stress, the more likely they were to perform well in tasks and the stronger their brain synchronization, since they tended to choose the delayed response strategy.ConclusionThe delayed response strategy may better unify dyad partners’ response modes, trigger synchronized psychological processes, and enable their brains to become synchronized. The study extends understanding of cooperation by comparing the contributions of different strategies underlying cooperative behavior with corresponding neural evidence.

Connectivity within the default mode network mediates the association between chronotype and sleep quality.

A late chronotype is associated with poor sleep quality, but the fundamental neural mechanism underlying this association remains unclear. Eyes-open resting-state functional MRI scans were obtained from 87 participants after extended wakefulness, and four subregions of the default mode network were extracted and analysed. Partial correlation analysis revealed that the functional connectivity between the precuneus and the medial prefrontal cortex (mPFC) was significantly correlated both with sleep quality and circadian preference of the participants. Mediation analysis found that the precuneus-mPFC link fully mediated the correlation between chronotype and sleep quality. We concluded that increased neural communication in the midline cores of the default mode network (DMN) may be responsible for the poor sleep quality of late chronotypes. As late chronotypes exhibit vulnerability to many mental disorders, our results can be used to refine pathophysiological models and provide therapy for such psychological disorders.

Dissociation between cortical and spinal excitability of the antagonist muscle during combined motor imagery and action observation

Inhibitory neural control of antagonist muscle is one of the fundamental neural mechanism of coordinated human limb movement. Previous studies have revealed that motor execution (ME) and motor imagery (MI) share many common neural substrates; however, whether inhibitory neural activity occurs during MI remains unknown. In addition, recent studies have demonstrated that a combined MI and action observation (MI + AO) produces strong neurophysiological changes compared with MI or AO alone. Therefore, we investigated inhibitory changes in cortical and spinal excitability of the antagonist muscle during MI + AO and ME. Single-pulse transcranial magnetic stimulation (TMS) experiments revealed that corticospinal excitability of the antagonist muscle was decreased during MI + AO. Conversely, F-wave experiments showed that F-wave persistence of the antagonist muscle increased. Paired-pulse TMS experiment also demonstrated that short-interval intracortical inhibition (SICI) did not contribute to this inhibition. Therefore, cortical mediated inhibition, except for SICI, may be related to this inhibition. Conversely, such clear inhibition of the antagonist muscle was not observed during ME, presumably owing to the effects of muscle contraction to decelerate the movements and/or sensory input accompanying the joint movements. These findings provide important insights into the neurophysiological differences between MI + AO and ME.

Brain-Heart Interactions Underlying Traditional Tibetan Buddhist Meditation.

Despite accumulating evidence suggesting improvement in one's well-being as a result of meditation, little is known about if or how the brain and the periphery interact to produce these behavioral and mental changes. We hypothesize that meditation reflects changes in the neural representations of visceral activity, such as cardiac behavior, and investigated the integration of neural and visceral systems and the spontaneous whole brain spatiotemporal dynamics underlying traditional Tibetan Buddhist meditation. In a large cohort of long-term Tibetan Buddhist monk meditation practitioners, we found distinct transient modulations of the neural response to heartbeats in the default mode network (DMN), along with large-scale network reconfigurations in the gamma and theta bands of electroencephalography (EEG) activity induced by meditation. Additionally, temporal-frontal network connectivity in the EEG theta band was negatively correlated with the duration of meditation experience, and gamma oscillations were uniquely, directionally coupled to theta oscillations during meditation. Overall, these data suggest that the neural representation of cardiac activity in the DMN and large-scale spatiotemporal network integrations underlie the fundamental neural mechanism of meditation and further imply that meditation may utilize cortical plasticity, inducing both immediate and long-lasting changes in the intrinsic organization and activity of brain networks.

Larger Auditory Cortical Area and Broader Frequency Tuning Underlie Absolute Pitch

Absolute pitch (AP), the ability of some musicians to precisely identify and name musical tones in isolation, is associated with a number of gross morphological changes in the brain, but the fundamental neural mechanisms underlying this ability have not been clear. We presented a series of logarithmic frequency sweeps to age- and sex-matched groups of musicians with or without AP and controls without musical training. We used fMRI and population receptive field (pRF) modeling to measure the responses in the auditory cortex in 61 human subjects. The tuning response of each fMRI voxel was characterized as Gaussian, with independent center frequency and bandwidth parameters. We identified three distinct tonotopic maps, corresponding to primary (A1), rostral (R), and rostral-temporal (RT) regions of auditory cortex. We initially hypothesized that AP abilities might manifest in sharper tuning in the auditory cortex. However, we observed that AP subjects had larger cortical area, with the increased area primarily devoted to broader frequency tuning. We observed anatomically that A1, R and RT were significantly larger in AP musicians than in non-AP musicians or control subjects, which did not differ significantly from each other. The increased cortical area in AP in areas A1 and R were primarily low frequency and broadly tuned, whereas the distribution of responses in area RT did not differ significantly. We conclude that AP abilities are associated with increased early auditory cortical area devoted to broad-frequency tuning and likely exploit increased ensemble encoding.SIGNIFICANCE STATEMENT Absolute pitch (AP), the ability of some musicians to precisely identify and name musical tones in isolation, is associated with a number of gross morphological changes in the brain, but the fundamental neural mechanisms have not been clear. Our study shows that AP musicians have significantly larger volume in early auditory cortex than non-AP musicians and non-musician controls and that this increased volume is primarily devoted to broad-frequency tuning. We conclude that AP musicians are likely able to exploit increased ensemble representations to encode and identify frequency.

A Probabilistic Analysis of Volume Transmission in the Brain

Volume transmission is a fundamental neural communication mechanism in which neurons in one brain nucleus modulate the neurotransmitter concentration in the extracellular space of a second nucleus. In this paper, we formulate and analyze a mathematical model of volume transmission to calculate the neurotransmitter concentration in the extracellular space. Our model consists of the diffusion equation in a bounded two- or three-dimensional domain that contains a set of interior holes that randomly switch between being either sources or sinks. The interior holes represent nerve varicosities that are sources of neurotransmitter when firing an action potential and are sinks otherwise. To analyze this random partial differential equation, we show that each realization of its solution can be represented as a certain expected local time of a Brownian particle in a corresponding realization of a random environment. Using this representation, we prove two surprising results. First, the expected neurotransmitter con...

Failing to learn from negative prediction errors: Obesity is associated with alterations in a fundamental neural learning mechanism

Prediction errors (PEs) encode the difference between expected and actual action outcomes in the brain via dopaminergic modulation. Integration of these learning signals ensures efficient behavioral adaptation. Obesity has recently been linked to altered dopaminergic fronto-striatal circuits, thus implying impairments in cognitive domains that rely on its integrity.28 obese and 30 lean human participants performed an implicit stimulus-response learning paradigm inside an fMRI scanner. Computational modeling and psycho-physiological interaction (PPI) analysis was utilized for assessing PE-related learning and associated functional connectivity. We show that human obesity is associated with insufficient incorporation of negative PEs into behavioral adaptation even in a non-food context, suggesting differences in a fundamental neural learning mechanism. Obese subjects were less efficient in using negative PEs to improve implicit learning performance, despite proper coding of PEs in striatum. We further observed lower functional coupling between ventral striatum and supplementary motor area in obese subjects subsequent to negative PEs. Importantly, strength of functional coupling predicted task performance and negative PE utilization.These findings show that obesity is linked to insufficient behavioral adaptation specifically in response to negative PEs, and to associated alterations in function and connectivity within the fronto-striatal system. Recognition of neural differences as a central characteristic of obesity hopefully paves the way to rethink established intervention strategies: Differential behavioral sensitivity to negative and positive PEs should be considered when designing intervention programs. Measures relying on penalization of unwanted behavior may prove less effective in obese subjects than alternative approaches.

Neural predictors of emotional inertia in daily life.

Assessing emotional dynamics in the brain offers insight into the fundamental neural and psychological mechanisms underlying emotion. One such dynamic is emotional inertia—the influence of one’s emotional state at one time point on one’s emotional state at a subsequent time point. Emotion inertia reflects emotional rigidity and poor emotion regulation as evidenced by its relationship to depression and neuroticism. In this study, we assessed changes in cerebral blood flow (CBF) from before to after an emotional task and used these changes to predict stress, positive and negative emotional inertia in daily life events. Cerebral blood flow changes in the lateral prefrontal cortex (lPFC) predicted decreased non-specific emotional inertia, suggesting that the lPFC may feature a general inhibitory mechanism responsible for limiting the impact that an emotional state from one event has on the emotional state of a subsequent event. CBF changes in the ventromedial prefrontal cortex and lateral occipital cortex were associated with positive emotional inertia and negative/stress inertia, respectively. These data advance the blossoming literature on the temporal dynamics of emotion in the brain and on the use of neural indices to predict mental health-relevant behavior in daily life.

Reconstructing the spectrotemporal modulations of real-life sounds from fMRI response patterns

Ethological views of brain functioning suggest that sound representations and computations in the auditory neural system are optimized finely to process and discriminate behaviorally relevant acoustic features and sounds (e.g., spectrotemporal modulations in the songs of zebra finches). Here, we show that modeling of neural sound representations in terms of frequency-specific spectrotemporal modulations enables accurate and specific reconstruction of real-life sounds from high-resolution functional magnetic resonance imaging (fMRI) response patterns in the human auditory cortex. Region-based analyses indicated that response patterns in separate portions of the auditory cortex are informative of distinctive sets of spectrotemporal modulations. Most relevantly, results revealed that in early auditory regions, and progressively more in surrounding regions, temporal modulations in a range relevant for speech analysis (∼2-4 Hz) were reconstructed more faithfully than other temporal modulations. In early auditory regions, this effect was frequency-dependent and only present for lower frequencies (<∼2 kHz), whereas for higher frequencies, reconstruction accuracy was higher for faster temporal modulations. Further analyses suggested that auditory cortical processing optimized for the fine-grained discrimination of speech and vocal sounds underlies this enhanced reconstruction accuracy. In sum, the present study introduces an approach to embed models of neural sound representations in the analysis of fMRI response patterns. Furthermore, it reveals that, in the human brain, even general purpose and fundamental neural processing mechanisms are shaped by the physical features of real-world stimuli that are most relevant for behavior (i.e., speech, voice).

Resting-State Neuroimaging and Neuropsychological Findings in Opioid Use Disorder during Abstinence: A Review.

Dependence to opiates, including illicit heroin and prescription pain killers, and treatment of the opioid use disorder (OUD) have been longstanding problems over the world. Despite intense efforts to scientific investigation and public health care, treatment outcomes have not significantly improved for the past 50 years. One reason behind the continuing use of heroin worldwide despite such efforts is its highly addictive nature. Brain imaging studies over the past two decades have made significant contribution to the understanding of the addictive properties as to be due in part to biological processes, specifically those in the brain structure and function. Moreover, traditional clinical neuropsychology studies also contribute to the account in part for the treatment-refractory nature of the drug abuse. However, there is a gap between those studies, and the rates of relapse are still high. Thus, a multidisciplinary approach is needed to understand the fundamental neural mechanism of OUD. How does the brain of an OUD patient functionally and cognitively differ from others? This brief review is to compare and contrast the current literature on non-invasive resting state neuroimaging and clinical neuropsychological studies with the focus on the abstinence stage in OUD. The results show as follow: Brain connectivity strength in the reward system, dysregulation of circuits associated with emotion and stress, enhanced beta and alpha power activity, and high impulsivity are induced by OUD.Some recovery signs in cognition are demonstrated in OUD subjects after prolonged abstinence, but not in the subjects undergoing methadone treatment.Normalization in the composition of brain oscillations especially in the temporal region is induced and restored by methadone treatment in roughly 6 months in mean duration for OUDs having a mean opioid-use history of 10 years.We hope that the review provides valuable implications for clinical research and practice and paves a new insight into the future path to the identification of potential biomarkers and clinical outcome predictors in OUD in the domains of brain regions, functions, and behaviors.