Who is that? Brain networks and mechanisms for identifying individuals

Social animals can identify conspecifics by many forms of sensory input. However, whether the neuronal computations that support this ability to identify individuals rely on modality-independent convergence or involve ongoing synergistic interactions along the multiple sensory streams remains controversial. Direct neuronal measurements at relevant brain sites could address such questions, but this requires better bridging the work in humans and animal models. Here, we overview recent studies in nonhuman primates on voice and face identity-sensitive pathways and evaluate the correspondences to relevant findings in humans. This synthesis provides insights into converging sensory streams in the primate anterior temporal lobe (ATL) for identity processing. Furthermore, we advance a model and suggest how alternative neuronal mechanisms could be tested

Specialization of the rostral prefrontal cortex for distinct analogy processes

Analogical reasoning is central to learning and abstract thinking. It involves using a more familiar situation (source) to make inferences about a less familiar situation (target). According to the predominant cognitive models, analogical reasoning includes 1) generation of structured mental representations and 2) mapping based on structural similarities between them. This study used functional magnetic resonance imaging to specify the role of rostral prefrontal cortex (PFC) in these distinct processes. An experimental paradigm was designed that enabled differentiation between these processes, by temporal separation of the presentation of the source and the target. Within rostral PFC, a lateral subregion was activated by analogy task both during study of the source (before the source could be compared with a target) and when the target appeared. This may suggest that this subregion supports fundamental analogy processes such as generating structured representations of stimuli but is not specific to one particular processing stage. By contrast, a dorsomedial subregion of rostral PFC showed an interaction between task (analogy vs. control) and period (more activated when the target appeared). We propose that this region is involved in comparison or mapping processes. These results add to the growing evidence for functional differentiation between rostral PFC subregions

Connectivity-based parcellation of the human frontal polar cortex

The frontal pole corresponds to Brodmann area (BA) 10, the largest single architectonic area in the human frontal lobe. Generally, BA10 is thought to contain two or three subregions that subserve broad functions such as multitasking, social cognition, attention, and episodic memory. However, there is a substantial debate about the functional and structural heterogeneity of this large frontal region. Previous connectivity-based parcellation studies have identified two or three subregions in the human frontal pole. Here, we used diffusion tensor imaging to assess structural connectivity of BA10 in 35 healthy subjects and delineated subregions based on this connectivity. This allowed us to determine the correspondence of structurally based subregions with the scheme previously defined functionally. Three subregions could be defined in each subject. However, these three subregions were not spatially consistent between subjects. Therefore, we accepted a solution with two subregions that encompassed the lateral and medial frontal pole. We then examined resting-state functional connectivity of the two subregions and found significant differences between their connectivities. The medial cluster was connected to nodes of the default-mode network, which is implicated in internally focused, self-related thought, and social cognition. The lateral cluster was connected to nodes of the executive control network, associated with directed attention and working memory. These findings support the concept that there are two major anatomical subregions of the frontal pole related to differences in functional connectivity

Altered Functional Connectivity of Striatum Based on the Integrated Connectivity Model in First-Episode Schizophrenia

Background: The human striatum is a heterogeneous structure involved in diverse functional domains that related to distinct striatum subregions. Striatal dysfunction was thought to be a fundamental element in schizophrenia. However, the connectivity pattern of striatum solely based on functional or structural characteristics leads to inconsistent findings in healthy adult and also schizophrenia. This study aims to develop an integrated striatal model and reveal the altered functional connectivity pattern of the striatum in schizophrenia. Methods: Two data-driven approaches, task-dependent meta-analytic connectivity modeling (MACM) and task-independent resting-state functional connectivity (RSFC), were used for seven anatomical connectivity-based striatum subregions to provide an integrated striatal model. Then, RSFC analyses of seven striatal subregions were applied to 45 first-episode schizophrenia (FES) and 27 healthy controls to examine the difference, based on the integrated model, of functional connectivity pattern of striatal subregions. Results: MACM and RSFC results showed that striatum subregions were associated with discrete cortical regions and involved in distinct cognitive processes. Besides, RSFC results overlapped with MACM findings but showed broader distributions. Importantly, significantly reduced functional connectivity was identified between limbic subregion and thalamus, medial prefrontal cortex, anterior cingulate cortex, and insula and also between executive subregions and thalamus, supplementary motor area, and insula in FES. Conclusions: Combing functional and structural connectivity information, this study provides the integrated model of corticostriatal subcircuits and confirms the abnormal functional connectivity of limbic and executive striatum subregions with different networks and thalamus, supporting the important role of the corticostriatal-thalamic loop in the pathophysiology of schizophrenia

Mapping the Structural Core of Human Cerebral Cortex

Structurally segregated and functionally specialized regions of the human cerebral cortex are interconnected by a dense network of cortico-cortical axonal pathways. By using diffusion spectrum imaging, we noninvasively mapped these pathways within and across cortical hemispheres in individual human participants. An analysis of the resulting large-scale structural brain networks reveals a structural core within posterior medial and parietal cerebral cortex, as well as several distinct temporal and frontal modules. Brain regions within the structural core share high degree, strength, and betweenness centrality, and they constitute connector hubs that link all major structural modules. The structural core contains brain regions that form the posterior components of the human default network. Looking both within and outside of core regions, we observed a substantial correspondence between structural connectivity and resting-state functional connectivity measured in the same participants. The spatial and topological centrality of the core within cortex suggests an important role in functional integration

Aberrant hippocampal subregion networks associated with the classifications of aMCI subjects: a longitudinal resting-state study

Background: Altered hippocampal structure and function is a valuable indicator of possible conversion from amnestic type mild cognitive impairment (aMCI) to Alzheimer’s disease (AD). However, little is known about the disrupted functional connectivity of hippocampus subregional networks in aMCI subjects. Methodology/Principal Findings: aMCI group-1 (n = 26) and controls group-1 (n = 18) underwent baseline and after approximately 20 months follow up resting-state fMRI scans. Integrity of distributed functional connectivity networks incorporating six hippocampal subregions (i.e. cornu ammonis, dentate gyrus and subicular complex, bilaterally) was then explored over time and comparisons made between groups. The ability of these extent longitudinal changes to separate unrelated groups of 30 subjects (aMCI-converters, n = 6; aMCI group-2, n = 12; controls group-2, n = 12) were further assessed. Six longitudinal hippocampus subregional functional connectivity networks showed similar changes in aMCI subjects over time, which were mainly associated with medial frontal gyrus, lateral temporal cortex, insula, posterior cingulate cortex (PCC) and cerebellum. However, the disconnection of hippocampal subregions and PCC may be a key factor of impaired episodic memory in aMCI, and the functional index of these longitudinal changes allowed well classifying independent samples of aMCI converters from non-converters (sensitivity was 83.3%, specificity was 83.3%) and controls (sensitivity was 83.3%, specificity was 91.7%). Conclusions/Significance: It demonstrated that the functional changes in resting-state hippocampus subregional networks could be an important and early indicator for dysfunction that may be particularly relevant to early stage changes and progression of aMCI subjects

PUTTING CRAVING INTO CONTEXT: EFFECTS OF PERCEIVED SMOKING OPPORTUNITY ON THE NEURAL RESPONSE TO CIGARETTE CUE EXPOSURE

Recent years have seen the emergence of research applying functional neuroimaging to the study of cue-elicited drug craving. This research has begun to identify a distributed system of brain activity during drug craving. Functional magnetic resonance imaging (fMRI) was used to examine the effects of smoking expectancy on the neural response to neutral (e.g., roll of tape) and smoking-related (holding a cigarette) stimuli in male cigarette smokers deprived of nicotine for 8 hours. As predicted, several brain regions exhibited differential activation during cigarette versus neutral cue exposure. Moreover, instructions about smoking opportunity affected cue-elicited activation in several regions. These results highlight the importance of perceived drug availability in the neurobiological response to drug cues

"Feeling" others' painful actions: the sensorimotor integration of pain and action information.

Sensorimotor regions of the brain have been implicated in simulation processes such as action understanding and empathy, but their functional role in these processes remains unspecified. We used functional magnetic resonance imaging (fMRI) to demonstrate that postcentral sensorimotor cortex integrates action and object information to derive the sensory outcomes of observed hand-object interactions. When subjects viewed others' hands grasping or withdrawing from objects that were either painful or nonpainful, distinct sensorimotor subregions emerged as showing preferential responses to different aspects of the stimuli: object information (noxious vs. innocuous), action information (grasps vs. withdrawals), and painful action outcomes (painful grasps vs. all other conditions). Activation in the latter region correlated with subjects' ratings of how painful each object would be to touch and their previous experience with the object. Viewing others' painful grasps also biased behavioral responses to actual tactile stimulation, a novel effect not seen for auditory control stimuli. Somatosensory cortices, including primary somatosensory areas 1/3b and 2 and parietal area PF, may therefore subserve somatomotor simulation processes by integrating action and object information to anticipate the sensory consequences of observed hand-object interactions

The Role of Amygdala Subregions in the Neurobiology of Social Anxiety Disorder

Social anxiety is characterised by fear and/or avoidance of social situations in which an individual may be scrutinised by others. Social anxiety is thought to exist as a spectrum, with individuals on the high-end experiencing frequent and severe anxiety in the context of social situations. When severe social anxiety is accompanied by distress and functional impairment, a diagnosis of social anxiety disorder (SAD) can be made. SAD is a prevalent and debilitating disorder that can be unremitting and pervasive in the absence of intervention. Current psychotherapeutic and pharmacotherapeutic treatments for SAD demonstrate limited efficacy in remitting symptoms. Therefore, it is important to achieve a better understanding of the neurobiological mechanisms implicated in this disorder and identify potential neural treatment targets to develop more efficacious treatments. This thesis aimed to further investigate the neurobiological mechanisms implicated in SAD (vs. controls) and the associations between neural functioning and social anxiety as a dimensional symptom, with a focus on the amygdala and four of its subregions (the amygdalostriatal, basolateral, centromedial, and superficial subregions). This was due to previous findings in the neuroimaging literature in SAD having consistently implicated the amygdala, albeit with mixed findings of both increased and decreased functioning in those with SAD compared to controls. In the literature to date, however, most studies had examined the amygdala as a singular homogenous region due to methodological limitations in being able to examine the functionally and structurally distinct subnuclei that make up this region. By examining the amygdala subregions through the use of multiband functional magnetic resonance imaging (fMRI), this thesis additionally sought to determine whether the mixed findings in the literature to date may be a result of amygdala subregion-specific activity and connectivity patterns. This was achieved through three research studies. Firstly, Study 1 involved a comprehensive systematic review that summarised the literature on resting-state neuroimaging in SAD with a focus on fMRI studies and findings specific to the amygdala and its subregions (Chapter 3). This was followed by two empirical studies which investigated the role of the amygdala and its subregions during resting-state (Study 2) and emotion processing (Study 3) fMRI paradigms (Chapters 5 and 6, respectively). Findings from the systematic review (Study 1) highlighted the mixed findings in the resting-state neuroimaging literature in SAD to date, along with methodological limitations relating to neuroimaging acquisition and analysis. The empirical studies sought to address these limitations and demonstrated differing amygdala subregion activity and connectivity patterns at rest and during emotion processing. In the resting-state fMRI study (Study 2), there were no statistically significant differences in functional connectivity of the amygdala and its subregions in those with SAD compared to controls. However, social anxiety severity was found to be positively associated with connectivity between the superficial subregion and the supramarginal gyrus. The superficial subregion, along with the basolateral and centromedial subregions, were also implicated in the task-based emotion processing fMRI study (Study 3). In response to happy, angry, and fearful faces, those with SAD (vs. controls) had hyperactivation of the superficial subregion, hypoconnectivity between the superficial subregion and the precuneus, and hyperconnectivity between the basolateral subregion and broader brain regions (i.e., the pre/postcentral gyrus and the supramarginal gyrus). Additionally, social anxiety severity was positively associated with superficial and centromedial activation. Overall, the findings from this thesis provide novel information to the current understanding of the neurobiology of SAD by demonstrating amygdala subregion-specific alterations. This has important implications for research, theory, and clinical practice that are detailed in the thesis discussion (Chapter 7). Briefly, in terms of research, findings from the thesis provide support for the continuing investigation of SAD using both dimensional and categorical approaches. This was evident by the findings from the two empirical papers which demonstrated positive associations between subregional activity and connectivity patterns and social anxiety severity. With regards to theory, differences in neural patterns that were observed at rest (Study 2) and during emotion processing (Study 3) provide support for distinct neurobiological models to be constructed based on whether those with SAD are in the absence or presence of social stimuli. This is in contrast to the most recently proposed neurobiological model of SAD which was informed by a combination of resting-state and task-based fMRI data. Finally, with regards to clinical practice, the findings from this thesis provide preliminary evidence of the superficial, basolateral, and centromedial subregions of the amygdala as being potential treatment targets that can be used to inform the development of more efficacious treatments for SAD