Diffusion time-related structure-function coupling reveals differential association with inter-individual variations in body mass index.

Body mass index (BMI) is an indicator of obesity, and recent neuroimaging studies have demonstrated that inter-individual variations in BMI are associated with altered brain structure and function. However, the mechanism underlying the alteration of structure-function correspondence according to BMI is under-investigated. In this study, we studied structural and functional connectivity derived from diffusion MRI tractography and inter-regional correlations of functional MRI time series, respectively. We combined the structural and functional connectivity information using the Riemannian optimization approach. First, the low-dimensional principal eigenvectors (i.e., gradients) of the structural connectivity were generated by applying diffusion map embedding with varying diffusion times. A transformation was identified so that the structural and functional embeddings share the same coordinate system, and subsequently, the functional connectivity matrix was simulated. Then, we generated gradients from the simulated functional connectivity matrix. We found the most apparent cortical hierarchical organization differentiating between low-level sensory and higher-order transmodal regions in the middle of the diffusion time, indicating that the hierarchical organization of the brain may reflect the intermediate mechanisms of mono- and polysynaptic communications. Associations between the functional gradients and BMI were strongest when the hierarchical structure was the most evident. Moreover, the gradient-BMI association map was related to the microstructural features, and the findings indicated that the BMI-related structure-function coupling was significantly associated with brain microstructure, particularly in higher-order transmodal areas. Finally, transcriptomic association analysis revealed the potential biological underpinnings specifying gene enrichment in the striatum, hypothalamus, and cortical cells. Our findings provide evidence that structure-function correspondence is strongly coupled with BMI when hierarchical organization is the most apparent and that the associations are related to the multiscale properties of the brain, leading to an advanced understanding of the neural mechanisms related to BMI.

GAN-MAT: Generative adversarial network-based microstructural profile covariance analysis toolbox.

Multimodal magnetic resonance imaging (MRI) provides complementary information for investigating brain structure and function; for example, an in vivo microstructure-sensitive proxy can be estimated using the ratio between T1- and T2-weighted structural MRI. However, acquiring multiple imaging modalities is challenging in patients with inattentive disorders. In this study, we proposed a comprehensive framework to provide multiple imaging features related to the brain microstructure using only T1-weighted MRI. Our toolbox consists of (i) synthesizing T2-weighted MRI from T1-weighted MRI using a conditional generative adversarial network; (ii) estimating microstructural features, including intracortical covariance and moment features of cortical layer-wise microstructural profiles; and (iii) generating a microstructural gradient, which is a low-dimensional representation of the intracortical microstructure profile. We trained and tested our toolbox using T1- and T2-weighted MRI scans of 1,104 healthy young adults obtained from the Human Connectome Project database. We found that the synthesized T2-weighted MRI was very similar to the actual image and that the synthesized data successfully reproduced the microstructural features. The toolbox was validated using an independent dataset containing healthy controls and patients with episodic migraine as well as the atypical developmental condition of autism spectrum disorder. Our toolbox may provide a new paradigm for analyzing multimodal structural MRI in the neuroscience community and is openly accessible at https://github.com/CAMIN-neuro/GAN-MAT.

Obesity and mortality in patients with COVID-19: A meta-analysis of prospective studies.

BACKGROUND AND OBJECTIVES: Previous prospective studies have reported inconsistent findings on the associ-ation between obesity and mortality in patients with COVID-19. This study aimed to investigate the associa-tion between them by using a meta-analysis of prospective studies. METHODS AND STUDY DESIGN: We searched PubMed and EMBASE to retrieve studies using keywords related to this topic on January 3, 2022. Data were extracted for a random-effects meta-analysis to calculate a pooled odds ratio (OR), relative risk (RR), or hazard ratio (HR) with a 95% confidence interval (CI). RESULTS: In the meta-analysis of 15 prospective cohort studies, obesity significantly increased the risk of mortality in patients with COVID-19 (OR/RR/HR, 1.52; 95% CI, 1.26 to 1.84; I2 = 90.4%). Most of the included studies were conducted in European (n = 10) and North American (n = 4) countries. In the subgroup meta-analysis by continent, there was a significant association between them in European countries (OR/RR/HR, 1.78; 95% CI, 1.30 to 2.43; I2 = 81.4%). Also, in the subgroup meta-analysis by data source, obesity was significantly associated with the increased mortality in patients with COVID-19 in both population- and hospital-based data. CONCLUSIONS: We found that obesity is associated with the increased risk of mortality in patients of COVID-19.

Effect of Coffee Consumption on Risk of Coronary Heart Disease in a Systematic Review and Meta-Analysis of Prospective Cohort Studies.

Previous prospective studies have reported inconsistent findings on the association between coffee consumption and the risk of coronary heart disease (CHD). This study aimed to investigate their association using a meta-analysis of prospective studies. We searched PubMed and EMBASE for prospective cohort studies of the association between coffee consumption and the risk of CHD in the general population. We conducted a random-effects meta-analysis and also subgroup meta-analyses by various factors. Of 870 studies searched from databases, 32 prospective cohort studies were included in the final analysis. In the main meta-analysis of all studies, no significant association between coffee consumption and the risk of CHD was observed (relative risk [RR] 1.05, 95% confidence interval [CI] 0.97 to 1.14, I2 = 64.9%). In the subgroup meta-analyses by gender, coffee consumption significantly increased the risk of CHD in men (RR 1.19, 95% CI 1.05 to 1.35, n = 17), whereas a nonsignificantly decreased risk of CHD was observed in women (RR 0.91, 95% CI 0.77 to 1.08, n = 11). Also, in the subgroup meta-analyses by follow-up period, coffee consumption significantly increased the risk of CHD in the follow-up of 20 years or longer (RR 1.16, 95% CI 1.06 to 1.27, n = 4) regardless of gender. In conclusion, in the current meta-analysis of prospective studies, we found that, overall, no significant association between coffee consumption and the risk of CHD was observed. However, coffee consumption showed a differential effect by gender, with an increased risk of CHD in men and a potentially decreased risk in women.

The effects of low intensity focused ultrasound on neuronal activity in pain processing regions in a rodent model of common peroneal nerve injury.

BACKGROUND: Non-invasive, external low intensity focused ultrasound (liFUS) offers promise for treating neuropathic pain when applied to the dorsal root ganglion (DRG). OBJECTIVE: We examine how external liFUS treatment applied to the L5 DRG affects neuronal changes in single-unit activity from the primary somatosensory cortex (SI) and anterior cingulate cortex (ACC) in a common peroneal nerve injury (CPNI) rodent model. METHODS: Male Sprague Dawley rats were divided into two cohorts: CPNI liFUS and CPNI sham liFUS. Baseline single-unit activity (SUA) recordings were taken 20 min prior to treatment and for 4 h post treatment in 20 min intervals, then analyzed for frequency and compared to baseline. Recordings from the SI and ACC were separated into pyramidal and interneurons based on waveform and principal component analysis. RESULTS: Following CPNI surgery, all rats (n = 30) displayed a significant increase in mechanical sensitivity. In CPNI liFUS rats, there was a significant increase in pyramidal neuron spike frequency in the SI region compared to the CPNI sham liFUS animals beginning at 120 min following liFUS treatment (p < 0.05). In the ACC, liFUS significantly attenuated interneuron firing beginning at 80 min after liFUS treatment (p < 0.05). CONCLUSION: We demonstrate that liFUS changed neuronal spiking in the SI and ACC regions 80 and 120 min after treatment, respectively, which may in part correlate with improved sensory thresholds. This may represent a mechanism of action how liFUS attenuates neuropathic pain. Understanding the impact of liFUS on pain circuits will help advance the use of liFUS as a non-invasive neuromodulation option.

COVID-19 Vaccine Uptake and Intent Among Emergency Healthcare Workers: A Cross-Sectional Survey.

OBJECTIVE: Vaccine hesitancy limits population protection from SARS-CoV (coronavirus disease [COVID-19]). Vaccine hesitancy among healthcare workers (HCW) could put patients and coworkers at risk. METHODS: We surveyed 475 emergency department and emergency medical service workers from January to February 2021 to determine vaccine intent/uptake, perceived COVID-19 vulnerability, and factors associated with vaccine intent/uptake. RESULTS: Although 79% of HCWs received or had plans to receive the COVID-19 vaccine, 21% had no intent/were unvaccinated; intent/uptake was lower among females (odds ratio [OR] = 0.34) and those with a history of COVID-19 infection (OR = 0.55), and higher among those with advanced degrees (OR = 3.53) and high perceived COVID-19 vulnerability (OR = 1.99). CONCLUSIONS: This study provides a timely assessment of vaccination status among frontline HCWs and highlights subgroups who may be at high risk of exposure and transmission.

Pain and Interoceptive Awareness Outcomes of Chronic Pain Patients With Spinal Cord Stimulation.

OBJECTIVES: Meditation has been shown to improve outcomes for chronic pain by increasing patients' awareness of their own bodies. Some patients have an innate ability to leverage their mind-body connection, and this interoceptive awareness may aid them in garnering pain relief. We explored whether spinal cord stimulation (SCS) patients with greater innate awareness had better outcomes. MATERIALS AND METHODS: We contacted 30 thoracic SCS patients with baseline and postoperative pain, psychological, and disability outcomes to complete the Multidimensional Assessment of Interoceptive Awareness (MAIA) survey. MAIA distinguishes between beneficial and maladaptive aspects of the perception of body sensations via six positive subscales (noticing, attention regulation, emotional awareness, self-regulation, body listening, and trusting) and two negative subscales (not distracting, not worrying). MAIA subscales and positive/negative groups were correlated with percentage change in Numerical Rating Scale (NRS), Oswestry Disability Index (ODI), Beck's Depression Inventory (BDI), Pain Catastrophizing Scale (PCS), and McGill Pain Questionnaire (MPQ). RESULTS: Patients included 14 males/16 females with a mean age of 58. At a mean follow-up of 14.13 months (range 6-26), NRS, ODI, BDI, PCS, and MPQ showed improvements. Positive traits correlated with improvements in pain (MAIA-self regulation with NRS-worst [p = 0.018], NRS-least [p = 0.042], NRS-average [p = 0.006], NRS-current [p = 0.001]; MAIA-body listening with MPQ-total [p = 0.016] and MPQ-sensory [p = 0.026]). Improvement in PCS-total was associated with higher scores in noticing (p = 0.002), attention regulation (p = 0.017), emotional awareness (p = 0.039), and trusting (p = 0.047). PCS-rumination correlated with MAIA-positive total (p = 0.012). In contrast, better attention regulation signified less improvement in ODI (p = 0.043) and MPQ affective (p = 0.026). CONCLUSIONS: Higher interoceptive awareness in SCS patients correlated with greater improvement following the procedure, particularly with regards to pain relief and pain catastrophizing. These findings suggest that patients with better mind-body connections may achieve greater pain relief following SCS in this patient population, thereby aiding providers in determining who may benefit from this intervention.

Effects of external low intensity focused ultrasound on electrophysiological changes in vivo in a rodent model of common peroneal nerve injury.

Non-invasive treatment methods for neuropathic pain are lacking. We assess how modulatory low intensity focused ultrasound (liFUS) at the L5 dorsal root ganglion (DRG) affects behavioral responses and sensory nerve action potentials (SNAPs) in a common peroneal nerve injury (CPNI) model. Rats were assessed for mechanical and thermal responses using Von Frey filaments (VFF) and the hot plate test (HPT) following CPNI surgery. Testing was repeated 24 h after liFUS treatment. Significant increases in mechanical and thermal sensory thresholds were seen post-liFUS treatment, indicating a reduction in sensitivity to pain (p < 0.0001, p = 0.02, respectively). Animals who received CPNI surgery had significant increases in SNAP latencies compared to sham CPNI surgery animals (p = 0.0003) before liFUS treatment. LiFUS induced significant reductions in SNAP latency in both CPNI liFUS and sham CPNI liFUS cohorts, for up to 35 min post treatment. No changes were seen in SNAP amplitude and there was no evidence of neuronal degeneration 24 h after liFUS treatment, showing that liFUS did not damage the tissue being modulated. This is the first in vivo study of the impact of liFUS on peripheral nerve electrophysiology in a model of chronic pain. This study demonstrates the effects of liFUS on peripheral nerve electrophysiology in vivo. We found that external liFUS treatment results in transient decreased latency in common peroneal nerve (CPN) sensory nerve action potentials (SNAPs) with no change in signal amplitude.

Low Intensity Focused Ultrasound Modulation of Vincristine Induced Neuropathy.

Previously, we showed internal low intensity focused ultrasound (liFUS) improves nociceptive thresholds in rats with vincristine-induced neuropathy (VIN) for 48-h post-treatment. Here, we perform more rigorous behavioral testing with the internal device and introduce external liFUS treatment. Behavioral testing confirmed VIN (Von Frey fibers, VFF; hot plate, HPT; locomotion, OFT). This was followed by internal or external liFUS treatment (2.5 W or 8 W, for 3 min, respectively) to the left L5 dorsal root ganglia (DRG). A thermocouple placed at the DRG documented temperature changes during treatment, to confirm the modulatory nature of our treatment. Behavioral testing was performed pre-liFUS, and for five consecutive days post-liFUS. Groups included: (1) VIN/liFUS, (2) saline/liFUS, (3) VIN/sham liFUS, and (4) saline/sham liFUS. Significant improvements in mechanical (VFF) and thermal (HPT) nociceptive thresholds were seen in the VIN/liFUS group following both internal and external treatment. Hematoxylin and Eosin, and Fluorojade staining showed no histological damage to the DRG. Internal liFUS treatment produced a mean temperature rise of 3.21 ±â€¯0.30 °C, whereas external liFUS resulted in a mean temperature rise of 1.78 °C ±â€¯0.21 °C. We demonstrate that, in a VIN rat model, external liFUS treatment of the L5 DRG significantly reduces nociceptive sensitivity thresholds without causing tissue damage.

Early Experience With New Generation Deep Brain Stimulation Leads in Parkinson's Disease and Essential Tremor Patients.

BACKGROUND: Newer generation deep brain stimulation (DBS) systems have recently become available in the United States. Data on real-life experience are limited. We present our initial experience incorporating newer generation DBS with Parkinson's disease (PD) and essential tremor (ET) patients. Newer systems allow for smart energy delivery and more intuitive programming and hardware modifications including constant current and directional segmented contacts. METHODS: We compared six-month outcomes between 42 newer generation and legacy leads implanted in 28 patients. Two cohorts each included 7 PD patients with bilateral subthalamic nucleus (STN) stimulation and 7 ET patients with unilateral ventral intermediate nucleus (VIM) stimulation of the thalamus. All directional leads included 6172 Infinity 8-Channel Directional leads and Infinity internal pulse generators (Abbott Neuromodulation, Plano, TX, USA) and nondirectional leads included lead 3389 with Activa SC for VIM and PC for STN (Medtronic, Minneapolis, MN, USA). RESULTS: Six-month outcomes for medication reduction and motor score improvements between new and legacy DBS systems in PD and ET patients were similar. Directionality was employed in 1/3 of patients. Therapeutic window (difference between amplitude when initial symptom relief was obtained and when intolerable side effects appeared with the contact being used) was significantly greater in new DBS systems in both PD (p = 0.005) and ET (p = 0.035) patients. The windows for new and legacy systems were 3.60 V ± 0.42 and 2.00 V ± 0.32 for STN and 3.06 V ± 0.44 and 1.85 V ± 0.28 for VIM, respectively. DISCUSSION: The therapeutic window of newer systems, whether or not directionality was used, was significantly greater than that of the legacy system, which suggests increased benefit and programming options. Improvements in hardware and programming interfaces in the newer systems may also contribute to wider therapeutic windows. We expect that as we alter workflow associated with newer technology, more patients will use directionality, and amplitudes will become lower.

Spinal Cord Stimulation.

Spinal cord stimulation (SCS) has been well established as a safe and effective treatment of pain derived from a wide variety of etiologies. Careful patient selection including a rigorous trial period and psychological evaluation are essential. When patients proceed to permanent implantation, various considerations should be made, such as the type of lead, type of anesthesia, and waveform patterns for SCS. This article discusses the common indications for SCS, patient selection criteria, and pertinent outcomes from randomized clinical trials related to common indications treated with SCS. Technical considerations, such as type of implant, anesthesia, and programming, are also discussed.