"Seeing Rain": Integrating phenomenological and Bayesian predictive coding approaches to visual hallucinations and self-disturbances (Ichstörungen) in schizophrenia.

We present a schizophrenia patient who reports "seeing rain" with attendant somatosensory features which separate him from his surroundings. Because visual/multimodal hallucinations are understudied in schizophrenia, we examine a case history to determine the role of these hallucinations in self-disturbances (Ichstörungen). Developed by the early Heidelberg School, self-disturbances comprise two components: 1. The self experiences its own automatic processing as alien to self in a split-off, "doubled-I." 2. In "I-paralysis," the disruption to automatic processing is now outside the self in omnipotent agents. Self-disturbances (as indicated by visual/multimodal hallucinations) involve impairment in the ability to predict moment-to-moment experiences in the ongoing perception-action cycle. The phenomenological approach to subjective experience of self-disturbances complements efforts to model psychosis using the computational framework of hierarchical predictive coding. We conclude that self-disturbances play an adaptive, compensatory role following the uncoupling of perception and action, and possibly, other low-level perceptual anomalies.

Sustained effects of corrupted feedback on perceptual inference.

Feedback is central to most forms of learning, and its reliability is therefore critical. Here, we investigated the effects of corrupted, and hence unreliable, feedback on perceptual inference. Within the framework of Bayesian inference, we hypothesised that corrupting feedback in a demanding perceptual task would compromise sensory information processing and bias inference towards prior information if available. These hypotheses were examined by a simulation and in two behavioural experiments with visual detection (experiment 1) and discrimination (experiment 2) tasks. Both experiments consisted of two sessions comprising intervention runs with either corrupted or uncorrupted (correct) feedback, and pre- and post-intervention tests to assess the effects of feedback. In the tests alone, additional prior beliefs were induced through predictive auditory cues to assess sustained effects of feedback on the balance between sensory evidence and prior beliefs. Both experiments and the simulation showed the hypothesised decrease in performance and increased reliance on prior beliefs after corrupted but not uncorrupted feedback. Exploratory analyses indicated reduced confidence regarding perceptual decisions during delivery of corrupted feedback. Our results suggest that corrupted feedback on perceptual decisions leads to sustained changes in perceptual inference, characterised by a shift from sensory likelihood to prior beliefs when those are accessible.

Efficacy of inpatient psychotherapy for major depressive disorder: a meta-analysis of controlled trials.

OBJECTIVE: This meta-analysis investigates the efficacy of inpatient psychotherapy in major depressive disorders compared to control conditions. METHODS: In total, 14 studies were entered into the meta-analysis with a total of 1.080 patients. Primary outcome was the standardized mean differences in self-rated depression outcomes. A priori planned subgroup analyses included the influence of different control conditions: (a) no psychiatric inpatient treatment (e.g., waitlist control), (b) treatment as usual (TAU; e.g., non-manualized clinical management), (c) TAU determined by study design (manualized/'placebo' control condition), as well as number of sessions and influence of self- vs. clinician ratings. RESULTS: The meta-analysis of 19 available comparisons resulted in a moderate pooled effect size showing a small and statistically significant benefit of the psychotherapeutic intervention over control conditions (g = 0.24, P < 0.001, I2  = 0%). This corresponds to a number needed to treat of 7.4. The effects of the interventions were stable over 12-month follow-up (g = 0.21, P < 0.01, I2  = 30%). Comparisons with waitlist or non-standardized control treatments tended to be associated with larger effect sizes than standardized control treatments. CONCLUSIONS: Despite some limitations (small number of studies), this meta-analysis provides evidence for a small but sustained effect of inpatient psychotherapy in patients with major depressive disorders.

Category-selective processing in the two visual pathways as a function of stimulus degradation by noise.

Understanding the organising principles and functional properties of the primate brain's numerous visually responsive cortical regions is one of the major goals in cognitive neuroscience. Functional magnetic resonance imaging (fMRI) studies have revealed that neural responses in higher-order visual cortex are shaped by object categories, task context, and spatiotemporal regularities. Beyond these properties, visual processing in the ventral pathway has been shown to be tightly linked to perceptual awareness, while the evidence regarding dorsal visual processing and awareness is mixed. Most previous studies targeting the dorsal pathway have used dichotomous "visible versus invisible" experimental designs and interocular suppression paradigms to modulate stimulus visibility. In this fMRI study, we sought to investigate category-selective processing of faces and tools in the ventral and dorsal visual streams as a function of parametric stimulus degradation by noise. Both frequentist and Bayesian statistics provide strong evidence for a linear relationship between category-selective processing and stimulus information in both visual pathways. Overall, multivariate category decoding accuracies turned out to be lower in the dorsal pathway. We discuss our results within the context of the emerging notion of highly interconnected visual streams, and provide an outlook on how future studies may help to further refine our understanding of the functional role of the dorsal pathway in visual object processing.

Decoding diagnosis and lifetime consumption in alcohol dependence from grey-matter pattern information.

OBJECTIVE: We investigated the potential of computer-based models to decode diagnosis and lifetime consumption in alcohol dependence (AD) from grey-matter pattern information. As machine-learning approaches to psychiatric neuroimaging have recently come under scrutiny due to unclear generalization and the opacity of algorithms, our investigation aimed to address a number of methodological criticisms. METHOD: Participants were adult individuals diagnosed with AD (N = 119) and substance-naïve controls (N = 97) ages 20-65 who underwent structural MRI. Machine-learning models were applied to predict diagnosis and lifetime alcohol consumption. RESULTS: A classification scheme based on regional grey matter attained 74% diagnostic accuracy and predicted lifetime consumption with high accuracy (r = 0.56, P < 10-10 ). A key advantage of the classification scheme was its algorithmic transparency, revealing cingulate, insular and inferior frontal cortices as important brain areas underlying classification. Validation of the classification scheme on data of an independent trial was successful with nearly identical accuracy, addressing the concern of generalization. Finally, compared to a blinded radiologist, computer-based classification showed higher accuracy and sensitivity, reduced age and gender biases, but lower specificity. CONCLUSION: Computer-based models applied to whole-brain grey-matter predicted diagnosis and lifetime consumption in AD with good accuracy. Computer-based classification may be particularly suited as a screening tool with high sensitivity.

[Mixed Episodes in Bipolar Disorders--Changes in DSM-5 and Treatment Recommendations]. / Die gemischte Episode bei bipolarer affektiver Störung--Änderungen im DSM-5 und aktuelle Behandlungsempfehlungen.

Mixed episodes in the course of affective disorders are challenging for any psychiatrist, because they are often characterized by a complicated and difficult treatment course (e. g. higher suicide rates) and a worse treatment outcome. In DSM-5, one of the main changes is that the diagnosis of a mixed episode was disestablished and replaced with affective episodes with so called "mixed features". This alteration markedly reduces the diagnostic threshold. The available literature on pharmacological treatment of mixed episodes is not sufficient; however, treatment with atypical antipsychotics, especially olanzapine and aripiprazole and the mood stabilizers valproate and carmabazepine has proved to be beneficial.

Exploring the boundary conditions of unconscious numerical priming effects with continuous flash suppression.

The scope and limits of unconscious processing are a controversial topic of research in experimental psychology. Particularly within the visual domain, a wide range of paradigms have been used to experimentally manipulate perceptual awareness. A recent study reported unconscious numerical processing during continuous flash suppression (CFS), which is a powerful variant of interocular suppression and disrupts the conscious perception of visual stimuli for up to seconds. Since this finding of a distance-dependent priming effect contradicts earlier results showing that interocular suppression abolishes semantic processing, we sought to investigate the boundary conditions of this effect in two experiments. Using statistical analyses and experimental designs that precluded an effect of target numerosity, we found evidence for identity priming, but no conclusive evidence for distance-dependent numerical priming under CFS. Our results suggest that previous conclusions on high-level numerical priming under interocular suppression may have been premature.

Revisiting the Lissajous figure as a tool to study bistable perception.

During bistable vision perception spontaneously "switches" between two mutually exclusive percepts despite constant sensory input. The endogenous nature of these perceptual transitions has motivated extensive research aimed at the underlying mechanisms, since spontaneous perceptual transitions of bistable stimuli should in principle allow for a dissociation of processes related to sensory stimulation from those related to conscious perception. However, transitions from one conscious percept to another are often not instantaneous, and participants usually report a considerable amount of mixed or unclear percepts. This feature of bistable vision makes it difficult to isolate transition-related visual processes. Here, we revisited an ambiguous depth-from-motion stimulus which was first introduced to experimental psychology more than 80 years ago. This rotating Lissajous figure might prove useful in complementing other bistable stimuli, since its perceptual transitions only occur at critical stimulus configurations and are virtually instantaneous, thus facilitating the construction of a perceptually equivalent replay condition. We found that three parameters of the Lissajous figure - complexity, line width, and rotational speed - differentially modulated its perceptual dominance durations and transition probabilities, thus providing experimenters with a versatile tool to study the perceptual dynamics of bistable vision.

[Long-acting injectable antipsychotics. Overview and advice for daily routine care]. / Depotantipsychotika. Überblick und Hinweise für die Praxis.

Recent investigations have demonstrated a significant reduction of relapse and hospitalization rates associated with the use of long-acting injectable antipsychotics (LAIs) in the treatment of schizophrenia. There are only marginal differences in the effectiveness of different specific LAIs. Furthermore, LAIs are comparable to the oral equivalents with respect to effectiveness and side effects. The occurrence of extrapyramidal motor disorders (EPD) is less frequent in second generation (SG) LAIs than in first generation (FG) LAIs. Moreover, specific characteristics of some substances should be considered: In SG-LAIs immediate onset of action is only applicable for olanzapine and paliperidone and FG-LAIs should always be given as a test dose first to assure a general tolerance. All LAIs have a high variability of plasma levels which complicates the dose titration. Last but not least, current research concerning long-term consequences of continuous treatment with antipsychotics and the potentially poorer response to antipsychotics should be considered.

Learning to detect but not to grasp suppressed visual stimuli.

A central implication of the two-visual-systems hypothesis (TVSH) is that the dorsal visuomotor system (vision-for-action) can make use of invisible information, whereas the ventral system (vision-for-perception) cannot (Milner & Goodale, 1995). Therefore, actions such as grasping movements should be influenced by invisible information while conscious reports remain unaffected. To test this assumption, we used a dichoptic stimulation technique--continuous flash suppression (CFS)--which has the potency to render stimuli invisible for up to seconds (Tsuchiya & Koch, 2005). In two experiments using CFS, participants were asked to grasp for invisible bars of different sizes (Experiment 1) or orientations (Experiment 2), or to report both measures verbally. Target visibility was measured trial-by-trial using the perceptual awareness scale (PAS). We found no evidence for the use of invisible information by the visuomotor system despite extensive training (600 trials) and the availability of haptic feedback. Participants neither learned to scale their maximum grip aperture to the size of the invisible stimulus, nor to align their hand to its orientation. Careful control of stimulus visibility across training sessions, however, revealed a robust tendency towards decreasing perceptual thresholds under CFS. We discuss our results within the framework of the TVSH and with respect to alternative models which emphasize the close functional interaction between the dorsal and ventral visual systems.

Access of emotional information to visual awareness in patients with major depressive disorder.

BACKGROUND: According to cognitive theories of depression, negative biases affect most cognitive processes including perception. Such depressive perception may result not only from biased cognitive appraisal but also from automatic processing biases that influence the access of sensory information to awareness. METHOD: Twenty patients with major depressive disorder (MDD) and 20 healthy control participants underwent behavioural testing with a variant of binocular rivalry, continuous flash suppression (CFS), to investigate the potency of emotional visual stimuli to gain access to awareness. While a neutral, fearful, happy or sad emotional face was presented to one eye, high-contrast dynamic patterns were presented to the other eye, resulting in initial suppression of the face from awareness. Participants indicated the location of the face with a key press as soon as it became visible. The modulation of suppression time by emotional expression was taken as an index of unconscious emotion processing. RESULTS: We found a significant difference in the emotional modulation of suppression time between MDD patients and controls. This difference was due to relatively shorter suppression of sad faces and, to a lesser degree, to longer suppression of happy faces in MDD. Suppression time modulation by sad expression correlated with change in self-reported severity of depression after 4 weeks. CONCLUSIONS: Our finding of preferential access to awareness for mood-congruent stimuli supports the notion that depressive perception may be related to altered sensory information processing even at automatic processing stages. Such perceptual biases towards mood-congruent information may reinforce depressed mood and contribute to negative cognitive biases.

[Evaluation of different protocols for the leg cuff technique for measurement of dynamic cerebral autoregulation]. / Evaluierung verschiedener Messprotokolle für die Leg-cuff-Methode zur Messung der dynamischen zerebralen Autoregulation.

AIM: Aaslid's leg cuff method is a well validated technique to measure dynamic cerebral autoregulation. In the literature different protocols to choose cuff pressure have been described. The aim of this study is to find a technique as accurate as possible without un-necessary inconvenience for the patient. METHOD: The leg cuff test with bilateral cuffs was performed on 10 young healthy volunteers with three different protocols (cuff pressure at systolic level, doppler controlled and 30 mmHg above systolic level). For each examination the autoregulation index invented by Tiecks and Mahony was calculated. Statistical modelling of correlated data was done with Generalized Estimating Equations. RESULTS: The choice of the protocol influences the quality of the actual autoregulation test. The most reliable protocol is also the most inconvenient one for the patient. We found no systematic bias of the protocol on the autoregulation index, but the relation between induced blood pressure drop and resulting autoregulation index was close to statistical significance. CONCLUSION: For the leg cuff test with bilateral cuffs in awake patients we recommend to apply the protocol proposed by Tiecks. Additional report of the magnitude of induced blood pressure drop would be helpful to improve the results' comparability.

A critique of functional localisers.

In this critique, we review the usefulness of functional localising scans in functional MRI studies. We consider their conceptual motivations and the implications for experimental design and inference. Functional localisers can often be viewed as acquiring data from cells that have been removed from an implicit factorial design. This perspective reveals their potentially restrictive nature. We deconstruct two examples from the recent literature to highlight the key issues. We conclude that localiser scans can be unnecessary and, in some instances, lead to a biased and inappropriately constrained characterisation of functional anatomy.

Effects of arousing emotional scenes on the distribution of visuospatial attention: changes with aging and early subcortical vascular dementia.

BACKGROUND: The modulation of attention by emotionally arousing stimuli is highly important for each individual's social function. Disturbances of emotional processing are a supportive feature for the diagnosis of subcortical vascular dementia (SVD). We address here whether these disturbances might be useful as an early disease marker. METHODS: In order to examine the modulation of visual attention by emotionally arousing stimuli of different valence, 12 elderly patients with early SVD, 12 age-comparable healthy adults and 12 young healthy subjects were studied while looking at pairs of pictures from the International Affective Picture Battery that were either neutral-neutral, neutral-positive or neutral-negative in terms of emotional content. Eye movements were recorded with an infrared eye-tracking system. The direction of the first saccade and the dwell time during the 10 s of presentation were measured and compared among groups with parametric tests. RESULTS: All subjects showed a modulation of initial attentional orienting as well as a higher percentage of dwell time towards the pictures containing emotional material. Patients with SVD and old controls did not differ in either experimental measure. Young patients showed a stronger bias towards emotionally negative material than both groups of older individuals. CONCLUSIONS: Modulation of visuospatial attention is preserved in early SVD. This might have implications for therapeutic interventional approaches. A weakened sustained attention towards negative but not positive emotional pictures in the elderly is in accordance with the socioemotional selectivity theory, describing a relative selection of positive stimuli with aging.

Contributions of sensory input, auditory search and verbal comprehension to cortical activity during speech processing.

We studied eight normal subjects in an fMRI experiment where they listened to natural speech sentences and to matched simple or complex speech envelope noises. Neither of the noises (simple or complex) were understood initially, but after the corresponding natural speech sentences had been heard, comprehension was close to perfect for the complex but still absent for the simple speech envelope noises. This setting thus involved identical stimuli that were understood or not and permitted to identify (i) a neural substrate of speech comprehension unconfounded by stimulus acoustic properties (common to natural speech and complex noises), (ii) putative correlates of auditory search for phonetic cues in noisy stimuli (common to simple and complex noises once the matching natural speech had been heard) and (iii) the cortical regions where speech comprehension and auditory search interact. We found correlates of speech comprehension in bilateral medial (BA21) and inferior (BA38 and BA38/21) temporal regions, whereas acoustic feature processing occurred in more dorsal temporal regions. The left posterior superior temporal cortex (Wernicke's area) responded to the acoustic complexity of the stimuli but was additionally sensitive to auditory search and speech comprehension. Attention was associated with recruitment of the dorsal part of Broca's area (BA44) and interaction of auditory attention and comprehension occurred in bilateral insulae, the anterior cingulate and the right medial frontal cortex. In combination, these results delineate a neuroanatomical framework for the functional components at work during natural speech processing, i.e. when comprehension results from concurrent acoustic processing and effortful auditory search.

The fuzzy frontier between subjective memory complaints and early dementia. A survey of patient management in German memory clinics.

BACKGROUND: Mild cognitive decline is frequent in the elderly population. Whether it is related to normal aging or an early phase of evolving dementia is difficult to ascertain with confidence, and accordingly there is a lack of consensus guidelines for diagnosis and therapy in such patients. We assessed the variability with which memory clinics deal with this problem in everyday practice. METHODS: We sent three fictitious case histories to all 85 German memory clinics that contained the results of clinical examination and neuropsychological test scores and asked for diagnosis and patient management. Patient 1 presented with complaints of mental decline but normal neuropsychological and neurological evaluation and normal daily living activities. Patient 2 came in as a control subject for a study and had impaired test scores but preserved daily living activities, and patient 3 was brought in by relatives with slight impairment of daily living activities and decline in some neuropsychological test scores but relatively spared memory scores. RESULTS: Most of the 51 respondents agreed in recommending further neuropsychological testing, a basic laboratory work-up, brain imaging, and a re-examination after 3-6 months. Yet, there was a high variability in the diagnostic terms used, in the additional diagnostic procedures proposed, and in the recommendations concerning therapeutic intervention and driving. CONCLUSIONS: The results reveal a need of practice guidelines for the use of diagnostic terms, therapeutic interventions and driving recommendations in patients between subjective memory complaints and early dementia.

Electroencephalographic signatures of attentional and cognitive default modes in spontaneous brain activity fluctuations at rest.

We assessed the relation between hemodynamic and electrical indices of brain function by performing simultaneous functional MRI (fMRI) and electroencephalography (EEG) in awake subjects at rest with eyes closed. Spontaneous power fluctuations of electrical rhythms were determined for multiple discrete frequency bands, and associated fMRI signal modulations were mapped on a voxel-by-voxel basis. There was little positive correlation of localized brain activity with alpha power (8-12 Hz), but strong and widespread negative correlation in lateral frontal and parietal cortices that are known to support attentional processes. Power in a 17-23 Hz range of beta activity was positively correlated with activity in retrosplenial, temporo-parietal, and dorsomedial prefrontal cortices. This set of areas has previously been characterized by high but coupled metabolism and blood flow at rest that decrease whenever subjects engage in explicit perception or action. The distributed patterns of fMRI activity that were correlated with power in different EEG bands overlapped strongly with those of functional connectivity, i.e., intrinsic covariations of regional activity at rest. This result indicates that, during resting wakefulness, and hence the absence of a task, these areas constitute separable and dynamic functional networks, and that activity in these networks is associated with distinct EEG signatures. Taken together with studies that have explicitly characterized the response properties of these distributed cortical systems, our findings may suggest that alpha oscillations signal a neural baseline with "inattention" whereas beta rhythms index spontaneous cognitive operations during conscious rest.

Pravastatin improves cerebral vasomotor reactivity in patients with subcortical small-vessel disease.

BACKGROUND AND PURPOSE: Recent investigations have suggested an important role of statins in the prevention of stroke and dementia independent of their lipid-lowering properties. Using transcranial Doppler sonography (TCD), we examined acetazolamide reactivity as a marker of cerebral vasoreactivity in patients with subcortical small-vessel disease before and after pravastatin treatment. METHODS: In 16 patients (mean age 68+/-10 years) with subcortical small-vessel disease, cerebral vasomotor reactivity was tested using TCD insonating the middle cerebral artery. Cerebral blood flow velocity (CBFV) increase after bolus injection of 1 g acetazolamide was determined before and after 2-month treatment with pravastatin sodium 20 mg daily. RESULTS: Relative CBFV increase was significantly greater after pravastatin treatment (41.9+/-23.7% versus 55.7+/-18.3%, P=0.004). Comparison of CBFV at rest before and after treatment with pravastatin did not show significant differences. There was a strong negative correlation between the pravastatin-induced enhancement of vasomotor reactivity and the pretreatment CBFV increase (beta=-0.64, P=0.019). No associations were found between the effect of pravastatin on vasomotor reactivity and pretreatment levels or changes of LDL cholesterol. CONCLUSIONS: This pilot study provides the first evidence for a significant improvement of cerebral vasomotor reactivity by statin therapy in patients with cerebral small-vessel disease. The results may help to elucidate the preventive effect of statins and provide insights into the pathophysiology of cerebral small-vessel disease.