Khurram, Obaid U.

Neuromotor control of sighs consists of two phases: Phase I, which resembles a preceding eupneic breath, and Phase II, an extra inspiration superimposed on Phase I. The diaphragm muscle (DIAm)—the primary inspiratory muscle in mammals—is activated during multiple behaviors, including sighs, and its activity can be quantified using electromyography (EMG). Although the biphasic structure of sighs has been described using airflow and pressure signals, how these phases are represented in DIAm EMG activity—and the underlying dynamics of DIAm motor unit (MU) recruitment—remains unclear. Previously we described that eupnea consists of a period of MU recruitment followed by a period of sustained MU activity before derecruitment. We hypothesize that during sighs Phase I follows a similar trajectory of MU recruitment as eupnea while Phase II reflects superimposed additional MU recruitment. DIAm EMG was recorded using fine wire electrodes in awake Sprague-Dawley rats (n=6) of both sexes. To determine the period of DIAm MU recruitment during both Phase I and Phase II, a stationarity analysis was performed. The stationarity analysis uses a reverse arrangement test applied to sequential, non-overlapping 10-ms bins across a longer analysis window. Because DIAm MU discharge rates rarely exceed 100 Hz, it is unlikely that a single MU fires more than once within each 10-ms window; thus, non-stationarity reflects MU recruitment rather than changes in discharge rate. An average of 17 ± 4 sighs per animal were identified (range: 10-20), with a frequency of 2.8 ± 0.1 min-1. Sighs had a burst duration of 1300 ± 405 ms, much longer than the burst duration of eupneic breaths (~598 ± 111 ms). During sighs there were two distinct periods of MU recruitment reflected by non-stationarity of the EMG signal. The MU recruitment duration of Phase I was significantly shorter than Phase II (100 ± 28 ms vs. 179 ± 53 ms, p = 0.041). The onset-to-peak duration during sighs averaged 489 ± 135 ms, with the duration of Phase I lasting longer than Phase II (298 ± 119 ms vs 179 ± 56 ms). It is important to note that Phase II is characterized by rapid, continuous recruitment throughout its duration. In contrast, Phase I had a longer overall duration, although the period of MU recruitment was relatively brief—similar to eupneic breathing. Using EMG stationarity in awake animals allowed us to characterize these underlying MU patterns without altering ventilation or disrupting the intact of the respiratory system. These results indicate that sighs reflect a distinct pattern generator superimposed on that generating eupneic breathing. It remains unclear whether sighs are triggered (e.g., reflexes) or spontaneously generated. Funding: NIH NHLBI 5R01HL146114 and NIA 5R01AG044615 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

The present study provides novel physiological insights into aging by measuring airway compliance and residual volume via forced oscillation perturbations using a programmable mechanical ventilator (flexiVent—currently considered a gold standard for in vivo lung function measurements). In addition, dynamic measurements of lung inflation reported herein may serve as early indicators of altered elastic properties. Taken together, the findings offer a comprehensive assessment of age-related changes in lung structure and function.

ABSTRACT Objective To evaluate demographic and clinical factors influencing survival in patients with major salivary gland tumors (MSGTs) using the surveillance, epidemiology, and end results (SEER) database. Study Design A retrospective cohort study using SEER data from 2000 to 2021. Setting Data were collected from the SEER registry, a comprehensive database capturing cancer statistics across the United States. Methods Patients diagnosed with major salivary gland malignancies were analyzed for demographic factors, including age, sex, race, marital status, and income, as well as clinical variables, including tumor grade and site. Stratification by sex was done to assess sex‐specific outcomes. Results The cohort included 13,869 patients. Key findings include that older age and male sex were associated with worse survival outcomes. Single patients had better survival than married individuals, likely due to younger age at diagnosis. Additionally, higher income and Asian/Pacific Islander race conferred a survival advantage. There were disparate impacts between males and females in income, marital status, and race, with higher income and marriage providing a survival advantage for male patients but none for females. Additionally, Black females but not Black males, and widowed females but not widowed males, had slightly increased hazard ratios compared to White individuals. Conclusion Men and women experience disparate effects that impact survival and outcomes in major salivary gland tumors. These findings highlight the need for targeted interventions to address disparities in care and improve survival outcomes while emphasizing the importance of further research to understand the underlying mechanisms driving these disparities.

Neuromotor control of the diaphragm muscle (DIAm) after C 2 spinal hemisection (C 2 SH) is impacted differentially between ipsilateral and contralateral sides. We show neural drive to ipsilateral phrenic motor neurons decreases after C 2 SH, leading to a reduction in the number of DIAm motor units (MUs) recruited. Contralateral neural drive increases after C 2 SH, leading to an increase in the number of MU recruited. These results provide novel information about the impact of C 2 SH on DIAm neuromotor control.

Abstract Motoneurons are the final common pathway for all motor commands and possess intrinsic electrical properties that must be tuned to control muscle across the full range of motor behaviours. Neuromodulatory input from the brainstem is probably essential for adapting motoneuron properties to match this diversity of motor tasks. A primary mechanism of this adaptation, control of dendritic persistent inward currents (PICs) in motoneurons by brainstem monoaminergic systems, generates both amplification and prolongation of synaptic inputs. While essential, there is an inherent tension between this amplification and prolongation. Although amplification by PICs allows for quick recruitment and acceleration of motoneuron discharge, PICs must be deactivated to derecruit motoneurons upon movement cessation. In contrast, during stabilizing or postural tasks, PIC‐induced prolongation of synaptic inputs is critical for sustained motoneuron discharge. Here, we designed two motor tasks that challenged the inhibitory control of PICs, generating unduly PIC prolongation that increases variability in human torque control. This included a paradigm combining a discrete motor task with a stabilizing task and another involving muscle length‐induced changes to the balance of excitatory and inhibitory inputs available for controlling PICs. We show that prolongation from PICs introduces difficulties in ankle torque control and that these difficulties are further degraded at shorter muscle lengths when PIC prolongation is greatest. These results highlight the necessity for inhibitory control of PICs and showcase issues introduced when inhibitory control is constrained. Our findings suggest that, like sensory systems, errors are inherent in motor systems. These errors are not due to problems in the perception of movement‐related sensory input but are embedded in the final stage of motor output. This has many implications relevant to clinical conditions (e.g. chronic stroke) where pathological shifts in monoamines may further amplify these errors. image Key points All motor commands are processed via spinal motoneurons, whose intrinsic electrical properties are adapted by brainstem neuromodulatory input. The effects of these neuromodulatory inputs (i.e. persistent inward currents; PICs) must be tightly regulated by inhibitory inputs to allow for the large repertoire of human motor behaviours. We designed two motor tasks to restrict the ability of inhibitory synaptic inputs to control PICs and show that this generates substantial errors that reduce the precision of motor output in humans. Our findings suggest that errors are inherent in motor systems and embedded in the final stage of motor output. This has many implications relevant to clinical conditions (e.g. chronic stroke) and may, speculatively, shed light on contributing factors to muscle cramps.

The neuromotor control of the diaphragm muscle (DIAm) in response to hypercapnia is not well understood. We show that both the number of motor units recruited and their discharge rates increase with hypercapnia, consistent with increased respiratory drive during hypercapnia. Potentially in response to this increased drive, the greatest effect of hypercapnia is on during the postinspiratory (descending) ramp of DIAm EMG activity, which shortens to facilitate higher respiratory rates.

The heterogeneity of diaphragm muscle (DIAm) activity in awake animals reflects real motor behavior diversity but makes assessments of eupneic breathing challenging. The present article uses an unsupervised machine learning model to identify eupneic breathing amidst a deluge of different DIAm electromyography (EMG) burst patterns in awake rats. This technique offers a scalable and reliable tool that improves efficiency of DIAm EMG analysis and minimizes potential sources of bias.

The diaphragm muscle (DIAm) as the major inspiratory pump is highly active. During breathing, fatigue resistant DIAm motor units are recruited that comprise type I and IIa fibers. Accordingly, these fibers have substantially higher mitochondrial volume density (MVD) and mitochondrial respiratory capacity (SDHmax) compared to more fatigable type IIx/IIb fibers. Cervical spinal cord injury disrupts descending inspiratory drive and markedly reduces eupneic activity of the DIAm. With C2 spinal cord hemisection (C2SH) DIAm activity on the ipsilateral side is reduced. Following a two-week period of C2SH, we found reduced MVD and SDHmax in type I and IIa DIAm fibers. As a result, we hypothesize that endurance of the DIAm is reduced. Female and male Sprague Dawley rats were used. EMG electrodes were placed in the left and right DIAm 3 days prior to C2SH surgery, and baseline recordings of eupneic DIAm activity were obtained in awake animals. The right C2 spinal cord was hemisected, and the extent of injury was confirmed by the absence of eupneic DIAm activity on the ipsilateral side while animals were anesthetized. Subsequently, DIAm EMG activity was recorded at 3, 7 and 14 days post C2SH. After two weeks, rats were anesthetized and the DIAm was excised. DIAm strips were cut and suspended in a tissue chamber containing Rees-Simpson solution maintained at 26oC, with thecostal margin clamped and the central tendon attached to a Cambridge Dual-Mode force/length transducer. DIAm strips were stimulated using platinum plate electrodes with supramaximal current (~250 mA) pulses (1 ms), and maximum specific force was determined at 75 Hz. The force-velocity relationship was then determined by systematically changing load, and maximum velocity (Vmax) was estimated based on curve fitting with the Hill-equation. Based on the force-velocity measurements peak power of the DIAm was calculated. Subsequently, the DIAm was repetitively stimulated and allowed to shorten at 30% maximum velocity (isovelocity approximating peak power output). Endurance of the DIAm was then determined as the duration that peak power output was sustained. Finally, the DIAm was rapidly frozen, and cross-sections were cut for fiber type and cross-sectional area (CSA) measurements. C2SH resulted in a marked decrease in eupneic DIAm EMG activity across the two-week period, which disproportionately affected type I and IIa DIAm fibers. However, there was no impact of C2SH on DIAm fiber type proportions or CSA. Following two-weeks C2SH, maximum specific force, Vmax, and peak power output of the DIAm were comparable between intact and injured sides. However, endurance of the DIAm was reduced on the injured side compared to the intact side. These results support our hypothesis that reduced activity of DIAm, reduces oxidative capacity of type I and IIa fibers and thereby reduces endurance. In clinical conditions such as mechanical ventilation DIAm activity is reduced and if maintained for longer periods of time this may affect DIAm endurance post weaning. Research supported by NIH grant: HL146114 (GCS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The diaphragm muscle (DIAm) is the primary inspiratory muscle in mammals. At baseline, expiration is passive; however, with increased CO2 expiration becomes active, involving the inhibition of postinspiratory DIAm activity. The neuromotor control of the DIAm involves both the recruitment and frequency coding of DIAm motor units (MU’s) and it is not clear which aspect plays a greater role with exposure to hypercapnia. The activity of DIAm MU’s can be split into three phases: recruitment, sustained activity, and derecruitment. The goal of the present study was to evaluate the effects of hypercapnia on the neuromotor control of the DIAm in awake Sprague-Dawley rats. We hypothesized that hypercapnia would lead to increased respiratory drive as estimated by the root-mean-square (RMS) EMG amplitude at the end of the recruitment phase. Accordingly, we implanted chronic fine-wire EMG electrodes into the mid-costal region of the right side of the DIAm in 10 (5 female, 5 male) anesthetized rats. Three days after recovery from surgery, we recorded DIAm EMG in lightly restrained awake rats during normocapnia and hypercapnia (7% CO2, 21% O2, balance N2). We estimated the duration of motor unit recruitment, sustained activity, and derecruitment by assessing the stationarity of DIAm EMG activity and used these durations to determine the RMS EMG amplitude at the completion of recruitment, at the peak, and immediately prior to derecruitment (normalized to the average peak RMS EMG amplitude during normocapnia within each animal). We found that the RMS EMG amplitude at the completion of recruitment was increased from ~75% to 85% with hypercapnia. Peak RMS EMG amplitude during hypercapnia increased from 100% to ~120%, while the amplitude at the onset of derecruitment increased from ~50% to 95%. These data suggest that ~70% of the total RMS EMG peak amplitude can be attributed primarily to motor unit recruitment, while the remaining ~30% can be attributed to frequency modulation during hypercapnia. Importantly the onset-to-offset amplitude difference was ~25% during normocapnia and ~15% during hypercapnia, suggesting that DIAm MU’s were derecruited at higher discharge rates with hypercapnia, likely due to inhibition. We also found that compared to normocapnia, respiratory rate increased from ~85 breaths/min to 125 breaths/min while the burst duration decreased from ~600 ms to ~400 ms during hypercapnia. The duty cycle was maintained around 80% for both, however the duty cycle of the sustained activity duration (i.e. the period during which MU’s are remaining activated) decreased from ~56% to ~28%. Taken together, our data suggest that hypercapnia in awake rats results in an increase in the number of motor units recruited and their discharge rates as well as changes in the phases of DIAm MU activity indicative of active expiration. Funded by NIH HL-146114. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.