The brain's default mode network (DMN) has become closely associated with self-referential mental activity, particularly in the resting-state. While the DMN is important for such processes, it has ...functions other than self-reference, and self-referential processes are supported by regions outside of the DMN. In our study of 88 participants, we examined self-referential and resting-state processes to clarify the extent to which DMN activity was common and distinct between the conditions. Within areas commonly activated by self-reference and rest we sought to identify those that showed additional functional specialization for self-referential processes: these being not only activated by self-reference and rest but also showing increased activity in self-reference versus rest. We examined the neural network properties of the identified ‘core-self’ DMN regions—in medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and inferior parietal lobule—using dynamic causal modeling. The optimal model identified was one in which self-related processes were driven via PCC activity and moderated by the regulatory influences of MPFC. We thus confirm the significance of these regions for self-related processes and extend our understanding of their functionally specialized roles.
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•Self-reference and rest-fixation evoked extensive common activation; though distinct differences were also evident.•Within commonly activated regions greater self-referential activation was shown in MPFC, PCC, and left IPL.•Dynamic causal modeling showed that self-related processes were driven via PCC activity, and moderated by MPFC.•We speculate that this brain model provides the basis for the conscious awareness of the self.
Analyses of functional interactions between large-scale brain networks have identified two broad systems that operate in apparent competition or antagonism with each other. One system, termed the ...default mode network (DMN), is thought to support internally oriented processing. The other system acts as a generic external attention system (EAS) and mediates attention to exogenous stimuli. Reports that the DMN and EAS show anticorrelated activity across a range of experimental paradigms suggest that competition between these systems supports adaptive behavior. Here, we used functional MRI to characterize functional interactions between the DMN and different EAS components during performance of a recollection task known to coactivate regions of both networks. Using methods to isolate task-related, context-dependent changes in functional connectivity between these systems, we show that increased cooperation between the DMN and a specific right-lateralized frontoparietal component of the EAS is associated with more rapid memory recollection. We also show that these cooperative dynamics are facilitated by a dynamic reconfiguration of the functional architecture of the DMN into core and transitional modules, with the latter serving to enhance integration with frontoparietal regions. In particular, the right posterior cingulate cortex may act as a critical information-processing hub that provokes these context-dependent reconfigurations from an intrinsic or default state of antagonism. Our findings highlight the dynamic, context-dependent nature of large-scale brain dynamics and shed light on their contribution to individual differences in behavior.
Patients with fibromyalgia (FM) show characteristically enhanced unpleasantness to painful and nonpainful sensations accompanied by altered neural responses. The diagnostic potential of such neural ...alterations, including their sensitivity and specificity to FM (vs healthy controls) is unknown. We identify a brain signature that characterizes FM central pathophysiology at the neural systems level. We included 37 patients with FM and 35 matched healthy controls, and analyzed functional magnetic resonance imaging responses to (1) painful pressure and (2) nonpainful multisensory (visual-auditory-tactile) stimulation. We used machine-learning techniques to identify a brain-based FM signature. When exposed to the same painful stimuli, patients with FM showed greater neurologic pain signature (NPS; Wager et al., 2013. An fMRI-based neurologic signature of physical pain. N Engl J Med 2013;368:1388-97) responses. In addition, a new pain-related classifier ("FM-pain") revealed augmented responses in sensory integration (insula/operculum) and self-referential (eg, medial prefrontal) regions in FM and reduced responses in the lateral frontal cortex. A "multisensory" classifier trained on nonpainful sensory stimulation revealed augmented responses in the insula/operculum, posterior cingulate, and medial prefrontal regions and reduced responses in the primary/secondary sensory cortices, basal ganglia, and cerebellum. Combined activity in the NPS, FM pain, and multisensory patterns classified patients vs controls with 92% sensitivity and 94% specificity in out-of-sample individuals. Enhanced NPS responses partly mediated mechanical hypersensitivity and correlated with depression and disability (Puncorrected < 0.05); FM-pain and multisensory responses correlated with clinical pain (Puncorrected < 0.05). The study provides initial characterization of individual patients with FM based on pathophysiological, symptom-related brain features. If replicated, these brain features may constitute objective neural targets for therapeutic interventions. The results establish a framework for assessing therapeutic mechanisms and predicting treatment response at the individual level.
Dysregulation of corticostriatal circuitry has long been thought to be critical in the etiology of psychotic disorders, although the differential roles played by dorsal and ventral systems in ...mediating risk for psychosis have been contentious.
To use resting-state functional magnetic resonance imaging to characterize disease-related, risk-related, and symptom-related changes of corticostriatal functional circuitry in patients with first-episode psychosis and their unaffected first-degree relatives.
This case-control cross-sectional study was conducted at a specialist early psychosis clinic, GlaxoSmithKline Clinical Unit, and magnetic resonance imaging facility. Nineteen patients with first-episode psychosis, 25 of their unaffected first-degree relatives, and 26 healthy control subjects were included in this study.
Voxelwise statistical parametric maps testing differences in the strength of functional connectivity between 6 striatal seed regions of interest (3 caudate and 3 putamen) per hemisphere and all other brain regions.
Disease-related changes, reflecting differences between patients and control subjects, involved widespread dysregulation of corticostriatal systems characterized most prominently by a dorsal-to-ventral gradient of hypoconnectivity to hyperconnectivity between striatal and prefrontal regions. A similar gradient was evident in comparisons between relatives and control subjects, identifying it as a genetically inherited risk phenotype. In patients, functional connectivity in risk-affected and disease-affected dorsal frontostriatal circuitry correlated with the severity of both positive and negative symptoms.
First-episode psychosis is associated with pronounced dysregulation of corticostriatal systems, characterized most prominently by hypoconnectivity of dorsal and hyperconnectivity of ventral frontostriatal circuits. These changes correlate with symptom severity and are also apparent in unaffected first-degree relatives, suggesting that they represent a putative risk phenotype for psychotic illness.
The self is experienced differently in depression. It is infused with pervasive low mood, and structured by negative self-related thoughts. The concept of the self has been difficult to define-one of ...the reasons it is now infrequently an object of enquiry for psychiatry-but findings from functional brain imaging and other neuroscience studies have provided new insights. They have elucidated how the self is supported by complex, hierarchical brain processes. Bodily sensations rise through the spinal cord, brainstem, and subcortical regions through to cortical networks, with the default mode network sitting at the apex, integrating interoceptive signals with information about the extended social environment. We discuss how this forms a "self axis", and demonstrate how this axis is set awry by depression. Our self-axis model of depression establishes a new perspective on the disorder. It emphasises the multi-level nature of depression, and how impacts made at different explanatory levels influence others along the axis. It suggests that diverse treatments might be effective for depression, from lifestyle interventions to psychotherapies to medications: they target different aspects of the self, but changes at one level of the self axis can affect others along it. Our framework for depression establishes a central role for the self, which might again become a useful focus of investigation.
There is growing interest in the nature of slow variations of the blood oxygen level-dependent (BOLD) signal observed in functional MRI resting-state studies. In humans, these slow BOLD variations ...are thought to reflect an underlying or intrinsic form of brain functional connectivity in discrete neuroanatomical systems. While these 'resting-state networks' may be relatively enduring phenomena, other evidence suggest that dynamic changes in their functional connectivity may also emerge depending on the brain state of subjects during scanning.
In this study, we examined healthy subjects (n = 24) with a mood induction paradigm during two continuous fMRI recordings to assess the effects of a change in self-generated mood state (neutral to sad) on the functional connectivity of these resting-state networks (n = 24). Using independent component analysis, we identified five networks that were common to both experimental states, each showing dominant signal fluctuations in the very low frequency domain (approximately 0.04 Hz). Between the two states, we observed apparent increases and decreases in the overall functional connectivity of these networks. Primary findings included increased connectivity strength of a paralimbic network involving the dorsal anterior cingulate and anterior insula cortices with subjects' increasing sadness and decreased functional connectivity of the 'default mode network'.
These findings support recent studies that suggest the functional connectivity of certain resting-state networks may, in part, reflect a dynamic image of the current brain state. In our study, this was linked to changes in subjective mood.
Cognitive control and working memory rely upon a common fronto-parietal network that includes the inferior frontal junction (IFJ), dorsolateral prefrontal cortex (dlPFC), pre-supplementary motor ...area/dorsal anterior cingulate cortex (pSMA/dACC), and intraparietal sulcus (IPS). This network is able to flexibly adapt its function in response to changing behavioral goals, mediating a wide range of cognitive demands. Here we apply dynamic causal modeling to functional magnetic resonance imaging data to characterize task-related alterations in the strength of network interactions across distinct cognitive processes. Evidence in favor of task-related connectivity dynamics was accrued across a very large space of possible network structures. Cognitive control and working memory demands were manipulated using a factorial combination of the multi-source interference task and a verbal 2-back working memory task, respectively. Both were found to alter the sensitivity of the IFJ to perceptual information, and to increase IFJ-to-pSMA/dACC connectivity. In contrast, increased connectivity from the pSMA/dACC to the IPS, as well as from the dlPFC to the IFJ, was uniquely driven by cognitive control demands; a task-induced negative influence of the dlPFC on the pSMA/dACC was specific to working memory demands. These results reflect a system of both shared and unique context-dependent dynamics within the fronto-parietal network. Mechanisms supporting cognitive engagement, response selection, and action evaluation may be shared across cognitive domains, while dynamic updating of task and context representations within this network are potentially specific to changing demands on cognitive control.
•Cognitive control and working memory rely on a common frontoparietal brain network.•Dynamic causal modeling used to assess shared and differential connectivity•Shared: cognitive engagement in inferior frontal junction•Shared: altered lateral-to-medial interactions, guiding action selection/evaluation•CC: altered rostral-to-caudal connectivity, updating task/context representations
•Reports a set of meta-analyses of human fMRI fear extinction studies involving over 1300 participants.•Human fear extinction learning and extinction recall are consistently distinct in their neural ...correlates.•The contribution of prefrontal cortical subregions to extinction appears to be more nuanced than what is currently suggested.
The study of fear extinction represents an important example of translational neuroscience in psychiatry and promises to improve the understanding and treatment of anxiety and fear-related disorders. We present the results of a set of meta-analyses of human fear extinction studies in healthy participants, conducted with functional magnetic resonance imaging (fMRI) and reporting whole-brain results. Meta-analyses of fear extinction learning primarily implicate consistent activation of brain regions linked to threat appraisal and experience, including the dorsal anterior cingulate and anterior insular cortices. An overlapping anatomical result was obtained from the meta-analysis of extinction recall studies, except when studies directly compared an extinguished threat stimulus to an unextinguished threat stimulus (instead of a safety stimulus). In this latter instance, more consistent activation was observed in dorsolateral and ventromedial prefrontal cortex regions, together with other areas including the hippocampus. While our results partially support the notion of a shared neuroanatomy between human and rodent models of extinction processes, they also encourage an expanded account of the neural basis of human fear extinction.
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