Deciphering Functional Connectivity Differences Between Motor Imagery and Execution of Target-Oriented Grasping.

This study aimed to delineate overlapping and distinctive functional connectivity in visual motor imagery, kinesthetic motor imagery, and motor execution of target-oriented grasping action of the right hand. Functional magnetic resonance imaging data were obtained from 18 right-handed healthy individuals during each condition. Seed-based connectivity and multi-voxel pattern analyses were employed after selecting seed regions with the left primary motor cortex and supplementary motor area. There was equivalent seed-based connectivity during the three conditions in the bilateral frontoparietal and temporal areas. When the seed region was the left primary motor cortex, increased connectivity was observed in the left cuneus and superior frontal area during visual and kinesthetic motor imageries, respectively, compared with that during motor execution. Multi-voxel pattern analyses revealed that each condition was differentiated by spatially distributed connectivity patterns of the left primary motor cortex within the right cerebellum VI, cerebellum crus II, and left lingual area. When the seed region was the left supplementary motor area, the connectivity patterns within the right putamen, thalamus, cerebellar areas IV-V, and left superior parietal lobule were significantly classified above chance level across the three conditions. The present findings improve our understanding of the spatial representation of functional connectivity and its specific patterns among motor imagery and motor execution. The strength and fine-grained connectivity patterns of the brain areas can discriminate between motor imagery and motor execution.

The Association Between Antihypertensive Drug Use and Hospitalization for Pneumonia in the General Population: A Case-Crossover Study Using the National Health Insurance Database of Korea.

BACKGROUND: Previous studies have reported an association between pneumonia risk and the use of certain drugs. We investigated the relationship between antihypertensive drugs and pneumonia in the general population. METHODS: This case-crossover study utilized the nationwide data of South Korea. We included participants who were hospitalized for pneumonia. A single case period was defined as 30 days before pneumonia onset, and two control periods were established (90-120 and 150-180 days before pneumonia onset). Further, we performed sensitivity and subgroup analyses (according to the presence of diabetes, documented disability, and whether participants were aged ≥ 70 years). We used conditional logistic regression models adjusted for covariates, such as angiotensin-converting-enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), other antihypertensives, statins, antipsychotics, benzodiazepine, and the number of outpatient visits. RESULTS: In total, 15,463 subjects were included in this study. ACE inhibitors (adjusted odds ratio [aOR], 0.660; 95% confidence interval [CI], 0.558-0.781), ARBs (aOR, 0.702; 95% CI, 0.640-0.770), and other antihypertensive drugs (aOR, 0.737; 95% CI, 0.665-0.816) were significantly associated with reduced pneumonia risk. Subgroup analyses according to the presence of diabetes mellitus, documented disability, and whether participants were aged ≥ 70 years consistently showed the association of antihypertensives with a reduced risk of hospitalization for pneumonia. CONCLUSION: All antihypertensive drug types were related to a lower risk of hospitalization for pneumonia in the general population. Our results implied that frequent medical service usage and protective immunity were primarily related to a reduced risk of pneumonia in the general population of South Korea.

Clinical effectiveness of the sequential 4-channel NMES compared with that of the conventional 2-channel NMES for the treatment of dysphagia in a prospective double-blind randomized controlled study.

BACKGROUND: To date, conventional swallowing therapies and 2-channel neuromuscular electrical stimulation (NMES) are standard treatments for dysphagia. The precise mechanism of 2-channel NMES treatment has not been determined, and there are controversies regarding the efficacy of this therapy. The sequential 4-channel NMES was recently developed and its action is based on the normal contractile sequence of swallowing-related muscles. OBJECTIVE: To evaluate and compare the rehabilitative effectiveness of the sequential 4-channel NMES with that of conventional 2-channel NMES. METHODS: In this prospective randomized case-control study, 26 subjects with dysphagia were enrolled. All participants received 2- or 4-channel NMES for 2-3 weeks (minimal session: 7 times, treatment duration: 300-800 min). Twelve subjects in the 4-channel NMES group and eleven subjects in the 2-channel NMES group completed the intervention. Initial and follow-up evaluations were performed using the videofluoroscopic dysphagia scale (VDS), the penetration-aspiration scale (PAS), the MD Anderson dysphagia inventory (MDADI), the functional oral intake scale (FOIS), and the Likert scale. RESULTS: The sequential 4-channel NMES group experienced significant improvement in their VDS (oral, pharyngeal, and total), PAS, FOIS, and MDADI (emotional, functional, and physical subsets) scores, based on their pretreatment data. VDS (oral, pharyngeal, and total) and MDADI (emotional and physical subsets) scores, but not PAS and FOIS scores, significantly improved in the 2-channel NMES group posttreatment. When the two groups were directly compared, the 4-channel NMES group showed significant improvement in oral and total VDS scores. CONCLUSIONS: The sequential 4-channel NMES, through its activation of the suprahyoid and thyrohyoid muscles, and other infrahyoid muscles mimicking physiological activation, may be a new effective treatment for dysphagia. TRIAL REGISTRATION: clinicaltrial.gov, registration number: NCT03670498, registered 13 September 2018, https://clinicaltrials.gov/ct2/show/NCT03670498?term=NCT03670498&draw=2&rank=1 .

Anti-Pituitary and Anti-Hypothalamus Autoantibody Associations with Inflammation and Persistent Hypogonadotropic Hypogonadism in Men with Traumatic Brain Injury.

Traumatic brain injury (TBI) and can lead to persistent hypogonadotropic hypogonadism (PHH) and poor outcomes. We hypothesized that autoimmune and inflammatory mechanisms contribute to PHH pathogenesis. Men with moderate-to-severe TBI (n = 143) were compared with healthy men (n = 39). The TBI group provided blood samples 1-12 months post-injury (n = 1225). TBI and healthy control (n = 39) samples were assayed for testosterone (T) and luteinizing hormone (LH) to adjudicate PHH status. TBI samples 1-6 months post-injury and control samples were assayed for immunoglobulin M (IgM)/immunoglobulin G (IgG) anti-pituitary autoantibodies (APA) and anti-hypothalamus autoantibodies (AHA). Tissue antigen specificity for APA and AHA was confirmed via immunohistochemistry (IHC). IgM and IgG autoantibodies for glial fibrillary acid protein (GFAP) (AGA) were evaluated to gauge APA and AHA production as a generalized autoimmune response to TBI and to evaluate the specificity of APA and AHA to PHH status. An inflammatory marker panel was used to assess relationships to autoantibody profiles and PHH status. Fifty-one men with TBI (36%) had PHH. An age-related decline in T levels by both TBI and PHH status were observed. Injured men had higher APA IgM, APA IgG, AHA IgM, AHA IgG, AGA IgM, and AGA IgG than controls (p < 0.0001 all comparisons). However, only APA IgM (p = 0.03) and AHA IgM (p = 0.03) levels were lower in the PHH than in the non-PHH group in multivariate analysis. There were no differences in IgG levels by PHH status. Multiple inflammatory markers were positively correlated with IgM autoantibody production. PHH was associated with higher soluble tumor-necrosis-factor receptors I/II, (sTNFRI, sTNFRII), regulated on activation, normal T-cell expressed and secreted (RANTES) and soluble interleukin-2-receptor-alpha (sIL-2Rα) levels. Higher IgM APA, and AHA, but not AGA, in the absence of PHH may suggest a beneficial or reparative role for neuroendocrine tissue-specific IgM autoantibody production against PHH development post-TBI.

Target-oriented motor imagery for grasping action: different characteristics of brain activation between kinesthetic and visual imagery.

Motor imagery (MI) for target-oriented movements, which is a basis for functional activities of daily living, can be more appropriate than non-target-oriented MI as tasks to promote motor recovery or brain-computer interface (BCI) applications. This study aimed to explore different characteristics of brain activation among target-oriented kinesthetic imagery (KI) and visual imagery (VI) in the first-person (VI-1) and third-person (VI-3) perspectives. Eighteen healthy volunteers were evaluated for MI ability, trained for the three types of target-oriented MIs, and scanned using 3 T functional magnetic resonance imaging (fMRI) under MI and perceptual control conditions, presented in a block design. Post-experimental questionnaires were administered after fMRI. Common brain regions activated during the three types of MI were the left premotor area and inferior parietal lobule, irrespective of the MI modalities or perspectives. Contrast analyses showed significantly increased brain activation only in the contrast of KI versus VI-1 and KI versus VI-3 for considerably extensive brain regions, including the supplementary motor area and insula. Neural activity in the orbitofrontal cortex and cerebellum during VI-1 and KI was significantly correlated with MI ability measured by mental chronometry and a self-reported questionnaire, respectively. These results can provide a basis in developing MI-based protocols for neurorehabilitation to improve motor recovery and BCI training in severely paralyzed individuals.

Vision-aided brain-machine interface training system for robotic arm control and clinical application on two patients with cervical spinal cord injury.

BACKGROUND: While spontaneous robotic arm control using motor imagery has been reported, most previous successful cases have used invasive approaches with advantages in spatial resolution. However, still many researchers continue to investigate methods for robotic arm control with noninvasive neural signal. Most of noninvasive control of robotic arm utilizes P300, steady state visually evoked potential, N2pc, and mental tasks differentiation. Even though these approaches demonstrated successful accuracy, they are limited in time efficiency and user intuition, and mostly require visual stimulation. Ultimately, velocity vector construction using electroencephalography activated by motion-related motor imagery can be considered as a substitution. In this study, a vision-aided brain-machine interface training system for robotic arm control is proposed and developed. METHODS: The proposed system uses a Microsoft Kinect to detect and estimates the 3D positions of the possible target objects. The predicted velocity vector for robot arm input is compensated using the artificial potential to follow an intended one among the possible targets. Two participants with cervical spinal cord injury trained with the system to explore its possible effects. RESULTS: In a situation with four possible targets, the proposed system significantly improved the distance error to the intended target compared to the unintended ones (p < 0.0001). Functional magnetic resonance imaging after five sessions of observation-based training with the developed system showed brain activation patterns with tendency of focusing to ipsilateral primary motor and sensory cortex, posterior parietal cortex, and contralateral cerebellum. However, shared control with blending parameter α less than 1 was not successful and success rate for touching an instructed target was less than the chance level (= 50%). CONCLUSIONS: The pilot clinical study utilizing the training system suggested potential beneficial effects in characterizing the brain activation patterns.

Kinematic effects of hyolaryngeal electrical stimulation therapy on hyoid excursion and laryngeal elevation.

The purpose of this study was to assess the effect of repeated sessions of electrical stimulation therapy (EST) on the neck muscles with respect to the stimulation site by using quantitative kinematic analysis of videofluoroscopic swallowing studies (VFSS) in dysphagia patients with acquired brain injury. We analyzed 50 patients in a tertiary hospital who were randomly assigned into two different treatment groups. One group received EST on the suprahyoid muscle only (SM), and the other group received stimulation with one pair of electrodes on the suprahyoid muscle and the other pair on the infrahyoid muscle (SI). All patients received 10-15 sessions of EST over 2-3 weeks. The VFSS was carried out before and after the treatment. Temporal and spatial parameters of the hyoid excursion and laryngeal elevation during swallowing were analyzed by two-dimensional motion analysis. The SM group (n = 25) revealed a significant increase in maximal anterior hyoid excursion distance (mean ± SEM = 1.56 ± 0.52 mm, p = 0.008) and velocity (8.76 ± 3.42 mm/s, p = 0.017), but there was no significant increase laryngeal elevation. The SI group (n = 25), however, showed a significant increase in maximal superior excursion distance (2.09 ± 0.78 mm, p = 0.013) and maximal absolute excursion distance (2.20 ± 0.82 mm, p = 0.013) of laryngeal elevation, but no significant increase in hyoid excursion. There were no significant differences between the two groups with respect to changes in maximal anterior hyoid excursion distance (p = 0.130) and velocity (p = 0.254), and maximal distance of superior laryngeal elevation (p = 0.525). EST on the suprahyoid muscle induced an increase in anterior hyoid excursion, and infrahyoid stimulation caused an increase in superior laryngeal elevation. Hyolaryngeal structural movements were increased in different aspects according to the stimulation sites. Targeted electrical stimulation based on pathophysiology is necessary.

Functional improvement and neuroplastic effects of anodal transcranial direct current stimulation (tDCS) delivered 1 day vs. 1 week after cerebral ischemia in rats.

Transcranial direct current stimulation (tDCS) is an emerging tool for improving recovery from stroke. However, there has been no trial to determine whether it has a therapeutic benefit in the early stage of cerebral ischemia, and there is no consensus on the optimal time window of stimulation. Here, we described the effects of anodal tDCS in early cerebral ischemia, assessing functional improvements and changes in neuronal plasticity, and identifying the optimal time window for delivering tDCS to maximize functional gains. Thirty rats were randomly assigned to three groups: sham (n=10); early tDCS (ET), receiving tDCS 1day after ischemia for 5 days (n=10), and late tDCS (LT), receiving tDCS 1 week after ischemia for 5 days (n=10). Both ET and LT groups showed improved Barnes maze performance and motor behavioral index scores. However, only the LT group exhibited improvement in beam balance test. Immunohistochemical stainings showed that the ET group reinforced notable MAP-2 expression and the LT group enhanced mainly the level of GAP-43 in both peri-lesional and contralesional cortex. These immunohistochemical results had significant correlation with behavioral and cognitive functions. However, brain MRI and (1)H MRS showed no significant differences among the three groups in ischemic volume and metabolic alteration. These results suggest that anodal tDCS has the potential to modulate neural plasticity around the ischemic penumbra and even in the contralesional area without aggravating infarction volume and metabolic alteration. The degree of functional improvement was slightly greater when tDCS was applied 1 week rather than 1 day after ischemic injury.

Effect of transcranial direct current stimulation on motor recovery in patients with subacute stroke.

OBJECTIVE: To test the hypothesis that 10 sessions of transcranial direct current stimulation combined with occupational therapy elicit more improvement in motor function of the paretic upper limb than sham stimulation in patients with subacute stroke. DESIGN: Eighteen patients with subacute stroke with hand motor impairment were randomly assigned to one of the three 10-day sessions of (a) anodal transcranial direct current stimulation over the affected motor cortex, (b) cathodal transcranial direct current stimulation over the unaffected motor cortex, or (c) sham stimulation. Blinded evaluators assessed upper limb motor impairment and global functional state with the Fugl-Meyer Assessment score and the Modified Barthel Index at baseline, 1 day after stimulation, and 6 mos after stimulation. RESULTS: Baseline scores for Fugl-Meyer Assessment and Modified Barthel Index were comparable in all groups (P > 0.05). At 6-mo follow-up, cathodal transcranial direct current stimulation led to a greater improvement in Fugl-Meyer Assessment than the sham procedure (P < 0.05). There was a significant inverse correlation between baseline Fugl-Meyer Assessment and Fugl-Meyer Assessment increase at 6 mos (r = -0.846; P < 0.01). CONCLUSIONS: Our results suggest a potentially beneficial effect of noninvasive cortical stimulation during rehabilitative motor training of patients who have suffered from subacute strokes.

Recovery of swallowing function is accompanied by the expansion of the cortical map.

To determine whether multiple sessions of electrical stimulation (ES) applied to neck muscles improve swallowing function and whether this improvement is accompanied by cortical reorganization in patients with dysphagia, before-after trials were performed on eight subjects. ES was applied for 1 hour, 5 days a week for 2 weeks. Swallowing function significantly improved after 2 weeks of ES, and this change was found to correlate with cortical reorganization measured by corticobulbar output maps. This study suggests that multiple sessions of ES applied to the neck muscles improve swallowing function via a mechanism involving long-term cortical reorganization.