No abstract

Inhibition of the amygdala slows down acquisition of conditioned eyeblink responses (CRs). Based on the two-stage or two-factor theory of aversive conditioning, amygdala-dependent conditioned fear is a necessary prerequisite to acquire eyeblink CRs, but is no longer needed after eyeblink CRs are attained. According to the sensory gating hypothesis of the amygdala, on the other hand, the amygdala modulates the salience of unconditioned and conditioned stimuli (US and CS) in eyeblink conditioning. We tested these two opposing assumptions in five groups of 20 young and healthy men. On day 1, three groups underwent fear acquisition training followed by acquisition of eyeblink CRs. On the next day (day 2), extinction was tested. In Group 1, fear and eyeblink extinction trials overlapped; in Group 2, fear and eyeblink extinction trials alternated; and in Group 3, fear extinction trials were followed by eyeblink extinction trials. Groups 4 and 5 were control conditions testing fear and eyeblink conditioning only. Preceding fear acquisition training facilitated acquisition of conditioned eyeblinks. Concomitant fear extinction impeded extinction of eyeblink CRs, which was accompanied by increased autonomic responses. Fear extinction, however, was not significantly altered by concomitant eyeblink extinction. Recall of fear CRs on day 2 was facilitated in Group 1 suggesting additive response summation. Findings are difficult to explain with the two-stage theory of aversive conditioning which predicts suppression of conditioned fear once conditioned eyeblinks are acquired. Facilitated acquisition and impeded extinction of eyeblink CRs, however, are in accordance with the sensory gating hypothesis of the amygdala. 4 Significance Statement It has been proposed that conditioned eyeblink responses, once established, may help to facilitate fear extinction. This has potential clinical relevance because extinction of learned fear responses is at the core of exposure therapy in the treatment of many anxiety disorders. Based on our findings this proposal has to be rejected. Our findings do not support the twostage theory of aversive conditioning which predicts suppression of conditioned fear once conditioned eyeblinks are acquired. Rather, we found that concomitant extinction of conditioned eyeblink and fear responses facilitated recall of conditioned fear responses, and impeded extinction of conditioned eyeblinks. Findings are best explained by increased salience of conditioned stimuli, and therefore support the sensory gating hypothesis of the amygdala.

Introduction: Language disorders - disorganized and incoherent speech in particular - are distinctive features of schizophrenia. Natural language processing (NLP) offers automated measures of incoherent speech as promising markers for schizophrenia. However, the scientific and clinical impact of NLP markers depends on their generalizability across contexts, samples, and languages, which we systematically assessed in the present study relying on a large, novel, cross-linguistic corpus. Methods: We collected a Danish (DK), German (GE), and Chinese (CH) cross-linguistic dataset involving transcripts from 187 participants with schizophrenia (111DK, 25GE, 51CH) and 200 matched controls (129DK, 29GE, 42CH) performing the Animated Triangle task. Fourteen previously published NLP coherence measures were calculated, and between-groups differences and association with symptoms were tested for cross-linguistic generalizability. Results: One coherence measure robustly generalized across samples and languages. We found several language-specific effects, some of which partially replicated previous findings (lower coherence in German and Chinese patients), while others did not (higher coherence in Danish patients). We found several associations between symptoms and measures of coherence, but the effects were generally inconsistent across languages and rating scales. Conclusions: Using a cumulative approach, we have shown that NLP findings of reduced semantic coherence in schizophrenia have limited generalizability across different languages, samples, and measures. We argue that several factors such as sociodemographic and clinical heterogeneity, cross-linguistic variation, and the different NLP measures reflecting different clinical aspects may be responsible for this variability. Future studies should take this variability into account in order to develop effective clinical applications targeting different patient populations.