Striatal Response to Reward Anticipation as a Biomarker for Schizophrenia and Negative Symptoms: Effects, Test-Retest Reliability, and Stability Across Sites.

BACKGROUND: Ventral striatal hypoactivation during reward anticipation has consistently been observed in patients with schizophrenia. In addition, that hypoactivation has been shown to correlate negatively with negative symptoms, and in particular with apathy. However, little is known about the stability of these results over time and their reliability across different centers. METHODS: In total, 67 patients with schizophrenia (15 females) and 55 healthy controls (13 females) were recruited in 2 centers in Switzerland and Germany. To assess the neural bases of reward anticipation, all participants performed a variant of the Monetary Incentive Delay task while undergoing event-related functional magnetic resonance imaging at baseline and after 3 months. Stability over time was measured using intra-class correlation (ICC(A,1)) and stability between centers was measured with mixed models. RESULTS: Results showed the expected ventral striatal hypoactivation in patients compared to controls during reward anticipation. We showed that these results were stable across centers. The primary analysis did not reveal an effect of time. Test-retest reliability was moderate for controls, and poor for patients. We did not find an association between ventral striatal hypoactivation and negative symptoms in patients. CONCLUSIONS: Our results align with the hypothesis that ventral striatal activation is related to modulation of motivational saliency during reward anticipation. They also confirm that patients with schizophrenia show impaired reward anticipation. However, the poor test-retest reliability and the absence of an association with symptoms suggests that further research is needed before ventral striatal activity can be used as a biomarker on the individual patient level.

Adaptive coding of reward in schizophrenia, its change over time and relation to apathy.

Adaptive coding of reward is the process by which neurons adapt their response to the context of available compensations. Higher rewards lead to a stronger brain response, but the increase of the response depends on the range of available rewards. A steeper increase is observed in a narrow range, and a more gradual slope in a wider range. In schizophrenia, adaptive coding appears affected in different domains, and in the reward domain in particular. Here we tested adaptive coding of reward in a large group of patients with schizophrenia (N = 86) and controls (N = 66). We assessed 1) the association between adaptive coding deficits and symptoms; 2) the longitudinal stability of deficits (the same task was performed three months apart); 3) the stability of results between two experimental sites. We used fMRI and the Monetary Incentive Delay task to assess participant' adaptation to two different reward ranges: a narrow and a wide range. We used a region of interest analysis, evaluating adaptation within striatal and visual regions. Patients and controls underwent a full demographic and clinical assessment. We found reduced adaptive coding in patients, due to a decreased slope in the narrow reward range, with respect to that of control participants in striatal but not visual regions. This pattern was observed at both research sites. Upon re-test, patients increased their narrow range slopes, showing improved adaptive coding, whereas controls slightly reduced them. At re-test, patients with overly steep slopes in the narrow range also showed higher levels of negative symptoms. Our data confirm deficits in reward adaptation in schizophrenia and reveal a practice effect in patients, leading to improvement, with steeper slopes upon retest. However, in some patients, an overly steep slope may result in poor discriminability of larger rewards, due to early saturation of the brain response. Together, the loss of precision of reward representation in new (first exposure, underadaptation) and more familiar (re-test, overadaptation) situations may contribute to the multiple motivational symptoms in schizophrenia.

Functional connectivity alterations between default mode network and occipital cortex in patients with obsessive-compulsive disorder (OCD).

Altered brain network connectivity is a potential biomarker for obsessive-compulsive disorder (OCD). A meta-analysis of resting-state MRI studies by Gürsel et al. (2018) described altered functional connectivity in OCD patients within and between the default mode network (DMN), the salience network (SN), and the frontoparietal network (FPN), as well as evidence for aberrant fronto-striatal circuitry. Here, we tested the replicability of these meta-analytic rsfMRI findings by measuring functional connectivity during resting-state fMRI in a new sample of OCD patients (n = 24) and matched controls (n = 33). We performed seed-to-voxel analyses using 30 seed regions from the prior meta-analysis. OCD patients showed reduced functional connectivity between the SN and the DMN compared to controls, replicating previous findings. We did not observe significant group differences of functional connectivity within the DMN, SN, nor FPN. Additionally, we observed reduced connectivity between the visual network to both the DMN and SN in OCD patients, in particular reduced functional connectivity between lateral parietal seeds and the left inferior lateral occipital pole. Furthermore, the right lateral parietal seed (associated with the DMN) was more strongly correlated with a cluster in the right lateral occipital cortex and precuneus (a region partly overlapping with the Dorsal Attentional Network (DAN)) in patients. Importantly, this latter finding was positively correlated to OCD symptom severity. Overall, our study partly replicated prior meta-analytic findings, highlighting hypoconnectivity between SN and DMN as a potential biomarker for OCD. Furthermore, we identified changes between the SN and the DMN with the visual network. This suggests that abnormal connectivity between cortex regions associated with abstract functions (transmodal regions such as the DMN), and cortex regions associated with constrained neural processing (unimodal regions such as the visual cortex), may be important in OCD.

Reduced mind wandering in patients with Parkinson's disease.

BACKGROUND: Mind Wandering (MW) refers to the process of disengaging from the immediate external environment and participating in internally driven mentation. This process has been suggested to be supported by a distributed set of brain regions, collectively referred to as the Default Mode Network (DMN). Recently, reduced recruitment and connectivity of the DMN has been described in Parkinson's disease (PD) patients compared to healthy controls. We thus aimed to explore whether PD patients with normal cognitive test scores show differential MW capabilities compared to healthy controls. METHODS: Thirty PD patients and thirty age-matched controls, all with a Montreal cognitive assessment (MoCA) score of 26 or above, performed a novel yet validated thought-sampling paradigm used to assess the frequency and extent of MW irrespective of cognitive load in which participants were asked to observe a series of geometric shapes and describe their thoughts after watching them. Shapes were presented one at a time for varying durations across nine trials. RESULTS: PD patients showed significantly less MW compared to the control. ANCOVA revealed a significant interaction indicating that the difference in MW scores was driven by trials with short stimulus presentation times. CONCLUSIONS: These findings provide evidence for decreased MW in PD patients. We propose that this is due to difficulties in performing MW within short time frames.

Immune Modulation and Treatment of Human Papilloma Virus-Related Warts with Energetics of Living Systems Acupuncture.

Background: Cutaneous warts are small skin lesions formed as a result of infection by the human papilloma virus (HPV). In the lesion, viral manipulation creates a microenvironment that favors virus survival and reproduction. Most lesions eventually regress, probably as a result of a Th1-mediated immune response. However, some warts fail to regress and become persistent. Objective: The efficacy of treatment of persistent HPV-caused warts with Energetics of Living Systems acupuncture and monitored immune system involvement was tested. Methods: Eighteen patients with persistent warts were recruited for the study; 9 received acupuncture treatment and 9 received placebo. Each patient was treated 4 times. Results: Clinical success was defined as total clearance of all lesions with no recurrence for 3 months. In the treatment group, clinical success was 36.6% versus 0% in the placebo group. In the treatment group, the level of interleukin (IL)-10 decreased. In a comparison of patients with cleared warts and overall patients with nonresponding warts, different expression levels of IL-8, IL-10, tumor necrosis factor-α, IL-6, and interferon-γ were found, although these differences were not always statistically significant. Trends of differences (not significant) were observed in leukocyte levels. Acupuncture eliminated persistent warts in some of the patients, along with inducing changes in immunologic parameters. Conclusions: Taking the clinical and immunologic outcomes together, clearance of persistent warts following acupuncture might be due to a shift toward a Th1 immune response, or an anti-inflammatory effect against the lesion-induced microenvironment.

A virtual reality system combined with biofeedback for treating pediatric chronic headache--a pilot study.

OBJECTIVE: Pediatric headache is highly widespread and is associated with distress and reduced quality of life. Pharmacological treatment of chronic headache in children has been only partially effective and, as in medication-overuse headache, can sometimes be counterproductive. Therefore, there is a substantial need to develop other effective methods of treatment. Here we present the rationale, feasibility, and preliminary results of a pilot study applying a novel system, combining virtual reality and biofeedback, aimed as an abortive treatment of pediatric chronic headache. DESIGN: A prospective single-arm open-label, pilot study. Ten children attending an outpatient pediatric neurology clinic were treated by the proposed system. Participants practiced relaxation with biofeedback and learned to associate successful relaxation with positive pain-free virtual images of themselves. RESULTS: Nine patients completed the 10-session intervention. Ratings of pain, daily functioning, and quality of life improved significantly at 1 and at 3 months posttreatment. Most patients reported applying their newly acquired relaxation and imagery skills to relieve headache outside the lab. CONCLUSION: This novel system, combining biofeedback and virtual reality, is feasible for pediatric use. Randomized controlled studies in larger populations are needed in order to determine the utility of the system in reducing headache, improving daily functioning, and elevating quality of life.