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"Harrison, Ben"
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Mapping the self in the brain's default mode network
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.
Journal Article
Does the human ventromedial prefrontal cortex support fear learning, fear extinction or both? A commentary on subregional contributions
Current models of human fear learning processes emphasize a primary contribution of the ventromedial prefrontal cortex (vmPFC) to fear inhibition (i.e., fear extinction). Here, we discuss crucial findings from recent brain imaging studies that highlight the role of vmPFC and its subregions in how fear is acquired (i.e., fear conditioning).
Journal Article
Neural signatures of conditioning, extinction learning, and extinction recall in posttraumatic stress disorder: a meta-analysis of functional magnetic resonance imaging studies
Establishing neurobiological markers of posttraumatic stress disorder (PTSD) is essential to aid in diagnosis and treatment development. Fear processing deficits are central to PTSD, and their neural signatures may be used as such markers.
Here, we conducted a meta-analysis of seven Pavlovian fear conditioning fMRI studies comparing 156 patients with PTSD and 148 trauma-exposed healthy controls (TEHC) using seed-based d-mapping, to contrast neural correlates of experimental phases, namely conditioning, extinction learning, and extinction recall.
Patients with PTSD, as compared to TEHCs, exhibited increased activation in the anterior hippocampus (extending to the amygdala) and medial prefrontal cortex during conditioning; in the anterior hippocampus-amygdala regions during extinction learning; and in the anterior hippocampus-amygdala and medial prefrontal areas during extinction recall. Yet, patients with PTSD have shown an overall decreased activation in the thalamus during all phases in this meta-analysis.
Findings from this metanalysis suggest that PTSD is characterized by increased activation in areas related to salience and threat, and lower activation in the thalamus, a key relay hub between subcortical areas. If replicated, these fear network alterations may serve as objective diagnostic markers for PTSD, and potential targets for novel treatment development, including pharmacological and brain stimulation interventions. Future longitudinal studies are needed to examine whether these observed network alteration in PTSD are the cause or the consequence of PTSD.
Journal Article
Competitive and cooperative dynamics of large-scale brain functional networks supporting recollection
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.
Journal Article
The self on its axis: a framework for understanding depression
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.
Journal Article
Regional, circuit and network heterogeneity of brain abnormalities in psychiatric disorders
The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case–control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive–compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience–ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks.
A new brain mapping approach tailored to individual people reveals that volume changes in psychiatric illness occur in highly variable locations across individuals, but that these differences often aggregate within common brain systems.
Journal Article
Effective connectivity within the frontoparietal control network differentiates cognitive control and working memory
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
Journal Article
Modulation of Brain Resting-State Networks by Sad Mood Induction
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.
Journal Article