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Introduction: Numerous modes or patterns of neural activity can be seen in the brain of individuals during the resting state. However, those functions do not persist long, and they are continuously altering in the brain. We have hypothesized that the brain activations during the resting state should themselves be responsible for this alteration of the activities. Methods: Using the resting-state fMRI data of 63 healthy young individuals, we estimated the causality effects of each resting-state activation map on all other networks. The resting-state networks were identified, their causality effects on the other components were extracted, the networks with the top 20% of the causality were chosen, and the networks which were under the influence of those causal networks were also identified. Results: Our results showed that the influence of each activation component over other components is different. The brain areas which showed the highest causality coefficients were subcortical regions, such as the brain stem, thalamus, and amygdala. On the other hand, nearly all the areas which were mostly under the causal effects were cortical regions. Discussion: In summary, our results suggest that subcortical brain areas exert a higher influence on cortical regions during the resting state, which could help in a better understanding the dynamic nature of brain functions. [ABSTRACT FROM AUTHOR]

There is a general consensus that schizophrenia (SZ) is characterized by major changes in the sense of self. Phenomenological studies suggest that these changes in the sense of self stem from a basic disturbance, hence the term 'basic self-disturbance'. While imaging studies demonstrate changes in various regions during self-focused tasks, the exact neural correlates of such basic self-disturbances remain unclear. If the self-disturbance is indeed basic and thereby underlies all other symptoms, one would expect it to be related to more global rather than local changes in the brain. Testing this hypothesis, we conducted a systematic review of fMRI studies on self in SZ. Our main findings are 1. Abnormal activity related to the self can be observed in a variety of different regions ranging from higher-order transmodal to lower-order unimodal regions, 2. These findings hold true across different tasks including self-reflection, self-referentiality, and self-agency, and 3. The global neural abnormalities related to the self in SZ correspond to all layers of the self, predominantly the mental and exteroceptive self. Such global neural disturbance of self converges well with the basic self-disturbance as described in phenomenology. [ABSTRACT FROM AUTHOR]

Age‐related variations in many regions and/or networks of the human brain have been uncovered using resting‐state functional magnetic resonance imaging. However, these findings did not account for the dynamical effect the brain's global activity (global signal [GS]) causes on local characteristics, which is measured by GS topography. To address this gap, we tested GS topography including its correlation with age using a large‐scale cross‐sectional adult lifespan dataset (n = 492). Both GS topography and its variation with age showed frequency‐specific patterns, reflecting the spatiotemporal characteristics of the dynamic change of GS topography with age. A general trend toward dedifferentiation of GS topography with age was observed in both spatial (i.e., less differences of GS between different regions) and temporal (i.e., less differences of GS between different frequencies) dimensions. Further, methodological control analyses suggested that although most age‐related dedifferentiation effects remained across different preprocessing strategies, some were triggered by neuro‐vascular coupling and physiological noises. Together, these results provide the first evidence for age‐related effects on global brain activity and its topographic‐dynamic representation in terms of spatiotemporal dedifferentiation. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) studies have demonstrated that intrinsic neuronal timescales (INT) undergo modulation by external stimulation during consciousness. It remains unclear if INT keep the ability for significant stimulus-induced modulation during primary unconscious states, such as sleep. This fMRI analysis addresses this question via a dataset that comprises an awake resting-state plus rest and stimulus states during sleep. We analyzed INT measured via temporal autocorrelation supported by median frequency (MF) in the frequency-domain. Our results were replicated using a biophysical model. There were two main findings: (1) INT prolonged while MF decreased from the awake resting-state to the N2 resting-state, and (2) INT shortened while MF increased during the auditory stimulus in sleep. The biophysical model supported these results by demonstrating prolonged INT in slowed neuronal populations that simulate the sleep resting-state compared to an awake state. Conversely, under sine wave input simulating the stimulus state during sleep, the model's regions yielded shortened INT that returned to the awake resting-state level. Our results highlight that INT preserve reactivity to stimuli in states of unconsciousness like sleep, enhancing our understanding of unconscious brain dynamics and their reactivity to stimuli. A fMRI analysis of human participants during conscious and unconscious states provides evidence that intrinsic neuronal timescales preserve their reactivity to environmental stimuli during sleep across seven local networks and across the complete cerebral cortex. [ABSTRACT FROM AUTHOR]

Introduction: The fMRI BOLD response to emotional stimuli highlighting the role of the medial prefrontal cortex (MPFC) has been thoroughly investigated. Recently, the relationship between emotion processing and GABA levels has been studied using MPFC proton magnetic resonance spectroscopy (1H-MRS). However, the role of GABAA receptors in the MPFC during emotion processing remains unexplored. Methods: Using [11C]flumazenil PET, we investigated the relationship between the binding potential of GABAA receptors and emotion processing as measured using simultaneous fMRI BOLD. We hypothesized a correlation between the percent signal change in the BOLD signal and the binding potential of GABAA receptors in the MPFC. In a combined simultaneous fMRI and [11C]flumazenil-PET study, we analyzed the data from 15 healthy subjects using visual emotional stimuli. Our task comprised two types of emotional processing: passive viewing and appraisal. Following the administration of a bolus plus infusion protocol, PET and fMRI data were simultaneously acquired in a hybrid 3 T MR-BrainPET. Results: We found a differential correlation of BOLD percent signal change with [11C]flumazenil binding potential in the MPFC. Specifically, [11C]flumazenil binding potential in the ventromedial prefrontal cortex (vMPFC) correlated with passive viewing of emotionally valenced pictures. In contrast, the [11C]flumazenil binding potential and the BOLD signal induced by picture appraisal did show a correlation in the paracingulate gyrus. Conclusion: Our data deliver first evidence for a relationship between MPFC GABAA receptors and emotion processing in the same region. Moreover, we observed that GABAA receptors appear to play different roles in emotion processing in the vMPFC (passive viewing) and paracingulate gyrus (appraisal). [ABSTRACT FROM AUTHOR]

Aim: Departing from existing neurobiological models of dissociation, the current study aims at conducting a quantitative meta‐analytic review of neural responses to emotional stimuli among individuals ascribed to the dissociative spectrum (DS). Accordingly, the study explored common and specific brain mechanisms across borderline personality disorder, conversion/somatoform disorders, posttraumatic stress disorder, posttraumatic stress disorder related to repeated interpersonal traumatic experiences, and dissociative disorders. Methods: The meta‐analysis included studies that administered emotional stimuli during functional magnetic resonance imaging acquisition among individuals included in the DS. There were two conducted meta‐analytic procedures: (i) a Bayesian network meta‐analysis for a region‐of‐interest–based approach; and (ii) robust voxel‐based approach. Results: Forty‐four independent studies were included for a total of 1384 individuals (DS = 741 patients). The network meta‐analysis showed specific patterns of neural activity considering an extended brain network involved in emotion regulation for each condition ascribed to the DS. The voxel‐based meta‐analysis highlighted an increased activity of dorsal anterior cingulate cortex as a common neurological signature of the DS. Conclusion: The common neural feature of the DS captures an implicit appraisal of emotion‐eliciting stimuli as threatening and/or noxious for mental and physical integrity of the individual together with painful subjective experiences associated with physiological emotional reactions. Specific brain responses across the DS suggested the engagement in different mechanisms to address emotional stimuli, including implicit avoidance reactions and attempts to overcontrol of affective states together with a disruption of integrative processes of emotional mind–body features. [ABSTRACT FROM AUTHOR]

Scale-free physiological processes are ubiquitous in the human organism. Resting-state functional MRI studies observed the loss of scale-free dynamics under anesthesia. In contrast, the modulation of scale-free dynamics during task-related activity remains an open question. We investigate scale-free dynamics in the cerebral cortex's unimodal periphery and transmodal core topography in rest and task states during three conscious levels (awake, sedation, and anesthesia) complemented by computational modelling (Stuart-Landau model). The empirical findings demonstrate that the loss of the brain's intrinsic scale-free dynamics in the core-periphery topography during anesthesia, where pink noise transforms into white noise, disrupts the brain's neuronal alignment with the task's temporal structure. The computational model shows that the stimuli's scale-free dynamics, namely pink noise distinguishes from brown and white noise, also modulate task-related activity. Together, we provide evidence for two mechanisms of consciousness, temporo-spatial nestedness and alignment, suggested by the Temporo-Spatial Theory of Consciousness (TTC). Summary: Investigation of scale-free brain dynamics via rest-task modulation across awake, sedative, and anesthetic states of consciousness shows that brain dynamics lose alignment to the task's temporal structure in anesthesia as in wakefulness. [ABSTRACT FROM AUTHOR]

Social anxiety disorder (SAD) is characterized by social anxiety/fear, self-attention, and interoception. Functional magnetic resonance imaging studies demonstrate increased activity during symptom-sensitive tasks in regions of the default-mode network (DMN), amygdala (AMG), and salience network (SN). What is the source of this task-unspecific symptom-sensitive hyperactivity in DMN? We address this question by probing SAD resting state (rs) changes in DMN including their relation to other regions as possible source of task-unspecific hyperactivity in the same regions. Our findings show the following: (1) rs-hypoconnectivity within-DMN regions; (2) rs-hyperconnectivity between DMN and AMG/SN; (3) task-evoked hyperactivity in the abnormal rs-regions of DMN and AMG/SN during different symptom-sensitive tasks; (4) negative relationship of rest and task changes in especially anterior DMN regions as their rs-hypoconnectivity is accompanied by task-unspecific hyperactivity; (5) abnormal top-down/bottom-up modulation between anterior DMN regions and AMG during rest and task. Findings demonstrate that rs-hypoconnectivity among DMN regions is negatively related to task-unspecific hyperactivity in DMN and AMG/SN. We propose a model of "Topography of the Anxious Self" in SAD (TAS-SAD). Abnormal DMN-AMG/SN topography during rest, as trait feature of an "unstable social self", is abnormally aggravated during SAD-sensitive situations resulting in task-related hyperactivity in the same regions with an "anxious self" as state feature. [ABSTRACT FROM AUTHOR]

Trait empathy is an essential personality feature in the intricacy of typical social inclinations of individuals. Empathy is likely supported by multilevel neuronal network functioning, whereas local topological properties determine network integrity. In the present functional MRI study (N = 116), we aimed to trace empathic traits to the intrinsic brain network architecture. Empathy was conceived as composed of two dimensions within the concept of pre-reflective, intersubjective understanding. Vicarious experience consists of the tendency to resonate with the feelings of other individuals, whereas intuitive understanding refers to a natural awareness of others' emotional states. Analyses of graph theoretical measures of centrality showed a relationship between the fronto-parietal network and psychometric measures of vicarious experience, whereas intuitive understanding was associated with sensorimotor and subcortical networks. Salience network regions could constitute hubs for information processing underlying both dimensions. The network properties related to empathy dimensions mainly concern inter-network information flow. Moreover, interaction effects implied several sex differences in the relationship between functional network organization and trait empathy. These results reveal that distinct intrinsic topological network features explain individual differences in separate dimensions of intersubjective understanding. The findings could help understand the impact of brain damage or stimulation through alterations of empathy-related network integrity. [ABSTRACT FROM AUTHOR]

The anticipation of control over aversive events in life is relevant for our mental health. Insights on the underlying neural mechanisms remain limited. We developed a new functional magnetic resonance imaging (fMRI) task that uses auditory stimuli to explore the neural correlates of (1) the anticipation of control over aversion and (2) the processing of aversion. In a sample of 25 healthy adults, we observed increased neural activation in the medial prefrontal cortex (ventromedial prefrontal cortex and rostral anterior cingulate cortex), other brain areas relevant for reward anticipation (ventral striatum, brainstem [ventral tegmental area], midcingulate cortex), and the posterior cingulate cortex when they anticipated control over aversion compared with anticipating no control (1). The processing of aversive sounds compared to neutral sounds (2) was associated with increased neural activation in the bilateral posterior insula. Our findings provide evidence for the important role of medial prefrontal regions in control anticipation and highlight the relevance of conceiving the neural mechanisms involved within a reward‐based framework. [ABSTRACT FROM AUTHOR]

PURPOSE: Gliomas are life-threatening brain tumors, and the extent of surgical resection is one of the strongest influences on survival rate. However, the proper distinction of infiltrated tissue remains elusive. The aim of this study was to use multimodal analyses to demarcate peritumoral tissue (PT) from tumoral (TT) and healthy tissue (HT). METHODS: A total of 40 patients with histologically confirmed glioma were recruited. We analyzed resting-state functional magnetic resonance imaging (rs-fMRI) using the voxel-based mean blood-oxygen-level-dependent (BOLD) signal and the corresponding structural MRI (s-MRI) alongside RNA sequencing, whole-exome sequencing, and histology results of biopsy samples obtained from PT, HT, and TT. RESULTS: We demarcated a functionally defined PT area where the mean BOLD signal gradually decreased near the edge of the tumor and extended beyond the TT borders (as defined by s-MRI), which was confirmed on a case-by-case basis. Correspondingly, genetic analyses showed a gene expression pattern and mutational landscape of the PT that were distinct from that seen in HT and TT. The genetic characterization of PT relative to HT and TT converged with the MRI-defined PT zones. This was confirmed in three individual cases after additional histologic analysis. A wider PT was associated with a longer progression-free survival, which suggests PT might act as an intermediate area between TT and HT. CONCLUSION: Combined multimodal imaging and genetic analyses can allow for an objective demarcation of the PT in glioma and a robust classification of the degree of infiltration of the PT. These findings could help improve both neurosurgical resection and radio-oncologic therapy. [ABSTRACT FROM AUTHOR]

Recent resting-state functional MRI (fMRI) studies have revealed that the global signal (GS) exhibits a nonuniform spatial distribution across the gray matter. Whether this topography is informative remains largely unknown. We therefore tested rest-task modulation of GS topography by analyzing static GS correlation and dynamic coactivation patterns in a large sample of an fMRI dataset (n = 837) from the Human Connectome Project. The GS topography in the resting state and in seven different tasks was first measured by correlating the GS with the local time series (GSCORR). In the resting state, high GSCORR was observed mainly in the primary sensory and motor regions, whereas low GSCORR was seen in the association brain areas. This pattern changed during the seven tasks, with mainly decreased GSCORR in sensorimotor cortex. Importantly, this rest-task modulation of GSCORR could be traced to transient coactivation patterns at the peak period of GS (GS-peak). By comparing the topography of GSCORR and respiration effects, we observed that the topography of respiration mimicked the topography of GS in the resting state, whereas both differed during the task states; because of such partial dissociation, we assume that GSCORR could not be equated with a respiration effect. Finally, rest-task modulation of GS topography could not be exclusively explained by other sources of physiological noise. Together, we here demonstrate the informative nature of GS topography by showing its rest-task modulation, the underlying dynamic coactivation patterns, and its partial dissociation from respiration effects during task states. Recent resting-state fMRI studies have shown that the global signal exhibits a nonuniform spatial distribution across gray matter, but is this informative? This neuroimaging study reveals novel insights into the informative nature of global signal by rest-task modulation of the global signal topography. [ABSTRACT FROM AUTHOR]

Background: Accumulating neuroimaging evidence suggests that abnormal intrinsic neural activity could underlie auditory verbal hallucinations (AVH) in patients with schizophrenia. However, little is known about the functional interplay between distinct intrinsic neural networks and their association with AVH. Methods: We investigated functional network connectivity (FNC) of distinct resting-state networks as well as the relationship between FNC strength and AVH symptom severity. Resting-state functional MRI data at 3 T were obtained for 14 healthy controls and 10 patients with schizophrenia presenting with persistent AVH. The data were analyzed using a spatial group independent component analysis, followed by constrained maximal lag correlations to determine FNC within and between groups. Results: Four components of interest, comprising language, attention, executive control networks, as well as the default-mode network (DMN), were selected for subsequent FNC analyses. Patients with persistent AVH showed lower FNC between the language network and the DMN (p < 0.05, corrected for false discovery rate). FNC strength, however, was not significantly related to symptom severity, as measured by the Psychotic Symptom Rating Scale. Conclusion: These findings suggest that disrupted FNC between a speech-related system and a network subserving self-referential processing is associated with AVH. The data are consistent with a model of disrupted self-attribution of speech generation and perception. [ABSTRACT FROM AUTHOR]

Hindsight bias (HB) is the tendency to retrospectively exaggerate one's foresight knowledge about the outcome of an event. Cognitive processes influenced by newly obtained outcome information are used to explain the HB phenomenon, but the neural correlates remain unknown. This study investigated HB in the context of election results using a memory design and functional magnetic resonance imaging for the first time. Participants were asked to predict and recall the percentage of votes obtained by (pairs of) candidates before and after an election. The results revealed that 88% of participants showed HB by recalling that their predictions were closer to the actual outcomes than they really were; and participants had HB for 38% of the events. The HB effect was associated with activation in the medial superior frontal gyrus and bilateral inferior frontal gyrus (IFG), which have been implicated in updating an old belief due to new information and is similar to the process of reconstruction bias. Furthermore, participants with a greater HB effect showed greater activation of the left IFG. In conclusion, we successfully observed the HB phenomenon in election results, and our imaging results suggested that the HB phenomenon might involve reconstruction bias. [ABSTRACT FROM AUTHOR]

Abstract Background Despite the great number of resting state functional connectivity studies on Eating Disorders (ED), no biomarkers could be detected yet. Therefore, we here focus on a different measure of resting state activity that is neuronal variability. The objective of this study was to investigate neuronal variability in the resting state of women with ED and to correlate possible differences with clinical and psychopathological indices. Methods 58 women respectively 25 with Anorexia Nervosa (AN), 16 with Bulimia Nervosa (BN) and 17 matched healthy controls (CN) were enrolled for the study. All participants were tested with a battery of psychometric tests and underwent a functional Magnetic Resonance Imaging (fMRI) resting state scanning. We investigated topographical patterns of variability measured by the Standard Deviation (SD) of the Blood-Oxygen-Level-Dependent (BOLD) signal (as a measure of neuronal variability) in the resting-state and their relationship to clinical and psychopathological indices. Results Neuronal variability was increased in both anorectic and bulimic subjects specifically in the Ventral Attention Network (VAN) compared to healthy controls. No significant differences were found in the other networks. Significant correlations were found between neuronal variability of VAN and various clinical and psychopathological indices. Conclusions We here show increased neuronal variability of VAN in ED patients. As the VAN is relevant for switching between endogenous and exogenous stimuli, our results showing increased neuronal variability suggest unstable balance between body attention and attention to external world. These results offer new perspective on the neurobiological basis of ED. Clinical and therapeutic implication will be discussed. [ABSTRACT FROM AUTHOR]

Abstract: Recent evidence shows that task‐deactivations are functionally relevant for cognitive performance. Indeed, higher cognitive engagement has been associated with higher suppression of activity in task‐deactivated brain regions ‐ usually ascribed to the Default Mode Network (DMN). Moreover, a negative correlation between these regions and areas actively engaged by the task is associated with better performance. DMN regions show positive modulation during autobiographical, social, and emotional tasks. However, it is not clear how processing of emotional stimuli affects the interplay between the DMN and executive brain regions. We studied this interplay in an fMRI experiment using emotional negative stimuli as distractors. Activity modulations induced by the emotional interference of negative stimuli were found in frontal, parietal, and visual areas, and were associated with modulations of functional connectivity between these task‐activated areas and DMN regions. A worse performance was predicted both by lower activity in the superior parietal cortex and higher connectivity between visual areas and frontal DMN regions. Connectivity between right inferior frontal gyrus and several DMN regions in the left hemisphere was related to the behavioral performance. This relation was weaker in the negative than in the neutral condition, likely suggesting less functional inhibitions of DMN regions during emotional processing. These results show that both executive and DMN regions are crucial for the emotional interference process and suggest that DMN connections are related to the interplay between externally‐directed and internally‐focused processes. Among DMN regions, superior frontal gyrus may be a key node in regulating the interference triggered by emotional stimuli. [ABSTRACT FROM AUTHOR]

This study represents a systematic review of the insights provided by resting state functional MRI (rs-fMRI) use in the glioma population. Following PRISMA guidelines, 45 studies were included in the review and were classified in glioma-related neuronal changes (n = 28) and eloquent area localization (n = 17). Despite the heterogeneous nature of the studies, there is considerable evidence of diffuse functional reorganization occurring in the setting of gliomas with local and interhemispheric functional connectivity alterations involving different functional networks. The studies showed evidence of decreased long distance functional connectivity and increased global local efficiency occurring in the setting of gliomas. The tumour grade seems to correlate with distinct functional connectivity changes. Overall, there is a potential clinical utility of rs-fMRI for identifying the functional brain network disruptions occurring in the setting of gliomas. Further studies utilizing standardized analytical methods are required to elucidate the mechanism through which gliomas induce global changes in brain connectivity. [ABSTRACT FROM AUTHOR]

Social perception commonly employs multiple sources of information. The present study aimed at investigating the integrative processing of affective social signals. Taskrelated and task-free functional magnetic resonance imaging was performed in 26 healthy adult participants during a social perception task concerning dynamic visual stimuli simultaneously depicting facial expressions of emotion and tactile sensations that could be either congruent or incongruent. Confounding effects due to affective valence, inhibitory top-down influences, cross-modal integration, and conflict processing were minimized. The results showed that the perception of congruent, compared to incongruent stimuli, elicited enhanced neural activity in a set of brain regions including left amygdala, bilateral posterior cingulate cortex (PCC), and left superior parietal cortex. These congruency effects did not differ as a function of emotion or sensation. A complementary task-related functional interaction analysis preliminarily suggested that amygdala activity depended on previous processing stages in fusiform gyrus and PCC. The findings provide support for the integrative processing of social information about others' feelings from manifold bodily sources (sensory-affective information) in amygdala and PCC. Given that the congruent stimuli were also judged as being more self-related and more familiar in terms of personal experience in an independent sample of participants, we speculate that such integrative processing might be mediated by the linking of external stimuli with self-experience. Finally, the prediction of task-related responses in amygdala by intrinsic functional connectivity between amygdala and PCC during a task-free state implies a neuro-functional basis for an individual predisposition for the integrative processing of social stimulus content. [ABSTRACT FROM AUTHOR]

We live in a dynamic environment, constantly confronted with approaching objects that we may either avoid or be forced to address. A multisensory and sensorimotor interface, the peripersonal space (PPS), mediates every physical interaction between our body and the environment. Behavioral investigations show high variability in the extension of PPS across individuals, but there is a lack of evidence on the neural underpinnings of these large individual differences. Here, we used approaching auditory stimuli and fMRI to capture the individual boundary of PPS and examine its neural underpinnings. Precisely, we tested the hypothesis that intertrial variability (ITV) in brain regions coding PPS predicts individual differences of its boundary at the behavioral level. Selectively in the premotor cortex, we found that ITV, rather than trial-averaged amplitude, of BOLD responses to far rather than near dynamic stimuli predicts the individual extension of PPS. Our results provide the first empirical support for the relevance of ITV of brain responses for individual differences in human behavior. [ABSTRACT FROM AUTHOR]

For accurate diagnosis and prognostic prediction of acquired brain injury (ABI), it is crucial to understand the neurobiological mechanisms underlying loss of consciousness. However, there is no consensus on which regions and networks act as biomarkers for consciousness level and recovery outcome in ABI. Using resting-state fMRI, we assessed intrinsic functional connectivity strength (FCS) of whole-brain networks in a large sample of 99 ABI patients with varying degrees of consciousness loss (including fully preserved consciousness state, minimally conscious state, unresponsive wakefulness syndrome/vegetative state, and coma) and 34 healthy control subjects. Consciousness level was evaluated using the Glasgow Coma Scale and Coma Recovery Scale-Revised on the day of fMRI scanning; recovery outcome was assessed using the Glasgow Outcome Scale 3 months after the fMRI scanning. One-way ANOVA of FCS, Spearman correlation analyses between FCS and the consciousness level and recovery outcome, and FCS-based multivariate pattern analysis were performed. We found decreased FCS with loss of consciousness primarily distributed in the posterior cingulate cortex/precuneus (PCC/PCU), medial prefrontal cortex, and lateral parietal cortex. The FCS values of these regions were significantly correlated with consciousness level and recovery outcome. Multivariate support vector machine discrimination analysis revealed that the FCS patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. These findings suggest that intrinsic functional connectivity patterns of the human posteromedial cortex could serve as a potential indicator for consciousness level and recovery outcome in individuals with ABI. [ABSTRACT FROM AUTHOR]

Recent functional magnetic resonance spectroscopy (fMRS) studies have shown changes in glutamate/glutamine (Glx) concentrations between resting-state and active-task conditions. However, the types of task used have been limited to sensory paradigms, and the regions from which Glx concentrations have been measured limited to sensory ones. This leaves open the question as to whether the same effect can be seen in higher-order brain regions during cognitive tasks. Cortical midline structures, especially the medial prefrontal cortex (MPFC), have been suggested to be involved in various such cognitive tasks. We, therefore set out to use fMRS to investigate the dynamics of Glx concentrations in the MPFC between resting-state and mental imagery task conditions. The auditory cortex was used as a control region. In addition, functional magnetic resonance imaging was used to explore task-related neural activity changes. The mental imagery task consisted of imagining swimming and was applied to a large sample of healthy participants ( n = 46). The participants were all competitive swimmers, ensuring proficiency in mental-swimming. Glx concentrations in the MPFC increased during the imagery task, as compared to resting-state periods preceding and following the task. These increases mirror BOLD activity changes in the same region during the task. No changes in either Glx concentrations or BOLD activity were seen in the auditory cortex. These findings contribute to our understanding of the biochemical basis of generating or manipulating mental representations and the MPFC's role in this. Hum Brain Mapp 36:3204-3212, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective: Alexithymia relates to difficulties recognizing and describing emotions. It has been linked to subjectively increased interoceptive awareness (IA) and to psychiatric illnesses such as major depressive disorder (MDD) and somatization. MDD in turn is characterized by aberrant emotion processing and IA on the subjective as well as on the neural level. However, a link between neural activity in response to IA and alexithymic traits in health and depression remains unclear. Methods: A well-established fMRI task was used to investigate neural activity during IA (heartbeat counting) and exteroceptive awareness (tone counting) in non-psychiatric controls (NC) and MDD. Firstly, comparing MDD and NC, a linear relationship between IA-related activity and scores of the Toronto Alexithymia Scale (TAS) was investigated through whole-brain regression. Secondly, NC were divided by median-split of TAS scores into groups showing low (NC-low) or high (NC-high) alexithymia. MDD and NC-high showed equally high TAS scores. Subsequently, IA-related neural activity was compared on a whole-brain level between the three independent samples (MDD, NC-low, NC-high). Results: Whole-brain regressions between MDD and NC revealed neural differences during IA as a function of TAS-DD (subscale difficulty describing feelings) in the supragenual anterior cingulate cortex (sACC; BA 24/32), which were due to negative associations between TAS-DD and IA-related activity in NC. Contrasting NC subgroups after median-split on a whole-brain level, high TAS scores were associated with decreased neural activity during IA in the sACC and increased insula activity. Though having equally high alexithymia scores, NC-high showed increased insula activity during IA compared to MDD, whilst both groups showed decreased activity in the sACC. Conclusions: Within the context of decreased sACC activity during IA in alexithymia (NC-high and MDD), increased insula activity might mirror a compensatory mechanism in NC-high, which is disrupted in MDD. [ABSTRACT FROM AUTHOR]

Self-experience anomalies are elementary features of schizophrenic pathology. Such deficits can have a profound impact on self-other relationship, but how they are related through aberrant brain function remains poorly understood. In this functional magnetic resonance imaging (fMRI) study, we provide new evidence for a cortical link between aberrant self-experience and social cognition in first-episode schizophrenia (FES). As identified in previous studies, ventral premotor cortex (vPMC) and posterior insula (pIC) are candidate brain regions underlying disturbances in both self-experience and self-other relationship due to their processing of predominantly externally guided (vPMC; goal-oriented behavior) and internally guided (pIC; interoception) stimuli. Results from functional interaction analysis in a sample of 24 FES patients and 22 healthy controls show aberrant functional interactions (background/intrinsic connectivity) of right vPMC and bilateral pIC with posterior cingulate cortex (PCC), a midline region that has been shown central in mediating self-experience. More specifically, our results show increased functional coupling between vPMC and PCC, which positively correlated with basic symptoms (subjective self-experience disturbances). pIC showed reduced functional coupling with PCC and postcentral gyrus and increased functional interactions with anterior insula. Taken together, our results suggest an imbalance in the processing between internally and externally guided information and its abnormal integration with self-referential processing as mediated by PCC. Due to our correlation findings, we suggest this imbalance to be closely related to basic symptoms in FES and thus anomalous self-experience. The findings further disentangle the cortical basis of how self-experience anomalies may pervade the social domain. [ABSTRACT FROM PUBLISHER]

Previous studies suggest that there may be a distinct relationship between spontaneous neural activity and subsequent or concurrent self-specific stimulus-induced activity. This study aims to test the impact of spontaneous activity as recorded in an eyes-open (EO) resting state as opposed to eyes-closed (EC) on self-specific versus non-self-specific auditory stimulus-induced activity in fMRI. In our first experiment we used self-specific stimuli comprised of the subject's own name and non-self-specific stimuli comprised of a friend's name and an unknown name, presented during EO versus EC baselines in a 3 name condition×2 baseline design. In Experiment 2 we directly measured spontaneous activity in the absence of stimuli during EO versus EC to confirm a modulatory effect of the two baseline conditions in the regions found to show an interaction effect in Experiment 1. Spontaneous activity during EO was significantly higher than during EC in bilateral auditory cortex and non-self-specific names yielded stronger signal changes relative to EO baseline than to EC. In contrast, there was no difference in response to self-specific names relative to EO baseline than to EC despite the difference between spontaneous activity levels. These results support an impact of spontaneous activity on stimulus-induced activity, moreover an impact that depends on the high-level stimulus characteristic of self-specificity. [ABSTRACT FROM AUTHOR]

Communication between cortical and subcortical regions is integral to a wide range of psychological processes and has been implicated in a number of psychiatric conditions. Studies in animals have provided insight into the biochemical and connectivity processes underlying such communication. However, to date no experiments that link these factors in humans in vivo have been carried out. To investigate the role of glutamate in individual differences in communication between the cortex – specifically the medial prefrontal cortex (mPFC) – and subcortical regions in humans, a combination of resting-state fMRI, DTI and MRS was performed. The subcortical target regions were the nucleus accumbens (NAc), dorsomedial thalamus (DMT), and periaqueductal grey (PAG). It was found that functional connectivity between the mPFC and each of the NAc and DMT was positively correlated with mPFC glutamate concentrations, whilst functional connectivity between the mPFC and PAG was negatively correlated with glutamate concentration. The correlations involving mPFC glutamate and FC between the mPFC and each of the DMT and PAG were mirrored by correlations with structural connectivity, providing evidence that the glutamatergic relationship may, in part, be due to direct connectivity. These results are in agreement with existing results from animal studies and may have relevance for MDD and schizophrenia. [ABSTRACT FROM AUTHOR]

Objectives. Borderline personality disorder (BPD) is characterized by a pervasive affective dysregulation. While recent imaging studies demonstrated the neural correlates of abnormal emotion processing in BPD and recently one study reported alterations of the reward circuit in this patient group, the exact neural mechanisms underlying the impact of abnormal emotion on reward behavior remain unclear. Methods. We therefore conducted an fMRI study in healthy controls and BPD patients to investigate the modulation of the anticipation of reward by simultaneously presented emotional pictures. Results. BPD patients revealed a disturbed differentiation between reward and non-reward anticipation in the bilateral pregenual anterior cingulate cortex if a positive or negative emotional picture is presented simultaneously. In the ventral striatum and the bilateral ventral tegmental area, BPD patients and healthy controls are able to differentiate between reward and non-reward even under emotional stimulation, but BPD patients show a reduced deactivation in the above mentioned regions compared to healthy controls. Conclusions. Altered emotion processing in BPD patients is likely to affect the reward system. More basic deficits in reward circuitry and other midline regions' level of resting state activity may contribute to this effect. [ABSTRACT FROM AUTHOR]

Objectives. In addition to affective-cognitive symptoms, patients with major depressive disorder (MDD) suffer from somato-vegetative symptoms, suggesting abnormal interoceptive awareness of their “material me”. While recent imaging studies have extensively investigated affective-cognitive symptoms in MDD, the neural correlates of somato-vegetative symptoms and abnormal interoception remain unclear. Since the “material me” has been especially associated with the anterior insula in healthy subjects, we hypothesized abnormalities in this region during interoceptive awareness in MDD. Methods. We therefore investigated behavioural and neural correlates of interoception in healthy and depressed subjects using the Body Perception Questionnaire (BPQ) and a well established heartbeat perception task in fMRI. Results. MDD patients showed significantly higher scores in the BPQ and reduced neural activity during rest periods, particularly in the bilateral anterior insula. In contrast to healthy subjects, BPQ scores no longer correlated with activity during rest periods in the anterior insula. Both BPQ scores and left anterior insula signal changes correlated with depression severity. Conclusions. We demonstrate for the first time abnormal body perception and altered activity in the insula during rest in MDD. Our results suggest that these behavioural and neural abnormalities are closely related to these patients’ somato-vegetative abnormalities and their abnormal “material me”. [ABSTRACT FROM AUTHOR]

• Simple input dynamics of a single timescale impact cognition during input processing. • The balance of slow and fast frequencies in the hippocampus is related to working memory performance. • The study of cognitive processes and neural activities should adopt a broader view of the dynamics of both task and brain. Working memory (WM) describes the dynamic process of maintenance and manipulation of information over a certain time delay. Neuronally, WM recruits a distributed network of cortical regions like the visual and dorsolateral prefrontal cortex as well as the subcortical hippocampus. How the input dynamics and subsequent neural dynamics impact WM remains unclear though. To answer this question, we combined the analysis of behavioral WM capacity with measuring neural dynamics through task-related power spectrum changes, e.g., median frequency (MF) in functional magnetic resonance imaging (fMRI). We show that the processing of the input dynamics, e.g., the task structure's specific timescale, leads to changes in the unimodal visual cortex's corresponding timescale which also relates to working memory capacity. While the more transmodal hippocampus relates to working memory capacity through its balance across multiple timescales or frequencies. In conclusion, we here show the relevance of both input dynamics and different neural timescales for WM capacity in uni – and transmodal regions like visual cortex and hippocampus for the subject's WM performance. [ABSTRACT FROM AUTHOR]

• VR environments help improve rehabilitation of impaired complex cognitive functions. • Combining neuroimaging and VR boosts ecological validity, generates practical gains. • These are the first neurofunctional predictive biomarkers of VR cognitive training. As Virtual reality (VR) is increasingly used in neurological disorders such as stroke, traumatic brain injury, or attention deficit disorder, the question of how it impacts the brain's neuronal activity and function becomes essential. VR can be combined with neuroimaging to offer invaluable insight into how the targeted brain areas respond to stimulation during neurorehabilitation training. That, in turn, could eventually serve as a predictive marker for therapeutic success. Functional magnetic resonance imaging (fMRI) identified neuronal activity related to blood flow to reveal with a high spatial resolution how activation patterns change, and restructuring occurs after VR training. Portable and quiet, electroencephalography (EEG) conveniently allows the clinician to track spontaneous electrical brain activity in high temporal resolution. Then, functional near-infrared spectroscopy (fNIRS) combines the spatial precision level of fMRIs with the portability and high temporal resolution of EEG to constitute an ideal measuring tool in virtual environments (VEs). This narrative review explores the role of VR and concurrent neuroimaging in cognitive rehabilitation. [ABSTRACT FROM AUTHOR]

Objective: Alterations in psychomotor dimension cut across different psychiatric disorders, such as schizophrenia (SCZ) and bipolar disorder (BD). This preliminary study aimed to investigate the organization of intrinsic brain activity in the subcortical-cortical sensorimotor system in SCZ (and BD) as characterized according to psychomotor dimension.Method: In this resting-state functional magnetic resonance imaging (fMRI) study, functional connectivity (FC) between thalamus and sensorimotor network (SMN), along with FC from substantia nigra (SN) and raphe nuclei (RN) to basal ganglia (BG) and thalamic regions, were investigated by using an a-priori-driven and dimensional approach. This was done in two datasets: SCZ patients showing inhibited psychomotricity (n = 18) vs. controls (n = 19); SCZ patients showing excited psychomotricity (n = 20) vs. controls (n = 108). Data from a third dataset of BD in inhibited depressive or manic phases (reflecting inhibited or excited psychomotricity) were used as control.Results: SCZ patients suffering from psychomotor inhibition showed decreased thalamus-SMN FC toward around-zero values paralleled by a concomitant reduction of SN-BG/thalamus FC and RN-BG/thalamus FC (as BD patients in inhibited depression). By contrast, SCZ patients suffering from psychomotor excitation exhibited increased thalamus-SMN FC toward positive values paralleled by a concomitant reduction of RN-BG/thalamus FC (as BD patients in mania).Conclusions: These findings suggest that patients exhibiting low or high levels of psychomotor activity show distinct patterns of thalamus-SMN coupling, which could be traced to specific deficit in SN- or RN-related connectivity. Notably, this was independent from the diagnosis of SCZ or BD, supporting an RDoC-like dimensional approach to psychomotricity. [ABSTRACT FROM AUTHOR]

• The ascending and descending phases of BOLD signal modulates face recognition. • Inter-regional phase lag distinguishes the face processing and frontoparietal systems. • Inter-regional phase lag in the infra-slow frequency range is essential for cognitive performance. Low frequency phase synchronization is an essential mechanism of information communication among brain regions. In the infra-slow frequency range (<0.1 Hz), inter-regional phase lag is of importance for brain function (e.g., anti-phase between the default mode network and task positive network). However, the role of phase lag in cognitive processing remains unclear. Based on the frequency tagging experimental paradigm and functional magnetic resonance imaging (fMRI) technique, we investigated inter-regional phase lag and phase coherence using a face recognition task (n = 30, 15 males/15 females). Phase coherence within the face processing system was significantly increased during task state, highlighting the importance of regular inter-regional phase relationship for face recognition. Moreover, results showed decreased phase lag within the core and extended face areas (face processing system) and increased phase lag between the face processing system and frontoparietal network, indicating a reorganization of inter-regional relationships of the two systems. Inter-regional phase lag was modulated by the task at ascending and descending phases of the fMRI signal, suggesting a phase-dependent inter-regional relationship. Furthermore, phase lags between visual cortex and amygdala and between visual cortex and motor area were positively related to reaction time, indicating better task performance depends on both rapid emotional detection pathway and visual-motor pathway. Overall, inter-regional phase synchronization in the infra-slow frequency range is of important for effective information communication and cognitive performance. [ABSTRACT FROM AUTHOR]

• The speed of infraslow neural wave is modulated by its phase cycle • There's a negative correlation between infraslow wave dynamics and intrinsic neural timescales • Movie-watching task slows down the neural waves associated with specific phase modulation The human brain is a highly dynamic organ that operates across a variety of timescales, the intrinsic neural timescales (INT). In addition to the INT, the neural waves featured by its phase-related processes including their cycles with peak/trough and rise/fall play a key role in shaping the brain's neural activity. However, the relationship between the brain's ongoing wave dynamics and INT remains yet unclear. In this study, we utilized functional magnetic resonance imaging (fMRI) rest and task data from the Human Connectome Project (HCP) to investigate the relationship of infraslow wave dynamics [as measured in terms of speed by changes in its peak frequency (PF)] with INT. Our findings reveal that: (i) the speed of phase dynamics (PF) is associated with distinct parts of the ongoing phase cycles, namely higher PF in peak/trough and lower PF in rise/fall; (ii) there exists a negative correlation between phase dynamics (PF) and INT such that slower PF relates to longer INT; (iii) exposure to a movie alters both PF and INT across the different phase cycles, yet their negative correlation remains intact. Collectively, our results demonstrate that INT relates to infraslow phase dynamics during both rest and task states. [ABSTRACT FROM AUTHOR]

Neural activity varies continually from moment to moment. Such temporal variability (TV) has been highlighted as a functionally specific brain property playing a fundamental role in cognition. We sought to investigate the mechanisms involved in TV changes between two basic behavioral states, namely having the eyes open (EO) or eyes closed (EC) in vivo in humans. To these ends we acquired BOLD fMRI, ASL, and [ 18 F]-fluoro-deoxyglucose PET in a group of healthy participants ( n  = 15), along with BOLD fMRI and [ 18 F]-flumazenil PET in a separate group ( n  = 19). Focusing on an EO- vs EC-sensitive region in the occipital cortex (identified in an independent sample), we show that TV is constrained in the EO condition compared to EC. This reduction is correlated with an increase in energy consumption and with regional GABA A receptor density. This suggests that the modulation of TV by behavioral state involves an increase in overall neural activity that is related to an increased effect from GABAergic inhibition in addition to any excitatory changes. These findings contribute to our understanding of the mechanisms underlying activity variability in the human brain and its control. [ABSTRACT FROM AUTHOR]

Schizophrenia has been described as a self-disorder, whereas social deficits are key features of the illness. Changes in "resting state" activity of brain networks involved in self-related processing have been consistently reported in schizophrenia, but their meaning for social perception deficits remains poorly understood. Here, we applied a novel approach investigating the relationship between task-evoked neural activity during social perception and functional organization of self-related brain networks during a "resting state". "Resting state" functional MRI was combined with task-related functional MRI using a social perception experiment. Twenty-one healthy control participants (HC) and 21 out-patients with a diagnosis of schizophrenia (SCH) were included. There were no significant differences concerning age, IQ, education and gender between the groups. Results showed reduced "resting state" functional connectivity between ventromedial prefrontal cortex and dorsal posterior cingulate cortex in SCH, compared to HC. During social perception, neural activity in dorsal posterior cingulate cortex and behavioral data indicated impaired congruence coding of social stimuli in SCH. Task-evoked activity during social perception in dorsal posterior cingulate cortex co-varied with dorsal posterior cingulate cortex-ventromedial prefrontal cortex functional connectivity during a "resting state" in HC, but not in SCH. Task-evoked activity also correlated with negative symptoms in SCH. These preliminary findings, showing disrupted prediction of social perception measures by "resting state" functioning of self-related brain networks in schizophrenia, provide important insight in the hypothesized link between self and social deficits. They also shed light on the meaning of "resting state" changes for tasks such as social perception. [ABSTRACT FROM AUTHOR]

Two aspects of the low frequency fluctuations of spontaneous brain activity have been proposed which reflect the complex and dynamic features of resting-state activity, namely temporal variability and signal synchronization. The relationship between them, especially its role in consciousness, nevertheless remains unclear. Our study examined the temporal variability and signal synchronization of spontaneous brain activity, as well as their relationship during loss of consciousness. We applied an intra-subject design of resting-state functional magnetic resonance imaging (rs-fMRI) in two conditions: during wakefulness, and under anesthesia with clinical unconsciousness. In addition, an independent group of patients with disorders of consciousness (DOC) was included in order to test the reliability of our findings. We observed a global reduction in the temporal variability, local and distant brain signal synchronization for subjects during anesthesia. Importantly, we found a link between temporal variability and both local and distant signal synchronizations during wakefulness: the higher the degree of temporal variability, the higher its intra-regional homogeneity and inter-regional functional connectivity. In contrast, this link was broken down under anesthesia, implying a decoupling between temporal variability and signal synchronization; this decoupling was reproduced in patients with DOC. Our results suggest that there exist some as yet unclear physiological mechanisms of consciousness which “couple” the two mathematically independent measures, temporal variability and signal synchronization of spontaneous brain activity. Our findings not only extend our current knowledge of the neural correlates of anesthetic-induced unconsciousness, but have implications for both computational neural modeling and clinical practice, such as in the diagnosis of loss of consciousness in patients with DOC. [ABSTRACT FROM AUTHOR]

Prominent theories propose that interoception modulates our behavioral and emotional responses involving decision-making and emotion regulation. Are the regions implicated in interoception also spatially related to and possibly nested within the networks of decision making and emotion regulation? Addressing this question, we performed three meta-analyses of functional magnetic resonance imaging studies to identify the regions that are commonly activated by the three domains using activation likelihood estimation (ALE). Additionally, we assessed the coactivation pattern of identified common regions using meta-analytic connectivity modeling (MACM). The results showed major overlaps of interoception with both decision making and emotion regulation in specifically the right dorsal anterior insula. The pairwise contrast analyses confirmed this finding and revealed conjunction-based activities in decision making and emotion regulation in the dorsal anterior cingulate cortex (dACC). MACM based on the identified insula revealed a widespread convergent coactivation pattern with the left anterior insula, dACC, and bilateral thalamus which, together, constitute the salience network. Among these co-activated regions, bilateral insula and the dACC were shared among all three domains. These results suggest that the regions mediating interoception including intero-exteroceptive integration and salience attribution are contained and thus spatially nested within the more extensive networks recruited during decision making and emotion regulation. [ABSTRACT FROM AUTHOR]

Multi-variate pattern analysis (MVPA) applied to BOLD-fMRI has proven successful at decoding complicated fMRI signal patterns associated with a variety of cognitive processes. One cognitive process, not yet investigated, is the mental representation of "Yes/No" thoughts that precede the actual overt response to a binary "Yes/No" question. In this study, we focus on examining: (1) whether spatial patterns of the hemodynamic response carry sufficient information to allow reliable decoding of "Yes/No" thoughts; and (2) whether decoding of "Yes/No" thoughts is independent of the intention to respond honestly or dishonestly. To achieve this goal, we conducted two separate experiments. Experiment 1, collected on a 3T scanner, examined the whole brain to identify regions that carry sufficient information to permit significantly above-chance prediction of "Yes/No" thoughts at the group level. In Experiment 2, collected on a 7T scanner, we focused on the regions identified in Experiment 1 to examine the capability of achieving high decoding accuracy at the single subject level. A set of regions - namely right superior temporal gyrus, left supra-marginal gyrus, and left middle frontal gyrus - exhibited high decoding power. Decoding accuracy for these regions increased with trial averaging. When 18 trials were averaged, the median accuracies were 82.5%, 77.5%, and 79.5%, respectively. When trials were separated according to deceptive intentions (set via experimental cues), and classifiers were trained on honest trials, but tested on trials where subjects were asked to deceive, the median accuracies of these regions still reached 66%, 75%, and 78.5%. These results provide evidence that concealed "Yes/No" thoughts are encoded in the BOLD signal, retaining some level of independence from the subject's intentions to answer honestly or dishonestly. These findings also suggest the theoretical possibility for more efficient brain-computer interfaces where subjects only need to think their answers to communicate. [ABSTRACT FROM AUTHOR]

Abstract: Understanding the mechanisms involved in perception and conception of oneself is a fundamental psychological topic with high relevance for psychiatric and neurological issues, and it is one of the great challenges in neuroscientific research. The paradigmatic single-case study presented here aimed to investigate different components of self- and other-processes and to elucidate corresponding neurobiological underpinnings. An eminent professional opera singer with profound performance experience has undergone functional magnetic resonance imaging and was exposed to excerpts of Mozart arias, sung by herself or another singer. The results indicate a distinction between self- and other conditions in cortical midline structures, differentially involved in self-related and self-referential processing. This lends further support to the assumption of cortical midline structures being involved in the neural processing of self-specific stimuli and also confirms the power of single case studies as a research tool. [Copyright &y& Elsevier]

Abstract: Self-referential processing involves a complex set of cognitive functions, posing challenges to delineating its independent neural correlates. While self-referential processing has been considered functionally intertwined with episodic memory, the present study explores their overlap and dissociability. Standard tasks for self-referential processing and episodic memory were combined into a single fMRI experiment. Contrasting the effects of self-relatedness and retrieval success allowed for the two processes to be delineated. Stimuli judged as self-referential specifically activated the posterior cingulate/anterior precuneus, the medial prefrontal cortex, and an inferior division of the inferior parietal lobule. In contrast, episodic memory retrieval specifically involved the posterior precuneus, the right anterior prefrontal cortex, and a superior division of the inferior parietal lobule (extending into superior parietal lobule). Overlapping activations were found in intermediate zones in the precuneus and the inferior parietal lobule, but not in the prefrontal cortex. While our data show common networks for both processes in the medial and lateral parietal cortex, three functional differentiations were also observed: (1) an anterior–posterior differentiation within the medial parietal cortex; (2) a medial–anterolateral differentiation within the prefrontal cortex; and, (3) an inferior–superior differentiation within the lateral parietal cortex for self-referential processing versus episodic memory retrieval. [Copyright &y& Elsevier]

Abstract: In a functional magnetic resonance imaging experiment, expectancy cues signaling emotional stimuli were used to study the personality trait of novelty seeking. BOLD responses to emotional expectancy were positively correlated with novelty-seeking scores in the medial prefrontal cortex. This correlation was strongest for the sub-dimension of exploratory excitability. [Copyright &y& Elsevier]

• A single session of real-time fMRI neurofeedback significantly reduced activation in the superior temporal gyrus (STG) post neurofeedback. • Reduction of activation in STG while ignoring voices reduced the severity of auditory hallucinations (AH) in patients with pharmacology-resistant AH. • There was a significant correlation between the reduction in STG activation and the reduction in AH scores post neurofeedback. Auditory hallucinations (AH) are one of the core symptoms of schizophrenia (SZ) and constitute a significant source of suffering and disability. One third of SZ patients experience pharmacology-resistant AH, so an alternative/complementary treatment strategy is needed to alleviate this debilitating condition. In this study, real-time functional Magnetic Resonance Imaging neurofeedback (rt-fMRI NFB), a non-invasive technique, was used to teach 10 SZ patients with pharmacology-resistant AH to modulate their brain activity in the superior temporal gyrus (STG), a key area in the neurophysiology of AH. A functional task was designed in order to provide patients with a specific strategy to help them modify their brain activity in the desired direction. Specifically, they received neurofeedback from their own STG and were trained to upregulate it while listening to their own voice recording and downregulate it while ignoring a stranger's voice recording. This guided performance neurofeedback training resulted in a) a significant reduction in STG activation while ignoring a stranger's voice, and b) reductions in AH scores after the neurofeedback session. A single, 21-minute session of rt-fMRI NFB was enough to produce these effects, suggesting that this approach may be an efficient and clinically viable alternative for the treatment of pharmacology-resistant AH. [ABSTRACT FROM AUTHOR]