Strength of spatial correlation between gray matter connectivity and patterns of proto-oncogene and neural network construction gene expression is associated with diffuse glioma survival.

Introduction: Like other forms of neuropathology, gliomas appear to spread along neural pathways. Accordingly, our group and others have previously shown that brain network connectivity is highly predictive of glioma survival. In this study, we aimed to examine the molecular mechanisms of this relationship via imaging transcriptomics. Methods: We retrospectively obtained presurgical, T1-weighted MRI datasets from 669 adult patients, newly diagnosed with diffuse glioma. We measured brain connectivity using gray matter networks and coregistered these data with a transcriptomic brain atlas to determine the spatial co-localization between brain connectivity and expression patterns for 14 proto-oncogenes and 3 neural network construction genes. Results: We found that all 17 genes were significantly co-localized with brain connectivity (p < 0.03, corrected). The strength of co-localization was highly predictive of overall survival in a cross-validated Cox Proportional Hazards model (mean area under the curve, AUC = 0.68 +/- 0.01) and significantly (p < 0.001) more so for a random forest survival model (mean AUC = 0.97 +/- 0.06). Bayesian network analysis demonstrated direct and indirect causal relationships among gene-brain co-localizations and survival. Gene ontology analysis showed that metabolic processes were overexpressed when spatial co-localization between brain connectivity and gene transcription was highest (p < 0.001). Drug-gene interaction analysis identified 84 potential candidate therapies based on our findings. Discussion: Our findings provide novel insights regarding how gene-brain connectivity interactions may affect glioma survival.

Impact of COVID-19-related experiences on health-related quality of life in cancer survivors in the United States.

OBJECTIVE: Little evidence exists on the impact of the COVID-19 pandemic on cancer survivors, limiting recommendations to improve health-related quality of life (HRQoL) in this population. We describe survivors' pandemic experiences and examine associations between COVID-19-related exposures, psychosocial experiences, and HRQoL. METHODS: Between May 2020-April 2021, survivors completed cross-sectional questionnaires capturing COVID-19-related exposures (e.g., exposure to virus, job loss); psychosocial experiences (i.e., COVID-19-related anxiety/depression, disruptions to health care and daily activities/social interactions, satisfaction with providers' response to COVID, financial hardship, perceived benefits of the pandemic, social support, and perceived stress management ability); and HRQoL. RESULTS: Data were collected from N = 11,325 survivors in the United States. Participants were mostly female (58%), White (89%) and non-Hispanic (88%), and age 63 on average. Breast cancer was the most common diagnosis (23%). Eight percent of participants reported being exposed to COVID-19; 1% tested positive. About 6% of participants lost their jobs, while 24% lost household income. Nearly 30% avoided attending in-person oncology appointments because of the pandemic. Poorer HRQoL was associated with demographic (younger age; female; non-Hispanic White), clinical (Medicare; stage IV disease; hematologic/digestive/respiratory system cancer), and psychosocial factors (low perceived benefits and stress management ability; more disruption to health care and daily activities/social interactions; financial hardship). CONCLUSIONS: COVID-19-related stressors were associated with various psychosocial experiences in cancer survivors, and these psychosocial experiences were associated with HRQoL above and beyond demographic and clinical factors.

Intraoperative language mapping guided by real-time visualization of gamma band modulation electrocorticograms: Case report and proof of concept.

Background: Electrocorticography (ECoG) language mapping is often performed extraoperatively, frequently involves offline processing, and relationships with direct cortical stimulation (DCS) remain variable. We sought to determine the feasibility and preliminary utility of an intraoperative language mapping approach guided by real-time visualization of electrocorticograms. Methods: A patient with astrocytoma underwent awake craniotomy with intraoperative language mapping, utilizing a dual iPad stimulus presentation system coupled to a real-time neural signal processing platform capable of both ECoG recording and delivery of DCS. Gamma band modulations in response to 4 language tasks at each electrode were visualized in real-time. Next, DCS was conducted for each neighboring electrode pair during language tasks. Results: All language tasks resulted in strongest heat map activation at an electrode pair in the anterior to mid superior temporal gyrus. Consistent speech arrest during DCS was observed for Object and Action naming tasks at these same electrodes, indicating good correspondence with ECoG heat map recordings. This region corresponded well with posterior language representation via preoperative functional MRI. Conclusions: Intraoperative real-time visualization of language task-based ECoG gamma band modulation is feasible and may help identify targets for DCS. If validated, this may improve the efficiency and accuracy of intraoperative language mapping.

Decoding the clinical effects of low-grade glioma-induced cortical excitability.

OBJECTIVE: Patients with low-grade glioma (LGG) in eloquent regions often present with seizures, and findings on detailed neuropsychological testing are often abnormal. This study evaluated the association between cortical excitability, seizures, and cognitive function in patients with LGG. METHODS: LGG patients who underwent transcranial magnetic stimulation (TMS) from January 2021 to December 2022 were studied. Cortical excitability was measured using the resting motor thresholds (RMTs) of the upper and lower extremities. Early postoperative seizures served as the seizure endpoint. Neuropsychological assessment was completed prior to surgery contemporaneous with the TMS studies. RESULTS: A total of 31 patients were analyzed for seizure outcome. Median (interquartile range [IQR]) upper-extremity RMT was 39% (34%-46%) of maximum stimulator output, and the median (IQR) lower-extremity RMT was 69% (51%-79%). Lower-extremity RMT was higher in patients with early postoperative seizures, especially in those with motor region tumors (p = 0.02); however, RMT was not associated with seizures at presentation or long-term seizure control. A total of 26 patients completed neuropsychological assessment. There were significant negative correlations between upper-extremity RMT and psychomotor processing speed (Wechsler Adult Intelligence Scale-Fourth Edition [WAIS-IV] Processing Speed Index r = -0.42, p = 0.031; WAIS-IV Coding r = -0.41, p = 0.036; WAIS-IV Symbol Search r = -0.39, p = 0.048), executive function (Trail Making Test Part B r = -0.41, p = 0.036), and hand dexterity (Grooved Pegboard Test r = -0.50, p = 0.047). CONCLUSIONS: RMT was positively correlated with early postoperative seizure risk and negatively correlated with psychomotor processing speed, executive function, and hand dexterity. These findings support the theory of local and regional resting oscillatory network dysfunction from a glioma-brain network.

Brain-computer interface relieves chronic chemotherapy-induced peripheral neuropathy: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) includes negative sensations that remain a major chronic problem for cancer survivors. Previous research demonstrated that neurofeedback (a closed-loop brain-computer interface [BCI]) was effective at treating CIPN versus a waitlist control (WLC). The authors' a priori hypothesis was that BCI would be superior to placebo feedback (placebo control [PLC]) and to WLC in alleviating CIPN and that changes in brain activity would predict symptom report. METHODS: Randomization to one of three conditions occurred between November 2014 and November 2018. Breast cancer survivors no longer in treatment were assessed at baseline, at the end of 20 treatment sessions, and 1 month later. Auditory and visual rewards were given over 20 sessions based on each patient's ability to modify their own electroencephalographic signals. The Pain Quality Assessment Scale (PQAS) at the end of treatment was the primary outcome, and changes in electroencephalographic signals and 1-month data also were examined. RESULTS: The BCI and PLC groups reported significant symptom reduction. The BCI group demonstrated larger effect size differences from the WLC group than the PLC group (mean change score: BCI vs. WLC, -2.60 vs. 0.38; 95% confidence interval, -3.67, -1.46 [p = .000; effect size, 1.07]; PLC, -2.26; 95% confidence interval, -3.33, -1.19 [p = .001 vs. WLC; effect size, 0.9]). At 1 month, symptoms continued to improve only for the BCI group. Targeted brain changes at the end of treatment predicted symptoms at 1 month for the BCI group only. CONCLUSIONS: BCI is a promising treatment for CIPN and may have a longer lasting effect than placebo (nonspecific BCI), which is an important consideration for long-term symptom relief. Although scientifically interesting, the ability to separate real from placebo treatment may not be as important as understanding the placebo effects differently from effects of the intervention. PLAIN LANGUAGE SUMMARY: Chemotherapy-induced nerve pain (neuropathy) can be disabling for cancer survivors; however, the way symptoms are felt depends on how the brain interprets the signals from nerves in the body. We determined that the perception of neuropathy can be changed by working directly with the brain. Survivors in our trial played 20 sessions of a type of video game that was designed to change the way the brain processed sensation and movement. In this, our second trial, we again observed significant improvement in symptoms that lasted after the treatment was complete.

Strength of spatial correlation between structural brain network connectivity and brain-wide patterns of proto-oncogene and neural network construction gene expression is associated with diffuse glioma survival.

Like other forms of neuropathology, gliomas appear to spread along neural pathways. Accordingly, our group and others have previously shown that brain network connectivity is highly predictive of glioma survival. In this study, we aimed to examine the molecular mechanisms of this relationship via imaging transcriptomics. We retrospectively obtained presurgical, T1-weighted MRI datasets from 669 adult patients, newly diagnosed with diffuse glioma. We measured brain connectivity using gray matter networks and coregistered these data with a transcriptomic brain atlas to determine the spatial co-localization between brain connectivity and expression patterns for 14 proto-oncogenes and 3 neural network construction genes. We found that all 17 genes were significantly co-localized with brain connectivity (p < 0.03, corrected). The strength of co-localization was highly predictive of overall survival in a cross-validated Cox Proportional Hazards model (mean area under the curve, AUC = 0.68 +/- 0.01) and significantly (p < 0.001) more so for a random forest survival model (mean AUC = 0.97 +/- 0.06). Bayesian network analysis demonstrated direct and indirect causal relationships among gene-brain co-localizations and survival. Gene ontology analysis showed that metabolic processes were overexpressed when spatial co-localization between brain connectivity and gene transcription was highest (p < 0.001). Drug-gene interaction analysis identified 84 potential candidate therapies based on our findings. Our findings provide novel insights regarding how gene-brain connectivity interactions may affect glioma survival.

Neuroimaging based biotypes for precision diagnosis and prognosis in cancer-related cognitive impairment.

Cancer related cognitive impairment (CRCI) is commonly associated with cancer and its treatments, yet the present binary diagnostic approach fails to capture the full spectrum of this syndrome. Cognitive function is highly complex and exists on a continuum that is poorly characterized by dichotomous categories. Advanced statistical methodologies applied to symptom assessments have demonstrated that there are multiple subclasses of CRCI. However, studies suggest that relying on symptom assessments alone may fail to account for significant differences in the neural mechanisms that underlie a specific cognitive phenotype. Treatment plans that address the specific physiologic mechanisms involved in an individual patient's condition is the heart of precision medicine. In this narrative review, we discuss how biotyping, a precision medicine framework being utilized in other mental disorders, could be applied to CRCI. Specifically, we discuss how neuroimaging can be used to determine biotypes of CRCI, which allow for increased precision in prediction and diagnosis of CRCI via biologic mechanistic data. Biotypes may also provide more precise clinical endpoints for intervention trials. Biotyping could be made more feasible with proxy imaging technologies or liquid biomarkers. Large cross-sectional phenotyping studies are needed in addition to evaluation of longitudinal trajectories, and data sharing/pooling is highly feasible with currently available digital infrastructures.

Development and initial psychometric evaluation of a COVID-related psychosocial experiences questionnaire for cancer survivors.

BACKGROUND: Cancer survivors are at elevated risk of psychological problems related to COVID-19, yet no published measure adequately assesses their psychosocial experiences during the pandemic. PURPOSE: Describe the development and factor structure of a comprehensive, self-report measure (COVID-19 Practical and Psychosocial Experiences questionnaire [COVID-PPE]) assessing the pandemic's impact on US cancer survivors. METHODS: The sample (n = 10,584) was divided into three groups to assess COVID-PPE factor structure by conducting: (1) initial calibration/exploratory analysis of the factor structure of 37 items (n = 5070), (2) confirmatory factor analysis of the best-fitting model (36 items after item removal; n = 5140), and (3) post-hoc confirmatory analysis with an additional six items not collected in the first two groups (42 items; n = 374). RESULTS: The final COVID-PPE was divided into two sets of subscales, conceptualized as Risk Factors and Protective Factors. The five Risk Factors subscales were labeled Anxiety Symptoms, Depression Symptoms, Health Care Disruptions, Disruptions to Daily Activities and Social Interactions, and Financial Hardship. The four Protective Factors subscales were labeled Perceived Benefits, Provider Satisfaction, Perceived Stress Management Skills, and Social Support. Internal consistency was acceptable for seven subscales (αs = 0.726-0.895; ωs = 0.802-0.895) but poor or questionable for the remaining two subscales (αs = 0.599-0.681; ωs = 0.586-0.692). CONCLUSIONS: To our knowledge, this is the first published self-report measure comprehensively capturing psychosocial impact-both positive and negative-of the pandemic on cancer survivors. Future work should evaluate predictive utility of COVID-PPE subscales, particularly as the pandemic evolves, which may inform recommendations for cancer survivors and facilitate identification of survivors most in need of intervention.

Behavioral and biologic characteristics of cancer-related cognitive impairment biotypes.

Psychiatric diagnosis is moving away from symptom-based classification and towards multi-dimensional, biologically-based characterization, or biotyping. We previously identified three biotypes of chemotherapy-related cognitive impairment based on functional brain connectivity. In this follow-up study of 80 chemotherapy-treated breast cancer survivors and 80 non-cancer controls, we evaluated additional factors to help explain biotype expression: neurofunctional stability, brain age, apolipoprotein (APOE) genotype, and psychoneurologic symptoms. We also compared the discriminative ability of a traditional, symptom-based cognitive impairment definition with that of biotypes. We found significant differences in cortical brain age (F = 10.50, p < 0.001), neurofunctional stability (F = 2.83, p = 0.041), APOE e4 genotype (X2 = 7.68, p = 0.050), and psychoneurological symptoms (Pillai = 0.378, p < 0.001) across the three biotypes. The more resilient Biotype 2 demonstrated significantly higher neurofunctional stability compared to the other biotypes. Symptom-based classification of cognitive impairment did not differentiate biologic or other behavioral variables, suggesting that traditional categorization of cancer-related cognitive effects may miss important characteristics which could inform targeted treatment strategies. Additionally, biotyping, but not symptom-typing, was able to distinguish survivors with cognitive versus psychological effects. Our results suggest that Biotype 1 survivors might benefit from first addressing symptoms of anxiety and fatigue, Biotype 3 might benefit from a treatment plan which includes sleep hygiene, and Biotype 2 might benefit most from cognitive skills training or rehabilitation. Future research should include additional demographic and clinical information to further investigate biotype expression related to risk and resilience and examine integration of more clinically feasible imaging approaches.

Comparative study of preoperative functional imaging combined with tractography for prediction of iatrogenic motor deficits.

OBJECTIVE: Robust preoperative imaging can improve the extent of resection in patients with brain tumors while minimizing postoperative neurological morbidity. Both structural and functional imaging techniques can provide helpful preoperative information. A recent study found that transcranial magnetic stimulation (TMS) tractography has significant predictive value for permanent deficits. The present study directly compares the predictive value of TMS tractography and task-based functional MRI (fMRI) tractography in the same cohort of glioma patients. METHODS: Clinical outcome data were collected from charts of patients with motor eloquent glioma and preoperative fMRI and TMS studies. The primary outcome was a new or worsened motor deficit present at the 3-month postoperative follow-up, which was termed a "permanent deficit." Postoperative MR images were overlaid onto preoperative plans to determine which imaging features were resected. Multiple fractional anisotropic thresholds (FATs) were screened for both TMS and fMRI tractography. The predictive value of the various thresholds was modeled using receiver operating characteristic curve analysis. RESULTS: Forty patients were included in this study. Six patients (15%) sustained permanent postoperative motor deficits. A significantly greater predictive value was found for TMS tractography than for fMRI tractography regardless of the FAT. Despite 35% of patients showing clinically relevant neuroplasticity captured by TMS, only 2.5% of patients showed a blood oxygen level-dependent signal displaced from the precentral gyrus. Comparing the best-performing FAT for both modalities, TMS seeded tractography showed superior predictive value across all metrics: sensitivity, specificity, positive predictive value, and negative predictive value. CONCLUSIONS: The results from this study indicate that the prediction of permanent deficits with TMS tractography is superior to that with fMRI tractography, possibly because TMS tractography captures clinically relevant neuroplasticity. However, future large-scale prospective studies are needed to fully illuminate the proper role of each modality in comprehensive presurgical workups for patients with motor-eloquent tumors.

Predicting overall survival in diffuse glioma from the presurgical connectome.

Diffuse gliomas are incurable brain tumors, yet there is significant heterogeneity in patient survival. Advanced computational techniques such as radiomics show potential for presurgical prediction of survival and other outcomes from neuroimaging. However, these techniques ignore non-lesioned brain features that could be essential for improving prediction accuracy. Gray matter covariance network (connectome) features were retrospectively identified from the T1-weighted MRIs of 305 adult patients diagnosed with diffuse glioma. These features were entered into a Cox proportional hazards model to predict overall survival with 10-folds cross-validation. The mean time-dependent area under the curve (AUC) of the connectome model was compared with the mean AUCs of clinical and radiomic models using a pairwise t-test with Bonferroni correction. One clinical model included only features that are known presurgery (clinical) and another included an advantaged set of features that are not typically known presurgery (clinical +). The median survival time for all patients was 134.2 months. The connectome model (AUC 0.88 ± 0.01) demonstrated superior performance (P < 0.001, corrected) compared to the clinical (AUC 0.61 ± 0.02), clinical + (AUC 0.79 ± 0.01) and radiomic models (AUC 0.75 ± 0.02). These findings indicate that the connectome is a feasible and reliable early biomarker for predicting survival in patients with diffuse glioma. Connectome and other whole-brain models could be valuable tools for precision medicine by informing patient risk stratification and treatment decision-making.

A randomized pilot study of oncology massage to treat chemotherapy-induced peripheral neuropathy.

This pilot randomized controlled trial investigated massage therapy for symptomatic relief of chemotherapy-induced peripheral neuropathy (CIPN) to determine the ideal weekly frequency and number of weeks of providing massage. We evaluated the feasibility and initial efficacy of a Swedish massage protocol to treat lower extremity (LE) CIPN. Inclusion criteria: LE neuropathy attributed to oxaliplatin, paclitaxel, or docetaxel, with no other attributable causes; ≥ 6 months since last chemotherapy; self-reported neuropathy score ≥ 3, 0-10 scale; age ≥ 18. Participant randomization (2:2:1:1) to one of four groups: LE (2) or head/neck/shoulder (control; 1) massage 3 times (3X) a week for 4 weeks; LE (2) or control (1) massage 2X/week for 6 weeks. Completion rate and the Pain Quality Assessment Scale (PQAS) was measured at baseline and 10 weeks later. 71 patients participated: 77.5% women; 57.7% (breast cancer), and 42.3% (GI cancer); mean age 60.3 y/o (range: 40-77); average > 3 years since last chemotherapy. Massage was deemed feasible: mean completion rates (max = 12) were 8.9 (SD 4.2) for 3X/week and 9.8 (SD 4.0) for 2X/week with no statistically significant differences. There were no statistically significant treatment group interactions in PQAS scores at 10-weeks follow-up. There was a statistically significant treatment schedule main effect for PQAS subscales (p < 0.05) at 10 weeks, with lower CIPN symptoms for 3X/week groups versus 2X/week groups. Improvements considered clinically significant favored the LE 3X/week group. Completion rates met pre-defined feasibility criteria. We seemed to observe better outcomes (CIPN symptom reduction) with the more intensive (3X/week for 4 weeks) massage intervention with no differences in adherence, regardless of whether the massage was directly to the CIPN-affected area or not. However, there was some suggestion that the massage program targeting the CIPN-affected area directly provided 3X a week for 4 weeks resulted in the best outcomes.

Transcranial magnetic stimulation tractography and the facilitation of gross total resection in a patient with a motor eloquent glioblastoma: illustrative case.

BACKGROUND: In patients with perieloquent tumors, neurosurgeons must use a variety of techniques to maximize survival while minimizing postoperative neurological morbidity. Recent publications have shown that conventional anatomical features may not always predict postoperative deficits. Additionally, scientific conceptualizations of complex brain function have shifted toward more dynamic, neuroplastic theories instead of traditional static, localizationist models. Functional imaging techniques have emerged as potential tools to incorporate these advances into modern neurosurgical care. In this case report, we describe our observations using preoperative transcranial magnetic stimulation data combined with tractography to guide a nontraditional surgical approach in a patient with a motor eloquent glioblastoma. OBSERVATIONS: The authors detail the use of preoperative functional and structural imaging to perform a gross total resection despite tumor infiltration of conventionally eloquent anatomical structures. The authors resected the precentral gyrus, specifically the paracentral lobule, localized using intraoperative mapping techniques. The patient demonstrated mild transient postoperative weakness and made a full neurological recovery by discharge 1 week later. LESSONS: Preoperative functional and structural imaging has potential to not only optimize patient selection and surgical planning, but also facilitate important intraoperative decisions. Innovative preoperative imaging techniques should be optimized and used to identify safely resectable structures.

Transcranial magnetic stimulation (TMS) seeded tractography provides superior prediction of eloquence compared to anatomic seeded tractography.

Background: For patients with brain tumors, maximizing the extent of resection while minimizing postoperative neurological morbidity requires accurate preoperative identification of eloquent structures. Recent studies have provided evidence that anatomy may not always predict eloquence. In this study, we directly compare transcranial magnetic stimulation (TMS) data combined with tractography to traditional anatomic grading criteria for predicting permanent deficits in patients with motor eloquent gliomas. Methods: We selected a cohort of 42 glioma patients with perirolandic tumors who underwent preoperative TMS mapping with subsequent resection and intraoperative mapping. We collected clinical outcome data from their chart with the primary outcome being new or worsened motor deficit present at 3 month follow up, termed "permanent deficit". We overlayed the postoperative resection cavity onto the preoperative MRI containing preoperative imaging features. Results: Almost half of the patients showed TMS positive points significantly displaced from the precentral gyrus, indicating tumor induced neuroplasticity. In multivariate regression, resection of TMS points was significantly predictive of permanent deficits while the resection of the precentral gyrus was not. TMS tractography showed significantly greater predictive value for permanent deficits compared to anatomic tractography, regardless of the fractional anisotropic (FA) threshold. For the best performing FA threshold of each modality, TMS tractography provided both higher positive and negative predictive value for identifying true nonresectable, eloquent cortical and subcortical structures. Conclusion: TMS has emerged as a preoperative mapping modality capable of capturing tumor induced plastic reorganization, challenging traditional presurgical imaging modalities.

Cross-Cultural Brain Activity Differences Between True and Sham Acupuncture for Xerostomia During Head and Neck Cancer Radiotherapy.

BACKGROUND: A prior phase III, multicenter (United States and China), clinical trial found true acupuncture (TA) resulted in lower xerostomia scores 12 months after radiotherapy than that of a standard care control group. This small pilot study examined brain function changes comparing TA to sham acupuncture (SA) in US and Fudan patients undergoing head and neck radiotherapy. METHODS: To determine cerebral activity during TA versus SA acupuncture, patients underwent electroencephalogram evaluation (EEG) immediately prior, during and after both conditions. Acupuncture occurred during weeks 3 to 5 of radiotherapy, with patients receiving either TA or SA, followed 2 to 3 days later by the other treatment in a counterbalanced manner. RESULTS: In the TA minus SA condition (N = 14 Fudan; N = 13 US), most changes were in the delta (0.5-3.5 Hz) and alpha (8-12 Hz) bandwidths. Delta was present in the frontal gyrus and parahippocampal gyrus. Alpha was present in the anterior and posterior cingulate, lingual gyrus, amygdala, precuneus, medial frontal gyrus, fusiform gyrus, and superior frontal gyrus. Maximal cortical differences in the Fudan cohort between TA and SA were in areas previously shown to be associated with (TA). In the US cohort, maximal differences between TA and SA were associated with areas which are usually decreased in TA conditions. CONCLUSIONS: There were distinct differences in brain function between those receiving TA and SA and there were clear differences between cultures, helping to explain the lack of placebo effect in the Fudan participants and strong placebo effect in the US patients.

Validation of Non-invasive Language Mapping Modalities for Eloquent Tumor Resection: A Pilot Study.

Many studies have established a link between extent of resection and survival in patients with gliomas. Surgeons must optimize the oncofunctional balance by maximizing the extent of resection and minimizing postoperative neurological morbidity. Preoperative functional imaging modalities are important tools for optimizing the oncofunctional balance. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) are non-invasive imaging modalities that can be used for preoperative functional language mapping. Scarce data exist evaluating the accuracy of these preoperative modalities for language mapping compared with gold standard intraoperative data in the same cohort. This study compares the accuracy of fMRI and TMS for language mapping compared with intraoperative direct cortical stimulation (DCS). We also identified significant predictors of preoperative functional imaging accuracy, as well as significant predictors of functional outcomes. Evidence from this study could inform clinical judgment as well as provide neuroscientific insight. We used geometric distances to determine copositivity between preoperative data and intraoperative data. Twenty-eight patients were included who underwent both preoperative fMRI and TMS procedures, as well as an awake craniotomy and intraoperative language mapping. We found that TMS shows significantly superior correlation to intraoperative DCS compared with fMRI. TMS also showed significantly higher sensitivity and negative predictive value than specificity and positive predictive value. Poor cognitive baseline was associated with decreased TMS accuracy as well as increased risk for worsened aphasia postoperatively. TMS has emerged as a promising preoperative language mapping tool. Future work should be done to identify the proper role of each imaging modality in a comprehensive, multimodal approach to optimize the oncofunctional balance.

TMS Seeded Diffusion Tensor Imaging Tractography Predicts Permanent Neurological Deficits.

Surgeons must optimize the onco-functional balance by maximizing the extent of resection and minimizing postoperative neurological morbidity. Optimal patient selection and surgical planning requires preoperative identification of nonresectable structures. Transcranial magnetic stimulation is a method of noninvasively mapping the cortical representations of the speech and motor systems. Despite recent promising data, its clinical relevance and appropriate role in a comprehensive mapping approach remains unknown. In this study, we aim to provide direct evidence regarding the clinical utility of transcranial magnetic stimulation by interrogating the eloquence of TMS points. Forty-two glioma patients were included in this retrospective study. We collected motor function outcomes 3 months postoperatively. We overlayed the postoperative MRI onto the preoperative MRI to visualize preoperative TMS points in the context of the surgical cavity. We then generated diffusion tensor imaging tractography to identify meaningful subsets of TMS points. We correlated the resection of preoperative imaging features with clinical outcomes. The resection of TMS-positive points was significantly predictive of permanent deficits (p = 0.05). However, four out of eight patients had TMS-positive points resected without a permanent deficit. DTI tractography at a 75% FA threshold identified which TMS points are essential and which are amenable to surgical resection. TMS combined with DTI tractography shows a significant prediction of postoperative neurological deficits with both a high positive predictive value and negative predictive value.

A Bayesian Dirichlet process community occupancy model to estimate community structure and species similarity.

Community occupancy models estimate species-specific parameters while sharing information across species by treating parameters as sampled from a common distribution. When communities consist of discrete groups, shrinkage of estimates toward the community mean can mask differences among groups. Infinite-mixture models using a Dirichlet process (DP) distribution, in which the number of latent groups is estimated from the data, have been proposed as a solution. In addition to community structure, these models estimate species similarity, which allows testing hypotheses about whether traits drive species response to environmental conditions. We develop a community occupancy model (COM) using a DP distribution to model species-level parameters. Because clustering algorithms are sensitive to dimensionality and distinctiveness of clusters, we conducted a simulation study to explore performance of the DP-COM with different dimensions (i.e., different numbers of model parameters with species-level DP random effects) and under varying cluster differences. Because the DP-COM is computationally expensive, we compared its estimates to a COM with a normal random species effect. We further applied the DP-COM model to a bird data set from Uganda. Estimates of the number of clusters and species cluster identity improved with increasing difference among clusters and increasing dimensions of the DP; but the number of clusters was always overestimated. Estimates of number of sites occupied and species and community-level covariate coefficients on occupancy probability were generally unbiased with (near-) nominal 95% Bayesian Credible Interval coverage. Accuracy of estimates from the normal and the DP-COM was similar. The DP-COM clustered 166 bird species into 27 clusters regarding their affiliation with open or woodland habitat and distance to oil wells. Estimates of covariate coefficients were similar between a normal and the DP-COM. Except sunbirds, species within a family were not more similar in their response to these covariates than the overall community. Given that estimates were consistent between the normal and the DP-COM, and considering the computational burden for the DP models, we recommend using the DP-COM only when the analysis focuses on community structure and species similarity, as these quantities can only be obtained under the DP-COM.

Effect of True and Sham Acupuncture on Radiation-Induced Xerostomia Among Patients With Head and Neck Cancer: A Randomized Clinical Trial.

Importance: Radiation-induced xerostomia (RIX) is a common, often debilitating, adverse effect of radiation therapy among patients with head and neck cancer. Quality of life can be severely affected, and current treatments have limited benefit. Objective: To determine if acupuncture can prevent RIX in patients with head and neck cancer undergoing radiation therapy. Design, Setting, and Participants: This 2-center, phase 3, randomized clinical trial compared a standard care control (SCC) with true acupuncture (TA) and sham acupuncture (SA) among patients with oropharyngeal or nasopharyngeal carcinoma who were undergoing radiation therapy in comprehensive cancer centers in the United States and China. Patients were enrolled between December 16, 2011, and July 7, 2015. Final follow-up was August 15, 2016. Analyses were conducted February 1 through 28, 2019. Intervention: Either TA or SA using a validated acupuncture placebo device was performed 3 times per week during a 6- to 7-week course of radiation therapy. Main Outcomes and Measures: The primary end point was RIX, as determined by the Xerostomia Questionnaire in which a higher score indicates worse RIX, for combined institutions 1 year after radiation therapy ended. Secondary outcomes included incidence of clinically significant xerostomia (score >30), salivary flow, quality of life, salivary constituents, and role of baseline expectancy related to acupuncture on outcomes. Results: Of 399 patients randomized, 339 were included in the final analysis (mean [SD] age, 51.3 [11.7] years; age range, 21-79 years; 258 [77.6%] men), including 112 patients in the TA group, 115 patients in the SA group, and 112 patients in the SCC group. For the primary aim, the adjusted least square mean (SD) xerostomia score in the TA group (26.6 [17.7]) was significantly lower than in the SCC group (34.8 [18.7]) (P = .001; effect size = -0.44) and marginally lower but not statistically significant different from the SA group (31.3 [18.6]) (P = .06; effect size = -0.26). Incidence of clinically significant xerostomia 1 year after radiation therapy ended followed a similar pattern, with 38 patients in the TA group (34.6%), 54 patients in the SA group (47.8%), and 60 patients in the SCC group (55.1%) experiencing clinically significant xerostomia (P = .009). Post hoc comparisons revealed a significant difference between the TA and SCC groups at both institutions, but TA was significantly different from SA only at Fudan University Cancer Center, Shanghai, China (estimated difference [SE]: TA vs SCC, -9.9 [2.5]; P < .001; SA vs SCC, -1.7 [2.5]; P = .50; TA vs SA, -8.2 [2.5]; P = .001), and SA was significantly different from SCC only at the University of Texas MD Anderson Cancer Center, Houston, Texas (estimated difference [SE]: TA vs SCC, -8.1 [3.4]; P = .016; SA vs SCC, -10.5 [3.3]; P = .002; TA vs SA, 2.4 [3.2]; P = .45). Conclusions and Relevance: This randomized clinical trial found that TA resulted in significantly fewer and less severe RIX symptoms 1 year after treatment vs SCC. However, further studies are needed to confirm clinical relevance and generalizability of this finding and to evaluate inconsistencies in response to sham acupuncture between patients in the United States and China. Trial Registration: ClinicalTrials.gov identifier: NCT01266044.