BACKGROUND:Patients with heart failure (HF) show abnormal autonomic activities, which may stem from altered functional connectivity (FC) between different brain sites. METHODS AND RESULTS:We evaluate insular and cerebellar FC with other brain areas, before, during, and after the Valsalva challenge, with functional magnetic resonance imaging in 35 HF and 35 control subjects. Significant insular FC emerged with striatum, thalamus, and anterior cingulate. While left and right cerebellar cortices showed significant FC with each other constituting the cerebellum network, the insula and cerebellum networks showed significant negative FC with each other at baseline, challenge, and recovery phases. The challenge induced increased FC within the insula and the cerebellum networks in both HF and controls. However, patients with HF showed more increased insular network FC, but less enhanced cerebellar FC. During the recovery phase, the negative FC between the insular network and cerebellum enhanced significantly in controls, but not in HF. Lower left ventricle ejection fraction was correlated with lower insula network FC, and impaired negative FC between cerebellum and the insula network in HF. CONCLUSIONS:Increased insular FC in patients with HF might contribute to exaggerated sympathetic tone. While impaired cerebellar FC and diminished negative interactions between cerebellum and insular systems may indicate impaired parasympathetic functions in HF.

STUDY OBJECTIVES: Patients with obstructive sleep apnea (OSA) show brain injury in sites responsible for autonomic, cognitive, and respiratory functions. Brain changes in OSA may vary with disease severity as assessed by the apnea-hypopnea index (AHI), which does not provide information about the apnea depth and length in contrast to oxygen desaturation. Although significant associations with brain injury and AHI are known in OSA, it is unclear whether AHI or the extent of oxygen desaturations better correlate with brain damage. We evaluated associations between brain changes, AHI, and oxygen desaturation using diffusion tensor imaging-based measures. METHODS: We acquired diffusion tensor imaging data from 19 patients with OSA using a 3.0-Tesla MRI scanner and calculated, normalized, and smoothed mean, axial, and radial diffusivity maps that were used for correlations between brain changes, oxygen desaturation, and AHI values. RESULTS: Positive correlations with extent of injury (mean, axial, and radial diffusivity values) and AHI appeared in the frontal areas, cingulate and insula, amygdala, hippocampus, and basal pons, and negative associations emerged in the putamen, internal-capsule, globus-pallidus, and cerebellar cortices. Regional diffusivity values and oxygen desaturation showed positive correlations in the cingulate, frontal, putamen, and cerebellar sites, and negative relationships in several areas, including the occipital cortex. CONCLUSIONS: Patients with OSA show negative and positive correlations, indicated by increased and decreased diffusivity values, resulting from chronic and acute changes in those areas. The extent of injury in OSA partially depends on the extent of AHI and oxygen desaturation, with the effects representing continued development from acute to chronic processes. CITATION: Sahib A, Roy B, Kang D, Aysola RS, Wen E, Kumar R. Relationships between brain tissue damage, oxygen desaturation, and disease severity in obstructive sleep apnea evaluated by diffusion tensor imaging. J Clin Sleep Med. 2022;18(12):2713-2721.

Children with long-standing obstructive sleep apnea (OSA) show evidence of neural injury and functional deficits in behavioral and cognitive regulatory brain regions that are reflected in symptoms of altered cognitive performance and behaviors. While we earlier showed reduced gray matter volume and increased and reduced regional cortical thicknesses, such structural changes give little indication of the underlying pathology. Brain tissue integrity in pediatric OSA subjects can reflect the nature and extent of injury or structural adaptation, and can be assessed by entropy tissue texture, a measure of local changes in signal intensity patterns from high-resolution magnetic resonance images. We collected high-resolution T1-weighted magnetic resonance images from 10 pediatric OSA (age, 7.9 ± 1.1 years; apnea-hypopnea-index, 8.8 ± 3.0 events/hour; body-mass-index, 20 ± 6.7 kg/m²; 7 male) and 8 healthy controls (age, 8.8 ± 1.6 years; body-mass-index, 19.6 ± 5.9 kg/m²; 5 female). Images were bias-corrected and entropy maps calculated, individual maps were normalized to a common space, smoothed, and compared between groups (ANCOVA; covariates: age, gender; SPM12, uncorrected-threshold p < 0.005). No significant differences in age (p = .48), gender (p = .59), or body-mass-index (p = .63) emerged between groups. In OSA children, several brain sites including the pre-frontal cortex, middle and posterior corpus callosum, thalamus, hippocampus, and cerebellar areas showed reduced entropy values, indicating tissue changes suggestive of acute insults. No regions showed higher entropy values in OSA. Children suffering from OSA display predominantly acute tissue injury in neural regions principally localized within autonomic, respiratory, cognitive, and neuropsychologic control, functions that correspond to previously-reported comorbidities associated with OSA. A range of acute processes, including hypoxia/re-oxygenation, repeated arousals, and episodic hypercarbia, may have contributed to regional brain tissue integrity changes in pediatric OSA.

Subanesthetic ketamine is found to induce fast-acting and pronounced antidepressant effects, even in treatment resistant depression (TRD). However, it remains unclear how ketamine modulates neural function at the brain systems-level to regulate emotion and behavior. Here, we examined treatment-related changes in the inhibitory control network after single and repeated ketamine therapy in TRD. Forty-seven TRD patients (mean age = 38, 19 women) and 32 healthy controls (mean age = 35, 18 women) performed a functional magnetic resonance imaging (fMRI) response inhibition task at baseline, and 37 patients completed the fMRI task and symptom scales again 24 h after receiving both one and four 0.5 mg/kg intravenous ketamine infusions. Analyses of fMRI data addressed effects of diagnosis, time, and differences between treatment remitters and non-remitters. Significant decreases in brain activation were observed in the inhibitory control network, including in prefrontal and parietal regions, and visual cortex following serial ketamine treatment, p < 0.05 corrected. Remitters were distinguished from non-remitters by having lower functional activation in the supplementary motor area (SMA) prior to treatment, which normalized towards controls following serial ketamine treatment. Results suggest that ketamine treatment leads to neurofunctional plasticity in executive control networks including the SMA during a response-inhibitory task. SMA changes relate to reductions in depressive symptoms, suggesting modulation of this network play an important role in therapeutic response. In addition, early changes in the SMA network during response inhibition appear predictive of overall treatment outcome, and may serve as a biomarker of treatment response.

Introduction: Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). While Magnetic Resonance Imaging (MRI) is a non-invasive gold standard to detect fatty liver, we demonstrate a low-cost and portable electrical impedance tomography (EIT) approach with circumferential abdominal electrodes for liver conductivity measurements. Methods and Results: A finite element model (FEM) was established to simulate decremental liver conductivity in response to incremental liver lipid content. To validate the FEM simulation, we performed EIT imaging on an ex vivo porcine liver in a non-conductive tank with 32 circumferentially-embedded electrodes, demonstrating a high-resolution output given a priori information on location and geometry. To further examine EIT capacity in fatty liver detection, we performed EIT measurements in age- and gender-matched New Zealand White rabbits (3 on normal, 3 on high-fat diets). Liver conductivity values were significantly distinct following the high-fat diet (p = 0.003 vs. normal diet, n=3), accompanied by histopathological evidence of hepatic fat accumulation. We further assessed EIT imaging in human subjects with MRI quantification for fat volume fraction based on Dixon procedures, demonstrating average liver conductivity of 0.331 S/m for subjects with low Body-Mass Index (BMI < 25 kg/m²) and 0.286 S/m for high BMI (> 25 kg/m²). Conclusion: We provide both the theoretical and experimental framework for a multi-scale EIT strategy to detect liver lipid content. Our preliminary studies pave the way to enhance the spatial resolution of EIT as a marker for fatty liver disease and metabolic syndrome.

Ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depressive disorder (MDD). Yet, how single and repeated ketamine treatment induces brain systems-level neuroplasticity underlying symptom improvement is unknown. Advanced multiband imaging (MB) pseudo-continuous arterial spin labeling (pCASL) perfusion MRI data was acquired from patients with treatment resistant depression (TRD) (N = 22, mean age=35.2 ± 9.95 SD, 27% female) at baseline, and 24 h after receiving single, and four subanesthetic (0.5 mg/kg) intravenous ketamine infusions. Changes in global and regional CBF were compared across time points, and relationships with overall mood, anhedonia and apathy were examined. Comparisons between patients at baseline and controls (N = 18, mean age=36.11 ± 14.5 SD, 57% female) established normalization of treatment effects. Results showed increased regional CBF in the cingulate and primary and higher-order visual association regions after first ketamine treatment. Baseline CBF in the fusiform, and acute changes in CBF in visual areas were related to symptom improvement after single and repeated ketamine treatment, respectively. In contrast, after serial infusion therapy, decreases in regional CBF were observed in the bilateral hippocampus and right insula with ketamine treatment. Findings demonstrate that neurophysiological changes occurring with single and repeated ketamine treatment follow both a regional and temporal pattern including sensory and limbic regions. Initial changes are observed in the posterior cingulate and precuneus and primary and higher-order visual areas, which relate to clinical responses. However, repeated exposure to ketamine, though not relating to clinical outcome, appears to engage deeper limbic structures and insula. ClinicalTrials.gov: Biomarkers of Fast Acting Therapies in Major Depression, https://clinicaltrials.gov/ct2/show/NCT02165449, NCT02165449.

Introduction: Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). While Magnetic Resonance Imaging (MRI) is a non-invasive gold standard to detect fatty liver, we demonstrate a low-cost and portable electrical impedance tomography (EIT) approach with circumferential abdominal electrodes for liver conductivity measurements.Methods and Results: A finite element model (FEM) was established to simulate decremental liver conductivity in response to incremental liver lipid content. To validate the FEM simulation, we performed EIT imaging on an ex vivo porcine liver in a non-conductive tank with 32 circumferentially-embedded electrodes, demonstrating a high-resolution output given a priori information on location and geometry. To further examine EIT capacity in fatty liver detection, we performed EIT measurements in age- and gender-matched New Zealand White rabbits (3 on normal, 3 on high-fat diets). Liver conductivity values were significantly distinct following the high-fat diet (p = 0.003 vs. normal diet, n=3), accompanied by histopathological evidence of hepatic fat accumulation. We further assessed EIT imaging in human subjects with MRI quantification for fat volume fraction based on Dixon procedures, demonstrating average liver conductivity of 0.331 S/m for subjects with low Body-Mass Index (BMI < 25 kg/m²) and 0.286 S/m for high BMI (> 25 kg/m²).Conclusion: We provide both the theoretical and experimental framework for a multi-scale EIT strategy to detect liver lipid content. Our preliminary studies pave the way to enhance the spatial resolution of EIT as a marker for fatty liver disease and metabolic syndrome.