Huppert Lab

@article{pmid38432051,

title = {Fatigue and perceived energy in a sample of older adults over 10 years: A resting state functional connectivity study of neural correlates},

author = {James B Hengenius and Rebecca Ehrenkranz and Xiaonan Zhu and Nancy W Glynn and Theodore J Huppert and Caterina Rosano},

doi = {10.1016/j.exger.2024.112388},

issn = {1873-6815},

year  = {2024},

date = {2024-03-01},

journal = {Exp Gerontol},

volume = {188},

pages = {112388},

abstract = {PURPOSE: Declining energy and increasing fatigue, common in older age, predict neurodegenerative conditions, but their neural substrates are not known. We examined brain resting state connectivity in relation to declining self-reported energy levels (SEL) and occurrence of fatigue over time.nnMETHODS: We examined resting-state functional MRI in 272 community dwelling older adults participating in the Health Aging and Body Composition Study (mean age 83 years; 57.4 % female; 40.8 % Black) with measures of fatigue and SEL collected at regular intervals over the prior ten years. Functional connectivity (FC) between cortex and striatum was examined separately for sensorimotor, executive, and limbic functional subregions. Logistic regression tested the association of FC in each network with prior fatigue state (reporting fatigue at least once or never reporting fatigue), and with SEL decline (divided into stable or declining SEL groups) and adjusted for demographic, physical function, mood, cognition, and comorbidities.nnRESULTS: Higher cortico-striatal FC in the right limbic network was associated with lower odds of reporting fatigue (better) at least once during the study period (adjusted odds ratio [95 % confidence interval], p-value: (0.747 [0.582, 0.955], 0.020), independent of SEL. Higher cortico-striatal FC in the right executive network was associated with higher odds of declining SEL (worse) during the study period (adjusted odds ratio [95 % confidence interval], p-value: (1.31 [1.01, 1.69], 0.041), independent of fatigue. Associations with other networks were not significant.nnCONCLUSIONS: In this cohort of older adults, the cortico-striatal functional connectivity of declining SEL appears distinct from that underlying fatigue. Studies to further assess the neural correlates of energy and fatigue, and their independent contribution to neurodegenerative conditions are warranted.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38367207,

title = {Prefrontal cortex activation while walking did not change but gait speed improved after a randomized physical therapy intervention},

author = {Andrea L Rosso and Emma M Baillargeon and Subashan Perera and Jessie VanSwearingen and Caterina Rosano and Theodore J Huppert and Jennifer S Brach},

doi = {10.1007/s40520-023-02666-7},

issn = {1720-8319},

year  = {2024},

date = {2024-02-01},

journal = {Aging Clin Exp Res},

volume = {36},

number = {1},

pages = {43},

abstract = {BACKGROUND: Higher prefrontal cortex (PFC) activation while walking may indicate reduced gait automaticity.nnAIM: We examine whether PFC activation during walking improves after training in older adults at risk for mobility disability.nnMETHODS: Forty-two adults aged ≥ 65 participated in a randomized clinical trial (NCT026637780) of a 12-week timing and coordination physical therapy intervention to improve walking (n = 20 intervention, n = 22 active control). PFC activation was measured by functional near-infrared spectroscopy (fNIRS) during four walking tasks over 15 m, each repeated 4 times: even surface walking, uneven surface walking, even dual-task, uneven dual-task; dual-task was reciting every other letter of the alphabet while walking. Gait speed and rate of correct letter generation were recorded. Linear mixed models tested between arm differences in change of fNIRS, gait speed, and letter generation from baseline to follow-up (12-week, 24-week, and 36-week).nnRESULTS: Intervention arms were similar in mean age (74.3 vs. 77.0) and baseline gait speed (0.96 vs. 0.93 m/s). Of 24 comparisons of between arm differences in the fNIRS signals, only two were significant which were not supported by differences at other follow-up times or on other tasks. Gait speed, particularly during dual-task conditions, and correct letter generation did improve post-intervention but improvements did not differ by arm.nnDISCUSSION AND CONCLUSIONS: After training, PFC activation during walking generally did not improve and did not differ by intervention arm. Improvements in gait speed without increased PFC activation may point toward more efficient neural control of walking.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38141227,

title = {Covariate-guided Bayesian mixture of spline experts for the analysis of multivariate high-density longitudinal data},

author = {Haoyi Fu and Lu Tang and Ori Rosen and Alison E Hipwell and Theodore J Huppert and Robert T Krafty},

doi = {10.1093/biostatistics/kxad034},

issn = {1468-4357},

year  = {2023},

date = {2023-12-01},

journal = {Biostatistics},

abstract = {With rapid development of techniques to measure brain activity and structure, statistical methods for analyzing modern brain-imaging data play an important role in the advancement of science. Imaging data that measure brain function are usually multivariate high-density longitudinal data and are heterogeneous across both imaging sources and subjects, which lead to various statistical and computational challenges. In this article, we propose a group-based method to cluster a collection of multivariate high-density longitudinal data via a Bayesian mixture of smoothing splines. Our method assumes each multivariate high-density longitudinal trajectory is a mixture of multiple components with different mixing weights. Time-independent covariates are assumed to be associated with the mixture components and are incorporated via logistic weights of a mixture-of-experts model. We formulate this approach under a fully Bayesian framework using Gibbs sampling where the number of components is selected based on a deviance information criterion. The proposed method is compared to existing methods via simulation studies and is applied to a study on functional near-infrared spectroscopy, which aims to understand infant emotional reactivity and recovery from stress. The results reveal distinct patterns of brain activity, as well as associations between these patterns and selected covariates.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37459978,

title = {Enhanced efficacy of CBT following augmentation with amygdala rtfMRI neurofeedback in depression},

author = {Laurie Compère and Greg J Siegle and Emily Riley and Sair Lazzaro and Marlene Strege and Elizabeth Pacoe and Gia Canovali and Scott Barb and Theodore Huppert and Kymberly Young},

doi = {10.1016/j.jad.2023.07.063},

issn = {1573-2517},

year  = {2023},

date = {2023-10-01},

journal = {J Affect Disord},

volume = {339},

pages = {495--501},

abstract = {BACKGROUND: Despite cognitive behavioral therapy (CBT) being a standard treatment in major depressive disorder (MDD), nearly half of patients do not respond. As one of the predictors of CBT's efficacy is amygdala reactivity to positive information, which is often decreased in MDD, we explored whether real-time fMRI neurofeedback (rtfMRI-nf) training to increase amygdala responses during positive memory recall prior CBT would enhance its efficacy.nnMETHODS: In a double-blind, placebo controlled, randomized clinical trial, 35 adults with MDD received two sessions of rtfMRI-nf training to increase their amygdala (experimental group, n = 16) or parietal (control group, n = 19) responses during positive memory neurofeedback prior to receiving 10 CBT sessions. Depressive symptomatology was monitored between the rtfMRI sessions, the first three, 9th and 10th sessions of CBT and at 6 months and 1 year follow-up.nnRESULTS: Participants in the experimental group showed decreased depressive symptomatology and higher remission rates at 6 months and 1 year follow-up than the control group. Analysis of CBT content highlighted that participants in the experimental group focused more on positive thinking and behaviors than the control group.nnLIMITATIONS: The study was relatively small and not sufficiently powered to detect small effects.nnCONCLUSIONS: CBT, when combined with amygdala neurofeedback, results in sustained clinical changes and leads to long-lasting clinical improvement, potentially by increasing focus on positive memories and cognitions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37828730,

title = {Unhealthy white matter connectivity, cognition, and racialization in older adults},

author = {Sarah K Royse and Beth E Snitz and James B Hengenius and Theodore J Huppert and Rebecca E Roush and Rebecca E Ehrenkranz and James D Wilson and Marnie Bertolet and Alexandria C Reese and Geraldine Cisneros and Katey Potopenko and James T Becker and Ann D Cohen and C Elizabeth Shaaban},

doi = {10.1002/alz.13494},

issn = {1552-5279},

year  = {2023},

date = {2023-10-01},

journal = {Alzheimers Dement},

abstract = {INTRODUCTION: White matter hyperintensities (WMH) may promote clinical Alzheimer's disease (AD) disparities between Black American (BA) and non-Hispanic White (nHW) populations. Using a novel measurement, unhealthy white matter connectivity (UWMC), we interrogated racialized group differences in associations between WMH in AD pathology-affected regions and cognition.nnMETHODS: UWMC is the proportion of white matter fibers that pass through WMH for every pair of brain regions. Individual regression models tested associations of UWMC in beta-amyloid (Aβ) or tau pathology-affected regions with cognition overall, stratified by racialized group, and with a racialized group interaction.nnRESULTS: In 201 older adults ranging from cognitively unimpaired to AD, BA participants exhibited greater UWMC and worse cognition than nHW participants. UWMC was negatively associated with cognition in 17 and 5 Aβ- and tau-affected regions, respectively. Racialization did not modify these relationships.nnDISCUSSION: Differential UWMC burden, not differential UWMC-and-cognition associations, may drive clinical AD disparities between racialized groups.nnHIGHLIGHTS: Unhealthy white matter connectivity (UWMC) in Alzheimer's disease (AD) pathology-affected brain regions is associated with cognition. Relationships between UWMC and cognition are similar between Black American (BA) and non-Hispanic White (nHW) individuals. More UWMC may partially drive higher clinical AD burden in BA versus nHW populations. UWMC risk factors, particularly social and environmental, should be identified.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36788804,

title = {Brain space image reconstruction of functional near-infrared spectroscopy using a Bayesian adaptive fused sparse overlapping group lasso model},

author = {Xuetong Zhai and Hendrik Santosa and Robert T Krafty and Theodore J Huppert},

doi = {10.1117/1.NPh.10.2.023516},

issn = {2329-423X},

year  = {2023},

date = {2023-04-01},

journal = {Neurophotonics},

volume = {10},

number = {2},

pages = {023516},

abstract = {SIGNIFICANCE: Functional near-infrared spectroscopy (fNIRS) is a noninvasive technology that uses low levels of nonionizing light in the range of red and near-infrared to record changes in the optical absorption and scattering of the underlying tissue that can be used to infer blood flow and oxygen changes during brain activity. The challenges and difficulties of reconstructing spatial images of hemoglobin changes from fNIRS data are mainly caused by the illposed nature of the optical inverse model.nnAIM: We describe a Bayesian approach combining several lasso-based regularizations to apply anatomy-prior information to solving the inverse model.nnAPPROACH: We built a Bayesian hierarchical model to solve the Bayesian adaptive fused sparse overlapping group lasso (Ba-FSOGL) model. The method is evaluated and validated using simulation and experimental datasets.nnRESULTS: We apply this approach to the simulation and experimental datasets to reconstruct a known brain activity. The reconstructed images and statistical plots are shown.nnCONCLUSION: We discuss the adaptation of this method to fNIRS data and demonstrate that this approach provides accurate image reconstruction with a low false-positive rate, through numerical simulations and application to experimental data collected during motor and sensory tasks.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36715078,

title = {Mother-child neural synchronization is time linked to mother-child positive affective state matching},

author = {Judith K Morgan and Hendrik Santosa and Kaetlyn K Conner and Rachel M Fridley and Erika E Forbes and Satish Iyengar and Heather M Joseph and Theodore J Huppert},

doi = {10.1093/scan/nsad001},

issn = {1749-5024},

year  = {2023},

date = {2023-02-01},

journal = {Soc Cogn Affect Neurosci},

volume = {18},

number = {1},

abstract = {In the first years of life, in which self-regulation occurs via external means, mother-child synchronization of positive affect (PA) facilitates regulation of child homeostatic systems. Mother-child affective synchrony may contribute to mother-child synchronization of neural systems, but limited research has explored this possibility. Participants were 41 healthy mother-child dyads (56% girls; Mage = 24.76 months; s.d. = 8.77 months, Range = 10-42 months). Mothers' and children's brain activities were assessed simultaneously using near-infrared spectroscopy while engaging in dyadic play. Mother and child PA during play were coded separately to characterize periods in which mothers and children (i) matched on high PA, (ii) matched on low/no PA or (iii) showed a mismatch in PA. Models evaluated moment-to-moment correlations between affective matching and neural synchrony in mother-child dyads. Greater positive affective synchrony, in which mother and child showed similarly high levels of PA but not similarly low levels of PA, was related to greater synchrony in medial and lateral frontal and temporoparietal regions. Age moderated associations between mother and child neural activities but only during moments of high PA state matching. Positive, synchronous mother-child interactions may foster greater neural responding in affective and social regions important for self-regulation and interpersonal bonds.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36507152,

title = {Introduction to the shared near infrared spectroscopy format},

author = {Stephen Tucker and Jay Dubb and Sreekanth Kura and Alexander von Lühmann and Robert Franke and Jörn M Horschig and Samuel Powell and Robert Oostenveld and Michael Lührs and Édouard Delaire and Zahra M Aghajan and Hanseok Yun and Meryem A Yücel and Qianqian Fang and Theodore J Huppert and Blaise B Frederick and Luca Pollonini and David Boas and Robert Luke},

doi = {10.1117/1.NPh.10.1.013507},

issn = {2329-423X},

year  = {2023},

date = {2023-01-01},

journal = {Neurophotonics},

volume = {10},

number = {1},

pages = {013507},

abstract = {SIGNIFICANCE: Functional near-infrared spectroscopy (fNIRS) is a popular neuroimaging technique with proliferating hardware platforms, analysis approaches, and software tools. There has not been a standardized file format for storing fNIRS data, which has hindered the sharing of data as well as the adoption and development of software tools.nnAIM: We endeavored to design a file format to facilitate the analysis and sharing of fNIRS data that is flexible enough to meet the community's needs and sufficiently defined to be implemented consistently across various hardware and software platforms.nnAPPROACH: The shared NIRS format (SNIRF) specification was developed in consultation with the academic and commercial fNIRS community and the Society for functional Near Infrared Spectroscopy.nnRESULTS: The SNIRF specification defines a format for fNIRS data acquired using continuous wave, frequency domain, time domain, and diffuse correlation spectroscopy devices.nnCONCLUSIONS: We present the SNIRF along with validation software and example datasets. Support for reading and writing SNIRF data has been implemented by major hardware and software platforms, and the format has found widespread use in the fNIRS community.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37339817,

title = {Real-time functional magnetic resonance imaging neurofeedback training of amygdala upregulation increases affective flexibility in depression},

author = {Laurie Compère and Greg J Siegle and Sair Lazzaro and Marlene Strege and Gia Canovali and Scott Barb and Theodore Huppert and Kymberly Young},

doi = {10.1503/jpn.220208},

issn = {1488-2434},

year  = {2023},

date = {2023-01-01},

journal = {J Psychiatry Neurosci},

volume = {48},

number = {3},

pages = {E232--E239},

abstract = {BACKGROUND: Decreased affective flexibility is associated with depression symptoms, and it has been suggested that common interventions may target this mechanism. To explore this hypothesis, we evaluated whether real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training to increase the amygdala responses during positive memory recall resulted in both symptom improvements, as has been observed previously, and flexibility to decrease amygdala reactivity in response to a cognitive task among patients with major depressive disorder (MDD).nnMETHODS: In a double-blind, placebo-controlled, randomized clinical trial, adults with MDD received 2 sessions of rtfMRI-nf training to increase their amygdala (experimental group) or parietal (control group) responses during positive autobiographical memory recall. We evaluated signal changes in the amygdala during both the positive memory neurofeedback and a subsequent counting condition.nnRESULTS: We included 38 adults with MDD, including 16 in the experimental group and 22 in the control group. In the experimental group, amygdala activity increased ( > 2.01, df < 27,  < 0.05,  > 0.5) and depressive symptoms decreased (-8.57, 95 % confidence interval [CI] -15.12 to -2.59;   = -3.06,  = 0.009,  = 1). Amygdala activity during the count condition decreased after rtfMRI-nf (-0.16, 95 % CI -0.23 to -0.09;   = 4.73,  < 0.001,  = 0.48) and was correlated with decreased depression scores ( = 0.46,  = 0.01). We replicated previous results and extended them to show decreased amygdala reactivity to a cognitive task during which no neurofeedback was provided.nnLIMITATIONS: The count condition was reported by participants as negative, but emotionality or accuracy during this condition was not assessed.nnCONCLUSION: These results suggest that nominally targeting unidimensional change in neural mechanisms could have implications for bidirectional control, increasing the likely reach and explanatory framework for how common depression interventions work. ClinicalTrials.gov NCT02709161.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35188831,

title = {MEG Oscillatory Slowing in Cognitive Impairment is Associated with the Presence of Subjective Cognitive Decline},

author = {Ricardo Bruña and David López-Sanz and Fernando Maestú and Ann D Cohen and Anto Bagic and Ted Huppert and Tae Kim and Rebecca E Roush and Betz Snitz and James T Becker},

doi = {10.1177/15500594221072708},

issn = {2169-5202},

year  = {2023},

date = {2023-01-01},

journal = {Clin EEG Neurosci},

volume = {54},

number = {1},

pages = {73--81},

abstract = {The mechanisms behind Alzheimer's disease are not yet fully described, and changes in the electrophysiology of patients across the continuum of the disease could help to understand them. In this work, we study the power spectral distribution of a set of 129 individuals from the Connectomics of Brian Aging and Dementia project.From this sample, we acquired task-free data, with eyes closed, and estimated the power spectral distribution in source space. We compared the spectral profiles of three groups of individuals: 70 healthy controls, 27 patients with amnestic MCI, and 32 individuals showing cognitive impairment without subjective complaints (IWOC).The results showed a slowing of the brain activity in the aMCI patients, when compared to both the healthy controls and the IWOC individuals. These differences appeared both as a decrease in power for high frequency oscillations and an increase in power in alpha oscillations. The slowing of the spectrum was significant mainly in parietal and medial frontal areas.We were able to validate the slowing of the brain activity in individuals with aMCI, appearing in our sample in areas related to the default mode network. However, this pattern did not appear in the IWOC individuals, suggesting that their condition is not part of the AD continuum. This work raises interesting questions about this group of individuals, and the underlying brain mechanisms behind their cognitive impairment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34657584,

title = {Suicide Notes, Attempts, and Attempt Lethality During Episodes of Ideation Among Suicidal Soldiers and Marines},

author = {Tierney K Huppert and Martina Fruhbauerova and Amanda H Kerbrat and Christopher R DeCou and Katherine Anne Comtois},

doi = {10.1080/13811118.2021.1988785},

issn = {1543-6136},

year  = {2023},

date = {2023-01-01},

journal = {Arch Suicide Res},

volume = {27},

number = {2},

pages = {261--274},

abstract = {OBJECTIVE: Suicide remains a significant public health problem among military personnel despite expanded suicide prevention efforts over the last two decades. It is important to understand the behavioral antecedents of suicide, including the writing of a suicide note, to inform efforts to identify imminent risk. However, the completion of a suicide note increasing the likelihood of making a suicide attempt (SA) and predicting a higher lethality SA during episodes of suicidality have not been evaluated.nnMETHOD: To determine whether or not the completion of a suicide note increased the likelihood of making a SA during a given episode of suicidal ideation (current or worst) and predicted a higher lethality SA, we conducted secondary data analysis with a sample of 657 help-seeking, active-duty U.S. Soldiers and Marines. We hypothesized that service members who completed a suicide note would be more likely to make a SA during that given episode of suicidality and make a higher lethality SA.nnRESULTS: Completion of a suicide note increased the likelihood of making a SA in both current and worst episodes of suicidal ideation. Additionally, writing a suicide note predicted making a higher lethality SA during a service member's current episode of ideation but not their worst episode.nnCONCLUSIONS: This is the first study to examine note-writing behavior during episodes of suicidal ideation rather than following a suicide death or attempt, demonstrating a non-trivial number (17%) had written a suicide note and this increased the likelihood of making a SA and a higher lethality SA.HIGHLIGHTSThe first study of suicide notes during periods of ideation regardless of attempt.A suicide note written during an episode of ideation predicted making an attempt.A suicide note predicted making a more lethal suicide attempt.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36162692,

title = {Reducing short term suicide risk after hospitalization: A randomized controlled trial of the Collaborative Assessment and Management of Suicidality},

author = {Katherine Anne Comtois and Karin E Hendricks and Christopher R DeCou and Samantha A Chalker and Amanda H Kerbrat and Jennifer Crumlish and Tierney K Huppert and David Jobes},

doi = {10.1016/j.jad.2022.09.042},

issn = {1573-2517},

year  = {2023},

date = {2023-01-01},

journal = {J Affect Disord},

volume = {320},

pages = {656--666},

abstract = {BACKGROUND: This study compared the "next day appointment" (NDA) use of the Collaborative Assessment and Management of Suicidality (CAMS) to treatment as usual (TAU) for individuals discharged from the hospital following a suicide-related crisis. We hypothesized that CAMS would significantly reduce suicidal thoughts and behaviors as well as improve psychological distress, quality of life/overall functioning, treatment retention and patient satisfaction.nnMETHODS: Participants were 150 individuals who had at least one lifetime actual, aborted, or interrupted attempt and were admitted following a suicide-related crisis. There were 75 participants in the experimental condition who received adherent CAMS and 75 participants who received TAU. Suicidal thoughts and behaviors, psychological distress, and quality of life/overall functioning were assessed at baseline and at 1, 3, 6, and 12 months post-baseline. Treatment retention and patient satisfaction were assessed at post-treatment.nnRESULTS: Participants in both conditions improved from baseline to 12 months but CAMS was not superior to TAU for the primary outcomes. A small but significant improvement was found in probability of suicidal ideation at 3 months favoring TAU and amount of suicidal ideation at 12 months favoring CAMS. CAMS participants experienced less psychological distress at 12 months compared to baseline.nnLIMITATIONS: The study was limited by only one research clinic, lower than expected recruitment, and imbalance of suicidal ideation at baseline.nnCONCLUSIONS: All participants improved but CAMS was not more effective than TAU. The NDA clinic was feasible and acceptable to clients and staff in both conditions and future research should investigate its potential benefit.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37456641,

title = {Targeted multidomain intervention for complex mTBI: protocol for a multisite randomized controlled trial in military-age civilians},

author = {R J Elbin and Alicia Trbovich and Melissa N Womble and Anne Mucha and Sheri Fedor and Katie Stephenson and Cyndi Holland and Christina Dollar and Patrick Sparto and Kori Durfee and Charity G Patterson and Clair N Smith and Theodore J Huppert and David O Okonkwo and Michael W Collins and Anthony P Kontos},

doi = {10.3389/fneur.2023.1085662},

issn = {1664-2295},

year  = {2023},

date = {2023-01-01},

journal = {Front Neurol},

volume = {14},

pages = {1085662},

abstract = {BACKGROUND: Mild traumatic brain injury (mTBI) affects ~18,000 military personnel each year, and although most will recover in 3-4 weeks, many experience persisting symptoms and impairment lasting months or longer. Current standard of care for U.S. military personnel with complex mTBI involves initial (<48 h) prescribed rest, followed by behavioral (e.g., physical activity, sleep regulation, stress reduction, hydration, nutrition), and symptom-guided management. There is growing agreement that mTBI involves different clinical profiles or subtypes that require a comprehensive multidomain evaluation and adjudication process, as well as a targeted approach to treatment. However, there is a lack of research examining the effectiveness of this approach to assessing and treating mTBI. This multisite randomized controlled trial (RCT) will determine the effectiveness of a targeted multidomain (T-MD) intervention (anxiety/mood, cognitive, migraine, ocular, vestibular; and sleep, autonomic) compared to usual care (behavioral management) in military-aged civilians with complex mTBI.nnMETHODS: This study employs a single-blinded, two-group repeated measures design. The RCT will enroll up to 250 military-aged civilians (18-49 yrs) with a diagnosed complex mTBI within 8 days to 6 months of injury from two concussion specialty clinics. The two study arms are a T-MD intervention and a usual care, behavioral management control group. All participants will complete a comprehensive, multidomain clinical evaluation at their first clinical visit. Information gathered from this evaluation will be used to adjudicate mTBI clinical profiles. Participants will then be randomized to either the 4-week T-MD or control arm. The T-MD group will receive targeted interventions that correspond to the patient's clinical profile (s) and the control group will receive behavioral management strategies. Primary outcomes for this study are changes from enrollment to post-intervention on the Neurobehavioral Symptom Inventory (NSI), Patient Global Impression of Change (PGIC), and functional near-infrared spectroscopy (fNIRS). Time to return to activity (RTA), and healthcare utilization costs will also be assessed.nnDISCUSSION: Study findings may inform a more effective approach to treat complex mTBI in military personnel and civilians, reduce morbidity, and accelerate safe return-to-duty/activity.nnETHICS AND DISSEMINATION: The study is approved by the University of Pittsburgh Institutional Review board and registered at clinicaltrials.gov. Dissemination plans include peer-reviewed publications and presentations at professional meetings.nnCLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, identifier: NCT04549532.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36226356,

title = {Assessing the relationship between maternal risk for attention deficit hyperactivity disorder and functional connectivity in their biological toddlers},

author = {Anastasia Kerr-German and Stuart F White and Hendrik Santosa and Aaron T Buss and Gaelle E Doucet},

doi = {10.1192/j.eurpsy.2022.2325},

issn = {1778-3585},

year  = {2022},

date = {2022-10-01},

journal = {Eur Psychiatry},

volume = {65},

number = {1},

pages = {e66},

abstract = {BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with increased risk for poor educational attainment and compromised social integration. Currently, clinical diagnosis rarely occurs before school-age, despite behavioral signs of ADHD in very early childhood. There is no known brain biomarker for ADHD risk in children ages 2-3 years-old.nnMETHODS: The current study aimed to investigate the functional connectivity (FC) associated with ADHD risk in 70 children aged 2.5 and 3.5 years via functional near-infrared spectroscopy (fNIRS) in bilateral frontal and parietal cortices; regions involved in attentional and goal-directed cognition. Children were instructed to passively watch videos for approximately 5 min. Risk for ADHD in each child was assessed via maternal symptoms of ADHD, and brain data was evaluated for FC.nnRESULTS: Higher risk for maternal ADHD was associated with lower FC in a left-sided parieto-frontal network. Further, the interaction between sex and risk for ADHD was significant, where FC reduction in a widespread bilateral parieto-frontal network was associated with higher risk in male, but not female, participants.nnCONCLUSIONS: These findings suggest functional organization differences in the parietal-frontal network in toddlers at risk for ADHD; potentially advancing the understanding of the neural mechanisms underlying the development of ADHD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35753183,

title = {Scale invariance in fNIRS as a measurement of cognitive load},

author = {Chu Zhuang and Kimberly L Meidenbauer and Omid Kardan and Andrew J Stier and Kyoung Whan Choe and Carlos Cardenas-Iniguez and Theodore J Huppert and Marc G Berman},

doi = {10.1016/j.cortex.2022.05.009},

issn = {1973-8102},

year  = {2022},

date = {2022-09-01},

journal = {Cortex},

volume = {154},

pages = {62--76},

abstract = {Scale invariant neural dynamics are a relatively new but effective means of measuring changes in brain states as a result of varied cognitive load and task difficulty. This study tests whether scale invariance (as measured by the Hurst exponent, H) can be used with functional near-infrared spectroscopy (fNIRS) to quantify cognitive load, paving the way for scale-invariance to be measured in a variety of real-world settings. We analyzed H extracted from the fNIRS time series while participants completed an N-back working memory task. Consistent with what has been demonstrated in fMRI, the current results showed that scale-invariance analysis significantly differentiated between task and rest periods as calculated from both oxy- (HbO) and deoxy-hemoglobin (HbR) concentration changes. Results from both channel-averaged H and a multivariate partial least squares approach (Task PLS) demonstrated higher H during the 1-back task than the 2-back task. These results were stronger for H derived from HbR than from HbO. This suggests that scale-free brain states are a robust signature of cognitive load and not limited by the specific neuroimaging modality employed. Further, as fNIRS is relatively portable and robust to motion-related artifacts, these preliminary results shed light on the promising future of measuring cognitive load in real life settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34726478,

title = {Sex Differences in Magnetoencephalography-Identified Functional Connectivity in the Human Connectome Project Connectomics of Brain Aging and Dementia Cohort},

author = {Ricardo Bruña and Fernando Maestú and David López-Sanz and Anto Bagic and Ann D Cohen and Yue-Fang Chang and Yu Cheng and Jack Doman and Ted Huppert and Tae Kim and Rebecca E Roush and Beth E Snitz and James T Becker},

doi = {10.1089/brain.2021.0059},

issn = {2158-0022},

year  = {2022},

date = {2022-08-01},

journal = {Brain Connect},

volume = {12},

number = {6},

pages = {561--570},

abstract = { The human brain shows modest traits of sexual dimorphism, with the female brain, on average, 10% smaller than the male brain. These differences do not imply a lowered cognitive performance, but suggest a more optimal brain organization in women. Here we evaluate the patterns of functional connectivity (FC) in women and men from the Connectomics of Brain Aging and Dementia sample.  We used phase locking values to calculate FC from the magnetoencephalography time series in a sample of 138 old adults (87 females and 51 males). We compared the FC patterns between sexes, with the intention of detecting regions with different levels of connectivity.  We found a frontal cluster, involving anterior cingulate and the medial frontal lobe, where women showed higher FC values than men. Involved connections included the following: (1) medial parietal areas, such as posterior cingulate cortices and precunei; (2) right insula; and (3) medium cingulate and paracingulate cortices. Moreover, these differences persisted when considering only cognitively intact individuals, but not when considering only cognitively impaired individuals.  Increased anteroposterior FC has been identified as a biomarker for increased risk of developing cognitive impairment or dementia. In our study, cognitively intact women showed higher levels of FC than their male counterparts. This result suggests that neurodegenerative processes could be taking place in these women, but the changes are undetected by current diagnosis tools. FC, as measured here, might be valuable for early identification of this neurodegeneration.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35990173,

title = {Correction of global physiology in resting-state functional near-infrared spectroscopy},

author = {Pradyumna Lanka and Heather Bortfeld and Theodore J Huppert},

doi = {10.1117/1.NPh.9.3.035003},

issn = {2329-423X},

year  = {2022},

date = {2022-07-01},

journal = {Neurophotonics},

volume = {9},

number = {3},

pages = {035003},

abstract = { Resting-state functional connectivity (RSFC) analyses of functional near-infrared spectroscopy (fNIRS) data reveal cortical connections and networks across the brain. Motion artifacts and systemic physiology in evoked fNIRS signals present unique analytical challenges, and methods that control for systemic physiological noise have been explored. Whether these same methods require modification when applied to resting-state fNIRS (RS-fNIRS) data remains unclear.  We systematically examined the sensitivity and specificity of several RSFC analysis pipelines to identify the best methods for correcting global systemic physiological signals in RS-fNIRS data.  Using numerically simulated RS-fNIRS data, we compared the rates of true and false positives for several connectivity analysis pipelines. Their performance was scored using receiver operating characteristic analysis. Pipelines included partial correlation and multivariate Granger causality, with and without short-separation measurements, and a modified multivariate causality model that included a non-traditional zeroth-lag cross term. We also examined the effects of pre-whitening and robust statistical estimators on performance.  Consistent with previous work on bivariate correlation models, our results demonstrate that robust statistics and pre-whitening are effective methods to correct for motion artifacts and autocorrelation in the fNIRS time series. Moreover, we found that pre-filtering using principal components extracted from short-separation fNIRS channels as part of a partial correlation model was most effective in reducing spurious correlations due to shared systemic physiology when the two signals of interest fluctuated synchronously. However, when there was a temporal lag between the signals, a multivariate Granger causality test incorporating the short-separation channels was better. Since it is unknown if such a lag exists in experimental data, we propose a modified version of Granger causality that includes the non-traditional zeroth-lag term as a compromising solution.  A combination of pre-whitening, robust statistical methods, and partial correlation in the processing pipeline to reduce autocorrelation, motion artifacts, and global physiology are suggested for obtaining statistically valid connectivity metrics with RS-fNIRS. Further studies should validate the effectiveness of these methods using human data.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35005833,

title = {To snack or not to snack: Using fNIRS to link inhibitory control to functional connectivity in the toddler brain},

author = {Anastasia Kerr-German and August Namuth and Hendrik Santosa and Aaron T Buss and Stuart White},

doi = {10.1111/desc.13229},

issn = {1467-7687},

year  = {2022},

date = {2022-07-01},

journal = {Dev Sci},

volume = {25},

number = {4},

pages = {e13229},

abstract = {Inhibitory control (IC) emerges in infancy, continues to develop throughout childhood and is linked to later life outcomes such as school achievement, prosocial behavior, and psychopathology. Little, however, is known about the neural processes underpinning IC, especially in 2-year-olds. In this study, we examine functional connectivity (FC) in 2.5-year-olds while recording hemodynamic responses via functional infrared spectroscopy (fNIRS) during a traditional snack delay task. We found that functional connectivity strength between left frontal and parietal cortex and bilateral parietal cortex were positively associated with performance on this task. The current findings present the first neural data for toddlers during this IC task. Further, these data are the first to link this self-regulatory process to differences in brain development within this population. Implications for future directions and work with clinical populations are discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35397288,

title = {Influence of serial subtraction tasks on transient characteristics of postural control},

author = {Cody A Reed and Camryn K DuBois and Keith A Hutchison and Theodore J Huppert and Scott M Monfort},

doi = {10.1016/j.humov.2022.102950},

issn = {1872-7646},

year  = {2022},

date = {2022-06-01},

journal = {Hum Mov Sci},

volume = {83},

pages = {102950},

abstract = {We sought to better understand the influence of cognitive perturbations on transient aspects of postural control. Twenty healthy, younger adults had their postural control assessed during eyes open quiet stance. Participants completed three different conditions that either had no cognitive perturbation present, an easy cognitive perturbation (i.e., serial subtraction by ones), or a more difficult cognitive perturbation (i.e., serial subtraction by sevens). All trials finished with 60 s of undisturbed eyes open quiet stance, which was the focus of the balance assessment. 95% confidence ellipse area (EA) was calculated for 5-s epochs throughout the trial. The difference in EA from the first epoch after participants started (onset) or stopped (offset) the cognitive task to the last epoch of the trial (i.e., 55-60 s after perturbation) was used to characterize transient postural control behavior. Functional near-infrared spectroscopy was also used to quantify changes in prefrontal cortex activation during the counting tasks to support interpretation of the transient balance findings. There was a significant effect of condition for transient balance characteristics following a cognitive perturbation (P < 0.001), with greater transient increases in postural sway for both difficult (Cohen's d = 0.40, P < 0.001) and easier (Cohen's d = 0.29, P = 0.013) cognitive perturbations relative to no cognitive perturbation. The onset of cognitive tasks was also associated with greater transient increases in postural sway than the offset of the cognitive tasks (Cohen's d = 0.24, P = 0.019). The functional near-infrared spectroscopy data indicated that a significant decrease in deoxygenated hemoglobin was observed for left Brodmann area 46 for both the subtraction by ones (T = -3.97; Benjamini-Hochberg significance value (q) = 0.008) and subtraction by sevens (T = -3.11; q = 0.036) conditions relative to the baseline condition. The subtraction by sevens condition was also associated with a relative increase in deoxygenated hemoglobin for the right Brodmann area 9 (T = 3.36; q = 0.026) compared to the subtraction by ones condition. In conclusion, serial subtraction can elicit transient increases in postural sway, with more difficult tasks and the onset of the cognitive-motor challenge exhibiting magnified effects. Additionally, even the cessation of a cognitive task (i.e., serial subtraction) can be associated with lingering perturbing effects on balance control.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}