Objective-Generalized social phobia involves fear/avoidance, specifically of social situations, whereas generalized anxiety disorder involves intrusive worry about diverse circumstances. It remains unclear the degree to which these two, often comorbid, conditions represent distinct disorders or alternative presentations of a single, core underlying pathology. Functional magnetic resonance imaging assessed the neural response to facial expressions in generalized social phobia and generalized anxiety disorder.Method-Individuals matched on age, IQ, and gender with generalized social phobia without generalized anxiety disorder (N=17), generalized anxiety disorder (N= 17), or no psychopathology (N=17) viewed neutral, fearful, and angry expressions while ostensibly making a simple gender judgment.Results-The patients with generalized social phobia without generalized anxiety disorder showed increased activation to fearful relative to neutral expressions in several regions, including the amygdala, compared to healthy individuals. This increased amygdala response related to selfreported anxiety in patients with generalized social phobia without generalized anxiety disorder. In contrast, patients with generalized anxiety disorder showed significantly less activation to fearful relative to neutral faces compared to the healthy individuals. They did show significantly increased response to angry expressions relative to healthy individuals in a lateral region of the middle frontal gyrus. This increased lateral frontal response related to self-reported anxiety in patients with generalized anxiety disorder.Conclusions-These results suggest that neural circuitry dysfunctions differ in generalized social phobia and generalized anxiety disorder.Generalized social phobia and generalized anxiety disorder are two highly prevalent, chronic, and disabling anxiety disorders (1,2) that are sometimes comorbid. Generalized social phobia involves fear/avoidance, specifically of social situations, whereas generalized anxiety disorder involves intrusive worry about a broader array of everyday life circumstances. Although both have considerable social and economic costs, disagreement exists concerning the degree to which the conditions result from a shared or unique pathophysiology. For example, high rates of comorbidity in cross-sectional and longitudinal studies suggest that the distinction between the two conditions may be relatively subtle at the descriptive level (3,4). On the other hand, data from family-based and therapeutic research suggest the two conditions can be dissociated. Specifically, such dissociation is reflected in patterns of disorder aggregation within families (5), as well as by the fact that generalized anxiety disorder, but not social phobia, responds to most tricyclic antidepressants and to buspirone (6-8). Because no brain-imaging study has directly compared the two conditions, it remains unclear whether the two disorders have dissociable neural correlates.The principal goal of the current study was to inves...

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We review the evidence for the concept of the “initial” or prototype brain. We outline four possible modes of brain evolution suggested by our new findings on the evolutionary status of the dolphin brain. The four modes involve various forms of deviation from and conformity to the hypothesized initial brain type. These include examples of conservative evolution, progressive evolution, and combinations of the two in which features of one or the other become dominant. The four types of neocortical organization in extant mammals may be the result of selective pressures on sensory/motor systems resulting in divergent patterns of brain phylogenesis. A modular “modification/multiplication” hypothesis is proposed as a mechanism of neocortical evolution in eutherians. Representative models of the initial ancestral group of mammals include not only extant basal Insectivora but also Chiroptera; we have found that dolphins and large whales have also retained many features of the archetypal or initial brain. This group evolved from the initial mammalian stock and returned to the aquatic environment some 50 million years ago. This unique experiment of nature shows the effects of radical changes in environment on brain-body adaptations and specializations. Although the dolphin brain has certain quantitative characteristics of the evolutionary changes seen in the higher terrestrial mammals, it has also retained many of the conservative structural features of the initial brain. Its neocortical organization is accordingly different, largely in a quantitative sense, from that of terrestrial models of the initial brain such as the hedgehog.

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Objective Generalized social phobia (GSP) is defined by a persistent fear of social disapproval. However, the neural underpinnings of this increased fear and its mediating factors are unclear. Using event-related fMRI, we examined whether the intent of an event, which mediates the neural response to social disapproval in healthy individuals, differentially affects response in GSP. Specifically, would patients with GSP show particularly increased response to embarrassing, unintentional transgressions? Method Sixteen patients with GSP and sixteen age, IQ, and gender matched healthy individuals read stories during fMRI scans that either involved neutral social events, unintentional social transgressions (e.g., choking on food at party, and coughing it up), or intentional social transgressions (e.g., disliking food at party, and spitting it out). Results Significant group-by-transgression interactions were observed within ventral regions of medial prefrontal cortex (MPFC). Healthy individuals tended to show increased BOLD responses to intentional, relative to unintentional transgressions. The patients with GSP, however, showed significantly increased responses to the unintentional transgressions. In addition, they rated the unintentional transgressions as significantly more embarrassing than the comparison individuals. We also observed significant group main effects within the amygdala and bilateral insula, reflecting elevated GSP responses within these regions to all event types. Conclusions These results further implicate the MPFC in the pathophysiology of GSP, specifically through its involvement in distorted self-referential processing. In addition, the current results further underscore the extended role of the amygdala and insula in the processing of social stimuli more generally in GSP.

Generalized social phobia (GSP) involves the fear of being negatively evaluated. Previous work suggests that self-referentiality, mediated by medial prefrontal cortex (MFPC), plays an important role in the disorder. However, it is not clear whether this anomalous MPFC response to selfrelated information in patients with GSP concerns an increased representation of their own or others' opinions. In this paper we examined whether GSP is associated with increased response to own (1 st person) or other individuals' (2 nd person) opinions relative to healthy individuals. Unmedicated individuals with GSP (n=15) and age, IQ, and gender-matched comparison individuals (n=15) read 1 st (e.g., I'm ugly), and 2 nd (e.g., You're ugly) person viewpoint comments during fMRI. We observed significant group-by-viewpoint interactions within ventral MPFC. Whereas the healthy comparison individuals showed significantly increased (or less decreased) BOLD responses to 1 st relative to 2 nd person viewpoints, the patients showed significantly increased responses to 2 nd relative to 1 st person viewpoints. The reduced BOLD responses to 1 st person viewpoint comments shown by the patients correlated significantly with severity of social anxiety symptom severity. These results underscore the importance of dysfunctional selfreferential processing and MPFC in GSP. We believe that these data reflect a reorganization of self-referential reasoning in the disorder with a self-concept perhaps atypically related to the view of others.

Optimistic bias (OB) is seen when individuals underestimate their probability of experiencing negative life events and overestimate their probability of experiencing positive life events. A reduced OB has been linked with increased depression symptoms . However, given the relevance of this information to mood and anxiety disorders, little is currently known regarding the neurobiology of OB. In the current study, we examine the neural basis of OB in healthy individuals (n=33) during probability estimation of future positive and negative events occurring to themselves relative to other, comparable individuals. In line with previous work, subjects showed significant OB; they considered themselves significantly more likely to experience future positive and significantly less likely to experience future negative events relative to comparable others. Positive, relative to negative events, un-modulated by subjects’ probability estimates, were associated with significantly greater activity within ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC). Moreover, responses within both regions to positive events negatively related to the healthy subjects’ self reports of depression symptoms. However, there was no significant modulation of activity in either region by the subject’s OB, objectified as the level to which they thought the event was more likely [positive events] or less likely [negative events] to occur to them relative to comparable others. In contrast, activity within rostral anterior cingulate cortex (rACC) was positively modulated by OB for positive events and activity within anterior insula and dorsomedial prefrontal cortex (dmPFC) was negatively modulated by OB for negative events. However, there was no significant relationship between responsiveness within these regions and self reports of depression symptoms. The data are discussed with reference to current models of vmPFC, rACC and anterior insula functioning.

On cytoarchitectonic grounds we have identified two distinct types of cortical formations composing the lateral gyrus (visual cortex) of the dolphin and have termed these heterolaminar cortex and homolaminar cortex. The heterolaminar cortex occupies the medial and lateral banks of the entolateral sulcus whereas the homolaminar cortex occupies the remainder of the lateral gyrus both lateral and medial to the entolateral sulcus. Each of these cortices exhibits special cytoarchitectonic features, a major difference being that heterolaminar cortex contains an incipient layer IV whereas layer IV is clearly absent in homolaminar cortex. Quantitative imaging procedures reveal that there is greater laminar differentiation in heterolaminar than in homolaminar cortex. Golgi analysis of neuronal forms and dendritic architecture confirms this distinction between the two types of cortex composing the lateral gyrus. Computer-assisted morphometric methods have been applied to both types of cortex and indicate by a variety of parameters several quantitative differences in the cellular numbers, types, and organization in each type of cortex. Both types of cortex, homolaminar and heterolaminar, exhibit a markedly higher cellular density in the posterior sector of the lateral gyrus than in the anterior sector. We have also for the first time been able to identify a columnar type of organization of the cetacean visual cortex and have described two types of cytoarchitectonic columns, major and minor, in each of these types of cortex. Comparisons in organization of these basic columnar units between the bat, representing a prototypic brain, and the dolphin reveal many similarities but also major quantitative differences in type of organization between the visual cortices in these species. Marked differences are also seen between the cytoarchitectonic columnar organization of the visual cortices in the dolphin and columnar organization of striate cortex in the human brain, the number of columns per unit of cortex in the human being almost twice that seen in the dolphin brain. Some phylogenetic implications of these findings are discussed in relation to the so-called "initial" type of cortical organization reconstructed largely by retrospective inference.