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1.
Article in English | MEDLINE | ID: mdl-36561350

ABSTRACT

The transition from high school to college is a taxing time for young adults. New students arriving on campus navigate a myriad of challenges centered around adapting to new living situations, financial needs, academic pressures and social demands. First-year students need to gain new skills and strategies to cope with these new demands in order to make good decisions, ease their transition to independent living and ultimately succeed. In general, first-generation students are less prepared when they enter college in comparison to non-first-generation students. This presents additional challenges for first-generation students to overcome and be successful during their college years. We study first-year students through the lens of mobile phone sensing across their first year at college, including all academic terms and breaks. We collect longitudinal mobile sensing data for N=180 first-year college students, where 27 of the students are first-generation, representing 15% of the study cohort and representative of the number of first-generation students admitted each year at the study institution, Dartmouth College. We discuss risk factors, behavioral patterns and mental health of first-generation and non-first-generation students. We propose a deep learning model that accurately predicts the mental health of first-generation students by taking into account important distinguishing behavioral factors of first-generation students. Our study, which uses the StudentLife app, offers data-informed insights that could be used to identify struggling students and provide new forms of phone-based interventions with the goal of keeping students on track.

2.
J Med Internet Res ; 23(6): e28892, 2021 06 04.
Article in English | MEDLINE | ID: mdl-33900935

ABSTRACT

BACKGROUND: Since late 2019, the lives of people across the globe have been disrupted by COVID-19. Millions of people have become infected with the disease, while billions of people have been continually asked or required by local and national governments to change their behavioral patterns. Previous research on the COVID-19 pandemic suggests that it is associated with large-scale behavioral and mental health changes; however, few studies have been able to track these changes with frequent, near real-time sampling or compare these changes to previous years of data for the same individuals. OBJECTIVE: By combining mobile phone sensing and self-reported mental health data in a cohort of college-aged students enrolled in a longitudinal study, we seek to understand the behavioral and mental health impacts associated with the COVID-19 pandemic, measured by interest across the United States in the search terms coronavirus and COVID fatigue. METHODS: Behaviors such as the number of locations visited, distance traveled, duration of phone use, number of phone unlocks, sleep duration, and sedentary time were measured using the StudentLife mobile smartphone sensing app. Depression and anxiety were assessed using weekly self-reported ecological momentary assessments, including the Patient Health Questionnaire-4. The participants were 217 undergraduate students. Differences in behaviors and self-reported mental health collected during the Spring 2020 term, as compared to previous terms in the same cohort, were modeled using mixed linear models. RESULTS: Linear mixed models demonstrated differences in phone use, sleep, sedentary time and number of locations visited associated with the COVID-19 pandemic. In further models, these behaviors were strongly associated with increased interest in COVID fatigue. When mental health metrics (eg, depression and anxiety) were added to the previous measures (week of term, number of locations visited, phone use, sedentary time), both anxiety and depression (P<.001) were significantly associated with interest in COVID fatigue. Notably, these behavioral and mental health changes are consistent with those observed around the initial implementation of COVID-19 lockdowns in the spring of 2020. CONCLUSIONS: In the initial lockdown phase of the COVID-19 pandemic, people spent more time on their phones, were more sedentary, visited fewer locations, and exhibited increased symptoms of anxiety and depression. As the pandemic persisted through the spring, people continued to exhibit very similar changes in both mental health and behaviors. Although these large-scale shifts in mental health and behaviors are unsurprising, understanding them is critical in disrupting the negative consequences to mental health during the ongoing pandemic.


Subject(s)
Behavior , COVID-19/epidemiology , Ecological Momentary Assessment , Mental Health/statistics & numerical data , Pandemics , Smartphone , Students/psychology , Adolescent , Anxiety/diagnosis , Cell Phone Use/statistics & numerical data , Depression/diagnosis , Female , Humans , Locomotion , Longitudinal Studies , Male , Mobile Applications , Sedentary Behavior , Self Report , Sleep , Surveys and Questionnaires , Young Adult
3.
Neuroimage ; 233: 117975, 2021 06.
Article in English | MEDLINE | ID: mdl-33762217

ABSTRACT

Shared information content is represented across brains in idiosyncratic functional topographies. Hyperalignment addresses these idiosyncrasies by using neural responses to project individuals' brain data into a common model space while maintaining the geometric relationships between distinct patterns of activity or connectivity. The dimensions of this common model capture functional profiles that are shared across individuals such as cortical response profiles collected during a common time-locked stimulus presentation (e.g. movie viewing) or functional connectivity profiles. Hyperalignment can use either response-based or connectivity-based input data to derive transformations that project individuals' neural data from anatomical space into the common model space. Previously, only response or connectivity profiles were used in the derivation of these transformations. In this study, we developed a new hyperalignment algorithm, hybrid hyperalignment, that derives transformations based on both response-based and connectivity-based information. We used three different movie-viewing fMRI datasets to test the performance of our new algorithm. Hybrid hyperalignment derives a single common model space that aligns response-based information as well as or better than response hyperalignment while simultaneously aligning connectivity-based information better than connectivity hyperalignment. These results suggest that a single common information space can encode both shared cortical response and functional connectivity profiles across individuals.


Subject(s)
Brain Mapping/methods , Cerebral Cortex/diagnostic imaging , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Motion Pictures , Nerve Net/diagnostic imaging , Adult , Cerebral Cortex/physiology , Female , Humans , Male , Nerve Net/physiology , Photic Stimulation/methods
4.
Depress Anxiety ; 38(6): 615-625, 2021 06.
Article in English | MEDLINE | ID: mdl-33621379

ABSTRACT

BACKGROUND: Poor social connection is a central feature of posttraumatic stress disorder (PTSD), but little is known about the neurocognitive processes associated with social difficulties in this population. We examined recruitment of the default network and behavioral responses during social working memory (SWM; i.e., maintaining and manipulating social information on a moment-to-moment basis) in relation to PTSD and social connection. METHODS: Participants with PTSD (n = 31) and a trauma-exposed control group (n = 21) underwent functional magnetic resonance imaging while completing a task in which they reasoned about two or four people's relationships in working memory (social condition) and alphabetized two or four people's names in working memory (nonsocial condition). Participants also completed measures of social connection (e.g., loneliness, social network size). RESULTS: Compared to trauma-exposed controls, individuals with PTSD reported smaller social networks (p = .032) and greater loneliness (p = .038). Individuals with PTSD showed a selective deficit in SWM accuracy (p = .029) and hyperactivation in the default network, particularly in the dorsomedial subsystem, on trials with four relationships to consider. Moreover, default network hyperactivation in the PTSD group (vs. trauma-exposed group) differentially related to social network size and loneliness (p's < .05). Participants with PTSD also showed less resting state functional connectivity within the dorsomedial subsystem than controls (p = .002), suggesting differences in the functional integrity of a subsystem key to SWM. CONCLUSIONS: SWM abnormalities in the default network may be a basic mechanism underlying poorer social connection in PTSD.


Subject(s)
Stress Disorders, Post-Traumatic , Humans , Loneliness , Magnetic Resonance Imaging , Memory, Short-Term , Stress Disorders, Post-Traumatic/diagnostic imaging
5.
Emotion ; 21(8): 1760-1770, 2021 Dec.
Article in English | MEDLINE | ID: mdl-35041440

ABSTRACT

Although mammals have a strong motivation to engage in social interaction, stress can significantly interfere with this desire. Indeed, research in nonhuman animals has shown that stress reduces social interaction, a phenomenon referred to as "stress-induced social avoidance." While stress and social disconnection are also intertwined in humans, to date, evidence that stress predicts reductions in social interaction is mixed, in part, because existing paradigms fail to capture social interaction naturalistically. To help overcome this barrier, we combined experience sampling and passive mobile sensing methods with time-lagged analyses (i.e., vector autoregressive modeling) to investigate the temporal impact of stress on real-world indices of social interaction. We found that, across a 2-month period, greater perceived stress on a given day predicted significantly decreased social interaction-measured by the amount of face to face conversation-the following day. Critically, the reverse pattern was not observed (i.e., social interaction did not temporally predict stress), and the effect of stress on social interaction was present while accounting for other related variables such as sleep, movement, and time spent at home. These findings are consistent with animal research on stress-induced social avoidance and lay the groundwork for creating naturalistic, mobile-sensing based human models to further elucidate the cycle between stress and real-world social interaction. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Social Behavior , Social Interaction , Communication , Humans , Stress, Psychological
6.
J Med Internet Res ; 22(6): e20185, 2020 06 17.
Article in English | MEDLINE | ID: mdl-32519963

ABSTRACT

BACKGROUND: The vast majority of people worldwide have been impacted by coronavirus disease (COVID-19). In addition to the millions of individuals who have been infected with the disease, billions of individuals have been asked or required by local and national governments to change their behavioral patterns. Previous research on epidemics or traumatic events suggests that this can lead to profound behavioral and mental health changes; however, researchers are rarely able to track these changes with frequent, near-real-time sampling or compare their findings to previous years of data for the same individuals. OBJECTIVE: By combining mobile phone sensing and self-reported mental health data among college students who have been participating in a longitudinal study for the past 2 years, we sought to answer two overarching questions. First, have the behaviors and mental health of the participants changed in response to the COVID-19 pandemic compared to previous time periods? Second, are these behavior and mental health changes associated with the relative news coverage of COVID-19 in the US media? METHODS: Behaviors such as the number of locations visited, distance traveled, duration of phone usage, number of phone unlocks, sleep duration, and sedentary time were measured using the StudentLife smartphone sensing app. Depression and anxiety were assessed using weekly self-reported ecological momentary assessments of the Patient Health Questionnaire-4. The participants were 217 undergraduate students, with 178 (82.0%) students providing data during the Winter 2020 term. Differences in behaviors and self-reported mental health collected during the Winter 2020 term compared to previous terms in the same cohort were modeled using mixed linear models. RESULTS: During the first academic term impacted by COVID-19 (Winter 2020), individuals were more sedentary and reported increased anxiety and depression symptoms (P<.001) relative to previous academic terms and subsequent academic breaks. Interactions between the Winter 2020 term and the week of the academic term (linear and quadratic) were significant. In a mixed linear model, phone usage, number of locations visited, and week of the term were strongly associated with increased amount of COVID-19-related news. When mental health metrics (eg, depression and anxiety) were added to the previous measures (week of term, number of locations visited, and phone usage), both anxiety (P<.001) and depression (P=.03) were significantly associated with COVID-19-related news. CONCLUSIONS: Compared with prior academic terms, individuals in the Winter 2020 term were more sedentary, anxious, and depressed. A wide variety of behaviors, including increased phone usage, decreased physical activity, and fewer locations visited, were associated with fluctuations in COVID-19 news reporting. While this large-scale shift in mental health and behavior is unsurprising, its characterization is particularly important to help guide the development of methods to reduce the impact of future catastrophic events on the mental health of the population.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/psychology , Ecological Momentary Assessment , Pneumonia, Viral/psychology , Smartphone , Students/psychology , Adolescent , Adult , COVID-19 , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Female , Humans , Longitudinal Studies , Male , Mental Health , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , SARS-CoV-2 , Young Adult
7.
JMIR Ment Health ; 7(6): e16684, 2020 Jun 10.
Article in English | MEDLINE | ID: mdl-32519971

ABSTRACT

BACKGROUND: Across college campuses, the prevalence of clinically relevant depression or anxiety is affecting more than 27% of the college population at some point between entry to college and graduation. Stress and self-esteem have both been hypothesized to contribute to depression and anxiety levels. Although contemporaneous relationships between these variables have been well-defined, the causal relationship between these mental health factors is not well understood, as frequent sampling can be invasive, and many of the current causal techniques are not well suited to investigate correlated variables. OBJECTIVE: This study aims to characterize the causal and contemporaneous networks between these critical mental health factors in a cohort of first-year college students and then determine if observed results replicate in a second, distinct cohort. METHODS: Ecological momentary assessments of depression, anxiety, stress, and self-esteem were obtained weekly from two cohorts of first-year college students for 40 weeks (1 academic year). We used the Peter and Clark Momentary Conditional Independence algorithm to identify the contemporaneous (t) and causal (t-1) network structures between these mental health metrics. RESULTS: All reported results are significant at P<.001 unless otherwise stated. Depression was causally influenced by self-esteem (t-1 rp, cohort 1 [C1]=-0.082, cohort 2 [C2]=-0.095) and itself (t-1 rp, C1=0.388, C2=0.382) in both cohorts. Anxiety was causally influenced by stress (t-1 rp, C1=0.095, C2=0.104), self-esteem (t-1 rp, C1=-0.067, C2=-0.064, P=.002), and itself (t-1 rp, of C1=0.293, C2=0.339) in both cohorts. A causal link between anxiety and depression was observed in the first cohort (t-1 rp, C1=0.109) and only observed in the second cohort with a more liberal threshold (t-1 rp, C2=0.044, P=.03). Self-esteem was only causally influenced by itself (t-1 rp, C1=0.389, C2=0.393). Stress was only causally influenced by itself (t-1 rp, C1=0.248, C2=0.273). Anxiety had positive contemporaneous links to depression (t rp, C1=0.462, C2=0.444) and stress (t rp, C1=0.354, C2=0.358). Self-esteem had negative contemporaneous links to each of the other three mental health metrics, with the strongest negative relationship being stress (t rp, C1=-0.334, C2=-0.340), followed by depression (t rp, C1=-0.302, C2=-0.274) and anxiety (t rp, C1=-0.256, C2=-0.208). Depression had positive contemporaneous links to anxiety (previously mentioned) and stress (t rp, C1=0.250, C2=0.231). CONCLUSIONS: This paper is an initial attempt to describe the contemporaneous and causal relationships among these four mental health metrics in college students. We replicated previous research identifying concurrent relationships between these variables and extended them by identifying causal links among these metrics. These results provide support for the vulnerability model of depression and anxiety. Understanding how causal factors impact the evolution of these mental states over time may provide key information for targeted treatment or, perhaps more importantly, preventative interventions for individuals at risk for depression and anxiety.

8.
Article in English | MEDLINE | ID: mdl-36540188

ABSTRACT

Brain circuit functioning and connectivity between specific regions allow us to learn, remember, recognize and think as humans. In this paper, we ask the question if mobile sensing from phones can predict brain functional connectivity. We study the brain resting-state functional connectivity (RSFC) between the ventromedial prefrontal cortex (vmPFC) and the amygdala, which has been shown by neuroscientists to be associated with mental illness such as anxiety and depression. We discuss initial results and insights from the NeuroSence study, an exploratory study of 105 first year college students using neuroimaging and mobile sensing across one semester. We observe correlations between several behavioral features from students' mobile phones and connectivity between vmPFC and amygdala, including conversation duration (r=0.365, p<0.001), sleep onset time (r=0.299, p<0.001) and the number of phone unlocks (r=0.253, p=0.029). We use a support vector classifier and 10-fold cross validation and show that we can classify whether students have higher (i.e., stronger) or lower (i.e., weaker) vmPFC-amygdala RSFC purely based on mobile sensing data with an F1 score of 0.793. To the best of our knowledge, this is the first paper to report that resting-state brain functional connectivity can be predicted using passive sensing data from mobile phones.

9.
Front Neurosci ; 13: 248, 2019.
Article in English | MEDLINE | ID: mdl-30949024

ABSTRACT

As smartphone usage has become increasingly prevalent in our society, so have rates of depression, particularly among young adults. Individual differences in smartphone usage patterns have been shown to reflect individual differences in underlying affective processes such as depression (Wang et al., 2018). In the current study, a positive relationship was identified between smartphone screen time (e.g., phone unlock duration) and resting-state functional connectivity (RSFC) between the subgenual cingulate cortex (sgCC), a brain region implicated in depression and antidepressant treatment response, and regions of the ventromedial/orbitofrontal cortex (OFC), such that increased phone usage was related to stronger connectivity between these regions. This cluster was subsequently used to constrain subsequent analyses looking at individual differences in depressive symptoms in the same cohort and observed partial replication in a separate cohort. Similar analyses were subsequently performed on metrics of circadian rhythm consistency showing a negative relationship between connectivity of the sgCC and OFC. The data and analyses presented here provide relatively simplistic preliminary analyses which replicate and provide an initial step in combining functional brain activity and smartphone usage patterns to better understand issues related to mental health. Smartphones are a prevalent part of modern life and the usage of mobile sensing data from smartphones promises to be an important tool for mental health diagnostics and neuroscience research.

10.
JMIR Mhealth Uhealth ; 7(3): e12084, 2019 03 19.
Article in English | MEDLINE | ID: mdl-30888327

ABSTRACT

BACKGROUND: Stress levels among college students have been on the rise for the last few decades. Currently, rates of reported stress among college students are at an all-time high. Traditionally, the dominant way to assess stress levels has been through pen-and-paper surveys. OBJECTIVE: The aim of this study is to use passive sensing data collected via mobile phones to obtain a rich and potentially less-biased source of data that can be used to help better understand stressors in the college experience. METHODS: We used a mobile sensing app, StudentLife, in tandem with a pictorial mobile phone-based measure of stress, the Mobile Photographic Stress Meter, to investigate the situations and contexts that are more likely to precipitate stress. RESULTS: Using recently developed methods for handling high-dimensional longitudinal data, penalized generalized estimating equations, we identified a set of mobile sensing features (absolute values of beta >0.001 and robust z>1.96) across the domains of social activity, movement, location, and ambient noise that were predictive of student stress levels. CONCLUSIONS: By combining recent statistical methods and mobile phone sensing, we have been able to study stressors in the college experience in a way that is more objective, detailed, and less intrusive than past research. Future work can leverage information gained from passive sensing and use that to develop real-time, targeted interventions for students experiencing a stressful time.


Subject(s)
Cell Phone/statistics & numerical data , Stress, Psychological/classification , Students/psychology , Adolescent , Adult , Cell Phone/trends , Female , Humans , Male , Mobile Applications/standards , Mobile Applications/trends , Photography/instrumentation , Photography/methods , Stress, Psychological/psychology , Students/statistics & numerical data , Surveys and Questionnaires , Universities/organization & administration , Universities/standards , Universities/statistics & numerical data
11.
Hum Brain Mapp ; 40(2): 361-376, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30251766

ABSTRACT

Neuroimaging studies have implicated a set of striatal and orbitofrontal cortex (OFC) regions that are commonly activated during reward processing tasks. Resting-state functional connectivity (RSFC) studies have demonstrated that the human brain is organized into several functional systems that show strong temporal coherence in the absence of goal-directed tasks. Here we use seed-based and graph-theory RSFC approaches to characterize the systems-level organization of putative reward regions of at rest. Peaks of connectivity from seed-based RSFC patterns for the nucleus accumbens (NAcc) and orbitofrontal cortex (OFC) were used to identify candidate reward regions which were merged with a previously used set of regions (Power et al., 2011). Graph-theory was then used to determine system-level membership for all regions. Several regions previously implicated in reward-processing (NAcc, lateral and medial OFC, and ventromedial prefrontal cortex) comprised a distinct, preferentially coupled system. This RSFC system is stable across a range of connectivity thresholds and shares strong overlap with meta-analyses of task-based reward studies. This reward system shares between-system connectivity with systems implicated in cognitive control and self-regulation, including the fronto-parietal, cingulo-opercular, and default systems. Differences may exist in the pathways through which control systems interact with reward system components. Whereas NAcc is functionally connected to cingulo-opercular and default systems, OFC regions show stronger connectivity with the fronto-parietal system. We propose that future work may be able to interrogate group or individual differences in connectivity profiles using the regions delineated in this work to explore potential relationships to appetitive behaviors, self-regulation failure, and addiction.


Subject(s)
Connectome , Nerve Net/physiology , Nucleus Accumbens/physiology , Prefrontal Cortex/physiology , Reward , Self-Control , Adolescent , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Net/diagnostic imaging , Nucleus Accumbens/diagnostic imaging , Prefrontal Cortex/diagnostic imaging , Young Adult
12.
Soc Cogn Affect Neurosci ; 12(5): 832-838, 2017 05 01.
Article in English | MEDLINE | ID: mdl-28158874

ABSTRACT

Previous neuroimaging work has shown that increased reward-related activity following exposure to food cues is predictive of self-control failure. The balance model suggests that self-regulation failures result from an imbalance in reward and executive control mechanisms. However, an open question is whether the relative balance of activity in brain systems associated with executive control (vs reward) supports self-regulatory outcomes when people encounter tempting cues in daily life. Sixty-nine chronic dieters, a population known for frequent lapses in self-control, completed a food cue-reactivity task during an fMRI scanning session, followed by a weeklong sampling of daily eating behaviors via ecological momentary assessment. We related participants' food cue activity in brain systems associated with executive control and reward to real-world eating patterns. Specifically, a balance score representing the amount of activity in brain regions associated with self-regulatory control, relative to automatic reward-related activity, predicted dieters' control over their eating behavior during the following week. This balance measure may reflect individual self-control capacity and be useful for examining self-regulation success in other domains and populations.


Subject(s)
Brain/physiology , Diet/psychology , Reward , Self-Control , Adolescent , Brain Mapping , Cues , Feeding Behavior , Female , Food , Humans , Individuality , Magnetic Resonance Imaging , Young Adult
13.
Cereb Cortex ; 26(1): 288-303, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25316338

ABSTRACT

The cortical surface is organized into a large number of cortical areas; however, these areas have not been comprehensively mapped in the human. Abrupt transitions in resting-state functional connectivity (RSFC) patterns can noninvasively identify locations of putative borders between cortical areas (RSFC-boundary mapping; Cohen et al. 2008). Here we describe a technique for using RSFC-boundary maps to define parcels that represent putative cortical areas. These parcels had highly homogenous RSFC patterns, indicating that they contained one unique RSFC signal; furthermore, the parcels were much more homogenous than a null model matched for parcel size when tested in two separate datasets. Several alternative parcellation schemes were tested this way, and no other parcellation was as homogenous as or had as large a difference compared with its null model. The boundary map-derived parcellation contained parcels that overlapped with architectonic mapping of areas 17, 2, 3, and 4. These parcels had a network structure similar to the known network structure of the brain, and their connectivity patterns were reliable across individual subjects. These observations suggest that RSFC-boundary map-derived parcels provide information about the location and extent of human cortical areas. A parcellation generated using this method is available at http://www.nil.wustl.edu/labs/petersen/Resources.html.


Subject(s)
Brain Mapping , Cerebral Cortex/physiology , Neural Pathways/physiology , Adult , Female , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Male , Young Adult
14.
Cereb Cortex ; 26(6): 2602-11, 2016 06.
Article in English | MEDLINE | ID: mdl-25994961

ABSTRACT

The prevalence of adolescent obesity has increased dramatically over the past three decades, and research has documented that the number of television shows viewed during childhood is associated with greater risk for obesity. In particular, considerable evidence suggests that exposure to food marketing promotes eating habits that contribute to obesity. The present study examines neural responses to dynamic food commercials in overweight and healthy-weight adolescents using functional magnetic resonance imaging (fMRI). Compared with non-food commercials, food commercials more strongly engaged regions involved in attention and saliency detection (occipital lobe, precuneus, superior temporal gyri, and right insula) and in processing rewards [left and right nucleus accumbens (NAcc) and left orbitofrontal cortex (OFC)]. Activity in the left OFC and right insula further correlated with subjects' percent body fat at the time of the scan. Interestingly, this reward-related activity to food commercials was accompanied by the additional recruitment of mouth-specific somatosensory-motor cortices-a finding that suggests the intriguing possibility that higher-adiposity adolescents mentally simulate eating behaviors and offers a potential neural mechanism for the formation and reinforcement of unhealthy eating habits that may hamper an individual's ability lose weight later in life.


Subject(s)
Advertising , Brain/physiopathology , Individuality , Motion Perception/physiology , Obesity/physiopathology , Reward , Adolescent , Brain Mapping , Child , Cohort Studies , Female , Food , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Obesity/psychology , Photic Stimulation/methods , Television
15.
J Cereb Blood Flow Metab ; 33(9): 1347-54, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23756687

ABSTRACT

Recent functional magnetic resonance imaging (fMRI) studies have emphasized the contributions of synchronized activity in distributed brain networks to cognitive processes in both health and disease. The brain's 'functional connectivity' is typically estimated from correlations in the activity time series of anatomically remote areas, and postulated to reflect information flow between neuronal populations. Although the topological properties of functional brain networks have been studied extensively, considerably less is known regarding the neurophysiological and biochemical factors underlying the temporal coordination of large neuronal ensembles. In this review, we highlight the critical contributions of high-frequency electrical oscillations in the γ-band (30 to 100 Hz) to the emergence of functional brain networks. After describing the neurobiological substrates of γ-band dynamics, we specifically discuss the elevated energy requirements of high-frequency neural oscillations, which represent a mechanistic link between the functional connectivity of brain regions and their respective metabolic demands. Experimental evidence is presented for the high oxygen and glucose consumption, and strong mitochondrial performance required to support rhythmic cortical activity in the γ-band. Finally, the implications of mitochondrial impairments and deficits in glucose metabolism for cognition and behavior are discussed in the context of neuropsychiatric and neurodegenerative syndromes characterized by large-scale changes in the organization of functional brain networks.


Subject(s)
Biological Clocks/physiology , Brain/metabolism , Energy Metabolism/physiology , Nerve Net/metabolism , Animals , Glucose/metabolism , Humans , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/physiopathology , Oxygen/metabolism
16.
Nat Methods ; 9(4): 363-6, 2012 Feb 19.
Article in English | MEDLINE | ID: mdl-22343343

ABSTRACT

Because off-target effects hamper interpretation and validation of RNAi screen data, we developed a bioinformatics method, genome-wide enrichment of seed sequence matches (GESS), to identify candidate off-targeted transcripts in primary screening data. GESS analysis revealed a prominent off-targeted transcript in several screens, including MAD2 (MAD2L1) in a screen for genes required for the spindle assembly checkpoint. GESS analysis results can enhance the validation rate in RNAi screens.


Subject(s)
Computational Biology/methods , RNA Interference , Transcription, Genetic/genetics , Animals , Base Sequence , Calcium-Binding Proteins/genetics , Cell Cycle Checkpoints/genetics , Cell Cycle Proteins/genetics , Databases, Genetic , Gene Library , Genome/genetics , Humans , Mad2 Proteins , Mice , Repressor Proteins/genetics , Reproducibility of Results , Spindle Apparatus/metabolism
17.
PLoS One ; 6(9): e25511, 2011.
Article in English | MEDLINE | ID: mdl-21966537

ABSTRACT

BACKGROUND: Automated time-lapse microscopy can visualize proliferation of large numbers of individual cells, enabling accurate measurement of the frequency of cell division and the duration of interphase and mitosis. However, extraction of quantitative information by manual inspection of time-lapse movies is too time-consuming to be useful for analysis of large experiments. METHODOLOGY/PRINCIPAL FINDINGS: Here we present an automated time-series approach that can measure changes in the duration of mitosis and interphase in individual cells expressing fluorescent histone 2B. The approach requires analysis of only 2 features, nuclear area and average intensity. Compared to supervised learning approaches, this method reduces processing time and does not require generation of training data sets. We demonstrate that this method is as sensitive as manual analysis in identifying small changes in interphase or mitotic duration induced by drug or siRNA treatment. CONCLUSIONS/SIGNIFICANCE: This approach should facilitate automated analysis of high-throughput time-lapse data sets to identify small molecules or gene products that influence timing of cell division.


Subject(s)
Interphase/physiology , Microscopy, Fluorescence/methods , Mitosis/physiology , Time-Lapse Imaging/methods , Cell Cycle/genetics , Cell Cycle/physiology , Cell Division/genetics , Cell Division/physiology , Cell Line , HeLa Cells , Histones/genetics , Histones/metabolism , Humans , Interphase/genetics , Mitosis/genetics
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