Fatigue and perceived energy in a sample of older adults over 10 years: A resting state functional connectivity study of neural correlates.

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Amygdala real-time fMRI neurofeedback upregulation in treatment resistant depression: Proof of concept and dose determination.

Previous work has shown that adults suffering from major depressive disorder (MDD) can increase their amygdala reactivity while recalling positive memories via real-time neurofeedback (rt-fMRI-nf) training, which is associated with reduction in depressive symptoms. This study investigated if this intervention could also be considered for patients suffering from MDD who do not respond to standard psychological and pharmacological interventions, i.e., treatment resistant (TR-MDD). 15 participants received 5 neurofeedback sessions. Outcome measures were depressive symptoms assessed by BDI scores up to 12 weeks following acute intervention, and amygdala activity changes from initial baseline to final transfer run during neurofeedback sessions (neurofeedback success). Participants succeeded in increasing their amygdala activity. A main effect of visit on BDI scores indicated a significant reduction in depressive symptomatology. Percent signal change in the amygdala showed a learning curve during the first session only. Neurofeedback success computed by session was significantly positive only during the second session. When examining the baseline amygdala response, baseline activity stabilized/asymptoted by session 3. This proof-of-concept study suggests that only two neurofeedback sessions are necessary to enable those patients to upregulate their amygdala activity, warranting a future RCT. Over the course of the rtfMRI-nf intervention, participants also reported reduced depressive symptomatology. Clinical trial registration number: NCT03428828 on ClinicalTrials.gov.

Prefrontal cortex activation while walking did not change but gait speed improved after a randomized physical therapy intervention.

BACKGROUND: Higher prefrontal cortex (PFC) activation while walking may indicate reduced gait automaticity. AIM: We examine whether PFC activation during walking improves after training in older adults at risk for mobility disability. METHODS: 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). RESULTS: 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. DISCUSSION 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.

Unhealthy white matter connectivity, cognition, and racialization in older adults.

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. METHODS: 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 (Aß) or tau pathology-affected regions with cognition overall, stratified by racialized group, and with a racialized group interaction. RESULTS: 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 Aß- and tau-affected regions, respectively. Racialization did not modify these relationships. DISCUSSION: Differential UWMC burden, not differential UWMC-and-cognition associations, may drive clinical AD disparities between racialized groups. HIGHLIGHTS: 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.

Covariate-guided Bayesian mixture of spline experts for the analysis of multivariate high-density longitudinal data.

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.

Targeted multidomain intervention for complex mTBI: protocol for a multisite randomized controlled trial in military-age civilians.

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. Methods: 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. Discussion: 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. Ethics 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. Clinical Trial Registration: www.clinicaltrials.gov, identifier: NCT04549532.

Enhanced efficacy of CBT following augmentation with amygdala rtfMRI neurofeedback in depression.

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. METHODS: 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. RESULTS: 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. LIMITATIONS: The study was relatively small and not sufficiently powered to detect small effects. CONCLUSIONS: 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.

Real-time functional magnetic resonance imaging neurofeedback training of amygdala upregulation increases affective flexibility in depression.

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). METHODS: 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. RESULTS: 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 (t > 2.01, df < 27, p < 0.05, d > 0.5) and depressive symptoms decreased (-8.57, 95 % confidence interval [CI] -15.12 to -2.59; t 13 = -3.06, p = 0.009, d = 1). Amygdala activity during the count condition decreased after rtfMRI-nf (-0.16, 95 % CI -0.23 to -0.09; t 396 = 4.73, p < 0.001, d = 0.48) and was correlated with decreased depression scores (r = 0.46, p = 0.01). We replicated previous results and extended them to show decreased amygdala reactivity to a cognitive task during which no neurofeedback was provided. LIMITATIONS: The count condition was reported by participants as negative, but emotionality or accuracy during this condition was not assessed. CONCLUSION: 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.Trial registration: ClinicalTrials.gov NCT02709161.

Brain space image reconstruction of functional near-infrared spectroscopy using a Bayesian adaptive fused sparse overlapping group lasso model.

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. Aim: We describe a Bayesian approach combining several lasso-based regularizations to apply anatomy-prior information to solving the inverse model. Approach: 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. Results: We apply this approach to the simulation and experimental datasets to reconstruct a known brain activity. The reconstructed images and statistical plots are shown. Conclusion: 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.

Mother-child neural synchronization is time linked to mother-child positive affective state matching.

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.

Introduction to the shared near infrared spectroscopy format.

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. Aim: 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. Approach: 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. Results: The SNIRF specification defines a format for fNIRS data acquired using continuous wave, frequency domain, time domain, and diffuse correlation spectroscopy devices. Conclusions: 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.

The use of functional near infrared spectroscopy and gait analysis to characterize cognitive and motor processing in early-stage patients with multiple sclerosis.

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. Objective: 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. Methods: 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. Results 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.

Correction of global physiology in resting-state functional near-infrared spectroscopy.

Significance: 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. Aim: 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. Approach: 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. Results: 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. Conclusions: 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.

Scale invariance in fNIRS as a measurement of cognitive load.

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.

Influence of serial subtraction tasks on transient characteristics of postural control.

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.

Offset analgesia is associated with opposing modulation of medial versus dorsolateral prefrontal cortex activations: A functional near-infrared spectroscopy study.

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.

Cortico-striatal functional connectivity and cerebral small vessel disease: Contribution to mild Parkinsonian signs.

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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Postpartum Depression Is Associated With Altered Neural Connectivity Between Affective and Mentalizing Regions During Mother-Infant Interactions.

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 in vivo 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 lower connectivity between the right temporoparietal junction and the lateral prefrontal cortex, but greater 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 lower ability to express and regulate her own emotions, but greater 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.

Cognition and Cerebrovascular Reactivity in Midlife Women With History of Preeclampsia and Placental Evidence of Maternal Vascular Malperfusion.

Background: 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. Methods: Women (n = 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; n = 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. Results: Between-group cognitive differences were significant for information processing speed (p = 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 (p = 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, p = 0.005) and executive function (ρ = 0.50, p = 0.03) independent of preeclampsia/MVM status. Conclusion: 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.

Dysfunction in interpersonal neural synchronization as a mechanism for social impairment in autism spectrum disorder.

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.