Search

Brain reorganization following spinal cord injury (SCI) has been well established using both animal and human studies. Yet, much is unknown regarding the mechanisms associated with positive functional recovery and negative secondary outcomes after SCI. In this study, we use functional near-infrared spectroscopy (fNIRS) to examine the cortical functional differences between individuals with SCI and age-matched healthy controls (HCs), during the performance of stimulus-induced motor tasks and resting-state conditions. We found an overall lower magnitude hemodynamic response curve in the SCI group than the HC group during finger tapping (FT) and finger tapping imagery with action observation (FTI+AO) conditions. We also report overall decreased resting state functional connectivity (RSFC) in the SCI group than HC group; however, significant differences were only found in the Slow-3 frequency range (0.073 to 0.1 Hz). Lastly, upon correlating task-based FC and RSFC with the duration of injury in the SCI group, we found that a longer injury duration was significantly associated with lower task-based FC within the medial sensorimotor network (mSMN) during the FT task condition. However, we found no significant association between RSFC and the duration of injury in individuals with SCI. These results provide insight regarding the use of fNIRS in rehabilitative therapies for individuals with SCI and allow for a better understanding of cortical functional alterations after SCI.

Background Patients undergoing surgical procedures are vulnerable to repetitive evoked or ongoing nociceptive barrage. Using functional near infrared spectroscopy, the authors aimed to evaluate the cortical hemodynamic signal power changes during ongoing nociception in healthy awake volunteers and in surgical patients under general anesthesia. The authors hypothesized that ongoing nociception to heat or surgical trauma would induce reductions in the power of cortical low-frequency hemodynamic oscillations in a similar manner as previously reported using functional magnetic resonance imaging for ongoing pain. Methods Cortical hemodynamic signals during noxious stimuli from the fontopolar cortex were evaluated in two groups: group 1, a healthy/conscious group (n = 15, all males) where ongoing noxious and innocuous heat stimulus was induced by a contact thermode to the dorsum of left hand; and group 2, a patient/unconscious group (n = 13, 3 males) receiving general anesthesia undergoing knee surgery. The fractional power of low-frequency hemodynamic signals was compared across stimulation conditions in the healthy awake group, and between patients who received standard anesthesia and those who received standard anesthesia with additional regional nerve block. Results A reduction of the total fractional power in both groups—specifically, a decrease in the slow-5 frequency band (0.01 to 0.027 Hz) of oxygenated hemoglobin concentration changes over the frontopolar cortex—was observed during ongoing noxious stimuli in the healthy awake group (paired t test, P = 0.017; effect size, 0.70), and during invasive procedures in the surgery group (paired t test, P = 0.003; effect size, 2.16). The reduction was partially reversed in patients who received a regional nerve block that likely diminished afferent nociceptive activity (two-sample t test, P = 0.002; effect size, 2.34). Conclusions These results suggest common power changes in slow-wave cortical hemodynamic oscillations during ongoing nociceptive processing in conscious and unconscious states. The observed signal may potentially promote future development of a surrogate signal to assess ongoing nociception under general anesthesia. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

It is well established that migraine is a multifactorial disorder. A deep understanding of migraine should be based upon both the underlying traits and the current states affected by different physiological, psychological, and environmental factors. At this point, there is no framework fully meeting these criteria. Here, we describe a broader view of the migraine disorder defined as a dysfunctional brain state and trait interaction. In this model, we consider events that may enhance or diminish migraine responsivity based on an individual’s trait and state. This could provide an expanded view for considering how migraine attacks are sometimes precipitated by “triggers” and sometimes not, how these factors only lead to migraine attacks in migraine patients, or how individuals with an increased risk for migraine do not show any symptoms at all. Summarizing recent studies and evidence that support the concept of migraine as a brain state–trait interaction can also contribute to improving patient care by highlighting the importance of precision medicine and applying measures that are able to capture how different traits and states work together to determine migraine.

Cerebrovascular reactivity (CVR) is routinely measured as a predictor of stroke in people with a high risk of ischemic attack. Neuroimaging techniques such as emission tomography, magnetic resonance imaging, and transcranial doppler are frequently used to measure CVR even though each technique has its limitations. Functional near-infrared spectroscopy (fNIRS), also based on the principle of neurovascular coupling, is relatively inexpensive, portable, and allows for the quantification of oxy- and deoxy-hemoglobin concentration changes at a high temporal resolution. This study examines the relationship between age and CVR using fNIRS in 45 young healthy adult participants aged 18–41 years (6 females, 26.64 ± 5.49 years) performing a simple breath holding task. Eighteen of the 45 participants were scanned again after a week to evaluate the feasibility of fNIRS in reliably measuring CVR. Results indicate (a) a negative relationship between age and hemodynamic measures of breath holding task in the sensorimotor cortex of 45 individuals and (b) widespread positive coactivation within medial sensorimotor regions and between medial sensorimotor regions with supplementary motor area and prefrontal cortex during breath holding with increasing age. The intraclass correlation coefficient (ICC) indicated only a low to fair/good reliability of the breath hold hemodynamic measures from sensorimotor and prefrontal cortices. However, the average hemodynamic response to breath holding from the two sessions were found to be temporally and spatially in correspondence. Future improvements in the sensitivity and reliability of fNIRS metrics could facilitate fNIRS-based assessment of cerebrovascular function as a potential clinical tool.

Chronic postsurgical pain (CPSP) results from a cascade of events in the peripheral and central nervous systems following surgery. Several clinical predictors, including the prior pain state, premorbid psychological state (e.g., anxiety, catastrophizing), intraoperative surgical load (establishment of peripheral and central sensitization), and acute postoperative pain management, may contribute to the patient's risk of developing CPSP. However, research on the neurobiological and biobehavioral mechanisms contributing to pediatric CPSP and effective preemptive/treatment strategies are still lacking. Here we evaluate the perisurgical process by identifying key problems and propose potential solutions for the pre-, intra-, and postoperative pain states to both prevent and manage the transition of acute to chronic pain. We propose an eight-step process involving preemptive and preventative analgesia, behavioral interventions, and the use of biomarkers (brain-based, inflammatory, or genetic) to facilitate timely evaluation and treatment of premorbid psychological factors, ongoing surgical pain, and postoperative pain to provide an overall improved outcome. By achieving this, we can begin to establish personalized precision medicine for children and adolescents presenting to surgery and subsequent treatment selection.La douleur chronique post-chirurgicale (DCPC) résulte d'une cascade d'événements dans les systèmes nerveux central et périphérique suite à une intervention chirurgicale. Plusieurs prédicteurs cliniques, y compris l'état douloureux antérieur, l'état psychologique prémorbide (p. ex., anxiété, catastrophisme), la charge chirurgicale peropératoire (établissement d'une sensibilisation périphérique et centrale) et la prise en charge de la douleur postopératoire aiguë, peuvent contribuer au risque du patient de développer une DCPC. Cependant, la recherche sur les mécanismes neurobiologiques et biocomportementaux contribuant à la DCPC pédiatrique et sur les stratégies de prévention et de traitement efficaces font encore défaut. Nous évaluons ici le processus périchirurgical en cernant les problémes clés et en proposant des solutions potentielles pour les états douloureux pré, per et postopératoires afin de prévenir et de prendre en charge la transition de la douleur aiguë à la douleur chronique. Nous proposons un processus en huit étapes impliquant l'analgésie préemptive et préventive, les interventions comportementales et l'utilisation de biomarqueurs (cérébraux, inflammatoires ou génétiques) pour faciliter l'évaluation et le traitement opportuns des facteurs psychologiques prémorbides, de la douleur chirurgicale persistante et de la douleur postopératoire afin d'améliorer le résultat global. En y parvenant, nous pouvons commencer à établir une médecine de précision personnalisée pour les enfants et les adolescents qui subissent une intervention chirurgicale et à la sélection du traitement qui s'ensuit.

Current pain assessment techniques based only on clinical evaluation and self-reports are not objective and may lead to inadequate treatment. Having a functional biomarker will add to the clinical fidelity, diagnosis, and perhaps improve treatment efficacy in patients. While many approaches have been deployed in pain biomarker discovery, functional near-infrared spectroscopy (fNIRS) is a technology that allows for non-invasive measurement of cortical hemodynamics. The utility of fNIRS is especially attractive given its ability to detect specific changes in the somatosensory and high-order cortices as well as its ability to measure (1) brain function similar to functional magnetic resonance imaging, (2) graded responses to noxious and innocuous stimuli, (3) analgesia, and (4) nociception under anesthesia. In this review, we evaluate the utility of fNIRS in nociception/pain with particular focus on its sensitivity and specificity, methodological advantages and limitations, and the current and potential applications in various pain conditions. Everything considered, fNIRS technology could enhance our ability to evaluate evoked and persistent pain across different age groups and clinical populations.

Introduction Functional near-infrared spectroscopy (fNIRS) allows for ongoing measures of brain functions during surgery. The ability to evaluate cumulative effects of painful/nociceptive events under general anesthesia remains a challenge. Through observing signal differences and setting boundaries for when observed events are known to produce pain/nociception, a program can trigger when the concentration of oxygenated hemoglobin goes beyond ±0.3 mM from 25 s after standardization. Method fNIRS signals were retrieved from patients undergoing knee surgery for anterior cruciate ligament repair under general anesthesia. Continuous fNIRS measures were measured from the primary somatosensory cortex (S1), which is known to be involved in evaluation of nociception, and the medial polar frontal cortex (mPFC), which are both involved in higher cortical functions (viz. cognition and emotion). Results A ±0.3 mM threshold for painful/nociceptive events was observed during surgical incisions at least twice, forming a basis for a potential near-real-time recording of pain/nociceptive events. Evidence through observed true positives in S1 and true negatives in mPFC are linked through statistically significant correlations and this threshold. Conclusion Our results show that standardizing and observing concentrations over 25 s using the ±0.3 mM threshold can be an arbiter of the continuous number of incisions performed on a patient, contributing to a potential intraoperative pain load index that correlates with post-operative levels of pain and potential pain chronification.

Significance: Functional near-infrared spectroscopy (fNIRS) has evaluated pain in awake and anesthetized states. Aim: We evaluated fNIRS signals under general anesthesia in patients undergoing knee surgery for anterior cruciate ligament repair. Approach: Patients were split into groups: those with regional nerve block (NB) and those without (non-NB). Continuous fNIRS measures came from three regions: the primary somatosensory cortex (S1), known to be involved in evaluation of nociception, the lateral prefrontal cortex (BA9), and the polar frontal cortex (BA10), both involved in higher cortical functions (such as cognition and emotion). Results: Our results show three significant differences in fNIRS signals to incision procedures between groups: (1) NB compared with non-NB was associated with a greater net positive hemodynamic response to pain procedures in S1; (2) dynamic correlation between the prefrontal cortex (PreFC) and S1 within 1 min of painful procedures are anticorrelated in NB while positively correlated in non-NB; and (3) hemodynamic measures of activation were similar at two separate time points during surgery (i.e., first and last incisions) in PreFC and S1 but showed significant differences in their overlap. Comparing pain levels immediately after surgery and during discharge from postoperative care revealed no significant differences in the pain levels between NB and non-NB. Conclusion: Our data suggest multiple pain events that occur during surgery using devised algorithms could potentially give a measure of “pain load.” This may allow for evaluation of central sensitization (i.e., a heightened state of the nervous system where noxious and non-noxious stimuli is perceived as painful) to postoperative pain levels and the resulting analgesic consumption. This evaluation could potentially predict postsurgical chronic neuropathic pain.

Anatomical studies of spinal cord injury (SCI) using magnetic resonance imaging (MRI) report diverging observations, from "no changes" to "tissue atrophy in motor and non-motor regions." These discrepancies among studies can be attributed to heterogeneity in extent, level, and post-injury duration observed within the SCI population. But, no studies have investigated structural changes associated with different levels of injury (paraplegia vs. tetraplegia). High-resolution MRI images were processed using a voxel-based morphometry technique to compare regional gray matter volume (GMV) between 16 complete paraplegia and 7 complete tetraplegia SCI subjects scanned within 2 years of injury when compared to 22 age-matched healthy controls using one-way analysis of covariance (ANCOVA). A post-hoc analysis using a region of interest-based approach was utilized to quantify GMV differences between healthy controls and subgroups of SCI. A voxel-wise one-sample t-test was also performed to evaluate the mean effect of post-injury duration on GMV of the SCI group. ANCOVA resulted in altered GMV in inferior frontal gyrus, bilateral mid orbital gyrus extending to rectal gyrus, and anterior cingulate cortex. Post-hoc analysis, in general, indicated GM atrophy after SCI, but tetraplegia showed a greater decrease in GMV when compared to paraplegia and healthy controls. Further, the GMV of the middle frontal gyrus, superior frontal gyrus, inferior frontal gyrus, insula, mid-orbital gyrus, and middle temporal gyrus was positively correlated with post-injury duration in both paraplegia and tetraplegia groups. GM atrophy after SCI is affected by level of cord injury, with higher levels of injury resulting in greater loss of GMV. Magnitude of GMV loss in the frontal cortex after SCI also appears to be dynamic within the first 2 years of injury. Understanding the effect of injury level and injury duration on structural changes after SCI can help to better understand the mechanisms leading to positive and negative clinical outcome in SCI patients.

Background Catheter radiofrequency (RF) ablation for cardiac arrhythmias is a painful procedure. Prior work using functional near-infrared spectroscopy (fNIRS) in patients under general anesthesia has indicated that ablation results in activity in pain-related cortical regions, presumably due to inadequate blockade of afferent nociceptors originating within the cardiac system. Having an objective brain-based measure for nociception and analgesia may in the future allow for enhanced analgesic control during surgical procedures. Hence, the primary aim of this study is to demonstrate that the administration of remifentanil, an opioid widely used during surgery, can attenuate the fNIRS cortical responses to cardiac ablation. Methods and findings We investigated the effects of continuous remifentanil on cortical hemodynamics during cardiac ablation under anesthesia. In a randomized, double-blinded, placebo (PL)-controlled trial, we examined 32 pediatric patients (mean age of 15.8 years,16 females) undergoing catheter ablation for cardiac arrhythmias at the Cardiology Department of Boston Children’s Hospital from October 2016 to March 2020; 9 received 0.9% NaCl, 12 received low-dose (LD) remifentanil (0.25 mcg/kg/min), and 11 received high-dose (HD) remifentanil (0.5 mcg/kg/min). The hemodynamic changes of primary somatosensory and prefrontal cortices were recorded during surgery using a continuous wave fNIRS system. The primary outcome measures were the changes in oxyhemoglobin concentration (NadirHbO, i.e., lowest oxyhemoglobin concentration and PeakHbO, i.e., peak change and area under the curve) of medial frontopolar cortex (mFPC), lateral prefrontal cortex (lPFC) and primary somatosensory cortex (S1) to ablation in PL versus remifentanil groups. Secondary measures included the fNIRS response to an auditory control condition. The data analysis was performed on an intention-to-treat (ITT) basis. Remifentanil group (dosage subgroups combined) was compared with PL, and a post hoc analysis was performed to identify dose effects. There were no adverse events. The groups were comparable in age, sex, and number of ablations. Results comparing remifentanil versus PL show that PL group exhibit greater NadirHbO in inferior mFPC (mean difference (MD) = 1.229, 95% confidence interval [CI] = 0.334, 2.124, p < 0.001) and superior mFPC (MD = 1.206, 95% CI = 0.303, 2.109, p = 0.001) and greater PeakHbO in inferior mFPC (MD = −1.138, 95% CI = −2.062, −0.214, p = 0.002) and superior mFPC (MD = −0.999, 95% CI = −1.961, −0.036, p = 0.008) in response to ablation. S1 activation from ablation was greatest in PL, then LD, and HD groups, but failed to reach significance, whereas lPFC activation to ablation was similar in all groups. Ablation versus auditory stimuli resulted in higher PeakHbO in inferior mFPC (MD = 0.053, 95% CI = 0.004, 0.101, p = 0.004) and superior mFPC (MD = 0.052, 95% CI = 0.013, 0.091, p < 0.001) and higher NadirHbO in posterior superior S1 (Pos. SS1; MD = −0.342, 95% CI = −0.680, −0.004, p = 0.007) during ablation of all patients. Remifentanil group had smaller NadirHbO in inferior mFPC (MD = 0.098, 95% CI = 0.009, 0.130, p = 0.003) and superior mFPC (MD = 0.096, 95% CI = 0.008, 0.116, p = 0.003) and smaller PeakHbO in superior mFPC (MD = −0.092, 95% CI = −0.680, −0.004, p = 0.007) during both the stimuli. Study limitations were small sample size, motion from surgery, indirect measure of nociception, and shallow penetration depth of fNIRS only allowing access to superficial cortical layers. Conclusions We observed cortical activity related to nociception during cardiac ablation under general anesthesia with remifentanil. It highlights the potential of fNIRS to provide an objective pain measure in unconscious patients, where cortical-based measures may be more accurate than current evaluation methods. Future research may expand on this application to produce a real-time indication of pain that will aid clinicians in providing immediate and adequate pain treatment. Trial registration ClinicalTrials.gov NCT02703090

Additional file 1. QA/QC and functional connectivity analyses of fNIRS data.

Functional magnetic resonance imaging (fMRI) studies of the resting state have provided consistent and reliable brain networks defined by spatially distinct regions whose interactions are both functionally segregated and integrated across the whole brain. Functional connections integrate multiple brain systems to produce unique networks attending to the different cognitive and sensory demands of the body. Detection and quantification of functional connectivity has been fundamental to the investigation of behavioral and clinical abnormalities in brain function using noninvasive human neuroimaging. It has expanded our ability to examine the brain physiology and pathophysiology across different age groups and clinical populations. Several techniques exist in literature to identify and quantify the functional connectivity metrics of brain regions using resting-state fMRI. In this chapter, we review the neurophysiological basis of resting-state functional connectivity and give a synopsis of the most established resting-state analysis techniques. We also summarize relevant findings from an array of clinical populations including neuropsychological disorders to emphasize the versatility of resting-state fMRI.

BackgroundPain is a highly prevalent symptom experienced by patients across numerous rare musculoskeletal conditions. Much remains unknown regarding the central, neurobiological processes associated with clinical pain in musculoskeletal disease states. Fibrodysplasia ossificans progressiva (FOP) is an inherited condition characterized by substantial physical disability and pain. FOP arises from mutations of the bone morphogenetic protein (BMP) receptor Activin A receptor type 1 (ACVR1) causing patients to undergo painful flare-ups as well as heterotopic ossification (HO) of skeletal muscles, tendons, ligaments, and fascia. To date, the neurobiological processes that underlie pain in FOP have rarely been investigated. We examined pain and central pain mechanism in FOP as a model primary musculoskeletal condition. Central nervous system (CNS) functional properties were investigated in FOP patients (N = 17) stratified into low (0–3; 0–10 Scale) and high (≥ 4) pain cohorts using functional near-infrared spectroscopy (fNIRS). Associations among clinical pain, mental health, and physical health were also quantified using responses derived from a battery of clinical questionnaires.ResultsResting-state fNIRS revealed suppressed power of hemodynamic activity within the slow-5 frequency sub-band (0.01–0.027 Hz) in the prefrontal cortex in high pain FOP patients, where reduced power of slow-5, prefrontal cortex oscillations exhibited robust negative correlations with pain levels. Higher clinical pain intensities were also associated with higher magnitudes of depressive symptoms.ConclusionsOur findings not only demonstrate a robust coupling among prefrontal cortex functionality and clinical pain in FOP but lays the groundwork for utilizing fNIRS to objectively monitor and central pain mechanisms in FOP and other musculoskeletal disorders.

Although unconscious processing is a key element of mental operation, its neural correlates have not been established. Also, clinical observations suggest that unconscious processing may be involved in the pathophysiology of post-traumatic stress disorder (PTSD), but the neurobiological mechanisms underlying such impairments remain unknown. The purpose of the present study was to examine putative mechanisms underlying unconscious processing by healthy participants and to determine whether these mechanisms may be altered in PTSD patients. Twenty patients with PTSD and 27 healthy individuals were administered a validated wheel of fortune-type gambling task during functional magnetic resonance imaging (fMRI). Unconscious processing was elicited using unconscious contextual framing of the zero monetary outcomes as “no loss,” “no gain” or as “neutral.” Brief passive visual processing of the “no loss” vs. “no gain” contrast by healthy participants yielded bilateral frontal-, temporal- and insular cortices and striatal activations. Between-group comparison revealed smaller activity in the left anterior prefrontal-, left dorsolateral prefrontal-, right temporal- and right insular cortices and in bilateral striatum in PTSD patients with the left dorsolateral prefrontal cortex activity been more pronounced in those with greater PTSD severity. These observations implicate frontal-, temporal-, and insular cortices along with the striatum in the putative mechanisms underlying unconscious processing of the monetary outcomes. Additionally, our results support the hypothesis that PTSD is associated with primary cortical and subcortical alterations involved in the above processes and that these alterations may be related to some aspects of PTSD symptomatology.

Cerebrovascular reactivity (CVR) is routinely measured as a predictor of stroke in people with a high risk of ischemic attack. Neuroimaging techniques such as emission tomography, magnetic resonance imaging, and transcranial doppler are frequently used to measure CVR even though each technique has its limitations. Functional near-infrared spectroscopy (fNIRS), also based on the principle of neurovascular coupling, is relatively inexpensive, portable, and allows for the quantification of oxy- and deoxy-hemoglobin concentration changes at a high temporal resolution. This study examines the relationship between age and CVR using fNIRS in 45 young healthy adult participants aged 18-41 years (6 females, 26.64 ± 5.49 years) performing a simple breath holding task. Eighteen of the 45 participants were scanned again after a week to evaluate the feasibility of fNIRS in reliably measuring CVR. Results indicate (a) a negative relationship between age and hemodynamic measures of breath holding task in the sensorimotor cortex of 45 individuals and (b) widespread positive coactivation within medial sensorimotor regions and between medial sensorimotor regions with supplementary motor area and prefrontal cortex during breath holding with increasing age. The intraclass correlation coefficient (ICC) indicated only a low to fair/good reliability of the breath hold hemodynamic measures from sensorimotor and prefrontal cortices. However, the average hemodynamic response to breath holding from the two sessions were found to be temporally and spatially in correspondence. Future improvements in the sensitivity and reliability of fNIRS metrics could facilitate fNIRS-based assessment of cerebrovascular function as a potential clinical tool.

Background. Neuroimaging studies of spinal cord injury (SCI) have mostly examined the functional organization of the cortex, with only limited focus on the subcortical substrates of the injury. However, thalamus is an important modulator and sensory relay that requires investigation at a subnuclei level to gain insight into the neuroplasticity following SCI. Objective. To use resting-state functional magnetic resonance imaging to examine the functional connectivity (FC) of thalamic subnuclei in complete SCI patients. Methods. A seed-based connectivity analysis was applied for 3 thalamic subnuclei: pulvinar, mediodorsal, and ventrolateral nucleus in each hemisphere. A nonparametric 2-sample t test with permutations was applied for each of the 6 thalamic seeds to compute FC differences between 22 healthy controls and 19 complete SCI patients with paraplegia. Results. Connectivity analysis showed a decrease in the FC of the bilateral mediodorsal nucleus with right superior temporal gyrus and anterior cingulate cortex in the SCI group. Similarly, the left ventrolateral nucleus exhibited decreased FC with left superior temporal gyrus in SCI group. In contrast, left pulvinar nucleus demonstrated an increase in FC with left inferior frontal gyrus and left inferior parietal lobule in SCI group. Our findings also indicate a negative relationship between postinjury durations and thalamic FC to regions of sensorimotor and visual cortices, where longer postinjury durations (~12 months) is associated with higher negative connectivity between these regions. Conclusion. This study provides evidence for reorganization in the thalamocortical connections known to be involved in multisensory integration and affective processing, with possible implications in the generation of sensory abnormalities after SCI.

Supplemental material, Supplementary_File for Resting-State Functional Connectivity of the Thalamus in Complete Spinal Cord Injury by Keerthana Deepti Karunakaran, Rui Yuan, Jie He, Jian Zhao, Jian-Ling Cui, Yu-Feng Zang, Zhong Zhang, Tara L. Alvarez and Bharat B. Biswal in Neurorehabilitation and Neural Repair

The objective of the study was to examine additive and synergistic effects of age and HIV infection on resting state (RS) intra- and inter-network functional connectivity (FC) of the brain. We also aimed to assess relationships with neurocognition and determine clinical-, treatment-, and health-related factors moderating intrinsic brain activity in aging HIV-positive (HIV+) individuals. The current report presents data on 54 HIV+ individuals (age M = 41, SD = 12 years) stabilized on cART and 54 socio-demographically matched healthy (HIV−) comparators (age M = 43, SD = 12 years), with cohort education mean of 16 years (SD = 12). Age at seroconversion ranged 20–55 years old. ANOVA assessed additive and synergistic effects of age and HIV in 133 ROIs. Bivariate statistics examined relationships of FC indices vulnerable to age-HIV interactions and neurocognitive domains T-scores (attention, executive, memory, psychomotor, semantic skills). Multivariate logistic models determined covariates of FC. This study found no statistically significant age-HIV effects on RS-FC after correcting for multiple comparisons except for synergistic effects on connectivity within cingulo-opercular network (CON) at the trending level. However, for uncorrected RS connectivity analyses, we observed HIV-related strengthening between regions of fronto-parietal network (FPN) and default mode network (DMN), and particular DMN regions and sensorimotor network (SMN). Simultaneously, FC weakening was observed within FPN and between other regions of DMN-SMN, in HIV+ vs. HIV- individuals. Ten ROI pairs revealed age-HIV interactions, with FC decreasing with age in HIV+, while increasing in controls. FC correlated with particular cognitive domains positively in HIV+ vs. negatively in HIV- group. Proportion of life prior-to-after HIV-seroconversion, post-infection years, and treatment determined within-FPN and SMN-DMN FC. In sum, highly functioning HIV+/cART+ patients do not reveal significantly altered RS-FC from healthy comparators. Nonetheless, the current findings uncorrected for multiple comparisons suggest that HIV infection may lead to simultaneous increases and decreases in FC in distinct brain regions even in patients successfully stabilized on cART. Moreover, RS-fMRI ROI-based analysis can be sensitive to age-HIV interactions, which are especially pronounced for inter-network FC in relation to neurocognition. Aging and treatment-related factors partially explain RS-FC in aging HIV+ patients.

This study examined the effects of age and HIV infection on the resting state (RS) functional connectivity (FC) of the brain and cognitive functioning. The objective was to evaluate the moderating role of age and HIV on the relationship between RS-FC and cognition. To examine RS-FC we implemented the Independent Component Analysis (ICA) and Regional Homogeneity (ReHo). Neurocognition was evaluated with comprehensive battery of standardized neuropsychological tests. Age and HIV were entered as the independent variables. The independent effects of age, HIV, and interaction effects of age-HIV on RS-fMRI measures (ICA, ReHo) were tested in 108 participants (age M = 42). RS-FC indices that exhibited age-HIV interactions were entered into further analysis. Bivariate correlation analysis was performed between the retained RS-FC indices and T-scores of neurocognitive domains (Attention, Executive, Memory, Psychomotor, Semantic Skills). Multivariate regression modeling determined the impact of age and HIV on these relationships. We found that in the ICA measures, HIV-seropositivity was decreasing RS-FC in the left middle occipital gyrus (p < .001). Age-HIV interaction was observed in the left superior frontal gyrus (LSupFrontG), where FC was decreasing with age in HIV+ (p < .001) and increasing in HIV- (p = .031). ReHo indices did not reveal significant effects. HIV strengthened the relationship between RS-FC in LSupFrontG, Memory and Psychomotor Factor scores. Aging weakened those relationships only in control group. In sum, age-HIV interaction effects are prominent rather in remote than local RS-FC. Seroconversion strengthens relationships between intrinsic brain activity and neurocognition, but no acceleration with years of age was noted in HIV+ individuals.

Iron deficiency continues to be the most prevalent micronutrient deficit worldwide. Since iron is involved in several processes including myelination, dopamine neurotransmission and neuronal metabolism, the presence of iron deficiency anemia in infancy relates to long-lasting neurofunctional effects. There is scarce data regarding whether these effects would extend to former iron deficient anemic human adults. Resting state fMRI is a novel technique to explore patterns of functional connectivity. Default Mode Network (DMN), one of the resting state networks, is deeply involved in memory, social cognition and self-referential processes. The four core regions consistently identified in the Default Mode Network are the medial prefrontal cortex, posterior cingulate/retrosplenial cortex, and left and right inferior parietal cortex. Therefore to investigate the DMN in former iron deficient anemic adults is a particularly useful approach to elucidate de long term effects on functional brain. We conducted this research to explore the connection between iron deficiency anemia in infancy and altered patterns of resting state brain functional networks in young adults. Resting-state fMRI studies were performed to 31 participants that belong to a follow-up study since infancy. Of them, 14 participants were former iron deficient anemic in infancy and 17 were controls, with mean age of 21.5 years (± 1.5) and 54.8% were males. Resting-state fMRI protocol was used and the data was analyzed using the seed based connectivity statistical analysis to assess the default mode network. We found that compared to controls, former iron deficient anemic subjects showed posterior DMN decreased connectivity to the left posterior cingulate cortex, whereas they exhibited increased anterior DMN connectivity to the right posterior cingulate cortex. Differences between groups were also apparent in the left medial frontal gyrus, with former iron deficient anemic participants having increased connectivity with areas included in DMN and dorsal attention networks. These preliminary results suggest different patterns of functional connectivity between former iron deficient anemic and control young adults. Indeed, iron deficiency anemia in infancy, a common nutritional problem among human infants, may turn out to be important for understanding the mechanisms of cognitive alterations, common in adulthood.