ASU Scholarship Showcase

The delicate tuning of digit forces to object properties can be disrupted by a number of neurological and musculoskeletal diseases. One such condition is Carpal Tunnel Syndrome (CTS), a compression neuropathy of the median nerve that causes sensory and motor deficits in a subset of digits in the hand. Whereas the effects of CTS on median nerve physiology are well understood, the extent to which it affects whole-hand manipulation remains to be addressed. CTS affects only the lateral three and a half digits, which raises the question of how the central nervous system integrates sensory feedback from affected and unaffected digits to plan and execute whole-hand object manipulation. We addressed this question by asking CTS patients and healthy controls to grasp, lift, and hold a grip device (445, 545, or 745 g) for several consecutive trials. We found that CTS patients were able to successfully adapt grip force to object weight. However, multi-digit force coordination in patients was characterized by lower discrimination of force modulation to lighter object weights, higher across-trial digit force variability, the consistent use of excessively large digit forces across consecutive trials, and a lower ability to minimize net moments on the object. Importantly, the mechanical requirement of attaining equilibrium of forces and torques caused CTS patients to exert excessive forces at both CTS-affected digits and digits with intact sensorimotor capabilities. These findings suggest that CTS-induced deficits in tactile sensitivity interfere with the formation of accurate sensorimotor memories of previous manipulations. Consequently, CTS patients use compensatory strategies to maximize grasp stability at the expense of exerting consistently larger multi-digit forces than controls. These behavioral deficits might be particularly detrimental for tasks that require fine regulation of fingertip forces for manipulating light or fragile objects.

Carpal tunnel syndrome (CTS) impairs sensation of a subset of digits. Although the effects of CTS on manipulation performed with CTS-affected digits have been studied using precision grip tasks, the extent to which CTS affects multi-digit force coordination has only recently been studied. Whole-hand manipulation studies have shown that CTS patients retain the ability to modulate multi-digit forces to object mass, mass distribution, and texture. However, CTS results in sensorimotor deficits relative to healthy controls, including significantly larger grip force and lower ability to balance the torques generated by the digits. Here we investigated the effects of CTS on multi-digit force modulation to object weight when manipulating an object with a variable number of fingers. We hypothesized that CTS patients would be able to modulate digit forces to object weight. However, as different grip types involve the exclusive use of CTS-affected digits (‘uniform’ grips) or a combination of CTS-affected and non-affected digits (‘mixed’ grips), we addressed the question of whether ‘mixed’ grips would reduce or worsen CTS-induced force coordination deficits. The former scenario would be due to adding digits with intact tactile feedback, whereas the latter scenario might occur due to a potentially greater challenge for the central nervous system of integrating ‘noisy’ and intact tactile feedback. CTS patients learned multi-digit force modulation to object weight regardless of grip type. Although controls exerted the same total grip force across all grip types, patients exerted significantly larger grip force than controls but only for manipulations with four and five digits. Importantly, this effect was due to CTS patients’ inability to change the finger force distribution when adding the ring and little fingers. These findings suggest that CTS primarily challenges sensorimotor integration processes for dexterous manipulation underlying the coordination of CTS-affected and non-affected digits.

Tactile perception is typically considered the result of cortical interpretation of afferent signals from a network of mechanical sensors underneath the skin. Yet, tactile illusion studies suggest that tactile perception can be elicited without afferent signals from mechanoceptors. Therefore, the extent that tactile perception arises from isomorphic mapping of tactile afferents onto the somatosensory cortex remains controversial. We tested whether isomorphic mapping of tactile afferent fibers onto the cortex leads directly to tactile perception by examining whether it is independent from proprioceptive input by evaluating the impact of different hand postures on the perception of a tactile illusion across fingertips. Using the Cutaneous Rabbit Effect, a well studied illusion evoking the perception that a stimulus occurs at a location where none has been delivered, we found that hand posture has a significant effect on the perception of the illusion across the fingertips. This finding emphasizes that tactile perception arises from integration of perceived mechanical and proprioceptive input and not purely from tactile interaction with the external environment.

Anticipatory force planning during grasping is based on visual cues about the object’s physical properties and sensorimotor memories of previous actions with grasped objects. Vision can be used to estimate object mass based on the object size to identify and recall sensorimotor memories of previously manipulated objects. It is not known whether subjects can use density cues to identify the object’s center of mass (CM) and create compensatory moments in an anticipatory fashion during initial object lifts to prevent tilt. We asked subjects (n = 8) to estimate CM location of visually symmetric objects of uniform densities (plastic or brass, symmetric CM) and non-uniform densities (mixture of plastic and brass, asymmetric CM). We then asked whether subjects can use density cues to scale fingertip forces when lifting the visually symmetric objects of uniform and non-uniform densities. Subjects were able to accurately estimate an object’s center of mass based on visual density cues. When the mass distribution was uniform, subjects could scale their fingertip forces in an anticipatory fashion based on the estimation. However, despite their ability to explicitly estimate CM location when object density was non-uniform, subjects were unable to scale their fingertip forces to create a compensatory moment and prevent tilt on initial lifts. Hefting object parts in the hand before the experiment did not affect this ability. This suggests a dichotomy between the ability to accurately identify the object’s CM location for objects with non-uniform density cues and the ability to utilize this information to correctly scale their fingertip forces. These results are discussed in the context of possible neural mechanisms underlying sensorimotor integration linking visual cues and anticipatory control of grasping.

Introduction: Apolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III_0a without glycosylation and apoC-III[subscript 0b] with glycosylation), monosialylated (apoC-III₁) or disialylated (apoC-III₂) proteoforms. Our aim was to clarify the relationship between apoC-III sialylation proteoforms with fasting plasma TG concentrations.

Methods: In 204 non-diabetic adolescent participants, the relative abundance of apoC-III plasma proteoforms was measured using mass spectrometric immunoassay.

Results: Compared with the healthy weight subgroup (n = 16), the ratios of apoC-III_0a, apoC-III_0b, and apoC-III₁ to apoC-III₂ were significantly greater in overweight (n = 33) and obese participants (n = 155). These ratios were positively correlated with BMI z-scores and negatively correlated with measures of insulin sensitivity (S[subscript i]). The relationship of apoC-III₁ / apoC-III₂ with S_i persisted after adjusting for BMI (p = 0.02). Fasting TG was correlated with the ratio of apoC-III_0a / apoC-III₂ (r = 0.47, p<0.001), apoC-III_0b / apoC-III₂ (r = 0.41, p<0.001), apoC-III₁ / apoC-III₂ (r = 0.43, p<0.001). By examining apoC-III concentrations, the association of apoC-III proteoforms with TG was driven by apoC-III_0a (r = 0.57, p<0.001), apoC-III_0b (r = 0.56. p<0.001) and apoC-III₁ (r = 0.67, p<0.001), but not apoC-III₂ (r = 0.006, p = 0.9) concentrations, indicating that apoC-III relationship with plasma TG differed in apoC-III₂ compared with the other proteoforms.

Conclusion: We conclude that apoC-III_0a, apoC-III_0b, and apoC-III₁, but not apoC-III₂ appear to be under metabolic control and associate with fasting plasma TG. Measurement of apoC-III proteoforms can offer insights into the biology of TG metabolism in obesity.

Pure coconut oil, lanolin, and acetaminophen were vaporized at rates of 1–50 mg/min, using a porous network exhibiting a temperature gradient from 5000 to 5500 K/mm, without incurring noticeable chemical changes due to combustion, oxidation, or other thermally-induced chemical structural changes. The newly coined term “ereptiospiration” is used here to describe this combination of thermal transpiration at high temperature gradients since the process can force the creation of thermal aerosols by rapid heating in a localized zone. Experimental data were generated for these materials using two different supports for metering the materials to the battery powered coil: namely, a stainless steel fiber bundle and a 3-D printed steel cartridge. Heating coconut oil, lanolin, or acetaminophen in a beaker to lower temperatures than those achieved at the surface of the coil showed noticeable and rapid degradation in the samples, while visual and olfactory observations for ereptiospiration showed no noticeable degradation in lanolin and coconut oil while HPLC chromatograms along with visual observation confirm that within the limit of detection, acetaminophen remains chemically unaltered by ereptiospiration.

Proteins can exist as multiple proteoforms in vivo, as a result of alternative splicing and single-nucleotide polymorphisms (SNPs), as well as posttranslational processing. To address their clinical significance in a context of diagnostic information, proteoforms require a more in-depth analysis. Mass spectrometric immunoassays (MSIA) have been devised for studying structural diversity in human proteins. MSIA enables protein profiling in a simple and high-throughput manner, by combining the selectivity of targeted immunoassays, with the specificity of mass spectrometric detection. MSIA has been used for qualitative and quantitative analysis of single and multiple proteoforms, distinguishing between normal fluctuations and changes related to clinical conditions. This mini review offers an overview of the development and application of mass spectrometric immunoassays for clinical and population proteomics studies. Provided are examples of some recent developments, and also discussed are the trends and challenges in mass spectrometry-based immunoassays for the next-phase of clinical applications.

The intact nervous system has an exquisite ability to modulate the activity of multiple muscles acting at one or more joints to produce an enormous range of actions. Seemingly simple tasks, such as reaching for an object or walking, in fact rely on very complex spatial and temporal patterns of muscle activations. Neurological disorders such as stroke and focal dystonia affect the ability to coordinate multi-joint movements. This article reviews the state of the art of research of muscle synergies in the intact and damaged nervous system, their implications for recovery and rehabilitation, and proposes avenues for research aimed at restoring the nervous system’s ability to control movement.

How the human brain controls hand movements to carry out different tasks is still debated. The concept of synergy has been proposed to indicate functional modules that may simplify the control of hand postures by simultaneously recruiting sets of muscles and joints. However, whether and to what extent synergic hand postures are encoded as such at a cortical level remains unknown. Here, we combined kinematic, electromyography, and brain activity measures obtained by functional magnetic resonance imaging while subjects performed a variety of movements towards virtual objects. Hand postural information, encoded through kinematic synergies, were represented in cortical areas devoted to hand motor control and successfully discriminated individual grasping movements, significantly outperforming alternative somatotopic or muscle-based models. Importantly, hand postural synergies were predicted by neural activation patterns within primary motor cortex. These findings support a novel cortical organization for hand movement control and open potential applications for brain-computer interfaces and neuroprostheses.

Human protein diversity arises as a result of alternative splicing, single nucleotide polymorphisms (SNPs) and posttranslational modifications. Because of these processes, each protein can exists as multiple variants in vivo. Tailored strategies are needed to study these protein variants and understand their role in health and disease. In this work we utilized quantitative mass spectrometric immunoassays to determine the protein variants concentration of beta-2-microglobulin, cystatin C, retinol binding protein, and transthyretin, in a population of 500 healthy individuals. Additionally, we determined the longitudinal concentration changes for the protein variants from four individuals over a 6 month period. Along with the native forms of the four proteins, 13 posttranslationally modified variants and 7 SNP-derived variants were detected and their concentration determined. Correlations of the variants concentration with geographical origin, gender, and age of the individuals were also examined. This work represents an important step toward building a catalog of protein variants concentrations and examining their longitudinal changes.