Targeting Treatment-Resistant Auditory Verbal Hallucinations in Schizophrenia with fMRI-Based Neurofeedback – Exploring Different Cases of Schizophrenia

Auditory verbal hallucinations (AVHs) are a hallmark of schizophrenia and can significantly impair patients' emotional, social, and occupational functioning. Despite progress in psychopharmacology, over 25% of schizophrenia patients suffer from treatment-resistant hallucinations. In the search for alternative treatment methods, neurofeedback (NF) emerges as a promising therapy tool. NF based on real-time functional magnetic resonance imaging (rt-fMRI) allows voluntarily change of the activity in a selected brain region - even in patients with schizophrenia. This study explored effects of NF on ongoing AVHs. The selected participants were trained in the self-regulation of activity in the anterior cingulate cortex (ACC), a key monitoring region involved in generation and intensity modulation of AVHs. Using rt-fMRI, three right-handed patients, suffering from schizophrenia and ongoing, treatment-resistant AVHs, learned control over ACC activity on three separate days. The effect of NF training on hallucinations' severity was assessed with the Auditory Vocal Hallucination Rating Scale (AVHRS) and on the affective state - with the Positive and Negative Affect Schedule (PANAS). All patients yielded significant upregulation of the ACC and reported subjective improvement in some aspects of AVHs (AVHRS) such as disturbance and suffering from the voices. In general, mood (PANAS) improved during NF training, though two patients reported worse mood after NF on the third day. ACC and reward system activity during NF learning and specific effects on mood and symptoms varied across the participants. None of them profited from the last training set in the prolonged three-session training. Moreover, individual differences emerged in brain networks activated with NF and in symptom changes, which were related to the patients' symptomatology and disease history. NF based on rt-fMRI seems a promising tool in therapy of AVHs. The patients, who suffered from continuous hallucinations for years, experienced symptom changes that may be attributed to the NF training. In order to assess the effectiveness of NF as a therapeutic method, this effect has to be studied systematically in larger groups; further, long-term effects need to be assessed. Particularly in schizophrenia, future NF studies should take into account the individual differences in reward processing, fatigue, and motivation to develop individualized training protocols

Virtual faces as a tool to study emotion recognition deficits in schizophrenia

Studies investigating emotion recognition in patients with schizophrenia predominantly presented photographs of facial expressions. Better control and higher flexibility of emotion displays could be afforded by virtual reality (VR). VR allows the manipulation of facial expression and can simulate social interactions in a controlled and yet more naturalistic environment. However, to our knowledge, there is no study that systematically investigated whether patients with schizophrenia show the same emotion recognition deficits when emotions are expressed by virtual as compared to natural faces. Twenty schizophrenia patients and 20 controls rated pictures of natural and virtual faces with respect to the basic emotion expressed (happiness, sadness, anger, fear, disgust, and neutrality). Consistent with our hypothesis, the results revealed that emotion recognition impairments also emerged for emotions expressed by virtual characters. As virtual in contrast to natural expressions only contain major emotional features, schizophrenia patients already seem to be impaired in the recognition of basic emotional features. This finding has practical implication as it supports the use of virtual emotional expressions for psychiatric research: the ease of changing facial features, animating avatar faces, and creating therapeutic simulations makes validated artificial expressions perfectly suited to study and treat emotion recognition deficits in schizophrenia

SpikeDeep-classifier: a deep-learning based fully automatic offline spike sorting algorithm

Objective. Advancements in electrode design have resulted in micro-electrode arrays with hundreds of channels for single cell recordings. In the resulting electrophysiological recordings, each implanted electrode can record spike activity (SA) of one or more neurons along with background activity (BA). The aim of this study is to isolate SA of each neural source. This process is called spike sorting or spike classification. Advanced spike sorting algorithms are time consuming because of the human intervention at various stages of the pipeline. Current approaches lack generalization because the values of hyperparameters are not fixed, even for multiple recording sessions of the same subject. In this study, a fully automatic spike sorting algorithm called "SpikeDeep-Classifier" is proposed. The values of hyperparameters remain fixed for all the evaluation data. Approach. The proposed approach is based on our previous study (SpikeDeeptector) and a novel background activity rejector (BAR), which are both supervised learning algorithms and an unsupervised learning algorithm (K-means). SpikeDeeptector and BAR are used to extract meaningful channels and remove BA from the extracted meaningful channels, respectively. The process of clustering becomes straight-forward once the BA is completely removed from the data. Then, K-means with a predefined maximum number of clusters is applied on the remaining data originating from neural sources only. Lastly, a similarity-based criterion and a threshold are used to keep distinct clusters and merge similar looking clusters. The proposed approach is called cluster accept or merge (CAOM) and it has only two hyperparameters (maximum number of clusters and similarity threshold) which are kept fixed for all the evaluation data after tuning. Main Results. We compared the results of our algorithm with ground-truth labels. The algorithm is evaluated on data of human patients and publicly available labeled non-human primates (NHPs) datasets. The average accuracy of BAR on datasets of human patients is 92.3% which is further reduced to 88.03% after (K-means + CAOM). In addition, the average accuracy of BAR on a publicly available labeled dataset of NHPs is 95.40% which reduces to 86.95% after (K-mean + CAOM). Lastly, we compared the performance of the SpikeDeep-Classifier with two human experts, where SpikeDeep-Classifier has produced comparable results. Significance. The results demonstrate that "SpikeDeep-Classifier" possesses the ability to generalize well on a versatile dataset and henceforth provides a generalized well on a versatile dataset and henceforth provides a generalized and fully automated solution to offline spike sorting

M & L Jaargang 21/5

Ann Verdonck, Piet Swimberghe en Veerle De Houwer Een edel en verfijnd genot. Polychromie in de woonkamer van woning Billiet te Brugge. [Noble and refined delight. A polychrome design for the living room of the Billiet house in Bruges.]Roger Deneef, Lydie Mondelaers en Susanne Van Aerschot-Van Haeverbeeck Het Sint-Kamillusgesticht te Bierbeek, monument voor een levensbeschouwing. [Saint-Camilllus Psychiatric Asylum at Bierbeek, monument to an ideology.]Lode De Clercq Vondsten van muurschilderingen in de Sint-Jacobskerk in Antwerpen. [Wall paintings discovered in Saint-Jacobs Church in Antwerp.]Linda Van Dyck en Marie-Hélène Ghisdal Een vroeg-15de-eeuwse muurschildering met de voorstelling van de man van smarten in de kathedraal van Antwerpen. Prachtige fragmenten van een minutieus uitgevoerde schildering.Dirk Van Eenhooge Middeleeuwse Brugse huizen: bouwhistorisch onderzoek in de huizen in Sint-Jacobs en Den Ancker. [Medieval Houses in Bruges (2): In Sint-Jacobs and Den Ancker.]Summar

Recognition Profile of Emotions in Natural and Virtual Faces

BACKGROUND: Computer-generated virtual faces become increasingly realistic including the simulation of emotional expressions. These faces can be used as well-controlled, realistic and dynamic stimuli in emotion research. However, the validity of virtual facial expressions in comparison to natural emotion displays still needs to be shown for the different emotions and different age groups. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-two healthy volunteers between the age of 20 and 60 rated pictures of natural human faces and faces of virtual characters (avatars) with respect to the expressed emotions: happiness, sadness, anger, fear, disgust, and neutral. Results indicate that virtual emotions were recognized comparable to natural ones. Recognition differences in virtual and natural faces depended on specific emotions: whereas disgust was difficult to convey with the current avatar technology, virtual sadness and fear achieved better recognition results than natural faces. Furthermore, emotion recognition rates decreased for virtual but not natural faces in participants over the age of 40. This specific age effect suggests that media exposure has an influence on emotion recognition. CONCLUSIONS/SIGNIFICANCE: Virtual and natural facial displays of emotion may be equally effective. Improved technology (e.g. better modelling of the naso-labial area) may lead to even better results as compared to trained actors. Due to the ease with which virtual human faces can be animated and manipulated, validated artificial emotional expressions will be of major relevance in future research and therapeutic applications

The auditory cortex of the bat Phyllostomus discolor: Localization and organization of basic response properties

<p>Abstract</p> <p>Background</p> <p>The mammalian auditory cortex can be subdivided into various fields characterized by neurophysiological and neuroarchitectural properties and by connections with different nuclei of the thalamus. Besides the primary auditory cortex, echolocating bats have cortical fields for the processing of temporal and spectral features of the echolocation pulses. This paper reports on location, neuroarchitecture and basic functional organization of the auditory cortex of the microchiropteran bat <it>Phyllostomus discolor </it>(family: Phyllostomidae).</p> <p>Results</p> <p>The auditory cortical area of <it>P. discolor </it>is located at parieto-temporal portions of the neocortex. It covers a rostro-caudal range of about 4800 μm and a medio-lateral distance of about 7000 μm on the flattened cortical surface.</p> <p>The auditory cortices of ten adult <it>P. discolor </it>were electrophysiologically mapped in detail. Responses of 849 units (single neurons and neuronal clusters up to three neurons) to pure tone stimulation were recorded extracellularly. Cortical units were characterized and classified depending on their response properties such as best frequency, auditory threshold, first spike latency, response duration, width and shape of the frequency response area and binaural interactions.</p> <p>Based on neurophysiological and neuroanatomical criteria, the auditory cortex of <it>P. discolor </it>could be subdivided into anterior and posterior ventral fields and anterior and posterior dorsal fields. The representation of response properties within the different auditory cortical fields was analyzed in detail. The two ventral fields were distinguished by their tonotopic organization with opposing frequency gradients. The dorsal cortical fields were not tonotopically organized but contained neurons that were responsive to high frequencies only.</p> <p>Conclusion</p> <p>The auditory cortex of <it>P. discolor </it>resembles the auditory cortex of other phyllostomid bats in size and basic functional organization. The tonotopically organized posterior ventral field might represent the primary auditory cortex and the tonotopically organized anterior ventral field seems to be similar to the anterior auditory field of other mammals. As most energy of the echolocation pulse of <it>P. discolor </it>is contained in the high-frequency range, the non-tonotopically organized high-frequency dorsal region seems to be particularly important for echolocation.</p

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical R

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Training-related changes in neural beta oscillations associated with implicit and explicit motor sequence learning

Abstract Many motor actions we perform have a sequential nature while learning a motor sequence involves both implicit and explicit processes. In this work, we developed a task design where participants concurrently learn an implicit and an explicit motor sequence across five training sessions, with EEG recordings at sessions 1 and 5. This intra-subject approach allowed us to study training-induced behavioral and neural changes specific to the explicit and implicit components. Based on previous reports of beta power modulations in sensorimotor networks related to sequence learning, we focused our analysis on beta oscillations at motor-cortical sites. On a behavioral level, substantial performance gains were evident early in learning in the explicit condition, plus slower performance gains across training sessions in both explicit and implicit sequence learning. Consistent with the behavioral trends, we observed a training-related increase in beta power in both sequence learning conditions, while the explicit condition displayed stronger beta power suppression during early learning. The initially stronger beta suppression and subsequent increase in beta power specific to the explicit component, correlated with enhanced behavioral performance, possibly reflecting higher cortical excitability. Our study suggests an involvement of motor-cortical beta oscillations in the explicit component of motor sequence learning