Functional network interactions in patients with schizophrenia with persistent auditory verbal hallucinations: A multimodal MRI fusion approach using three-way pICA.

Over the last decade, there have been an increasing number of functional magnetic resonance imaging (fMRI) studies examining brain activity in schizophrenia (SZ) patients with persistent auditory verbal hallucinations (AVH) using either task-based or resting-state fMRI (rs-fMRI) paradigms. Such data have been conventionally collected and analyzed as distinct modalities, disregarding putative crossmodal interactions. Recently, it has become possible to incorporate two or more modalities in one comprehensive analysis to uncover hidden patterns of neural dysfunction not sufficiently captured by separate analysis. A novel multivariate fusion approach to multimodal data analysis, i.e., parallel independent component analysis (pICA), has been previously shown to be a powerful tool in this regard. We utilized three-way pICA to study covarying components among fractional amplitude of low-frequency fluctuations (fALFF) for rs-MRI and task-based activation computed from an alertness and a working memory (WM) paradigm of 15 SZ patients with AVH, 16 non-hallucinating SZ patients (nAVH), and 19 healthy controls (HC). The strongest connected triplet (false discovery rate (FDR)-corrected pairwise correlations) comprised a frontostriatal/temporal network (fALFF), a temporal/sensorimotor network (alertness task), and a frontoparietal network (WM task). Frontoparietal and frontostriatal/temporal network strength significantly differed between AVH patients and HC. Phenomenological features such as omnipotence and malevolence of AVH were associated with temporal/sensorimotor and frontoparietal network strength. The transmodal data confirm a complex interplay of neural systems subserving attentional processes and cognitive control interacting with speech and language processing networks. In addition, the data emphasize the importance of sensorimotor regions modulating specific symptom dimensions of AVH.

Structure/function interrelationships in patients with schizophrenia who have persistent auditory verbal hallucinations: A multimodal MRI study using parallel ICA.

There is accumulating neuroimaging evidence for both structural and functional abnormalities in schizophrenia patients with persistent auditory verbal hallucinations (AVH). So far, the direct interrelationships between altered structural and functional changes underlying AVH are unknown. Recently, it has become possible to reveal hidden patterns of neural dysfunction not sufficiently captured by separate analysis of these two modalities. A data-driven fusion method called parallel independent component analysis (p-ICA) is able to identify maximally independent components of each imaging modality as well as the link between them. In the present study, we utilized p-ICA to study covarying components among gray matter volume maps computed from structural MRI (sMRI) and fractional amplitude of low-frequency fluctuations (fALFF) maps computed from resting-state functional MRI (rs-fMRI) data of 15 schizophrenia patients with AVH, 16 non-hallucinating schizophrenia patients (nAVH), and 19 healthy controls (HC). We found a significant correlation (r = 0.548, n = 50, p < .001) between a sMRI component and a rs-fMRI component, which was significantly different between the AVH and non AVH group (nAVH). The rs-fMRI component comprised temporal cortex and cortical midline regions, the sMRI component included predominantly fronto-temporo-parietal regions. Distinct clinical features, as measured by the Psychotic Symptoms Rating Scale (PSYRATS), were associated with two different modality specific rs-fMRI components. There was a significant correlation between a predominantly parietal resting-state network and the physical dimension of PSYRATS and the posterior cingulate/temporal cortex network and the emotional dimension of PSYRATS. These data suggest AVH-specific interrelationships between intrinsic network activity and GMV, together with modality-specific associations with distinct symptom dimensions of AVH.

Positivity-approach training for depressive symptoms: A randomized controlled trial.

OBJECTIVE: Depression is highly comorbid and depressive symptoms are very common. Symptom severity adversely affects treatment outcome and later health status. Established interventions for depression leave ample room for improvement. Short interventions that target specific vulnerabilities emerge as plausible augmentation strategies. In this study, we tested the efficacy of a computerized general positivity-approach training and its effect on depressive symptoms. METHODS: Patients (N = 240) with various diagnoses of mental disorders who received treatment-as-usual in an inpatient setting were randomly assigned to also receive either 4 sessions of a positivity-approach training or 4 sessions of sham training. Depression severity was assessed at baseline and post-treatment. Training data were analyzed for a subset of 111 patients. RESULTS: Depressive symptoms were reduced more after positivity-approach training than after sham training. Initial depression symptom severity moderated the intervention effects, such that approach tendencies and depression symptoms were only affected positively among patients with higher levels of initial depression symptom severity. CONCLUSIONS: The findings provide preliminary support for positivity-approach training as an add-on treatment option for depressive symptoms.

Cortical folding abnormalities in patients with schizophrenia who have persistent auditory verbal hallucinations.

In schizophrenia temporal cortical volume loss differs between patients presenting with persistent auditory verbal hallucinations (pAVH) in contrast to those without hallucinatory symptoms (nAVH). However, it is unknown whether this deficit reflects a neural signature of neurodevelopmental origin or if abnormal temporal cortical volume is reflective of factors which may be relevant at later stages of the disorder. Here, we tested the hypothesis that local gyrification index (LGI) in regions of the temporal cortex differs between patients with pAVH (n=10) and healthy controls (n=14), and that abnormal temporal LGI discriminates between pAVH and nAVH (n=10). Structural magnetic resonance imaging at 3T along with surface-based data analysis methods was used. Contrary to our expectations, patients with pAVH showed lower LGI in Broca´s region compared to both healthy persons and nAVH. Compared to nAVH, those individuals presenting with pAVH also showed lower LGI in right Broca's homologue and right superior middle frontal cortex, together with increased LGI in the precuneus and superior parietal cortex. Regions with abnormal LGI common to both patient samples were found in anterior cingulate and superior frontal areas. Inferior cortical regions exhibiting abnormal LGI in pAVH patients were associated with overall symptom load (BPRS), but not with measures of AVH symptom severity. The pattern of abnormal cortical folding in this sample suggests a neurodevelopmental signature in Broca's region, consistent with current AVH models emphasizing the pivotal role of language circuits and inner speech. Temporal cortical deficits may characterize patients with pAVH during later stages of the disorder.

Noninvasive brain stimulation for the treatment of auditory verbal hallucinations in schizophrenia: methods, effects and challenges.

This mini-review focuses on noninvasive brain stimulation techniques as an augmentation method for the treatment of persistent auditory verbal hallucinations (AVH) in patients with schizophrenia. Paradigmatically, we place emphasis on transcranial magnetic stimulation (TMS). We specifically discuss rationales of stimulation and consider methodological questions together with issues of phenotypic diversity in individuals with drug-refractory and persistent AVH. Eventually, we provide a brief outlook for future investigations and treatment directions. Taken together, current evidence suggests TMS as a promising method in the treatment of AVH. Low-frequency stimulation of the superior temporal cortex (STC) may reduce symptom severity and frequency. Yet clinical effects are of relatively short duration and effect sizes appear to decrease over time along with publication of larger trials. Apart from considering other innovative stimulation techniques, such as transcranial Direct Current Stimulation (tDCS), and optimizing stimulation protocols, treatment of AVH using noninvasive brain stimulation will essentially rely on accurate identification of potential responders and non-responders for these treatment modalities. In this regard, future studies will need to consider distinct phenotypic presentations of AVH in patients with schizophrenia, together with the putative functional neurocircuitry underlying these phenotypes.

Attention bias modification in specific fears: Spiders versus snakes.

BACKGROUND AND OBJECTIVES: Attention Bias Modification (ABM) is used to manipulate attention biases in anxiety disorders. It has been successful in reducing attention biases and anxious symptoms in social anxiety and generalized anxiety, but not yet in specific fears and phobias. METHODS: We designed a new version of the dot-probe training task, aiming to train fearful participants' attention away from or towards pictures of threatening stimuli. Moreover, we studied whether the training also affected participants' avoidance behavior and their physical arousal upon being confronted with a real threat object. RESULTS: In Experiment 1, students with fear of spiders were trained. We found that the attention manipulation was successful, but the training failed to affect behavior or arousal. In Experiment 2, the same procedure was used on snake-fearful students. Again, attention was trained in the expected directions. Moreover, participants whose attention had been trained away from snakes showed lower physiological arousal upon being confronted with a real snake. LIMITATIONS: The study involved healthy students with normal distribution of the fear of spider/snake. Future research with clinical sample could help with determining the generalizability of the current findings. CONCLUSIONS: The effect of ABM on specific phobia is still in question. The finding in the present study suggested the possibility to alter attentional bias with a dot-probe task with general positive stimuli and this training could even affect the behavior while encountering a real threat.

Studies to improve the extraction yields of incurred pesticide residues from crops using the QuEChERS method.

The influence of various factors on the extraction yields of incurred pesticides from crops using the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method was thoroughly studied. These factors included extraction time, extraction temperature, agitation approach, and in the case of dry commodities, sample comminution grade. Extraction yields increased with increasing extraction time, eventually reaching a plateau. Extraction temperature also played an important role in speeding up extraction, whereas the agitation approach had little influence. Based on our results we propose an extension of the first QuEChERS extraction step to 15 min when using deep frozen samples and to 2 min when using samples at ambient temperature. The extension of the second QuEChERS extraction step was shown to be less effective. Mechanical shakers can be used to facilitate extraction. This minor modification of the QuEChERS method does not alter its simple structure nor increase the manual labor and costs involved. It was further shown that the extraction yields of incurred pesticides strongly depend on their physiochemical properties, with lipophilic pesticides typically showing stronger retardation and higher yields when extraction time and/or temperature are increased. The impact of prolonging the first QuEChERS extraction step from 1 to 15 min on the extraction yields of incurred pesticides from frozen samples was studied on 132 real samples containing 85 different pesticides throughout the polarity range and representing 55 different commodity types. Out of the 408 pesticide/commodity combinations studied, 34% showed >25% yield increases when the extraction time was extended to 15 min. Also, more than half of the 132 studied samples contained at least one incurred pesticide for which the extraction yield increased by more than 25%. Similar extraction retardation effects were also observed for spiked pesticides but only if these were spiked on commodities with intact surface, not to homogenates thereof.