Huppert Lab

@article{pmid34957653,

title = {Cortico-striatal functional connectivity and cerebral small vessel disease: Contribution to mild Parkinsonian signs},

author = {James B Hengenius and Nicolaas I Bohnen and Andrea Rosso and Theodore J Huppert and Caterina Rosano},

doi = {10.1111/jon.12949},

issn = {1552-6569},

year  = {2022},

date = {2022-03-01},

journal = {J Neuroimaging},

volume = {32},

number = {2},

pages = {352--362},

abstract = {BACKGROUND AND PURPOSE: Mild Parkinsonian signs (MPS) are common in older adults. We hypothesized that MPS are associated with lower functional connectivity (FC) in dopamine-dependent cortico-striatal networks, and these associations vary with white matter hyperintensity (WMH), a risk factor for MPS.nnMETHODS: We examined resting-state functional MRI in 266 participants (mean age 83; 57% female; 41% African American) with data on MPS (Unified Parkinson's Disease Rating Scale), demographics, cognition, muscle-skeletal, and cardiometabolic health. 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 MPS, adjusted for covariates. Interactions of FC by WMH were tested; and analyses were repeated stratified by WMH above/below the median.nnRESULTS: Compared to those without MPS, those with MPS had lower cortico-striatal FC in the left executive network (adjusted odds ratio [95% confidence interval], p-value: 0.188 [0.043, 0.824], .027). The interaction with WMH was p = .064; left executive FC was inversely associated with MPS for high WMH (0.077 [0.010, 0.599], .014) but not low WMH participants (1.245 [0.128, 12.132], .850).nnCONCLUSIONS: MPS appear related to lower executive network FC, robust to adjustment for other risk factors, and stronger for those with higher burden of WMH. Future longitudinal studies should examine the interplay between cerebral small vessel disease and connectivity influencing MPS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35083928,

title = {Offset analgesia is associated with opposing modulation of medial versus dorsolateral prefrontal cortex activations: A functional near-infrared spectroscopy study},

author = {Benedict J Alter and Hendrik Santosa and Quynh H Nguyen and Theodore J Huppert and Ajay D Wasan},

doi = {10.1177/17448069221074991},

issn = {1744-8069},

year  = {2022},

date = {2022-01-01},

journal = {Mol Pain},

volume = {18},

pages = {17448069221074991},

abstract = {Offset analgesia is defined by a dramatic drop in perceived pain intensity with a relatively small decrease in noxious input. Although functional magnetic resonance imaging studies implicate subcortical descending inhibitory circuits during offset analgesia, the role of cortical areas remains unclear. The current study identifies cortical correlates of offset analgesia using functional near infrared spectroscopy (fNIRS). Twenty-four healthy volunteers underwent fNIRS scanning during offset (OS) and control (Con) heat stimuli applied to the forearm. After controlling for non-neural hemodynamic responses in superficial tissues, widespread increases in cortical oxygenated hemoglobin concentration were observed, reflecting cortical activation during heat pain. OS-Con contrasts revealed deactivations in bilateral medial prefrontal cortex (mPFC) and bilateral somatosensory cortex (SSC) associated with offset analgesia. Right dorsolateral prefrontal cortex (dlPFC) showed activation only during OS. These data demonstrate opposing cortical activation patterns during offset analgesia and support a model in which right dlPFC underlies ongoing evaluation of pain intensity change. With predictions of decreasing pain intensity, right dlPFC activation likely inhibits ascending noxious input via subcortical pathways resulting in SSC and mPFC deactivation. This study identifies cortical circuitry underlying offset analgesia and introduces the use of fNIRS to study pain modulation in an outpatient clinical environment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36105774,

title = {The use of functional near infrared spectroscopy and gait analysis to characterize cognitive and motor processing in early-stage patients with multiple sclerosis},

author = {Maria Adelia de Aratanha and Joana Bisol Balardin and Carolina Cardoso do Amaral and Shirley S Lacerda and Tiago Abrão Setrak Sowmy and Theodore J Huppert and Rodrigo Barbosa Thomaz and Danielli S Speciali and Birajara Machado and Elisa Harumi Kozasa},

doi = {10.3389/fneur.2022.937231},

issn = {1664-2295},

year  = {2022},

date = {2022-01-01},

journal = {Front Neurol},

volume = {13},

pages = {937231},

abstract = {BACKGROUND: Dual-task paradigms are a known tool to evaluate possible impairments in the motor and cognitive function in patients with multiple sclerosis (MS). A technique to evaluate the cortical function during movement is functional near-infrared spectroscopy (fNIRS). The evaluation of the MS course or its treatment by associating fNIRS with gait measurements may be flexible and low-cost; however, there are no feasibility studies in the literature using these combined techniques in early-stage patients with MS.nnOBJECTIVE: To evaluate cortical hemodynamics using fNIRS and gait parameters in patients at early stages of MS and in healthy controls during a dual-task paradigm.nnMETHODS: Participants performed cognitive tasks while walking to simulate daily activities. Cortical activation maps and gait variability were used to evaluate differences between 19 healthy controls and 20 patients with MS.nnRESULTS AND CONCLUSION: The results suggest an enhanced cortical activation in the motor planning areas already at the early stages of MS when compared to controls. We have also shown that a systematic analysis of the spatiotemporal gait variability parameters indicates differences in the patient population. The association of cortical and gait parameters may reveal possible compensatory mechanisms related to gait during dual tasking at the early stages of the disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33847461,

title = {Dysfunction in interpersonal neural synchronization as a mechanism for social impairment in autism spectrum disorder},

author = {Laura E Quiñones-Camacho and Frank A Fishburn and Katherine Belardi and Diane L Williams and Theodore J Huppert and Susan B Perlman},

doi = {10.1002/aur.2513},

issn = {1939-3806},

year  = {2021},

date = {2021-08-01},

journal = {Autism Res},

volume = {14},

number = {8},

pages = {1585--1596},

abstract = {Social deficits in autism spectrum disorder (ASD) have been linked to atypical activation of the mentalizing network. This work, however, has been limited by a focus on the brain activity of a single person during computerized social tasks rather than exploring brain activity during in vivo interactions. The current study assessed neural synchronization during a conversation as a mechanism for social impairment in adults with ASD (n = 24) and matched controls (n = 26). Functional near-infrared spectroscopy (fNIRS) data were collected from the prefrontal cortex (PFC) and tempoparietal junction (TPJ). Participants self-reported on their social communication and videos of the interaction were coded for utterances and conversational turns. As expected, controls showed more neural synchrony than participants with ASD in the TPJ. Also as expected, controls showed less social communication impairment than participants with ASD. However, participants with ASD did not have fewer utterances compared with control subjects. Overall, less neural synchrony in the TPJ was associated with higher social impairment and marginally fewer utterances. Our findings advance our understanding of social difficulties in ASD by linking them to decreased neural synchronization of the TPJ. LAY SUMMARY: The coordination of brain responses is important for efficient social interactions. The current study explored the coordination of brain responses in neurotypical adults and adults with ASD to investigate if difficulties in social interactions are related to difficulties coordinating brain responses in ASD. We found that participants with ASD had more difficulties coordinating brain responses during a conversation with an interacting partner. Additionally, we found that the level of coordination in brain responses was linked to problems with social communication.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33716158,

title = {Cardiac-induced cerebral pulsatility, brain structure, and cognition in middle and older-aged adults},

author = {Tae Kim and Sang-Young Kim and Vikas Agarwal and Annie Cohen and Rebecca Roush and Yue-Fang Chang and Yu Cheng and Beth Snitz and Theodore J Huppert and Anto Bagic and M Ilyas Kamboh and Jack Doman and James T Becker},

doi = {10.1016/j.neuroimage.2021.117956},

issn = {1095-9572},

year  = {2021},

date = {2021-06-01},

journal = {Neuroimage},

volume = {233},

pages = {117956},

abstract = {Changes of cardiac-induced regional pulsatility can be associated with specific regions of brain volumetric changes, and these are related with cognitive alterations. Thus, mapping of cardiac pulsatility over the entire brain can be helpful to assess these relationships. A total of 108 subjects (age: 66.5 ± 8.4 years, 68 females, 52 healthy controls, 11 subjective cognitive decline, 17 impaired without complaints, 19 MCI and 9 AD) participated. The pulsatility map was obtained directly from resting-state functional MRI time-series data at 3T. Regional brain volumes were segmented from anatomical MRI. Multidomain neuropsychological battery was performed to test memory, language, attention and visuospatial construction. The Montreal Cognitive Assessment (MoCA) was also administered. The sparse partial least square (SPLS) method, which is desirable for better interpreting high-dimensional variables, was applied for the relationship between the entire brain voxels of pulsatility and 45 segmented brain volumes. A multiple holdout SPLS framework was used to optimize sparsity for assessing the pulsatility-volume relationship model and to test the reliability by fitting the models to 9 different splits of the data. We found statistically significant associations between subsets of pulsatility voxels and subsets of segmented brain volumes by rejecting the omnibus null hypothesis (any of 9 splits has p < 0.0056 (=0.05/9) with the Bonferroni correction). The pulsatility was positively associated with the lateral ventricle, choroid plexus, inferior lateral ventricle, and 3rd ventricle and negatively associated with hippocampus, ventral DC, and thalamus volumes for the first pulsatility-volume relationship. The pulsatility had an additional negative relationship with the amygdala and brain stem volumes for the second pulsatility-volume relationship. The spatial distribution of correlated pulsatility was observed in major feeding arteries to the brain regions, ventricles, and sagittal sinus. The indirect mediating pathways through the volumetric changes were statistically significant between the pulsatility and multiple cognitive measures (p < 0.01). Thus, the cerebral pulsatility, along with volumetric measurements, could be a potential marker for better understanding of pathophysiology and monitoring disease progression in age-related neurodegenerative disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33955838,

title = {Perceived Utility and Characterization of Personal Google Search Histories to Detect Data Patterns Proximal to a Suicide Attempt in Individuals Who Previously Attempted Suicide: Pilot Cohort Study},

author = {Patricia A Areán and Abhishek Pratap and Honor Hsin and Tierney K Huppert and Karin E Hendricks and Patrick J Heagerty and Trevor Cohen and Courtney Bagge and Katherine Anne Comtois},

doi = {10.2196/27918},

issn = {1438-8871},

year  = {2021},

date = {2021-05-01},

journal = {J Med Internet Res},

volume = {23},

number = {5},

pages = {e27918},

abstract = {BACKGROUND: Despite decades of research to better understand suicide risk and to develop detection and prevention methods, suicide is still one of the leading causes of death globally. While large-scale studies using real-world evidence from electronic health records can identify who is at risk, they have not been successful at pinpointing when someone is at risk. Personalized social media and online search history data, by contrast, could provide an ongoing real-world datastream revealing internal thoughts and personal states of mind.nnOBJECTIVE: We conducted this study to determine the feasibility and acceptability of using personalized online information-seeking behavior in the identification of risk for suicide attempts.nnMETHODS: This was a cohort survey study to assess attitudes of participants with a prior suicide attempt about using web search data for suicide prevention purposes, dates of lifetime suicide attempts, and an optional one-time download of their past web searches on Google. The study was conducted at the University of Washington School of Medicine Psychiatry Research Offices. The main outcomes were participants' opinions on internet search data for suicide prediction and intervention and any potential change in online information-seeking behavior proximal to a suicide attempt. Individualized nonparametric association analysis was used to assess the magnitude of difference in web search data features derived from time periods proximal (7, 15, 30, and 60 days) to the suicide attempts versus the typical (baseline) search behavior of participants.nnRESULTS: A total of 62 participants who had attempted suicide in the past agreed to participate in the study. Internet search activity varied from person to person (median 2-24 searches per day). Changes in online search behavior proximal to suicide attempts were evident up to 60 days before attempt. For a subset of attempts (7/30, 23%) search features showed associations from 2 months to a week before the attempt. The top 3 search constructs associated with attempts were online searching patterns (9/30 attempts, 30%), semantic relatedness of search queries to suicide methods (7/30 attempts, 23%), and anger (7/30 attempts, 23%). Participants (40/59, 68%) indicated that use of this personalized web search data for prevention purposes was acceptable with noninvasive potential interventions such as connection to a real person (eg, friend, family member, or counselor); however, concerns were raised about detection accuracy, privacy, and the potential for overly invasive intervention.nnCONCLUSIONS: Changes in online search behavior may be a useful and acceptable means of detecting suicide risk. Personalized analysis of online information-seeking behavior showed notable changes in search behavior and search terms that are tied to early warning signs of suicide and are evident 2 months to 7 days before a suicide attempt.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33503483,

title = {Load-dependent relationships between frontal fNIRS activity and performance: A data-driven PLS approach},

author = {Kimberly L Meidenbauer and Kyoung Whan Choe and Carlos Cardenas-Iniguez and Theodore J Huppert and Marc G Berman},

doi = {10.1016/j.neuroimage.2021.117795},

issn = {1095-9572},

year  = {2021},

date = {2021-04-01},

journal = {Neuroimage},

volume = {230},

pages = {117795},

abstract = {Neuroimaging research frequently demonstrates load-dependent activation in prefrontal and parietal cortex during working memory tasks such as the N-back. Most of this work has been conducted in fMRI, but functional near-infrared spectroscopy (fNIRS) is gaining traction as a less invasive and more flexible alternative to measuring cortical hemodynamics. Few fNIRS studies, however, have examined how working memory load-dependent changes in brain hemodynamics relate to performance. The current study employs a newly developed and robust statistical analysis of task-based fNIRS data in a large sample, and demonstrates the utility of data-driven, multivariate analyses to link brain activation and behavior in this modality. Seventy participants completed a standard N-back task with three N-back levels (N = 1, 2, 3) while fNIRS data were collected from frontal and parietal cortex. Overall, participants showed reliably greater fronto-parietal activation for the 2-back versus the 1-back task, suggesting fronto-parietal fNIRS measurements are sensitive to differences in cognitive load. The results for 3-back were much less consistent, potentially due to poor behavioral performance in the 3-back task. To address this, a multivariate analysis (behavioral partial least squares, PLS) was conducted to examine the interaction between fNIRS activation and performance at each N-back level. Results of the PLS analysis demonstrated differences in the relationship between accuracy and change in the deoxyhemoglobin fNIRS signal as a function of N-back level in eight mid-frontal channels. Specifically, greater reductions in deoxyhemoglobin (i.e., more activation) were positively related to performance on the 3-back task, unrelated to accuracy in the 2-back task, and negatively associated with accuracy in the 1-back task. This pattern of results suggests that the metabolic demands correlated with neural activity required for high levels of accuracy vary as a consequence of task difficulty/cognitive load, whereby more automaticity during the 1-back task (less mid-frontal activity) predicted superior performance on this relatively easy task, and successful engagement of this mid-frontal region was required for high accuracy on a more difficult and cognitively demanding 3-back task. In summary, we show that fNIRS activity can track working memory load and can uncover significant associations between brain activity and performance, thus opening the door for this modality to be used in more wide-spread applications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33570976,

title = {How do neural processes give rise to cognition? Simultaneously predicting brain and behavior with a dynamic model of visual working memory},

author = {Aaron T Buss and Vincent A Magnotta and Will Penny and Gregor Schöner and Theodore J Huppert and John P Spencer},

doi = {10.1037/rev0000264},

issn = {1939-1471},

year  = {2021},

date = {2021-03-01},

journal = {Psychol Rev},

volume = {128},

number = {2},

pages = {362--395},

abstract = {There is consensus that activation within distributed functional brain networks underlies human thought. The impact of this consensus is limited, however, by a gap that exists between data-driven correlational analyses that specify where functional brain activity is localized using functional magnetic resonance imaging (fMRI), and neural process accounts that specify how neural activity unfolds through time to give rise to behavior. Here, we show how an integrative cognitive neuroscience approach may bridge this gap. In an exemplary study of visual working memory, we use multilevel Bayesian statistics to demonstrate that a neural dynamic model simultaneously explains behavioral data and predicts localized patterns of brain activity, outperforming standard analytic approaches to fMRI. The model explains performance on both correct trials and incorrect trials where errors in change detection emerge from neural fluctuations amplified by neural interaction. Critically, predictions of the model run counter to cognitive theories of the origin of errors in change detection. Results reveal neural patterns predicted by the model within regions of the dorsal attention network that have been the focus of much debate. The model-based analysis suggests that key areas in the dorsal attention network such as the intraparietal sulcus play a central role in change detection rather than working memory maintenance, counter to previous interpretations of fMRI studies. More generally, the integrative cognitive neuroscience approach used here establishes a framework for directly testing theories of cognitive and brain function using the combined power of behavioral and fMRI data. (PsycInfo Database Record (c) 2021 APA, all rights reserved).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33536034,

title = {Brain lateralization in children with upper-limb reduction deficiency},

author = {Jorge M Zuniga and James E Pierce and Christopher Copeland and Claudia Cortes-Reyes and David Salazar and YingYing Wang and K M Arun and Theodore Huppert},

doi = {10.1186/s12984-020-00803-1},

issn = {1743-0003},

year  = {2021},

date = {2021-02-01},

journal = {J Neuroeng Rehabil},

volume = {18},

number = {1},

pages = {24},

abstract = {BACKGROUND: The purpose of the current study was to determine the influence of upper-limb prostheses on brain activity and gross dexterity in children with congenital unilateral upper-limb reduction deficiencies (ULD) compared to typically developing children (TD).nnMETHODS: Five children with ULD (3 boys, 2 girls, 8.76 ± 3.37 years of age) and five age- and sex-matched TD children (3 boys, 2 girls, 8.96 ± 3.23 years of age) performed a gross manual dexterity task (Box and Block Test) while measuring brain activity (functional near-infrared spectroscopy; fNIRS).nnRESULTS: There were no significant differences (p = 0.948) in gross dexterity performance between the ULD group with prosthesis (7.23 ± 3.37 blocks per minute) and TD group with the prosthetic simulator (7.63 ± 5.61 blocks per minute). However, there was a significant (p = 0.001) difference in Laterality Index (LI) between the ULD group with prosthesis (LI = - 0.2888 ± 0.0205) and TD group with simulator (LI = 0.0504 ± 0.0296) showing in a significant ipsilateral control for the ULD group. Thus, the major finding of the present investigation was that children with ULD, unlike the control group, showed significant activation in the ipsilateral motor cortex on the non-preferred side using a prosthesis during a gross manual dexterity task.nnCONCLUSIONS: This ipsilateral response may be a compensation strategy in which the existing cortical representations of the non-affected (preferred) side are been used by the affected (non-preferred) side to operate the prosthesis. This study is the first to report altered lateralization in children with ULD while using a prosthesis. Trial registration The clinical trial (ClinicalTrial.gov ID: NCT04110730 and unique protocol ID: IRB # 614-16-FB) was registered on October 1, 2019 ( https://clinicaltrials.gov/ct2/show/NCT04110730 ) and posted on October 1, 2019. The study start date was January 10, 2020. The first participant was enrolled on January 14, 2020, and the trial is scheduled to be completed by August 23, 2023. The trial was updated January 18, 2020 and is currently recruiting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32420776,

title = {Prehospital Patient Care Protocols for Suicidality in Washington State},

author = {Christopher R DeCou and Tierney Huppert and Kosuke Kume and Perry Veras and Katherine Anne Comtois and Thomas Rea},

doi = {10.1080/10903127.2020.1771489},

issn = {1545-0066},

year  = {2021},

date = {2021-01-01},

journal = {Prehosp Emerg Care},

volume = {25},

number = {3},

pages = {432--437},

abstract = {BACKGROUND: Patients with suicidal thoughts and behavior represent a growing proportion of patients who present for Emergency Department care. Many of these patients arrive via ambulance. Several brief suicide- or self-harm-specific interventions have been developed for implementation in the Emergency Department setting. However, there is a dearth of training resources, patient care guidelines, and policy guidance to assist prehospital care providers in the treatment of EMS patients who are suicidal. We evaluated prehospital patient care protocols in Washington State to assess for the presence-absence of any suicide and/or self-harm specific protocols, as well as the inclusion of procedures above and beyond conventional approaches to scene safety and transport to the Emergency Department.nnMETHODS: Prehospital patient care protocols were obtained for all counties in Washington State. Researchers rated protocols across seven domains, including the mention of any suicide- or self-harm-specific procedures.nnRESULTS: Approximately one-third of counties had any suicide- or self-harm-specific content in prehospital patient care protocols. There was no association between county-level rurality-urbanicity and the presence-absence of suicide- or self-harm-specific care.nnCONCLUSION: These findings demonstrated that little guidance exists for EMS providers in Washington State with regard to the screening or treatment of suicidal patients, above and beyond scene safety and transportation to hospital-based care. Development of guidelines for prehospital suicide care, as well as enhanced screening, assessment, and collaboration with on-call crisis resources has the potential to expand the scope of prehospital treatment for suicidal patients, and reduce burdens on patients, EMS providers, and Emergency Departments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33437847,

title = {Enhanced spatiotemporal resolution imaging of neuronal activity using joint electroencephalography and diffuse optical tomography},

author = {Jiaming Cao and Theodore J Huppert and Pulkit Grover and Jana M Kainerstorfer},

doi = {10.1117/1.NPh.8.1.015002},

issn = {2329-423X},

year  = {2021},

date = {2021-01-01},

journal = {Neurophotonics},

volume = {8},

number = {1},

pages = {015002},

abstract = { Electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) are both commonly used methodologies for neuronal source reconstruction. While EEG has high temporal resolution (millisecond-scale), its spatial resolution is on the order of centimeters. On the other hand, in comparison to EEG, fNIRS, or diffuse optical tomography (DOT), when used for source reconstruction, can achieve relatively high spatial resolution (millimeter-scale), but its temporal resolution is poor because the hemodynamics that it measures evolve on the order of several seconds. This has important neuroscientific implications: e.g., if two spatially close neuronal sources are activated sequentially with only a small temporal separation, single-modal measurements using either EEG or DOT alone would fail to resolve them correctly.  We attempt to address this issue by performing joint EEG and DOT neuronal source reconstruction.  We propose an algorithm that utilizes DOT reconstruction as the spatial prior of EEG reconstruction, and demonstrate the improvements using simulations based on the ICBM152 brain atlas.  We show that neuronal sources can be reconstructed with higher spatiotemporal resolution using our algorithm than using either modality individually. Further, we study how the performance of the proposed algorithm can be affected by the locations of the neuronal sources, and how the performance can be enhanced by improving the placement of EEG electrodes and DOT optodes.  We demonstrate using simulations that two sources separated by 2.3-3.3 cm and 50 ms can be recovered accurately using the proposed algorithm by suitably combining EEG and DOT, but not by either in isolation. We also show that the performance can be enhanced by optimizing the electrode and optode placement according to the locations of the neuronal sources.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35185514,

title = {Tract Specific White Matter Lesion Load Affects White Matter Microstructure and Their Relationships With Functional Connectivity and Cognitive Decline},

author = {Tae Kim and Howard J Aizenstein and Beth E Snitz and Yu Cheng and Yue-Fang Chang and Rebecca E Roush and Theodore J Huppert and Annie Cohen and Jack Doman and James T Becker},

doi = {10.3389/fnagi.2021.760663},

issn = {1663-4365},

year  = {2021},

date = {2021-01-01},

journal = {Front Aging Neurosci},

volume = {13},

pages = {760663},

abstract = {White matter hyperintensities (WMHs) are associated with cognitive decline. Assessing the effect of WMH on WM microstructural changes and its relationships with structural and functional connectivity to multiple cognitive domains are helpful to better understand the pathophysiological processes of cognitive impairment. 65 participants (49 normal and 16 MCI subjects, age: 67.4 ± 8.3 years, 44 females) were studied at 3T. The WMHs and fifty fiber tracts were automatically segmented from the T1/T2-weighted images and diffusion-weighted images, respectively. Tract-profiles of WMH were compared with those of apparent fiber density (AFD). The relationship between AFD and tract connectivity (TC) was assessed. Functional connectivity (FC) between tract ends obtained from resting-state functional MRI was examined in relation to TC. Tract-specific relationships of WMH, TC and FC with a multi-domain neuropsychological test battery and Montreal Cognitive Assessment (MoCA) were also separately assessed by lasso linear regression. Indirect pathways of TC and FC between WMH and multiple cognitive measures were tested using the mediation analysis. Higher WMH loads in WM tracts were locally matched with the reduced AFD, which was related to decrease in TC. However, no direct relationship was found between TC and FC. Tract-specific changes on WMH, TC and FC for each cognitive performance may explain that macro- and microstructural and functional changes are associated differently with each cognitive domain in a fiber specific manner. In these identified tracts, the differences between normal and MCI for WMH and TC were increased, and the relationships of WMH, TC and FC with cognitive outcomes were more significant, compared to the results from all tracts. Indirect pathways of two-step (TC-FC) between WMH and all cognitive domains were significant ( < 0.0083 with Bonferroni correction), while the separated indirect pathways through TC and through FC were different depending on cognitive domain. Deterioration in specific cognitive domains may be affected by alterations in a set of different tracts that are differently associated with macrostructural, microstructural, and function changes. Thus, assessments of WMH and its associated changes on specific tracts help for better understanding of the interrelationships of multiple changes in cognitive impairment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34816247,

title = {Postpartum Depression Is Associated With Altered Neural Connectivity Between Affective and Mentalizing Regions During Mother-Infant Interactions},

author = {Judith K Morgan and Hendrik Santosa and Rachel M Fridley and Kaetlyn K Conner and Alison E Hipwell and Erika E Forbes and Theodore J Huppert},

doi = {10.3389/fgwh.2021.744649},

issn = {2673-5059},

year  = {2021},

date = {2021-01-01},

journal = {Front Glob Womens Health},

volume = {2},

pages = {744649},

abstract = {Although there has been growing interest in mood-related neural alterations in women in the initial weeks postpartum, recent work has demonstrated that postpartum depression often lingers for months or years following birth. However, research evaluating the impact of depression on maternal brain function during mother-infant interactions in the late postpartum period is lacking. The current study tested the hypothesis that depressive symptoms at 12-months postpartum are associated with neural alterations in affective and social neural regions, using near-infrared spectroscopy during  mother-infant interactions. Participants were 23 birth mothers of 12-month-old infants (60% boys). While undergoing near-infrared spectroscopy, mothers engaged in an ecologically valid interactive task in which they looked at an age-appropriate book with their infants. Mothers also reported on their depressive symptoms in the past week and were rated on their observed levels of maternal sensitivity during mother-infant play. Greater depressive severity at 12-months postpartum was related to  connectivity between the right temporoparietal junction and the lateral prefrontal cortex, but  connectivity between the right temporoparietal junction and anterior medial prefrontal cortex during mother-infant interaction. Given the putative functions of these neural regions within the maternal brain network, our findings suggest that in the context of depression, postpartum mothers' mentalizing about her infants' thoughts and feelings may be related to  ability to express and regulate her own emotions, but  ability to engage in emotional bonding with her infant. Future work should explore how connectivity among these regions is associated with longitudinal changes in maternal behavior, especially in the context of changes in mothers' depressive symptoms (e.g., with treatment) over time.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34690734,

title = {Connectomics in Brain Aging and Dementia - The Background and Design of a Study of a Connectome Related to Human Disease},

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

doi = {10.3389/fnagi.2021.669490},

issn = {1663-4365},

year  = {2021},

date = {2021-01-01},

journal = {Front Aging Neurosci},

volume = {13},

pages = {669490},

abstract = {The natural history of Alzheimer's Disease (AD) includes significant alterations in the human connectome, and this disconnection results in the dementia of AD. The organizing principle of our research project is the idea that the expression of cognitive dysfunction in the elderly is the result of two independent processes - the neuropathology associated with AD, and second the neuropathological changes of cerebrovascular disease. Synaptic loss, senile plaques, and neurofibrillary tangles are the functional and diagnostic hallmarks of AD, but it is the structural changes as a consequence of vascular disease that reduce brain reserve and compensation, resulting in an earlier expression of the clinical dementia syndrome. This work is being completed under the auspices of the Human Connectome Project (HCP). We have achieved an equal representation of Black individuals (vs. White individuals) and enrolled 60% Women. Each of the participants contributes demographic, behavioral and laboratory data. We acquire data relative to vascular risk, and the participants also undergo  amyloid imaging, and magnetoencephalography (MEG). All of the data are publicly available under the HCP guidelines using the Connectome Coordinating Facility and the NIMH Data Archive. Locally, we use these data to address specific questions related to structure, function, AD, aging and vascular disease in multi-modality studies leveraging the differential advantages of magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), MEG, and  beta amyloid imaging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34017243,

title = {Cognition and Cerebrovascular Reactivity in Midlife Women With History of Preeclampsia and Placental Evidence of Maternal Vascular Malperfusion},

author = {C Elizabeth Shaaban and Caterina Rosano and Ann D Cohen and Theodore Huppert and Meryl A Butters and James Hengenius and W Tony Parks and Janet M Catov},

doi = {10.3389/fnagi.2021.637574},

issn = {1663-4365},

year  = {2021},

date = {2021-01-01},

journal = {Front Aging Neurosci},

volume = {13},

pages = {637574},

abstract = { Preeclampsia is emerging as a sex-specific risk factor for cerebral small vessel disease (SVD) and dementia, but the reason is unknown. We assessed the relationship of maternal vascular malperfusion (MVM), a marker of placental SVD, with cognition and cerebral SVD in women with and without preeclampsia. We hypothesized women with both preeclampsia and MVM would perform worst on information processing speed and executive function.  Women ( = 45; mean 10.5 years post-delivery; mean age: 41 years; 42.2% Black) were classified as preeclampsia-/MVM-, preeclampsia+/MVM-, or preeclampsia+/MVM+. Information processing speed, executive function, and memory were assessed. In a pilot sub-study of cerebrovascular reactivity (CVR;  = 22), cerebral blood flow during room-air breathing and breath-hold induced hypercapnia were obtained via arterial spin labeling MRI. Non-parametric tests and regression models were used to test associations.  Between-group cognitive differences were significant for information processing speed ( = 0.02); preeclampsia+/MVM+ had the lowest scores. Cerebral blood flow increased from room-air to breath-hold, globally and in all regions in the three groups, except the preeclampsia+/MVM+ parietal region ( = 0.12). Lower parietal CVR (less change from room-air breathing to breath-holding) was correlated with poorer information processing speed (partial ρ = 0.63,  = 0.005) and executive function (ρ = 0.50,  = 0.03) independent of preeclampsia/MVM status.  Compared to women without preeclampsia and MVM, midlife women with both preeclampsia and MVM have worse information processing speed and may have blunted parietal CVR, an area important for information processing speed and executive function. MVM in women with preeclampsia is a promising sex-specific indicator of cerebrovascular integrity in midlife.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33994978,

title = {Decoding Multiple Sound-Categories in the Auditory Cortex by Neural Networks: An fNIRS Study},

author = {So-Hyeon Yoo and Hendrik Santosa and Chang-Seok Kim and Keum-Shik Hong},

doi = {10.3389/fnhum.2021.636191},

issn = {1662-5161},

year  = {2021},

date = {2021-01-01},

journal = {Front Hum Neurosci},

volume = {15},

pages = {636191},

abstract = {This study aims to decode the hemodynamic responses (HRs) evoked by multiple sound-categories using functional near-infrared spectroscopy (fNIRS). The six different sounds were given as stimuli (English, non-English, annoying, nature, music, and gunshot). The oxy-hemoglobin (HbO) concentration changes are measured in both hemispheres of the auditory cortex while 18 healthy subjects listen to 10-s blocks of six sound-categories. Long short-term memory (LSTM) networks were used as a classifier. The classification accuracy was 20.38 ± 4.63% with six class classification. Though LSTM networks' performance was a little higher than chance levels, it is noteworthy that we could classify the data subject-wise without feature selections.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31769511,

title = {Parent-child neural synchrony: a novel approach to elucidating dyadic correlates of preschool irritability},

author = {Laura E Quiñones-Camacho and Frank A Fishburn and M Catalina Camacho and Christina O Hlutkowsky and Theodore J Huppert and Lauren S Wakschlag and Susan B Perlman},

doi = {10.1111/jcpp.13165},

issn = {1469-7610},

year  = {2020},

date = {2020-11-01},

journal = {J Child Psychol Psychiatry},

volume = {61},

number = {11},

pages = {1213--1223},

abstract = {BACKGROUND: Research to date has largely conceptualized irritability in terms of intraindividual differences. However, the role of interpersonal dyadic processes has received little consideration. Nevertheless, difficulties in how parent-child dyads synchronize during interactions may be an important correlate of irritably in early childhood. Innovations in developmentally sensitive neuroimaging methods now enable the use of measures of neural synchrony to quantify synchronous responses in parent-child dyads and can help clarify the neural underpinnings of these difficulties. We introduce the Disruptive Behavior Diagnostic Observation Schedule: Biological Synchrony (DB-DOS:BioSync) as a paradigm for exploring parent-child neural synchrony as a potential biological mechanism for interpersonal difficulties in preschool psychopathology.nnMETHODS: Using functional near-infrared spectroscopy (fNIRS) 4- to 5-year-olds (N = 116) and their mothers completed the DB-DOS:BioSync while assessing neural synchrony during mild frustration and recovery. Child irritability was measured using a latent irritability factor that was calculated from four developmentally sensitive indicators.nnRESULTS: Both the mild frustration and the recovery contexts resulted in neural synchrony. However, less neural synchrony during the recovery context only was associated with more child irritability.nnCONCLUSIONS: Our results suggest that recovering after a frustrating period might be particularly challenging for children high in irritability and offer support for the use of the DB-DOS:BioSync task to elucidate interpersonal neural mechanisms of developmental psychopathology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32995360,

title = {Using anatomically defined regions-of-interest to adjust for head-size and probe alignment in functional near-infrared spectroscopy},

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

doi = {10.1117/1.NPh.7.3.035008},

issn = {2329-423X},

year  = {2020},

date = {2020-07-01},

journal = {Neurophotonics},

volume = {7},

number = {3},

pages = {035008},

abstract = { Functional near-infrared spectroscopy (fNIRS) uses surface-placed light sources and detectors to record underlying changes in the brain due to fluctuations in hemoglobin levels and oxygenation. Since these measurements are recorded from the surface of the scalp, the mapping from underlying regions-of-interest (ROIs) in the brain space to the fNIRS channel space measurements depends on the registration of the sensors, the anatomy of the head/brain, and the sensitivity of these diffuse measurements through the tissue. However, small displacements in the probe position can change the distribution of recorded brain activity across the fNIRS measurements.  We propose an approach using either individual or atlas-based brain-space anatomical information to define ROI-based statistical hypotheses to test the null involvement of specific regions, which allows us to test the analogous ROI across subjects while adjusting for fNIRS probe placement and sensitivity differences due to head size variations without a localizer task.  We use the optical forward model to project the underlying brain-space ROI into a tapered contrast vector, which defines the relative weighting of the fNIRS channels contributing to the ROI and allows us to test the null hypothesis of no brain activity in this region during a functional task. We demonstrate this method through simulation and compare the sensitivity-specificity of this approach to other conventional methods.  We examine the performance of this method in the scenario where head size and probe registration are both an accurately known parameters and where this is subject to unknown experimental errors. This method is compared with the performance of the conventional method using 364 different simulation parameter combinations.  The proposed method is always recommended in ROI-based analysis, since it significantly improves the analysis performance without a localizer task, wherever the fNIRS probe registration is known or unknown.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32995361,

title = {Quantitative comparison of correction techniques for removing systemic physiological signal in functional near-infrared spectroscopy studies},

author = {Hendrik Santosa and Xuetong Zhai and Frank Fishburn and Patrick J Sparto and Theodore J Huppert},

doi = {10.1117/1.NPh.7.3.035009},

issn = {2329-423X},

year  = {2020},

date = {2020-07-01},

journal = {Neurophotonics},

volume = {7},

number = {3},

pages = {035009},

abstract = { Isolating task-evoked brain signals from background physiological noise (e.g., cardiac, respiratory, and blood pressure fluctuations) poses a major challenge for the analysis of functional near-infrared spectroscopy (fNIRS) data.  The performance of several analytic methods to separate background physiological noise from brain activity including spatial and temporal filtering, regression, component analysis, and the use of short-separation (SS) measurements were quantitatively compared.  Using experimentally recorded background signals (breath-hold task), receiver operating characteristics simulations were performed by adding various levels of additive synthetic "brain" responses in order to examine the sensitivity and specificity of several previously proposed analytic approaches.  We found that the use of SS fNIRS channels as regressors of no-interest within a linear regression model was the best performing approach examined. Furthermore, we found that the addition of all available SS data, including all recorded channels and both hemoglobin species, improved the method performance despite the additional degrees-of-freedom of the models. When SS data were not available, we found that principal component filtering using a separate baseline scan was the best alternative.  The use of multiple SS measurements as regressors of no interest implemented in a robust, iteratively prewhitened, general linear model has the best performance of the tested existing methods.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}