Implicit assumptions and interpretation bias in youth with severe, chronic social phobia.

Interpretation bias and dysfunctional social assumptions are proposed to play a pivotal role in the development and maintenance of social phobia (SP), especially in youth. In this study, we aimed to investigate disorder-specific implicit assumptions of rejection and implicit interpretation bias in youth with severe, chronic SP and healthy controls (CG). Twenty-seven youth with SP in inpatient/day-care treatment (M age = 15.6 years, 74% female) and 24 healthy controls (M age = 15.7 years, 54% female) were included. The Implicit Association Test (IAT) and the Affect Misattribution Procedure (AMP) were completed to assess implicit assumptions and interpretation bias related to the processing of social and affective stimuli. No group differences were observed for the IAT controlling for depressive symptoms in the analyses. However, group differences were found regarding interpretation bias (p = .017, η2p = .137). Correlations between implicit scores and explicit questionnaire results were medium to large in the SP group (r =|.28| to |.54|, pall ≤ .05), but lower in the control group (r =|.04| to |.46|, pall ≤ .05). Our results confirm the finding of an interpretation bias in youth SP, especially regarding the implicit processing of faces, whereas implicit dysfunctional social assumptions of being rejected do not seem to be specific for SP. Future research should investigate the causal relationship of assumptions/interpretation bias and SP.

Test-retest reliability of prepulse inhibition (PPI) and PPI correlation with working memory.

OBJECTIVE: Sensorimotor gating is experimentally operationalized by the prepulse inhibition (PPI) of the startle response (SR). Previous studies suggest high test-retest reliability of PPI and potential correlation with working memory (WM). Here, we aimed to validate and extend the test-retest reliability of PPI in healthy humans and its correlation with WM performance. METHODS: We applied an acoustic startle PPI paradigm with four different prepulse intensities (64, 68, 72 and 76 dB) and two different WM tasks [n-back, change detection task (CDT)] in a group of 26 healthy adults (final sample size n = 23). To assess test-retest reliability, we performed all tests on two separate days ~27 days (range: 21-32 days) apart. RESULTS: We were able to confirm high test-retest reliability of the PPI with a mean intraclass correlation (ICC) of > 0.80 and significant positive correlation of PPI with n-back but not with CDT performance. Detailed analysis showed that PPI across all prepulse intensities significantly correlated with both the 2-back and 0-back conditions, suggesting regulation by cross-conditional processes (e.g. attention). However, when removing the 0-back component from the 2-back data, we found a specific and significant correlation with WM for the 76-dB PPI condition. CONCLUSION: With the present study, we were able to confirm the high test-retest reliability of the PPI in humans and could validate and expand on its correlation with WM performance.

Reliable and efficient recording of the error-related negativity with a speeded Eriksen Flanker Task.

OBJECTIVE: There is accumulating evidence that the error-related negativity (ERN), an event-related potential elicited after erroneous actions, is altered in different psychiatric disorders and may help to guide treatment options. Thus, the ERN is a promising candidate as a psychiatric biomarker. Basic methodological requirements for a biomarker are that their measurements are standardised and reliable. The aim of the present study was to establish ERN acquisition in a reliable, time-efficient and patient-friendly way for use in clinical practice. METHODS: Healthy subjects performed a speeded Eriksen Flanker Task that increases the number of errors. In a test-retest design (N = 14) with two sessions separated by 28 days we assessed the reliability of the ERN. To ensure external validity, we aimed to replicate previously reported correlation patterns of ERN amplitude with (A) number of errors and (B) negative affect. In order to optimise the clinical use of the task, we determined to which extent the task can be shortened while keeping reliability >0.80. RESULTS: We found excellent reliability of the ERN (intraclass correlation coefficients = 0.806-0.947) and replicated ERN correlation patterns. The task can be halved to a patient-friendly length of 200 trials (recorded in 8 min) keeping reliability >0.80. CONCLUSIONS: The modified task provides reliable and efficient recording of the ERN, facilitating its use as a psychiatric biomarker.

Predictable information in neural signals during resting state is reduced in autism spectrum disorder.

The neurophysiological underpinnings of the nonsocial symptoms of autism spectrum disorder (ASD) which include sensory and perceptual atypicalities remain poorly understood. Well-known accounts of less dominant top-down influences and more dominant bottom-up processes compete to explain these characteristics. These accounts have been recently embedded in the popular framework of predictive coding theory. To differentiate between competing accounts, we studied altered information dynamics in ASD by quantifying predictable information in neural signals. Predictable information in neural signals measures the amount of stored information that is used for the next time step of a neural process. Thus, predictable information limits the (prior) information which might be available for other brain areas, for example, to build predictions for upcoming sensory information. We studied predictable information in neural signals based on resting-state magnetoencephalography (MEG) recordings of 19 ASD patients and 19 neurotypical controls aged between 14 and 27 years. Using whole-brain beamformer source analysis, we found reduced predictable information in ASD patients across the whole brain, but in particular in posterior regions of the default mode network. In these regions, epoch-by-epoch predictable information was positively correlated with source power in the alpha and beta frequency range as well as autocorrelation decay time. Predictable information in precuneus and cerebellum was negatively associated with nonsocial symptom severity, indicating a relevance of the analysis of predictable information for clinical research in ASD. Our findings are compatible with the assumption that use or precision of prior knowledge is reduced in ASD patients.

Maturation of interhemispheric signal propagation in autism spectrum disorder and typically developing controls: a TMS-EEG study.

Brain maturation from childhood to adulthood is associated with changes in structural and functional connectivity between remote brain regions. Altered connectivity plays an important role in the pathology of autism spectrum disorder (ASD), a severe neurodevelopmental disorder. ASD is associated with abnormal brain development and structurally altered interhemispheric connections. Cortico-cortical connectivity can be studied by a combination of transcranial magnetic stimulation (TMS) with concurrent EEG (TMS-EEG). TMS-evoked Interhemispheric Signal Propagation (ISP) is a correlate of interhemispheric connectivity related to the microstructure of the corpus callosum (CC). We used TMS-EEG to measure ISP in 22 ASD subjects (10-21 years) and 22 typically developing control subjects (9-19 years). We expected (1) maturational changes of ISP from childhood to young adulthood and also (2) reduced interhemispheric signal transfer in ASD. ISP was positively correlated with age in both ASD and typically developing control subjects. No difference in ISP between ASD and typically developing controls was found. Our findings demonstrate maturation of effective interhemispheric connectivity during adolescence. As ISP is related to the microstructure of the CC, the developmental change of ISP likely reflects maturation of the CC during the second life decade. The results support ISP as a valid parameter reflecting functional interhemispheric connectivity. Our results do not support a global deficit of interhemispheric connectivity in ASD.

Simple and complex acoustic regularities are encoded at different levels of the auditory hierarchy.

The detection of auditory stimuli that deviate from a simple or complex auditory regularity is reflected by the mismatch negativity component of the human auditory evoked potential. Moreover, simple deviants of an oddball paradigm modulate the preceding middle-latency response of the auditory evoked potential. For the frequency oddball paradigms it has been shown that the Nb wave, at approximately 40 ms from stimulus onset, is enhanced in response to deviant compared with standard stimuli. In this study we tested whether the detection of auditory deviants in a (frequency-location) feature-conjunction paradigm is reflected by modulations of the Na, Pa or Nb wave of healthy human participants. In addition, a frequency oddball paradigm was applied to directly contrast the results of a simple and a complex invariance. Feature-conjunction deviants did not elicit any modulations of the tested middle-latency waves. Deviants of the frequency oddball paradigm, by contrast, elicited an enhancement of the Nb wave, confirming the outcome of precedent studies. In both conditions a significant mismatch negativity component was elicited, which showed larger amplitudes and shorter latencies in the oddball condition than in the feature-conjunction condition. These findings corroborate the idea that simple auditory regularities are encoded upstream of those of more complex auditory features and are in line with the idea of a hierarchically working auditory novelty system.

Reward processing in adolescents with social phobia and depression.

OBJECTIVE: Impaired reward processing has been found in individuals with anxiety, but also major depressive disorder (MDD). Here, we studied neural correlates of reward anticipation and processing in a sample of youth with severe social phobia and comorbid depression (SP/MDD) and investigated the specific contribution of SP and MDD symptoms. METHODS: 15 affected, unmedicated and 25 typically developing (TD) youth completed a monetary gambling task, which included a positive, negative and ambiguous reward condition. Event-related potentials representing cue processing (cue P300), reward anticipation (stimulus preceding negativity, SPN), reward sensitivity (feedback related negativity, FRN) and reward processing (reward P300) were analysed. RESULTS: Reduced amplitudes of the right hemispheric (r)SPN and reward P300 were observed in SP/MDD compared to TD. Within the SP/MDD group SP symptoms correlated with larger rSPN, and FRN amplitudes. MDD symptoms correlated with smaller rSPN and smaller FRN positive-negative difference wave. CONCLUSIONS: Reward anticipation and feedback processing are reduced in SP/MDD. Higher SP symptoms are associated with stronger neural activation during reward anticipation and reward sensitivity. Depressive symptoms are associated with decreased reward anticipation and sensitivity. Findings are in line with the theory of heightened vigilance in anxiety and blunted reward processing due to anhedonia in MDD. SIGNIFICANCE: The study results can inform behavioural interventions for SP and MDD.

Neural Responses to a Working Memory Task in Acute Depressed and Remitted Phases in Bipolar Patients.

(1) Cognitive impairments such as working memory (WM) deficits are amongst the most common dysfunctions characterizing bipolar disorder (BD) patients, severely contributing to functional impairment. We aimed to investigate WM performance and associated brain activation during the acute phase of BD and to observe changes in the same patients during remission. (2) Frontal brain activation was recorded using functional near-infrared spectroscopy (fNIRS) during n-back task conditions (one-back, two-back and three-back) in BD patients in their acute depressive (n = 32) and remitted (n = 15) phases as well as in healthy controls (n = 30). (3) Comparison of BD patients during their acute phase with controls showed a trend (p = 0.08) towards lower dorsolateral prefrontal cortex (dlPFC) activation. In the remitted phase, BD patients showed lower dlPFC and ventrolateral prefrontal cortex (vlPFC) activation (p = 0.02) compared to controls. No difference in dlPFC and vlPFC activation between BD patients' phases was found. (4) Our results showed decreased working memory performance in BD patients during the working memory task in the acute phase of disease. Working memory performance improved in the remitted phase of the disease but was still particularly attenuated for the more demanding conditions.

Euthymic patients with predominantly manic polarity avoid happy faces in a dot probe task.

BACKGROUND: Some studies suggest a mood-congruent attentional bias in bipolar patients. However, for euthymic patients, especially in dependence on the predominant polarity, there is little and inconsistent data. A clearer understanding of emotion-related attentional biases and their relationship to dysfunctional emotion regulation could help improving the diagnostics and treatment of bipolar disorder (BD). Twenty bipolar patients in a depressive state (BP-acute-D), 32 euthymic patients with manic (BP-euth-M) or depressive (BP-euth-D) predominant polarity, and 20 healthy control participants (HC) performed a dot-probe task (DPT) with happy and sad faces presented for 250 ms or 1250 ms in two different runs. Emotion regulation strategies were assessed with two questionnaires. RESULTS: In the short presentation condition of the DPT, BP-euth-M showed less attention for happy faces than HC (p = .03, r = - 0.48). BP-acute-D scored lower in cognitive reappraisal and putting into perspective and higher in suppression, catastrophizing, and rumination than HC. BP-euth-M scored higher in rumination and BP-euth-D lower in putting into perspective and higher in catastrophizing than HC. In BP-euth-D and HC, bias scores for sad faces in the longer presentation condition and reappraisal scores correlated positively. CONCLUSIONS: Results of the DPT suggest an avoidance of happy faces for BP-euth-M which we interpret as a protection mechanism for triggers of mania. That individuals who apply more reappraisal show more selective attention to sad faces could on the one hand reflect a mental effort in reevaluating the sad emotional input and on the other hand a greater tolerance for it.

Deviance-Related Responses along the Auditory Hierarchy: Combined FFR, MLR and MMN Evidence.

The mismatch negativity (MMN) provides a correlate of automatic auditory discrimination in human auditory cortex that is elicited in response to violation of any acoustic regularity. Recently, deviance-related responses were found at much earlier cortical processing stages as reflected by the middle latency response (MLR) of the auditory evoked potential, and even at the level of the auditory brainstem as reflected by the frequency following response (FFR). However, no study has reported deviance-related responses in the FFR, MLR and long latency response (LLR) concurrently in a single recording protocol. Amplitude-modulated (AM) sounds were presented to healthy human participants in a frequency oddball paradigm to investigate deviance-related responses along the auditory hierarchy in the ranges of FFR, MLR and LLR. AM frequency deviants modulated the FFR, the Na and Nb components of the MLR, and the LLR eliciting the MMN. These findings demonstrate that it is possible to elicit deviance-related responses at three different levels (FFR, MLR and LLR) in one single recording protocol, highlight the involvement of the whole auditory hierarchy in deviance detection and have implications for cognitive and clinical auditory neuroscience. Moreover, the present protocol provides a new research tool into clinical neuroscience so that the functional integrity of the auditory novelty system can now be tested as a whole in a range of clinical populations where the MMN was previously shown to be defective.

Ultrafast tracking of sound location changes as revealed by human auditory evoked potentials.

The rapid discrimination of auditory location information enables grouping and selectively attending to specific sound sources. The typical indicator of auditory change detection is the mismatch negativity (MMN) occurring at a latency of about 100-250 ms. However, recent studies have revealed the existence of earlier markers of frequency deviance detection in the middle-latency response (MLR). Here, we measured the MLR and MMN to changes in sound location. Clicks were presented in either the left or right hemifields during oddball (rare 30°-shifts in location), reversed oddball, and control (sounds occurring equiprobably from five locations) conditions. Clicks at deviant locations elicited an MMN and an enhanced Na component of the MLR peaking at 20 ms compared to clicks at standard or control locations. Whereas MMN was not significantly lateralized, the Na effect showed a contralateral dominance. These findings indicate that, also for sound location changes, early detection processes exist upstream of MMN.

Fast detection of unexpected sound intensity decrements as revealed by human evoked potentials.

The detection of deviant sounds is a crucial function of the auditory system and is reflected by the automatically elicited mismatch negativity (MMN), an auditory evoked potential at 100 to 250 ms from stimulus onset. It has recently been shown that rarely occurring frequency and location deviants in an oddball paradigm trigger a more negative response than standard sounds at very early latencies in the middle latency response of the human auditory evoked potential. This fast and early ability of the auditory system is corroborated by the finding of neurons in the animal auditory cortex and subcortical structures, which restore their adapted responsiveness to standard sounds, when a rare change in a sound feature occurs. In this study, we investigated whether the detection of intensity deviants is also reflected at shorter latencies than those of the MMN. Auditory evoked potentials in response to click sounds were analyzed regarding the auditory brain stem response, the middle latency response (MLR) and the MMN. Rare stimuli with a lower intensity level than standard stimuli elicited (in addition to an MMN) a more negative potential in the MLR at the transition from the Na to the Pa component at circa 24 ms from stimulus onset. This finding, together with the studies about frequency and location changes, suggests that the early automatic detection of deviant sounds in an oddball paradigm is a general property of the auditory system.