Real-world complex systems may be mathematically modeled as graphs, revealing properties of the system. Here we study graphs of functional brain organization in healthy adults using resting state ...functional connectivity MRI. We propose two novel brain-wide graphs, one of 264 putative functional areas, the other a modification of voxelwise networks that eliminates potentially artificial short-distance relationships. These graphs contain many subgraphs in good agreement with known functional brain systems. Other subgraphs lack established functional identities; we suggest possible functional characteristics for these subgraphs. Further, graph measures of the areal network indicate that the default mode subgraph shares network properties with sensory and motor subgraphs: it is internally integrated but isolated from other subgraphs, much like a “processing” system. The modified voxelwise graph also reveals spatial motifs in the patterning of systems across the cortex.
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► Areal and modified voxelwise graph definitions are proposed ► Subgraphs reflect known and unknown brain systems ► Default mode, sensory, and motor systems share network properties ► Functional systems are patterned across the cortex with spatial regularities
Autism spectrum disorders (ASD) are diagnosed based on early-manifesting clinical symptoms, including markedly impaired social communication. We assessed the viability of resting-state functional MRI ...(rs-fMRI) connectivity measures as diagnostic biomarkers for ASD and investigated which connectivity features are predictive of a diagnosis.
Rs-fMRI scans from 59 high functioning males with ASD and 59 age- and IQ-matched typically developing (TD) males were used to build a series of machine learning classifiers. Classification features were obtained using 3 sets of brain regions. Another set of classifiers was built from participants' scores on behavioral metrics. An additional age and IQ-matched cohort of 178 individuals (89 ASD; 89 TD) from the Autism Brain Imaging Data Exchange (ABIDE) open-access dataset (http://fcon_1000.projects.nitrc.org/indi/abide/) were included for replication.
High classification accuracy was achieved through several rs-fMRI methods (peak accuracy 76.67%). However, classification via behavioral measures consistently surpassed rs-fMRI classifiers (peak accuracy 95.19%). The class probability estimates, P(ASD|fMRI data), from brain-based classifiers significantly correlated with scores on a measure of social functioning, the Social Responsiveness Scale (SRS), as did the most informative features from 2 of the 3 sets of brain-based features. The most informative connections predominantly originated from regions strongly associated with social functioning.
While individuals can be classified as having ASD with statistically significant accuracy from their rs-fMRI scans alone, this method falls short of biomarker standards. Classification methods provided further evidence that ASD functional connectivity is characterized by dysfunction of large-scale functional networks, particularly those involved in social information processing.
The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates.
To estimate age-specific risks of breast, ovarian, and contralateral breast cancer ...for mutation carriers and to evaluate risk modification by family cancer history and mutation location.
Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years.
BRCA1/2 mutations, family cancer history, and mutation location.
Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer.
Among 3886 women (median age, 38 years; interquartile range IQR, 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72% (95% CI, 65%-79%) for BRCA1 and 69% (95% CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for BRCA1 and 17% (95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio HR for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for ≥2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11-1.93; P=.007) and c.2831-c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36-2.74; P<.001).
These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.
Although typically identified in early childhood, the social communication symptoms and adaptive behavior deficits that are characteristic of autism spectrum disorder (ASD) persist throughout the ...lifespan. Despite this persistence, even individuals without cooccurring intellectual disability show substantial heterogeneity in outcomes. Previous studies have found various behavioral assessments such as intelligence quotient (IQ), early language ability, and baseline autistic traits and adaptive behavior scores to be predictive of outcome, but most of the variance in functioning remains unexplained by such factors. In this study, we investigated to what extent functional brain connectivity measures obtained from resting-state functional connectivity MRI (rs-fcMRI) could predict the variance left unexplained by age and behavior (follow-up latency and baseline autistic traits and adaptive behavior scores) in two measures of outcome—adaptive behaviors and autistic traits at least 1 y postscan (mean follow-up latency = 2 y, 10 mo). We found that connectivity involving the so-called salience network (SN), default-mode network (DMN), and frontoparietal task control network (FPTCN) was highly predictive of future autistic traits and the change in autistic traits and adaptive behavior over the same time period. Furthermore, functional connectivity involving the SN, which is predominantly composed of the anterior insula and the dorsal anterior cingulate, predicted reliable improvement in adaptive behaviors with 100% sensitivity and 70.59% precision. From rs-fcMRI data, our study successfully predicted heterogeneity in outcomes for individuals with ASD that was unaccounted for by simple behavioral metrics and provides unique evidence for networks underlying long-term symptom abatement.
Prediction of Individual Brain Maturity Using fMRI Dosenbach, Nico U. F.; Nardos, Binyam; Cohen, Alexander L. ...
Science (American Association for the Advancement of Science),
09/2010, Letnik:
329, Številka:
5997
Journal Article
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Group functional connectivity magnetic resonance imaging (fcAARI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector ...machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals' brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain's major functional networks.
Sensory information is represented and elaborated in hierarchical cortical systems that are thought to be dedicated to individual sensory modalities. This traditional view of sensory cortex ...organization has been challenged by recent evidence of multimodal responses in primary and association sensory areas. Although it is indisputable that sensory areas respond to multiple modalities, it remains unclear whether these multimodal responses reflect selective information processing for particular stimulus features. Here, we used fMRI adaptation to identify brain regions that are sensitive to the temporal frequency information contained in auditory, tactile, and audiotactile stimulus sequences. A number of brain regions distributed over the parietal and temporal lobes exhibited frequency-selective temporal response modulation for both auditory and tactile stimulus events, as indexed by repetition suppression effects. A smaller set of regions responded to crossmodal adaptation sequences in a frequency-dependent manner. Despite an extensive overlap of multimodal frequency-selective responses across the parietal and temporal lobes, representational similarity analysis revealed a cortical “regional landscape” that clearly reflected distinct somatosensory and auditory processing systems that converged on modality-invariant areas. These structured relationships between brain regions were also evident in spontaneous signal fluctuation patterns measured at rest. Our results reveal that multimodal processing in human cortex can be feature-specific and that multimodal frequency representations are embedded in the intrinsically hierarchical organization of cortical sensory systems.
•Traditional brain organization models are marked by the segregation of sensory signals in modality-dedicated brain regions.•fMRI adaptation identified cortical regions exhibiting sensitivity to both tactile and auditory frequency information.•Multivariate response patterns provide clear evidence of modality-based cortical organization.•Spontaneous BOLD signal fluctuation patterns recapitulate modality-based cortical organization.•Feature-specific auditory and tactile processing are co-embedded in traditionally-defined cortical systems.
Abstract
Recent studies have challenged the traditional notion of modality-dedicated cortical systems by showing that audition and touch evoke responses in the same sensory brain regions. While much ...of this work has focused on somatosensory responses in auditory regions, fewer studies have investigated sound responses and representations in somatosensory regions. In this functional magnetic resonance imaging (fMRI) study, we measured BOLD signal changes in participants performing an auditory frequency discrimination task and characterized activation patterns related to stimulus frequency using both univariate and multivariate analysis approaches. Outside of bilateral temporal lobe regions, we observed robust and frequency-specific responses to auditory stimulation in classically defined somatosensory areas. Moreover, using representational similarity analysis to define the relationships between multi-voxel activation patterns for all sound pairs, we found clear similarity patterns for auditory responses in the parietal lobe that correlated significantly with perceptual similarity judgments. Our results demonstrate that auditory frequency representations can be distributed over brain regions traditionally considered to be dedicated to somatosensation. The broad distribution of auditory and tactile responses over parietal and temporal regions reveals a number of candidate brain areas that could support general temporal frequency processing and mediate the extensive and robust perceptual interactions between audition and touch.
Understanding potential response of forest carbon (C) and nutrient storage to warming is important for climate mitigation policies. Unfortunately, those responses are difficult to predict in ...seasonally dry forests, in part, because ecosystem processes are highly sensitive to both changes in temperature and precipitation. We investigated how warming might alter stocks of C, nitrogen (N), and phosphorus (P) in vegetation and the entire regolith (soil + weathered bedrock or “saprock”) using a space‐for‐time substitution along a bioclimatic gradient in the Sierra Nevada, California. The pine‐oak and mixed‐conifer forests between 1,160–2,015 m elevation have more optimal climates (not too dry or hot) for ecosystem productivity, soil weathering, and cycling of essential elements than the oak savannah (405 m) and subalpine forest (2,700 m). We found decreases in overstory vegetation nutrient stocks with decreasing elevation because of enhanced water limitation and greater occurrence of disturbances. Stocks of C, N, and P in the entire regolith peaked at the pine‐oak and mixed‐conifer forests across the bioclimatic gradient, driven by thicker regolith profiles and greater nutrient input rates. These observations suggest long‐term warming will decrease ecosystem nutrient storage at the warmer, transitional pine‐oak zone, but will increase nutrient storage at the colder, subalpine zone. Assuming steady‐state conditions, we found the mean residence time of ecosystem C decreased with projected rising air temperatures and increased following a major drought event across the bioclimatic gradient. Our study emphasizes potentially elevation‐dependent changes in nutrient storage and C persistence with warming in seasonally dry forests.
Plain Language Summary
Carbon accumulation in forest ecosystems is a promising natural climate solution to offset rising temperatures. However, major knowledge gaps exist on warming impacts on carbon storage in seasonally dry forests, where ecosystem processes are highly sensitive to both changes in temperature and precipitation. We investigated nutrient pools in vegetation, soil, and weathered bedrock along a 2,300‐m bioclimatic gradient in the Sierra Nevada, California. We observed unimodal changes in ecosystem nutrient stocks with decreasing elevation, suggesting long‐term warming will decrease nutrient storage at relatively warm sites (e.g., transitional pine‐oak zone), but will increase nutrient storage at cold sites (e.g., subalpine zone). Deep soil and weathered bedrock respond to a changing climate similarly to surficial soils, demonstrating the importance of accounting for deep carbon to accurately assess carbon turnover rates. Estimated average time (assuming steady‐state) that a carbon atom resides in forests from initial photosynthetic fixation until respiration loss increases with projected rising air temperatures and decreases following a major drought event, which emphasizes the complex response of carbon storage to warmer and drier conditions. Our study provides a broader understanding of how ecosystem structure and function may respond to warming in Mediterranean‐climate regions, some of the most vulnerable to climate change.
Key Points
In Mediterranean‐climate regions, warming will decrease forest storage of C, N, and P at warmer sites but not at colder sites
Climatic impacts on soil C storage can remain substantial even in deep soil and weathered bedrock
Ecosystem C residence times will decrease with rising air temperatures but will increase with major droughts
Neutrophils are a short-lived, terminally differentiated, innate immune cell, that are critical first responders during infection. Research into neutrophil-pathogen interactions in fish has primarily ...employed cells derived from the pro-nephros and nephros. Since these sites are also the location of neutrophil and other immune cell development, there may be some ambiguity in maturation and functional ability of these cells, and difficulty in differentiating the effects of neutrophils from those of macrophages and monocytes. In contrast, peripheral blood circulating neutrophils are mature and ready to respond, thus it may be more physiologically relevant to use these cells for immune studies when evaluating interactions with blood-borne pathogens. The enrichment of tropical, euryhaline fish blood cells cannot follow classic mammalian enrichment methods for several reasons: Fish have nucleated red blood cells (RBC's), a high number of reticulocytes, a very low number of granulocytic leukocytes and an osmotic tolerance, rendering techniques such as water lysis ineffective. Enrichment of neutrophils, while minimizing RBC contamination, is imperative for studies where luminescence or fluorescence signals may be confounded by background from an overabundance of RBC's. We have optimized a method for enriching neutrophils from peripheral blood, with an initial settlement step employing 6% dextran (Mr 450,000–650,000), for 30–60 min at room temperature, followed by density separation on an 8-step Percoll density gradient. This method provides a cell suspension comprising 20–50% neutrophils, free of contamination from reticulocytes. These are then suitable for luminometric or fluorometric downstream analyses.
•Dextran effectively separates reticulocytes and red blood cells from neutrophils in peripheral blood.•Subsequent density separation on Percoll enables reproducible functional assays of peripheral blood neutrophils.•Functional assessment of respiratory burst via stimulated neutrophils requires removal of red blood cells.
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