Humans integrate information communicated by speech and gestures. Functional magnetic resonance imaging (fMRI) studies suggest that the posterior superior temporal sulcus (STS) and adjacent gyri are ...relevant for multisensory integration. However, a connectivity model representing this essential combinatory process is still missing. Here, we used dynamic causal modeling for fMRI to analyze the effective connectivity pattern between middle temporal gyrus (MTG), occipital cortex (OC) and STS associated with auditory verbal, visual gesture-related, and integrative processing, respectively, to unveil the neural mechanisms underlying integration of intrinsically meaningful gestures (e.g., “Thumbs-up gesture”) and corresponding speech.
20 participants were presented videos of an actor either performing intrinsic meaningful gestures in the context of German or Russian sentences, or speaking a German sentence without gesture, while performing a content judgment task.
The connectivity analyses resulted in a winning model that included bidirectional intrinsic connectivity between all areas. Furthermore, the model included modulations of both connections to the STS (OC→STS; MTG→STS), and non-linear modulatory effects of the STS on bidirectional connections between MTG and OC. Coupling strength in the occipital pathway (OC→STS) correlated with gesture related advantages in task performance, whereas the temporal pathway (MTG→STS) correlated with performance in the speech only condition. Coupling between MTG and OC correlated negatively with subsequent memory performance for sentences of the Gesture-German condition.
Our model provides a first step towards a better understanding of speech-gesture integration on network level. It corroborates the importance of the STS during audio-visual integration by showing that this region inhibits direct auditory-visual coupling.
Display omitted
•Humans integrate information communicated by speech and gestures.•The superior temporal sulcus (STS) is relevant for multisensory integration.•We used dynamic causal modeling to unveil the neural mechanisms of integration.•The STS received auditory/visual input and reduced direct auditory-visual coupling.•Better understanding of speech-gesture integration on network level.
•We developed a new sequential-set fear conditioning paradigm for EEG research.•This paradigm allows to uncover the learning curve of neural responses to threat.•Short-, mid-, and long-latency ERP ...effects grew from early to late conditioning.•Long-latency ERPs gradually diminished throughout extinction.
Electrophysiological studies in rodents allow recording neural activity during threats with high temporal and spatial precision. Although fMRI has helped translate insights about the anatomy of underlying brain circuits to humans, the temporal dynamics of neural fear processes remain opaque and require EEG. To date, studies on electrophysiological brain signals in humans have helped to elucidate underlying perceptual and attentional processes, but have widely ignored how fear memory traces evolve over time. The low signal-to-noise ratio of EEG demands aggregations across high numbers of trials, which will wash out transient neurobiological processes that are induced by learning and prone to habituation. Here, our goal was to unravel the plasticity and temporal emergence of EEG responses during fear conditioning. To this end, we developed a new sequential-set fear conditioning paradigm that comprises three successive acquisition and extinction phases, each with a novel CS+/CS- set. Each set consists of two different neutral faces on different background colors which serve as CS+ and CS-, respectively. Thereby, this design provides sufficient trials for EEG analyses while tripling the relative amount of trials that tap into more transient neurobiological processes. Consistent with prior studies on ERP components, data-driven topographic EEG analyses revealed that ERP amplitudes were potentiated during time periods from 33–60 ms, 108–200 ms, and 468–820 ms indicating that fear conditioning prioritizes early sensory processing in the brain, but also facilitates neural responding during later attentional and evaluative stages. Importantly, averaging across the three CS+/CS- sets allowed us to probe the temporal evolution of neural processes: Responses during each of the three time windows gradually increased from early to late fear conditioning, while long-latency (460–730 ms) electrocortical responses diminished throughout fear extinction. Our novel paradigm demonstrates how short-, mid-, and long-latency EEG responses change during fear conditioning and extinction, findings that enlighten the learning curve of neurophysiological responses to threat in humans.
Display omitted
Adapting threat-related memories towards changing environments is a fundamental ability of organisms. One central process of fear reduction is suggested to be extinction learning, experimentally ...modeled by extinction training that is repeated exposure to a previously conditioned stimulus (CS) without providing the expected negative consequence (unconditioned stimulus, US). Although extinction training is well investigated, evidence regarding process-related changes in neural activation over time is still missing. Using optimized delayed extinction training in a multicentric trial we tested whether: 1) extinction training elicited decreasing CS-specific neural activation and subjective ratings, 2) extinguished conditioned fear would return after presentation of the US (reinstatement), and 3) results are comparable across different assessment sites and repeated measures. We included 100 healthy subjects (measured twice, 13-week-interval) from six sites. 24 h after fear acquisition training, extinction training, including a reinstatement test, was applied during fMRI. Alongside, participants had to rate subjective US-expectancy, arousal and valence. In the course of the extinction training, we found decreasing neural activation in the insula and cingulate cortex as well as decreasing US-expectancy, arousal and negative valence towards CS+. Re-exposure to the US after extinction training was associated with a temporary increase in neural activation in the anterior cingulate cortex (exploratory analysis) and changes in US-expectancy and arousal ratings. While ICCs-values were low, findings from small groups suggest highly consistent effects across time-points and sites. Therefore, this delayed extinction fMRI-paradigm provides a solid basis for the investigation of differences in neural fear-related mechanisms as a function of anxiety-pathology and exposure-based treatment.
•Data-driven, multivariate statistical approach for structural MRI data.•Identification of gyrification cluster patterns beyond diagnostic categories.•Data-driven subgroups are discriminative in ...transdiagnostic disease risk factors.•Using DSM diagnoses had little power in discriminating global gyrification patterns.
Multivariate data-driven statistical approaches offer the opportunity to study multi-dimensional interdependences between a large set of biological parameters, such as high-dimensional brain imaging data. For gyrification, a putative marker of early neurodevelopment, direct comparisons of patterns among multiple psychiatric disorders and investigations of potential heterogeneity of gyrification within one disorder and a transdiagnostic characterization of neuroanatomical features are lacking.
In this study we used a data-driven, multivariate statistical approach to analyze cortical gyrification in a large cohort of N = 1028 patients with major psychiatric disorders (Major depressive disorder: n = 783, bipolar disorder: n = 129, schizoaffective disorder: n = 44, schizophrenia: n = 72) to identify cluster patterns of gyrification beyond diagnostic categories.
Cluster analysis applied on gyrification data of 68 brain regions (DK-40 atlas) identified three clusters showing difference in overall (global) gyrification and minor regional variation (regions). Newly, data-driven subgroups are further discriminative in cognition and transdiagnostic disease risk factors.
Results indicate that gyrification is associated with transdiagnostic risk factors rather than diagnostic categories and further imply a more global role of gyrification related to mental health than a disorder specific one. Our findings support previous studies highlighting the importance of association cortices involved in psychopathology. Explorative, data-driven approaches like ours can help to elucidate if the brain imaging data on hand and its a priori applied grouping actually has the potential to find meaningful effects or if previous hypotheses about the phenotype as well as its grouping have to be revisited.
Speech is a promising biomarker for schizophrenia spectrum disorder (SSD) and major depressive disorder (MDD). This proof of principle study investigates previously studied speech acoustics in ...combination with a novel application of voice pathology features as objective and reproducible classifiers for depression, schizophrenia, and healthy controls (HC). Speech and voice features for classification were calculated from recordings of picture descriptions from 240 speech samples (20 participants with SSD, 20 with MDD, and 20 HC each with 4 samples). Binary classification support vector machine (SVM) models classified the disorder groups and HC. For each feature, the permutation feature importance was calculated, and the top 25% most important features were used to compare differences between the disorder groups and HC including correlations between the important features and symptom severity scores. Multiple kernels for SVM were tested and the pairwise models with the best performing kernel (3-degree polynomial) were highly accurate for each classification: 0.947 for HC vs. SSD, 0.920 for HC vs. MDD, and 0.932 for SSD vs. MDD. The relatively most important features were measures of articulation coordination, number of pauses per minute, and speech variability. There were moderate correlations between important features and positive symptoms for SSD. The important features suggest that speech characteristics relating to psychomotor slowing, alogia, and flat affect differ between HC, SSD, and MDD.
Temporal neural synchrony disruption can be linked to a variety of symptoms of major depressive disorder (MDD), including mood rigidity and the inability to break the cycle of negative emotion or ...attention biases. This might imply that altered dynamic neural synchrony may play a role in the persistence and exacerbation of MDD symptoms. Our study aimed to investigate the changes in whole-brain dynamic patterns of the brain functional connectivity and activity related to depression using the hidden Markov model (HMM) on resting-state functional magnetic resonance imaging (rs-fMRI) data. We compared the patterns of brain functional dynamics in a large sample of 314 patients with MDD (65.9% female; age (mean ± standard deviation): 35.9 ± 13.4) and 498 healthy controls (59.4% female; age: 34.0 ± 12.8). The HMM model was used to explain variations in rs-fMRI functional connectivity and averaged functional activity across the whole-brain by using a set of six unique recurring states. This study compared the proportion of time spent in each state and the average duration of visits to each state to assess stability between different groups. Compared to healthy controls, patients with MDD showed significantly higher proportional time spent and temporal stability in a state characterized by weak functional connectivity within and between all brain networks and relatively strong averaged functional activity of regions located in the somatosensory motor (SMN), salience (SN), and dorsal attention (DAN) networks. Both proportional time spent and temporal stability of this brain state was significantly associated with depression severity. Healthy controls, in contrast to the MDD group, showed proportional time spent and temporal stability in a state with relatively strong functional connectivity within and between all brain networks but weak averaged functional activity across the whole brain. These findings suggest that disrupted brain functional synchrony across time is present in MDD and associated with current depression severity.
Integrating visual and auditory information during gesture-speech integration (GSI) is important for successful social communication, which is often impaired in schizophrenia. Several studies ...suggested the posterior superior temporal sulcus (pSTS) to be a relevant multisensory integration site. However, intact STS activation patterns were often reported in patients. Thus, here we used Dynamic Causal Modelling (DCM) to analyze whether information processing in schizophrenia spectrum disorders (SSD) is impaired during GSI on network level.
We investigated GSI in three different samples. First, we replicated a recently published connectivity model for GSI in a healthy subject group (n = 19). Second, we investigated differences between patients with SSD and a matched healthy control group (n = 17 each). Participants were presented videos of an actor performing intrinsically meaningful gestures accompanied by spoken sentences in German or Russian, or just telling a German sentence without gestures.
Across all groups, fMRI analyses revealed similar activation patterns, and DCM analyses resulted in the same winning model for GSI. This finding directly replicates previous results. However, patients revealed significantly reduced connectivity in the verbal pathway (from left middle temporal gyrus (MTG) to left STS). The clinical significance of this connection is supported by its correlations with the severity of concretism and a subscale of negative symptoms (SANS).
Our model confirms the importance of the pSTS as integration site during audio-visual integration. Patients showed generally intact connectivity during GSI, but revealed impaired information transfer via the verbal pathway. This might be the basis of interpersonal communication problems in patients with SSD.
Negative stressful life events and deprivation of social support play critical roles in the development and maintenance of major depressive disorder (MDD). The present study aimed to investigate in a ...large sample of patients with MDD and healthy control participants (HCs) whether these effects are also reflected in white matter (WM) integrity.
In this diffusion tensor imaging study, 793 patients with MDD and 793 age- and sex-matched HCs were drawn from the Marburg-Münster Affective Disorders Cohort Study (MACS) and completed the Life Events Questionnaire (LEQ) and Social Support Questionnaire (SSQ). Generalized linear models were performed to test voxelwise associations between fractional anisotropy (FA) and diagnosis (analysis 1), LEQ (analysis 2), and SSQ (analysis 3). We examined whether SSQ interacts with LEQ on FA or is independently associated with improved WM integrity (analysis 4).
Patients with MDD showed lower FA in several frontotemporal association fibers compared with HCs (pTFCE-FWE = .028). Across both groups, LEQ correlated negatively with FA in widely distributed WM tracts (pTFCE-FWE = .023), while SSQ correlated positively with FA in the corpus callosum (pTFCE-FWE = .043). Modeling the combined association of both variables on FA revealed significant—and antagonistic—main effects of LEQ (pTFCE-FWE = .031) and SSQ (pTFCE-FWE = .037), but no interaction of SSQ × LEQ.
Our results indicate that negative stressful life events and social support are both related to WM integrity in opposing directions. The associations did not differ between patients with MDD and HCs, suggesting more general, rather than depression-specific, mechanisms. Furthermore, social support appears to contribute to improved WM integrity independent of stressful life events.
Depressive symptoms seem to be interrelated in a complex and self-reinforcing way. To gain a better understanding of this complexity, the inclusion of theoretically relevant constructs (such as risk ...and protective factors) offers a comprehensive view into the complex mechanisms underlying depression.
Cross-sectional data from individuals diagnosed with a major depressive disorder (N = 986) and healthy controls (N = 1049) were analyzed. Participants self-reported their depressive symptoms, as well as several risk factors and protective factors. Regularized partial correlation networks were estimated for each group and compared using a network comparison test.
Symptoms of depression were more strongly connected in the network of depressed patients than in healthy controls. Among the risk factors, perceived stress, the experience of negative life events, emotional neglect, and emotional abuse were the most centrally embedded in both networks. However, the centrality of risk factors did not significantly differ between the two groups. Among the protective factors, social support, personal competence, and acceptance were the most central in both networks, where the latter was significantly more strongly associated with the symptom of self-hate in depressed patients.
The network analysis revealed that key symptoms of depression were more strongly connected for depressed patients than for healthy controls, and that risk and protective factors play an important role, particularly perceived stress in both groups and an accepting attitude for depressed patients. However, the purpose of this study is hypothesis generating and assisting in the potential selection of non-symptom nodes for future research.
•Symptoms of depression are interrelated in a complex and self-reinforcing way.•The inclusion of risk and protective factors offers a more comprehensive view into depression.•Key symptoms of depression were indecisiveness and lack of satisfaction.•Perceived stress plays an important role in healthy controls and depressed patients.•An accepting attitude seems especially beneficial for depressed patients.
PDF
