Long-term, home-based transcranial direct current stimulation coupled with computerized cognitive training in frontotemporal dementia: A case report.

We present the case of a 62-year-old woman with probable behavioral variant of frontotemporal dementia (bvFTD) with cognitive/language deficits who demonstrated improved performance on cognitive/language testing and in functional tasks following long-term, home-based transcranial direct current stimulation (tDCS) coupled with computerized cognitive training (CCT). The patient underwent home-based tDCS (anode on the left prefrontal cortex and cathode on the right homologue) for 46 sessions over 10 weeks along with CCT. On post-treatment testing, the patient improved by 3 points on the Mini-Mental State Exam (MMSE) (23 to 26). She also showed improvement on several cognitive/language tasks, such as immediate recall of single words and word pairs, total accurate words in sentence repetition, delayed recall, semantic processing, and sentence level comprehension. There was no decline in several other cognitive and language tasks. Family members reported subjective improvements in expressiveness, communication, and interaction with others as well as increased attention to grooming and style which contrasted with her pre-treatment condition. This report suggests that home-based tDCS combined with CCT for an extended period may slow decline, and improve cognitive/language performance and everyday function in FTD.

Long-term, Home-based Transcranial Direct Current Stimulation Coupled with Computerized Cognitive Training in Frontotemporal Dementia: A Case Report: A 62-year-old woman with probable behavioral variant of frontotemporal dementia (bvFTD) improved on cognitive/language testing and in functional tasks following long-term, home-based transcranial direct current stimulation (tDCS) coupled with computerized cognitive training (CCT). The patient underwent home-based tDCS for 46 sessions over 10 weeks along with CCT. On post-treatment testing, the patient improved by three points on the Mini-Mental State Exam (MMSE) (23 to 26). She also improved immediate recall of single words and word pairs, total accurate words in sentence repetition, delayed recall, semantic processing, and sentence level comprehension. There was no decline in several other cognitive and language tasks. Family members described improvements in expressiveness, communication, and interaction with others and increased attention to grooming and style which was different from her pre-treatment condition. This case report suggests that home-based tDCS combined with CCT for an extended period may slow decline and improve cognitive/language performance and everyday function in FTD.

Baseline functional connectivity predicts who will benefit from neuromodulation: evidence from primary progressive aphasia.

Background: Identifying the characteristics of individuals who demonstrate response to an intervention allows us to predict who is most likely to benefit from certain interventions. Prediction is challenging in rare and heterogeneous diseases, such as primary progressive aphasia (PPA), that have varying clinical manifestations. We aimed to determine the characteristics of those who will benefit most from transcranial direct current stimulation (tDCS) of the left inferior frontal gyrus (IFG) using a novel heterogeneity and group identification analysis. Methods: We compared the predictive ability of demographic and clinical patient characteristics (e.g., PPA variant and disease progression, baseline language performance) vs. functional connectivity alone (from resting-state fMRI) in the same cohort. Results: Functional connectivity alone had the highest predictive value for outcomes, explaining 62% and 75% of tDCS effect of variance in generalization (semantic fluency) and in the trained outcome of the clinical trial (written naming), contrasted with <15% predicted by clinical characteristics, including baseline language performance. Patients with higher baseline functional connectivity between the left IFG (opercularis and triangularis), and between the middle temporal pole and posterior superior temporal gyrus, were most likely to benefit from tDCS. Conclusions: We show the importance of a baseline 7-minute functional connectivity scan in predicting tDCS outcomes, and point towards a precision medicine approach in neuromodulation studies. The study has important implications for clinical trials and practice, providing a statistical method that addresses heterogeneity in patient populations and allowing accurate prediction and enrollment of those who will most likely benefit from specific interventions.

Home-Based Transcranial Direct Current Stimulation in Primary Progressive Aphasia: A Pilot Study.

BACKGROUND: This study aims to determine (a) if home-based anodal transcranial direct current stimulation (a-tDCS) delivered to the left supramarginal gyrus (SMG) coupled with verbal short-term memory/working memory (vSTM/WM) treatment ("RAM", short for "Repeat After Me") is more effective than sham-tDCS in improving vSTM/WM in patients with primary progressive aphasia (PPA), and (b) whether tDCS effects generalize to other language and cognitive abilities. METHODS: Seven PPA participants received home-based a-tDCS and sham-tDCS coupled with RAM treatment in separate conditions in a double-blind design. The treatment task required participants to repeat word spans comprising semantically and phonologically unrelated words in the same and reverse order. The evaluation of treatment effects was carried out using the same tasks as in the treatment but with different items (near-transfer effects) and tasks that were not directly related to the treatment (far-transfer effects). RESULTS: A-tDCS showed (a) a significant effect in improving vSTM abilities, measured by word span backward, and (b) a generalization of this effect to other language abilities, namely, spelling (both real words and pseudowords) and learning (retention and delayed recall). CONCLUSIONS: These preliminary results indicate that vSTM/WM intervention can improve performance in trained vSTM/WM tasks in patients with PPA, especially when augmented with home-based tDCS over the left SMG.

Brain total creatine differs between primary progressive aphasia (PPA) subtypes and correlates with disease severity.

Primary progressive aphasia (PPA) is comprised of three subtypes: logopenic (lvPPA), non-fluent (nfvPPA), and semantic (svPPA). We used magnetic resonance spectroscopy (MRS) to measure tissue-corrected metabolite levels in the left inferior frontal gyrus (IFG) and right sensorimotor cortex (SMC) from 61 PPA patients. We aimed to: (1) characterize subtype differences in metabolites; and (2) test for metabolite associations with symptom severity. tCr differed by subtype across the left IFG and right SMC. tCr levels were lowest in lvPPA and highest in svPPA. tCr levels predicted lvPPA versus svPPA diagnosis. Higher IFG tCr and lower Glx correlated with greater disease severity. As tCr is involved in brain energy metabolism, svPPA pathology might involve changes in specific cellular energy processes. Perturbations to cellular energy homeostasis in language areas may contribute to symptoms. Reduced cortical excitatory capacity (i.e. lower Glx) in language regions may also contribute to symptoms. Thus, tCr may be useful for differentiating between PPA subtypes, and both tCr and Glx might have utility in understanding PPA mechanisms and tracking progression.

A deep learning system for differential diagnosis of skin diseases.

Skin conditions affect 1.9 billion people. Because of a shortage of dermatologists, most cases are seen instead by general practitioners with lower diagnostic accuracy. We present a deep learning system (DLS) to provide a differential diagnosis of skin conditions using 16,114 de-identified cases (photographs and clinical data) from a teledermatology practice serving 17 sites. The DLS distinguishes between 26 common skin conditions, representing 80% of cases seen in primary care, while also providing a secondary prediction covering 419 skin conditions. On 963 validation cases, where a rotating panel of three board-certified dermatologists defined the reference standard, the DLS was non-inferior to six other dermatologists and superior to six primary care physicians (PCPs) and six nurse practitioners (NPs) (top-1 accuracy: 0.66 DLS, 0.63 dermatologists, 0.44 PCPs and 0.40 NPs). These results highlight the potential of the DLS to assist general practitioners in diagnosing skin conditions.

Avoidable tragedies: Disparities in healthcare access among medically underserved women diagnosed with cervical cancer.

BACKGROUND: The purpose was to identify barriers including logistical and health belief correlates of late stage presentation of cervical cancer (CxCa) among medically underserved women presenting to a safety net health care system. METHODS: Women presenting with newly diagnosed CxCa were asked to complete a detailed health belief survey that included questions about barriers to care and their knowledge of CxCa. All information was collected prior to initiating cancer treatment. Comparisons were made among women diagnosed at early stages of disease amendable to surgical treatment (≤IB1) and those diagnosed at a stage requiring local-regional or systemic/palliative treatment (≥IB2). RESULTS: Among the 138 women, 21.7% were diagnosed with ≤lB1 disease, while 78.3% were diagnosed with ≥IB2 disease. Late-stage diagnosis was associated with a greater number of emergency room (ER) visits (p<.001) and blood transfusions (p<.001) prior to diagnosis. Compared to 88% with ≤lB1 disease, only 53% of patients with ≥IB2 disease had a car (p=.003). Women with ≥IB2 disease were more likely to be without a primary care provider (75.0% vs. 42.3%, p=.001). CONCLUSION: Access to transportation and lack of a regular primary care provider or a medical home are associated with late-stage of CxCa at diagnosis. Many medically underserved women continue to use the ER as their primary source of health care, and as a result their CxCa is diagnosed in advanced stages, with higher medical costs and lower chances of cure. The lack of Medicaid expansion in Texas may result in a worsening of this situation.

Assessment of sexual activity and dysfunction in medically underserved women with gynecologic cancers.

BACKGROUND: Sexual dysfunction is a common long-term side effect of treatments for gynecologic cancer. Studies of sexual problems in gynecologic cancer survivors overrepresent White non-Hispanic, highly educated, and married women. Less is known about the sexual health needs of women in medically underserved populations. We therefore conducted a study to characterize sexual activity and sexual function in this population. METHODS: We recruited patients attending two gynecologic oncology clinics in a large public healthcare system that primarily serves uninsured and low-income patients. Participants were invited to complete a one-time survey to assess sexual function, sexual communication, sexual distress, relationship adjustment, depression, anxiety, prior help-seeking and help-seeking preferences, and reasons for sexual inactivity. Data were analyzed using descriptive statistics and multivariate models to predict sexual activity status and sexual dysfunction. RESULTS: Among 243 participants, the majority (n=160, 65.8%) were not sexually active in the past 4weeks, most often due to lack of a partner or lack of desire for sex. Just over one-fourth of sexually active participants were identified as likely cases of sexual dysfunction. Greater endorsement of depressive symptoms predicted both sexual inactivity and sexual dysfunction in multivariate analyses. Prior help-seeking for sexual problems was uncommon; however, a significant minority of participants expressed interest in receiving care for sexual problems. CONCLUSIONS: Gynecologic cancer survivors in our medically underserved population have high rates of sexual inactivity and sexual dysfunction. Future research should identify feasible strategies to address barriers to sexual healthcare in low-resource settings.

The leaf-area shrinkage effect can bias paleoclimate and ecology research.

PREMISE OF THE STUDY: Leaf area is a key trait that links plant form, function, and environment. Measures of leaf area can be biased because leaf area is often estimated from dried or fossilized specimens that have shrunk by an unknown amount. We tested the common assumption that this shrinkage is negligible. METHODS: We measured shrinkage by comparing dry and fresh leaf area in 3401 leaves of 380 temperate and tropical species and used phylogenetic and trait-based approaches to determine predictors of this shrinkage. We also tested the effects of rehydration and simulated fossilization on shrinkage in four species. KEY RESULTS: We found that dried leaves shrink in area by an average of 22% and a maximum of 82%. Shrinkage in dried leaves can be predicted by multiple morphological traits with a standard deviation of 7.8%. We also found that mud burial, a proxy for compression fossilization, caused negligible shrinkage, and that rehydration, a potential treatment of dried herbarium specimens, eliminated shrinkage. CONCLUSIONS: Our findings indicate that the amount of shrinkage is driven by variation in leaf area, leaf thickness, evergreenness, and woodiness and can be reversed by rehydration. The amount of shrinkage may also be a useful trait related to ecologically and physiological differences in drought tolerance and plant life history.