Tablet Technology for Writing and Drawing during Functional Magnetic Resonance Imaging: A Review.

Functional magnetic resonance imaging (fMRI) is a powerful modality to study brain activity. To approximate naturalistic writing and drawing behaviours inside the scanner, many fMRI-compatible tablet technologies have been developed. The digitizing feature of the tablets also allows examination of behavioural kinematics with greater detail than using paper. With enhanced ecological validity, tablet devices have advanced the fields of neuropsychological tests, neurosurgery, and neurolinguistics. Specifically, tablet devices have been used to adopt many traditional paper-based writing and drawing neuropsychological tests for fMRI. In functional neurosurgery, tablet technologies have enabled intra-operative brain mapping during awake craniotomy in brain tumour patients, as well as quantitative tremor assessment for treatment outcome monitoring. Tablet devices also play an important role in identifying the neural correlates of writing in the healthy and diseased brain. The fMRI-compatible tablets provide an excellent platform to support naturalistic motor responses and examine detailed behavioural kinematics.

The relationship between symptom burden and systemic inflammation differs between male and female athletes following concussion.

BACKGROUND: Inflammation appears to be an important component of concussion pathophysiology. However, its relationship to symptom burden is unclear. Therefore, the purpose of this study was to evaluate the relationship between symptoms and inflammatory biomarkers measured in the blood of male and female athletes following a sport-related concussion (SRC). RESULTS: Forty athletes (n = 20 male, n = 20 female) from nine interuniversity sport teams at a single institution provided blood samples within one week of an SRC. Twenty inflammatory biomarkers were quantitated by immunoassay. The Sport Concussion Assessment Tool version 5 (SCAT-5) was used to evaluate symptoms. Partial least squares (PLS) analyses were used to evaluate the relationship(s) between biomarkers and symptoms. In males, a positive correlation between interferon (IFN)-γ and symptom severity was observed following SRC. The relationship between IFN-γ and symptoms was significant among all symptom clusters, with cognitive symptoms displaying the largest effect. In females, a significant negative relationship was observed between symptom severity and cytokines IFN-γ, tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO); a positive relationship was observed between symptom severity and MCP-4. Inflammatory mediators were significantly associated with all symptom clusters in females; the somatic symptom cluster displayed the largest effect. CONCLUSION: These results provide supportive evidence of a divergent relationship between inflammation and symptom burden in male and female athletes following SRC. Future investigations should be cognizant of the potentially sex-specific pathophysiology underlying symptom presentation.

Peripheral blood neuroendocrine hormones are associated with clinical indices of sport-related concussion.

The purpose of this study was to evaluate the relationship between neuroendocrine hormones and clinical recovery following sport-related concussion (SRC). Ninety-five athletes (n = 56 male, n = 39 female) from a cohort of 11 interuniversity sport teams at a single institution provided blood samples; twenty six athletes with SRC were recruited 2-7 days post-injury, and 69 uninjured athletes recruited prior to the start of their competitive season. Concentrations of seven neuroendocrine hormones were quantitated in either plasma or serum by solid-phase chemiluminescent immunoassay. The Sport Concussion Assessment Tool version 5 (SCAT-5) was used to evaluate symptoms at the time of blood sampling in all athletes. Multivariate partial least squares (PLS) analyses were used to evaluate the relationship between blood hormone concentrations and both (1) time to physician medical clearance and (2) initial symptom burden. A negative relationship was observed between time to medical clearance and both dehydroepiandrosterone sulfate (DHEA-S) and progesterone; a positive relationship was found between time to medical clearance and prolactin. Cognitive, somatic, fatigue and emotion symptom clusters were associated with distinct neuroendocrine signatures. Perturbations to the neuroendocrine system in athletes following SRC may contribute to initial symptom burden and longer recovery times.

Brain connectivity tracks effects of chemotherapy separately from behavioral measures.

Several studies in cancer research have suggested that cognitive dysfunction following chemotherapy, referred to in lay terms as "chemobrain", is a serious problem. At present, the changes in integrative brain function that underlie such dysfunction remain poorly understood. Recent developments in neuroimaging suggest that patterns of functional connectivity can provide a broadly applicable neuromarker of cognitive performance and other psychometric measures. The current study used multivariate analysis methods to identify patterns of disruption in resting state functional connectivity of the brain due to chemotherapy and the degree to which the disruptions can be linked to behavioral measures of distress and cognitive performance. Sixty two women (22 healthy control, 18 patients treated with adjuvant chemotherapy, and 22 treated without chemotherapy) were evaluated with neurocognitive measures followed by self-report questionnaires and open eyes resting-state fMRI scanning at three time points: diagnosis (M0, pre-adjuvant treatment), 1 month (M1), and 7 months (M7) after treatment. The results indicated deficits in cognitive health of breast cancer patients immediately after chemotherapy that improved over time. This psychological trajectory was paralleled by a disruption and later recovery of resting-state functional connectivity, mostly in the parietal and frontal brain regions. Mediation analysis showed that the functional connectivity alteration pattern is a separable treatment symptom from the decreased cognitive health. Current study indicates that more targeted support for patients should be developed to ameliorate these multi-faceted side effects of chemotherapy treatment on neural functioning and cognitive health.

Reliability of Task-Based fMRI for Preoperative Planning: A Test-Retest Study in Brain Tumor Patients and Healthy Controls.

BACKGROUND: Functional magnetic resonance imaging (fMRI) continues to develop as a clinical tool for patients with brain cancer, offering data that may directly influence surgical decisions. Unfortunately, routine integration of preoperative fMRI has been limited by concerns about reliability. Many pertinent studies have been undertaken involving healthy controls, but work involving brain tumor patients has been limited. To develop fMRI fully as a clinical tool, it will be critical to examine these reliability issues among patients with brain tumors. The present work is the first to extensively characterize differences in activation map quality between brain tumor patients and healthy controls, including the effects of tumor grade and the chosen behavioral testing paradigm on reliability outcomes. METHOD: Test-retest data were collected for a group of low-grade (n = 6) and high-grade glioma (n = 6) patients, and for matched healthy controls (n = 12), who performed motor and language tasks during a single fMRI session. Reliability was characterized by the spatial overlap and displacement of brain activity clusters, BOLD signal stability, and the laterality index. Significance testing was performed to assess differences in reliability between the patients and controls, and low-grade and high-grade patients; as well as between different fMRI testing paradigms. RESULTS: There were few significant differences in fMRI reliability measures between patients and controls. Reliability was significantly lower when comparing high-grade tumor patients to controls, or to low-grade tumor patients. The motor task produced more reliable activation patterns than the language tasks, as did the rhyming task in comparison to the phonemic fluency task. CONCLUSION: In low-grade glioma patients, fMRI data are as reliable as healthy control subjects. For high-grade glioma patients, further investigation is required to determine the underlying causes of reduced reliability. To maximize reliability outcomes, testing paradigms should be carefully selected to generate robust activation patterns.

Scale-free brain dynamics under physical and psychological distress: pre-treatment effects in women diagnosed with breast cancer.

Stressful life events are related to negative outcomes, including physical and psychological manifestations of distress, and behavioral deficits. Patients diagnosed with breast cancer report impaired attention and working memory prior to adjuvant therapy, which may be induced by distress. In this article, we examine whether brain dynamics show systematic changes due to the distress associated with cancer diagnosis. We hypothesized that impaired working memory is associated with suppression of "long-memory" neuronal dynamics; we tested this by measuring scale-free ("fractal") brain dynamics, quantified by the Hurst exponent (H). Fractal scaling refers to signals that do not occur at a specific time-scale, possessing a spectral power curve P(f)∝ f(-ß); they are "long-memory" processes, with significant autocorrelations. In a BOLD functional magnetic resonance imaging study, we scanned three groups during a working memory task: women scheduled to receive chemotherapy or radiotherapy and aged-matched controls. Surprisingly, patients' BOLD signal exhibited greater H with increasing intensity of anticipated treatment. However, an analysis of H and functional connectivity against self-reported measures of psychological distress (Worry, Anxiety, Depression) and physical distress (Fatigue, Sleep problems) revealed significant interactions. The modulation of (Worry, Anxiety) versus (Fatigue, Sleep Problems, Depression) showed the strongest effect, where higher worry and lower fatigue was related to reduced H in regions involved in visuospatial search, attention, and memory processing. This is also linked to decreased functional connectivity in these brain regions. Our results indicate that the distress associated with cancer diagnosis alters BOLD scaling, and H is a sensitive measure of the interaction between psychological versus physical distress.

The functional connectivity landscape of the human brain.

Functional brain networks emerge and dissipate over a primarily static anatomical foundation. The dynamic basis of these networks is inter-regional communication involving local and distal regions. It is assumed that inter-regional distances play a pivotal role in modulating network dynamics. Using three different neuroimaging modalities, 6 datasets were evaluated to determine whether experimental manipulations asymmetrically affect functional relationships based on the distance between brain regions in human participants. Contrary to previous assumptions, here we show that short- and long-range connections are equally likely to strengthen or weaken in response to task demands. Additionally, connections between homotopic areas are the most stable and less likely to change compared to any other type of connection. Our results point to a functional connectivity landscape characterized by fluid transitions between local specialization and global integration. This ability to mediate functional properties irrespective of spatial distance may engender a diverse repertoire of cognitive processes when faced with a dynamic environment.

Algorithm and simulation for real-time positron emission based tumor tracking using a linear fiducial marker.

The effectiveness of radiotherapy in cancer treatment remains significantly limited by the accuracy of tumor dose delivery. The ideal solution lies in real-time localization of patient tumors during therapy; one such method is by tracking implanted low-activity positron emitters using two pairs of orthogonally placed gamma-ray detectors. Prior studies have examined multiple point sources, which have potential patient complications during implantation. A linear source geometry is proposed as a less invasive alternative, with potential higher-precision tracking. A source localization algorithm has been devised using cost-function minimization of the source position estimate relative to annihilation gamma coincidence lines. The algorithm was tested via Monte Carlo simulation methods using a Geant4 application for emission tomography (GATE) package for a source of length of 2.00 cm and width of 0.1 mm. The midpoint of the linear marker was located within submillimeter accuracy at 200 coincidence events and the orientation of the source determined with less than 5 degrees (0.087 rad) angular deviation at 300 events. At an optimal event count of 700, tracking had mean midpoint error of 0.48 +/- 0.26 mm and mean angular deviation of 0.041 +/- 0.023 rad (1.4 degrees +/- 0.8 degree). The source and tracking algorithm may prove effective for future clinical implementation in radiotherapy treatment.