On the integrity of functional brain networks in schizophrenia, Parkinson's disease, and advanced age: Evidence from connectivity-based single-subject classification.

Previous whole-brain functional connectivity studies achieved successful classifications of patients and healthy controls but only offered limited specificity as to affected brain systems. Here, we examined whether the connectivity patterns of functional systems affected in schizophrenia (SCZ), Parkinson's disease (PD), or normal aging equally translate into high classification accuracies for these conditions. We compared classification performance between pre-defined networks for each group and, for any given network, between groups. Separate support vector machine classifications of 86 SCZ patients, 80 PD patients, and 95 older adults relative to their matched healthy/young controls, respectively, were performed on functional connectivity in 12 task-based, meta-analytically defined networks using 25 replications of a nested 10-fold cross-validation scheme. Classification performance of the various networks clearly differed between conditions, as those networks that best classified one disease were usually non-informative for the other. For SCZ, but not PD, emotion-processing, empathy, and cognitive action control networks distinguished patients most accurately from controls. For PD, but not SCZ, networks subserving autobiographical or semantic memory, motor execution, and theory-of-mind cognition yielded the best classifications. In contrast, young-old classification was excellent based on all networks and outperformed both clinical classifications. Our pattern-classification approach captured associations between clinical and developmental conditions and functional network integrity with a higher level of specificity than did previous whole-brain analyses. Taken together, our results support resting-state connectivity as a marker of functional dysregulation in specific networks known to be affected by SCZ and PD, while suggesting that aging affects network integrity in a more global way. Hum Brain Mapp 38:5845-5858, 2017. © 2017 Wiley Periodicals, Inc.

Long-Term Effects of the Collagenase of the Bacterium Clostridium histolyticum for the Treatment of Capsular Fibrosis After Silicone Implants.

BACKGROUND: Capsular contracture remains the most frequent long-term complication after augmentation mammoplasty with silicone implants. Thereby, the main part of the fibrotic capsule is collagen. The collagenase of the bacterium Clostridium histolyticum is approved for the treatment of fibrotic diseases and has been demonstrated to be effective for capsular fibrosis treatment in the short term. However, long-term effectiveness is currently unknown but mandatory for clinical utilization. MATERIALS AND METHODS: Forty-eight rats received miniature silicone implants and an injection with either collagenase (treatment group) or plain solvent solution (control group) 120 days post insertion. Ten and 60 days after the injections, the rats underwent 7-Tesla magnetic resonance imaging (MRI) and high-resolution ultrasound (HR-US). Capsule tissue was harvested, and capsule thickness and collagen density were evaluated through histology. Furthermore, the expression levels of inflammatory (CD68, IL4, IL10, IL12, IL13), pro-, and anti-fibrotic (TGFb1, TGFb3, Smad3, Col1-4) genes were analyzed using qRT-PCR. RESULTS: On days 10 and 60 after injection of collagenase, histology showed that capsule thickness was significantly reduced in the treatment group when compared with the control (p < 0.05). Thickness measurements were verified by MRI and HR-US analysis. Skin perforation occurred in two cases after collagenase injection. The initial up-regulation of pro-fibrotic and inflammatory genes 10 days after collagenase injection did not persist in the long term. Contrarily, on day 60, a slight trend towards lower expression levels with a significant down-regulation of TGFb3 was detected in the treatment group. CONCLUSION: The collagenase of the bacterium C. histolyticum effectively degrades capsular fibrosis around silicone implants with stable outcomes throughout 60 days post injection. Skin perforation and adequate and uniform drug distribution within the implant pocket are issues that need to be addressed. Further studies are warranted to clarify whether collagenase injections have the potential to become a viable treatment option for capsular contracture. NO LEVEL ASSIGNED: This journal requires that authors 46 assign a level of evidence to each article. For a full 47 description of these Evidence-Based Medicine ratings, 48 please refer to the Table of Contents or the online 49 Instructions to Authors. www.springer.com/00266 .