Test-retest reliability of resting-state cerebral blood flow quantification using pulsed Arterial Spin Labeling (PASL) over 3 weeks vs 8 weeks in healthy controls.

Arterial Spin Labeling is a valuable functional imaging tool for both clinical and research purposes. However, little is known about the test-retest reliability of cerebral blood flow measurements over longer periods. In this study, we investigated the reliability of pulsed Arterial Spin Labeling in assessing cerebral blood flow over a 3 (n = 28) vs 8 (n = 19) weeks interscan interval in 47 healthy participants. As a measure of cerebral blood flow reliability, we calculated voxel-wise, whole-brain, and regions of interest intraclass correlation coefficients. The whole-brain mean resting-state cerebral blood flow showed good to excellent reliability over time for both periods (intraclass correlation coefficients = 0.85 for the 3-week delay, intraclass correlation coefficients = 0.53 for the 8-week delay). However, the voxel-wise and regions of interest intraclass correlation coefficients fluctuated at 8-week compared to the 3-week interval, especially within cortical areas. These results confirmed previous findings that Arterial Spin Labeling could be used as a reliable method to assess brain perfusion. However, as the reliability seemed to decrease over time, caution is warranted when performing correlations with other variables, especially in clinical populations.

Data for the project management, life cycle inventory, costings and energy production of a ground-mounted photovoltaic farm in Greece.

Data was collected using standard communication equipment and invoices provided by an established civil construction and renewable energy development and operation company. Data referring to the construction, costings, operation and environmental impacts of a photovoltaic farm were recorded into four distinct Excel files namely: i) Project Management Data, ii) Life Cycle Inventory (LCI), iii) Electricity Generation Data and iv) Operational Cost Data. For the project management, the given quantities of the resources used in each activity could be further combined with the costs from different geographical and time regions to estimate overall project implementation costs for similar projects. The LCI data for the materials and transportation used can set the basis for life cycle assessment modelling of ground-mounted photovoltaic farms of that size and type. The electricity generation data along with meteorological parameters and location coordinates can be further enhanced to predict and manage energy generation and cashflow of expectations installations of this type and size over time. Finally, the data referring to a number of cost categories('maintenance costs', 'operational costs', 'insurance costs' and 'any other costs'), especially combined with the previously mentioned types of data could support a holistic technoeconomic and environmental assessment of comparable commercial photovoltaic installations. In addition, these data can be used for a comparative multi-disciplinary evaluation between photovoltaics and among various renewable electricity generation alternatives and traditional fossil fuel-based options as well.

Using virtual reality to assess gesture performance deficits in schizophrenia patients.

Introduction: Gesture performance deficits are prevalent in schizophrenia patients and are strongly associated with poor social communication skills and community functioning, affecting their overall quality of life. Currently, video-recording technology is widely used in clinical settings to assess gesture production deficits in schizophrenia patients. Nevertheless, the subjective evaluation of video-recordings can encumber task assessment. The present study will aim to use virtual reality to examine its potential use as an alternative tool to objectively measure gesture performance accuracy in schizophrenia patients and healthy controls. Methods: Gesture performance in the virtual reality setting will be based on the well-established Test of Upper Limb Apraxia. Participants will be immersed in a virtual environment where they will experience themselves being embodied in a collocated virtual body seen from a first-person perspective. Motion trackers will be placed on participants' hands and elbows to track upper body movements in real-time, and to record gesture movement for later analysis. Participants will see a virtual agent sitting across from them, with a virtual table in between. The agent will perform various types of gestures and the participants' task will be to imitate those gestures as accurately as possible. Measurements from the tracking devices will be stored and analyzed to address gesture performance accuracy across groups. Discussion: This study aims to provide objective measurements of gesture performance accuracy in schizophrenia patients. If successful, the results will provide new knowledge to the gesture literature and offer the potential for novel therapeutic interventions using virtual reality technologies. Such interventions can improve gesturing and thus advance social communication skills in schizophrenia patients.

Neural Correlates of Formal Thought Disorder Dimensions in Psychosis.

BACKGROUND AND HYPOTHESIS: Formal thought disorder (FTD) is a core symptom of psychosis, but its neural correlates remain poorly understood. This study tested whether four FTD dimensions differ in their association with brain perfusion and brain structure. STUDY DESIGN: This cross-sectional study investigated 110 patients with schizophrenia spectrum disorders using 3T magnetic resonance imaging (MRI). The Thought and Language Disorder scale (TALD) was utilized, which comprises four subscales: Objective Positive (OP), Objective Negative (ON), Subjective Positive (SP), and Subjective Negative (SN). Resting-state cerebral blood flow (rsCBF), cortical thickness (CortTh), gray matter volume (GMV), and diffusion MRI tractography were tested for associations with TALD subscales controlling for age, medication, total intracranial volume, and for variance of the 3 other TALD subscales. STUDY RESULTS: Following Bonferroni correction, the FTD dimensions presented distinct neural correlates. OP scores were associated with increased rsCBF and increased GMV in the right cerebellum lingual gyrus. Higher SP scores were linked to increased GMV in bilateral prefrontal cortex. In contrast, ON was associated with increased GMV in the right premotor cortex. At more liberal statistical thresholds, higher SP was associated with increased CortTh in the right inferior frontal gyrus, whereas SN scores were linked to decreased GMV in the right prefrontal lobe, the left inferior temporal gyrus, and the left supplementary motor area. Unadjusted analyses mostly corroborated these findings. CONCLUSION: These findings stress the heterogeneity in FTD, suggesting distinct neural patterns for specific FTD experiences. In sum, FTD in psychosis may require distinct treatment strategies and further mechanistic investigations on single-item levels.

Brain Stimulation and Group Therapy to Improve Gesture and Social Skills in Schizophrenia-The Study Protocol of a Randomized, Sham-Controlled, Three-Arm, Double-Blind Trial.

An important component of nonverbal communication is gesture performance, which is strongly impaired in 2/3 of patients with schizophrenia. Gesture deficits in schizophrenia are linked to poor social functioning and reduced quality of life. Therefore, interventions that can help alleviate these deficits in schizophrenia are crucial. Here, we describe an ongoing randomized, double-blind 3-arm, sham-controlled trial that combines two interventions to reduce gesture deficits in schizophrenia patients. The combined interventions are continuous theta burst stimulation (cTBS) and social cognitive remediation therapy (SCRT). We will randomize 72 patients with schizophrenia spectrum disorders in three different groups of 24 patients. The first group will receive real cTBS and real SCRT, the second group will receive sham cTBS and real SCRT, and finally the third group will receive sham SCRT. Here, the sham treatments are, as per definition, inactive interventions that mimic as closely as possible the real treatments (similar to placebo). In addition, 24 age- and gender-matched controls with no interventions will be added for comparison. Measures of nonverbal communication, social cognition, and multimodal brain imaging will be applied at baseline and after intervention. The main research aim of this project will be to test whether the combination of cTBS and SCRT improves gesture performance and social functioning in schizophrenia patients more than standalone cTBS, SCRT or sham psychotherapy. We hypothesize that the patient group receiving the combined interventions will be superior in improving gesture performance. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04106427].

Using dynamic point light display stimuli to assess gesture deficits in schizophrenia.

BACKGROUND: Gesture deficits are ubiquitous in schizophrenia patients contributing to poor social communication and functional outcome. Given the dynamic nature of social communications, the current study aimed to explore the underlying socio-cognitive processes associated with point-light-displays (PLDs) of communicative gestures in the absence of any other confounding visual characteristics, and compare them to other well-established stimuli of gestures such as pictures by examining their association with symptom severity and motor-cognitive modalities. METHODS: We included 39-stable schizophrenia outpatients and 27-age-gender matched controls and assessed gesture processing using two tasks. The first task used static stimuli of pictures of a person performing a gesture. The limbs executing the gesture were missing and participants' task was to choose the correct gesture from three-options provided. The second task included videos of dynamic PLDs interacting with each other. One PLD performed communicative gestures, while the other PLD imitated/followed these performed gestures. Participants had to indicate, which of the two PLDs was imitating/following the other. Additionally, we evaluated symptom severity, as well as, motor and cognitive parameters. RESULTS: Patients underperformed in both gesture tasks compared to controls. Task performance for static stimuli was associated with blunted affect, motor coordination and sequencing domains, while PLD performance was associated with expressive gestures and sensory integration processes. DISCUSSION: Gesture representations of static and dynamic stimuli are associated with distinct processes contributing to poor social communication in schizophrenia, requiring novel therapeutic interventions. Such stimuli can easily be applied remotely for screening socio-cognitive deficits in schizophrenia.

Motor abnormalities are associated with poor social and functional outcomes in schizophrenia.

BACKGROUND: Up to 50% of patients with schizophrenia are suffering from motor abnormalities, which may contribute to decreased quality of life, impaired work capacity, and a reduced life expectancy by 10-20 years. However, the effect of motor abnormalities on social and global functioning, as well as, functional capacity is not clear. We hypothesized, that the presence of motor abnormalities is associated with poorer functional outcomes in patients with schizophrenia. METHODS: We collected data on 5 different motor abnormalities in 156 patients suffering from schizophrenia spectrum disorders: parkinsonism, catatonia, dyskinesia, neurological soft signs and psychomotor slowing (PS). Additionally, we used three different scales to evaluate the functional outcomes in these patients: the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS) which use clinicians' judgment; and one using a performance-based measure of functional capacity, the brief version of the UCSD Performance-based Skills Assessment (UPSA-B). RESULTS: Our analysis demonstrated that patients with catatonia (all F > 4.5; p < 0.035) and parkinsonism (all F > 4.9; p < 0.027) scored lower on GAF and SOFAS compared to patients without catatonia and parkinsonism. In contrast, no significant difference on functional outcomes between patients with dyskinesia versus without dyskinesia exist in our study. Furthermore, there are statistically significant negative correlations for parkinsonism and PS with GAF, SOFAS and UPSA-B (all tau are at least -0.152, p-value <0.036). We also found significant negative correlations between catatonia and both GAF & SOFAS (all tau are at least -0.203, p-value<0.001) and between NES and SOFAS (tau = -0.137, p-value = 0.033). CONCLUSION: Here, we showed that four of the most common motor abnormalities observed in schizophrenia were associated with at least one of the patients' functional outcomes. The stronger the motor impairment was the worse the global and social functioning. Future studies need to test, whether amelioration of motor abnormalities is linked to improved community functioning.

The Impact of Poor Nonverbal Social Perception on Functional Capacity in Schizophrenia.

Background: Nonverbal social perception is the ability to interpret the intentions and dispositions of others by evaluating cues such as facial expressions, body movements, and emotional prosody. Nonverbal social perception plays a key role in social cognition and is fundamental for successful social interactions. Patients with schizophrenia have severe impairments in nonverbal social perception leading to social isolation and withdrawal. Collectively, these aforementioned deficits affect patients' quality of life. Here, we compare nonverbal social perception in patients with schizophrenia and controls and examine how nonverbal social perception relates to daily functioning. Methods: We compared nonverbal social perception in 41 stable outpatients with schizophrenia and 30 healthy controls using the Mini Profile of Nonverbal Sensitivity (Mini-PONS). The participants evaluated 64 video clips showing a female actor demonstrating various nonverbal social cues. Participants were asked to choose one of two options that best described the observed scenario. We correlated clinical ratings (Positive and Negative Syndrome Scale, Brief Negative Syndrome Scale), Self-report of Negative Symptoms, and functional assessments (functional capacity and functional outcome) with Mini-PONS scores. Results: Patients performed significantly poorer in the Mini-PONS compared to controls, suggesting deficits in nonverbal social perception. These deficits were not associated with either positive symptoms or negative symptoms (including self-report). However, impaired nonverbal social perception correlated with distinctive domains of BNSS (mainly avolition and blunted affect), as well as functional capacity and functional outcome in patients. Conclusion: We demonstrate that nonverbal social perception is impaired in stable outpatients with schizophrenia. Nonverbal social perception is directly related to specific negative symptom domains, functional capacity and functional outcome. These findings underline the importance of nonverbal social perception for patients' everyday life and call for novel therapeutic approaches to alleviate nonverbal social perception deficits.

Human movements do not look the same in a tilted world: Gravitational constraints influence the perception of biological motion.

We investigated whether gravitational constraints influence the interaction of visual, proprioceptive and vestibular cues for Biological Motion Perception (BMP). Participants were asked to distinguish between plausible and random point-light movements, while passively placed in either an upright or a tilted body orientation. Manipulating the body orientation with respect to gravity leads to different gravitational signals transmitted by the visual, proprioceptive, and vestibular systems. Participants were overall faster in distinguishing plausible point-light movements than random movements. Critically, response times for biologically plausible point-light movements - but not for random movements - were significantly prolonged in the tilted body orientation. Our results suggest that BMP depends not only on the spatial-temporal cues embedded in point-light movements but also rely on the congruency between current gravitational signals detected by the sensory systems and our previous knowledge of terrestrial gravity. STATEMENT OF RELEVANCE: As humankind is preparing for a new space age, understanding how gravity influences behaviour and cognition has never been more pressing. All living organisms have evolved to survive in a terrestrial gravitational field. Although we cannot consciously feel gravity, it has an impact in our life: it affects how we move and interact with the external environment. The sensory signals from the vestibular system are continuously combined with visual and proprioceptive cues to help us in maintaining a stable representation of the world. Here we placed participants in a tilted body orientation and were able to determine that a conflict between prior gravitational knowledge and what was actively sensed about gravity affected human Biological Movement Perception. Humans suffer changes in perception under non-terrestrial gravity conditions that may potentially compromise performance during space exploration.

Psychopharmacological treatment is not associated with reduced suicide ideation and reattempts in an observational follow-up study of suicide attempters.

BACKGROUND: Disorders of mental health are major risk factors for suicidal behavior and require adequate treatment. However, the effect of psychotropic medication on suicidal behavior is unclear. METHODS: The 120 participants in a randomized clinical trial of a brief therapy for suicide attempters (Attempted Suicide Short Intervention Program, ASSIP) reported on repeated suicide attempts, suicidal ideation, depression, and medication in the treatment as usual (TAU), at baseline, 6, 12, 18, and 24 months follow-up. The RCT had no influence on medication prescribed. Drugs prescribed were categorized as any psychotropic, antidepressants plus lithium, and antipsychotics. To assess the effect of long-term medication we identified participants with periods of continuous use of psychotropics and antidepressants plus lithium over twelve months or more, and medication-free participants for the same drug categories during the same time period. RESULTS: Reattempts and suicide ideation decreased in all drug categories. When comparing participants on medication fulfilling the definition of long-term use with participants without medication, reattempts and suicidal ideation were higher in the psychotropics and the antidepressants/lithium groups. These drug categories were associated with higher depression scores in comparison to no-medication. The survival analysis revealed a higher risk of reattempts in the long-term antidepressants/lithium group in comparison to no-medication. Treatment with the brief psychological therapy ASSIP, added to medication, was associated with a lower risk of reattempts. LIMITATIONS: The study relied on the patients' reports on treatment as usual in a randomized controlled clinical trial. Blood levels of the psychotropic compounds were not assessed. CONCLUSIONS: In this observational study of the TAU condition in a clinical trial of a brief psychological therapy for patients who had recently attempted suicide, psychotropic drug use over twelve months or more was not associated with reduced suicide ideation and reattempts. Depression scores suggest that patients on psychotropic medication had more psychiatric pathology. This may be a confounding factor for the effect of medication on suicidal behavior.

Hand gesture performance is impaired in major depressive disorder: A matter of working memory performance?

OBJECTIVE: Individuals with depression exhibit numerous interpersonal deficits. As effective use of gestures is critical for social communication, it is possible that depressed individuals' interpersonal deficits may be due to deficits in gesture performance. The present study thus compared gesture performance of depressed patients and controls and examined whether these deficits relate to cognitive and other domains of dysfunction. METHODS: Gesture performance was evaluated in 30 depressed patients and 30 controls using the Test of Upper Limb Apraxia (TULIA). Clinical rating scales were assessed to determine if gesture deficits were associated with motor, cognitive or functional outcomes. RESULTS: Compared to controls, depressed patients exhibited impaired gesture performance with 2/3 of the patients demonstrating gesture deficits. Within depressed patients, gesture performance was highly correlated with working memory abilities. In contrast, no association between gesture performance and gestural knowledge, psychomotor retardation, depression severity, or frontal dysfunction was observed in patients. LIMITATIONS: This is a cross-sectional study and a larger size would have allowed for confident detection of more subtle, but potentially relevant effects. CONCLUSION: Gesture performance is impaired in depressed patients, and appears to be related to poor working memory abilities, suggesting a disruption in the retrieval of gestural cues indicative of a distinct clinical phenomenon that might be related to social functioning.

Nonverbal communication remains untouched: No beneficial effect of symptomatic improvement on poor gesture performance in schizophrenia.

BACKGROUND: Gestures are an important part of communication. Patients with schizophrenia present gesture deficits that tend to deteriorate in the course of the disease and hamper functional outcome. This gesture deficit has been associated with motor abnormalities, cognitive impairment, and psychotic symptoms. Unaffected, first-degree relatives of schizophrenia patients share some subclinical motor and cognitive abnormalities. We aimed to investigate, whether gesture performance changes with symptomatic improvement in patients, and to test the longitudinal performance in unaffected, first-degree relatives. METHODS: In this study, we measured gesture performance using a validated test in 33 patients, 29 first-degree relatives and 38 healthy controls. Measurements were completed shortly after admission and before discharge in patients. Performance was rated blindly by experts using video recordings of the gesture task. Additionally, we evaluated cognitive function and psychotic symptoms at both visits. RESULTS: Gesture performance was poorer in relatives compared to controls and poorer in patients compared to both relatives and controls. Patients showed an improvement in psychopathology but a significant decrease in gesture performance at follow-up, while performance in the other groups remained stable. Proportional change of gesture performance correlated with change of cognitive function in patients, whereas there were no correlations with change of cognitive function in the other groups. CONCLUSION: While symptom severity was reduced, the gesture deficit further deteriorated in schizophrenia. The finding argues for distinct processes contributing to poor nonverbal communication skills in patients, requiring novel alternative treatment efforts.

What is the potential of neurostimulation in the treatment of motor symptoms in schizophrenia?

INTRODUCTION: Motor abnormalities in schizophrenia are frequent and linked to poor social functioning and low quality of life. To date, there are no effective treatments available to alleviate these motor impairments. Previous studies have linked altered connections within the cerebral motor circuits to motor abnormalities. AREAS COVERED: This perspective article will discuss the efficacy of noninvasive brain stimulation (NIBS) techniques as a potential therapeutic tool in improving motor impairments in schizophrenia. EXPERT OPINION: The cortical motor network is easily accessible using NIBS, which has been proven reliable in restoring motor functioning across different pathologies. It is important to establish protocols that explore optimal treatment targets, timing, and duration of the stimulation, as well as, the standardization of motor assessments in order to compare across different brain stimulation methodologies. The authors believe NIBS to be ideal in restoring and improving motor impairments in schizophrenia.

Using Virtual Reality as a Tool in the Rehabilitation of Movement Abnormalities in Schizophrenia.

Movement abnormalities are prevalent across all stages of schizophrenia contributing to poor social functioning and reduced quality of life. To date, treatments are scarce, often involving pharmacological agents, but none have been shown to improve movement abnormalities effectively. Virtual reality (VR) is a tool used to simulate virtual environments where behavioral performance can be quantified safely across different tasks while exerting control over stimulus delivery, feedback and measurement in real time. Sensory information is transmitted via a head mounted display allowing users to directly interact with virtual objects and bodies using gestures and body movements in the real world to perform different actions, permitting a sense of immersion in the simulated virtual environment. Although, VR has been widely used for successful motor rehabilitation in a variety of different neurological domains, none have been exploited for motor rehabilitation in schizophrenia. The objectives of this article are to review movement abnormalities specific to schizophrenia, and how VR can be utilized to restore and improve motor functioning in patients with schizophrenia. Constructing VR-mediated motor-cognitive interventions that can help in retaining and transferring the learned outcomes to real life are also discussed.

Lateralized modulation of beta-band power in sensorimotor areas during action observation.

The cortical network for action observation includes areas of the visual cortex and non-visual areas, including areas of the motoric system. Parts of this network are known for their contralateral organization during motion execution, i.e., they predominantly control and respond to movements of the contralateral body side. We were interested whether this lateralized organization was also present during action observation. Human participants viewed point-light displays of human actors, where the actor was facing and moving either to the right or to the left, while participants' neuromagnetic activity was recorded using magnetoencephalography (MEG). We found that right and left facing movements elicited different activity in left and right motoric areas. This lateralization effect was found in two distinct spatio-temporal-spectral clusters: An early lateralization effect in medial sensors at 12-16 Hz and ~276-675 ms after stimulus onset, and a second cluster in more lateral sensors at 22-28 Hz and ~1275-1775 ms. Our results demonstrate that in addition to the known somatotopic organization of parts of the human motoric system, these areas also show a lateralization effect during action observation. Thus, our results indicate that the hemispheric organization of one's own body map known for motion execution extends to the visual observation of others' bodily actions and movements.

Association of survivin splice variants with prognosis and treatment of breast cancer.

The purpose of this study was the overview of current knowledge regarding the use of survivin and its isoforms in prognosis and treatment of breast cancer. An advanced search of Medline was performed using the following search strategy: "(survivin isoforms) OR (survivin transcript variants) AND (breast cancer) AND (neoplasm OR tumor OR cancer OR carcinoma)". Relevant studies were retrieved and processed thoroughly in order to analyze the related data. Besides wild-type survivin full-length transcript, another six splice variants have been identified. Overexpression of survivin and its isoforms leads to shorter overall and disease-free survival; the transcript variants are correlated with apoptosis and could assist prognosis prediction. It has been proved through numerous studies that inhibiting survivin isoforms might become a promising target of drug therapy of carcinomas. Use of small molecule YM155 could offer new therapy for triple negative breast cancer patients, while, chemotherapy with 5-fluorouracil + epirubicin + cyclophosphamide and Tax-Epi could be guided by survivin splice variants measurements. Survivin transcript variants could become prognostic biomarkers and could provide information about clinical management of patients suffering from breast cancer.

Distinct spatio-temporal profiles of beta-oscillations within visual and sensorimotor areas during action recognition as revealed by MEG.

The neural correlates of action recognition have been widely studied in visual and sensorimotor areas of the human brain. However, the role of neuronal oscillations involved during the process of action recognition remains unclear. Here, we were interested in how the plausibility of an action modulates neuronal oscillations in visual and sensorimotor areas. Subjects viewed point-light displays (PLDs) of biomechanically plausible and implausible versions of the same actions. Using magnetoencephalography (MEG), we examined dynamic changes of oscillatory activity during these action recognition processes. While both actions elicited oscillatory activity in visual and sensorimotor areas in several frequency bands, a significant difference was confined to the beta-band (∼20 Hz). An increase of power for plausible actions was observed in left temporal, parieto-occipital and sensorimotor areas of the brain, in the beta-band in successive order between 1650 and 2650 msec. These distinct spatio-temporal beta-band profiles suggest that the action recognition process is modulated by the degree of biomechanical plausibility of the action, and that spectral power in the beta-band may provide a functional interaction between visual and sensorimotor areas in humans.

Validation of a real-time quantitative polymerase chain reaction method for the quantification of 3 survivin transcripts and evaluation in breast cancer tissues.

BACKGROUND: Survivin is a novel antiapoptotic gene, which is a member of the inhibitor of apoptosis protein (IAP) family. Recently, 3 splice variants of this gene were cloned and characterized. This study aimed to validate a sensitive and specific method for the detection of survivin variants in breast cancer. METHODS: Real-time quantitative polymerase chain reaction (qPCR) was performed on the cDNA with a reverse primer specific for each splice variant and a pair of common hybridization probes. RESULTS: The expression of wild-type survivin was significantly correlated with survivin-2b, survivin-ΔEx3, and the ratio of survivin-ΔEx3 to wild-type survivin (P < .001). The ratio of survivin-2b to wild-type survivin was strongly associated with the ratio of survivin-ΔEx3 to wild-type survivin (P < .001). There was a strong positive association between the grade of the tumor and survivin-2b mRNA, survivin-ΔEx3 mRNA, and the ratio of survivin-ΔEx3 to wild-type survivin mRNA (P < .05). The ratio of survivin-2b to wild-type survivin was significantly associated with the presence of estrogen receptors (P = .05). CONCLUSION: Our validated data suggest that survivin isoforms may be related to clinicopathological features and could be used as molecular prognostic tools or as new therapy targets.