Transdiagnostic brain responses to disorder-related threat across four psychiatric disorders.

BACKGROUND: There is an ongoing debate whether transdiagnostic neural mechanisms are shared by different anxiety-related disorders or whether different disorders show distinct neural correlates. To investigate this issue, studies controlling for design and stimuli across multiple anxiety-related disorders are needed. METHOD: The present functional magnetic resonance imaging study investigated neural correlates of visual disorder-related threat processing across unmedicated patients suffering from panic disorder (n = 20), social anxiety disorder (n = 20), dental phobia (n = 16) and post-traumatic stress disorder (n = 11) relative to healthy controls (HC; n = 67). Each patient group and the corresponding HC group saw a tailor-made picture set with 50 disorder-related and 50 neutral scenes. RESULTS: Across all patients, increased activation to disorder-related v. neutral scenes was found in subregions of the bilateral amygdala. In addition, activation of the lateral amygdala to disorder-related v. neutral scenes correlated positively with subjective anxiety ratings of scenes across patients. Furthermore, whole-brain analysis revealed increased responses to disorder-related threat across the four disorders in middle, medial and superior frontal regions, (para-)limbic regions, such as the insula and thalamus, as well as in the brainstem and occipital lobe. We found no disorder-specific brain responses. CONCLUSIONS: The results suggest that pathologically heightened lateral amygdala activation is linked to experienced anxiety across anxiety disorders and trauma- and stressor-related disorders. Furthermore, the transdiagnostically shared activation network points to a common neural basis of abnormal responses to disorder-related threat stimuli across the four investigated disorders.

Neural correlates of trait anxiety in fear extinction.

BACKGROUND: Fear conditioning involves the amygdala as the main neural structure for learning fear responses whereas fear extinction mainly activates the inhibitory prefrontal cortex (PFC). In this study we investigated whether individual differences in trait anxiety affect amygdala and dorsal anterior cingulate cortex (dACC) activation during fear conditioning and extinction. METHOD: Thirty-two healthy subjects were investigated by functional magnetic resonance imaging (fMRI) at 3 T while performing a cued fear-conditioning task. All participants completed the trait version of the State-Trait Anxiety Inventory (STAI-T). Activations of the amygdala and the dACC were examined with respect to the effects of trait anxiety. RESULTS: Analysis of the fMRI data demonstrated enhanced activation in fear-related brain areas, such as the insula and the ACC, during both fear conditioning and extinction. Activation of the amygdala appeared only during the late acquisition phase whereas deactivation was observed during extinction. Regression analyses revealed that highly trait-anxious subjects exhibited sustained amygdala activation and reduced dACC involvement during the extinction of conditioned responses. CONCLUSIONS: This study reveals that high levels of trait anxiety are associated with both increased amygdala activation and reduced dACC recruitment during the extinction of conditioned fear. This hyper-responsivity of the amygdala and the deficient cognitive control during the extinction of conditioned fear in anxious subjects reflect an increased resistance to extinct fear responses and may thereby enhance the vulnerability to developing anxiety disorders.

ERP indices for response inhibition are related to anxiety-related personality traits.

Anxiety is often associated with impaired cognitive control and avoidance behaviour. The aim of this study was to investigate the effect of anxiety-related personality traits, such as anxiety sensitivity and trait anxiety, on event-related potentials of response inhibition in a standard Go/Nogo-paradigm. We focused on the Nogo-N2 and Nogo-P3 components, which probably represent different sub-processes of response inhibition. The Nogo-N2 was mainly influenced by trait anxiety, while it was slightly affected by anxiety sensitivity. In contrast, the Nogo-P3 was significantly associated with anxiety sensitivity, but was less affected by trait anxiety. Thus, anxious subjects seem to maintain a higher level of cognitive control to prepare and to monitor the outcome of their actions, which is differentially reflected in Nogo-N2 and Nogo-P3 potentials. Our results show that anxiety-related personality traits modulate electrophysiological responses related to cognitive control processes and should be taken into consideration in studies investigating response inhibition.

The functional anatomy of semantic retrieval is influenced by gender, menstrual cycle, and sex hormones.

This study examines the neurobiology of semantic retrieval and describes the influence of gender, menstrual cycle, and sex hormones on semantic networks. Healthy right-handed subjects (12 men, 12 women) were investigated with 3T-fMRI during synonym generation. Behavioral performance and sex hormone levels were assessed. Women were examined during the early follicular and midluteal cycle phase. The activation pattern in all groups involved left frontal and temporal as well as bilateral medial frontal, cingulate, occipital, basal ganglia, and cerebellar regions. Men showed greater left frontal activation than women in both menstrual cycle phases. Women yielded high correlations of left prefrontal activation with estradiol in the midluteal phase and with progesterone in both phases. Testosterone levels correlated highly with left prefrontal activation in all three groups. In all, we describe a cerebral network involved in semantic processing and demonstrate that it is significantly affected by gender and sex steroid hormones.

Functional anatomy of visuo-spatial working memory during mental rotation is influenced by sex, menstrual cycle, and sex steroid hormones.

Recent observations indicate that sex and level of steroid hormones may influence cortical networks associated with specific cognitive functions, in particular visuo-spatial abilities. The present study probed the influence of sex, menstrual cycle, and sex steroid hormones on 3D mental rotation and brain function using 3-T fMRI. Twelve healthy women and 12 men were investigated. Menstrual cycle and hormone levels were assessed. The early follicular and midluteal phase of the menstrual cycle were chosen to examine short-term cyclical changes. Parietal and frontal areas were activated during mental rotation in both sexes. Significant differences between men and women were revealed in both phases of menstrual cycle. In men we observed a significant correlation of activation levels with testosterone levels in the left parietal lobe (BA 40). In women, a cycle-dependent correlation pattern was observed for testosterone: brain activation correlated with this male hormone only during the early follicular phase. In both cycle phases females' brain activation was significantly correlated with estradiol in frontal and parietal areas. Our study provides evidence that fMRI-related activity during performance of cognitive tasks varies across sex and phases of the menstrual cycle. The variation might be partly explained by better task performance in men, but our results indicate that further explanations like basic neuronal or neurovascular effects modulated by steroid hormones must be considered. Both estradiol and testosterone levels may influence fMRI signals of cognitive tasks, which should affect selection of subjects for future fMRI studies.

How does the brain accommodate to increased task difficulty in word finding? A functional MRI study.

In functional imaging of the brain, the difficulty of a task may be critical for the pattern of activation. Increased task difficulty could lead to increased activation in task-specific regions or to activation of additional, "compensatory" regions. A previous study with functional transcranial Doppler sonography (fTCD) showed no evidence that increased difficulty in word retrieval leads to a recruitment of areas homologous to language-related regions. The question remains how the brain accommodates increasing task difficulty. Because of limitations of fTCD method, we used functional magnetic resonance imaging (fMRI) in this study. We manipulated word retrieval difficulty in healthy subjects (n = 14) to determine whether the classical language-related brain regions are activated with increasing difficulty in word retrieval. fMRI demonstrated that with increased task difficulty (I) the lateralization of language-associated brain activation remained constant, (II) no additional activation of language-related regions of the dominant hemisphere, nor of homologous regions of the subdominant hemisphere, was evident, (III) additional activation was found in right posterior parietal cortex--typically associated with sustained attention and executive control. Thus, increased difficulty in word retrieval leads to coactivation of distinct brain areas, working together in a large cognitive network, rather than to increased activation of typically language-related areas.

Morphological and orthographic similarity in visual word recognition.

The differential impact of orthographic and morphological relatedness on visual word recognition was investigated in a series of priming experiments in Dutch and German. With lexical decision and naming tasks, repetition priming and contiguous priming procedures, and masked and unmasked prime presentation, a pattern of results emerged with qualitative differences between the effects of morphological and form relatedness. With lexical decision, mere orthographic similarity between primes and targets (e.g., keller-KELLER, cellar-ladle) produced negative effects, whereas morphological relatedness (e.g., kellen-KELLE, ladles-ladle) consistently resulted in facilitation. With the naming task, positive priming effects were found for morphological as well as for mere form similarity. On the basis of these results, a model of the lexicon is proposed in which information about word form is represented separately from morphological structure and in which processing at the form level is characterized in terms of activation of, and competition between, form-related entries.

The locus of the effects of sentential-semantic context in spoken-word processing.

Models of word recognition differ with respect to where the effects of sentential-semantic context are to be located. Using a crossmodal priming technique, this research investigated the availability of lexical entries as a function of stimulus information and contextual constraint. To investigate the exact locus of the effects of sentential contexts, probes that were associatively related to contextually appropriate and inappropriate words were presented at various positions before and concurrent with the spoken word. The results show that sentential contexts do not preselect a set of contextually appropriate words before any sensory information about the spoken word is available. Moreover, during lexical access, defined here as the initial contact with lexical entries and their semantic and syntactic properties, both contextually appropriate and inappropriate words are activated. Contextual effects are located after lexical access, at a point in time during word processing where the sensory input by itself is still insufficiently informative to disambiguate between the activated entries. This suggests that sentential-semantic contexts have their effects during the process of selecting one of the activated candidates for recognition.