ASU Scholarship Showcase

Dexterous manipulation relies on modulation of digit forces as a function of digit placement. However, little is known about the sense of position of the vertical distance between finger pads relative to each other. We quantified subjects' ability to match perceived vertical distance between the thumb and index finger pads (d_y) of the right hand (“reference” hand) using the same or opposite hand (“test” hand) after a 10-second delay without vision of the hands. The reference hand digits were passively placed non-collinearly so that the thumb was higher or lower than the index finger (d_y = 30 or –30 mm, respectively) or collinearly (d_y = 0 mm). Subjects reproduced reference hand d_y by using a congruent or inverse test hand posture while exerting negligible digit forces onto a handle. We hypothesized that matching error (reference hand d_y minus test hand d_y) would be greater (a) for collinear than non-collinear d_ys, (b) when reference and test hand postures were not congruent, and (c) when subjects reproduced dy using the opposite hand. Our results confirmed our hypotheses. Under-estimation errors were produced when the postures of reference and test hand were not congruent, and when test hand was the opposite hand. These findings indicate that perceived finger pad distance is reproduced less accurately (1) with the opposite than the same hand and (2) when higher-level processing of the somatosensory feedback is required for non-congruent hand postures. We propose that erroneous sensing of finger pad distance, if not compensated for during contact and onset of manipulation, might lead to manipulation performance errors as digit forces have to be modulated to perceived digit placement.

Background: The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in cancer cells. It has therefore been postulated that the high-fat, low-carbohydrate, adequate protein ketogenic diet (KD) may be useful in the treatment of brain tumors. We have demonstrated that the KD enhances survival and potentiates standard therapy in a mouse model of malignant glioma, yet the mechanisms are not fully understood.

Methods: To explore the effects of the KD on various aspects of tumor growth and progression, we used the immunocompetent, syngeneic GL261-Luc2 mouse model of malignant glioma.

Results: Tumors from animals maintained on KD showed reduced expression of the hypoxia marker carbonic anhydrase 9, hypoxia inducible factor 1-alpha, and decreased activation of nuclear factor kappa B. Additionally, tumors from animals maintained on KD had reduced tumor microvasculature and decreased expression of vascular endothelial growth factor receptor 2, matrix metalloproteinase-2 and vimentin. Peritumoral edema was significantly reduced in animals fed the KD and protein analyses showed altered expression of zona occludens-1 and aquaporin-4.

Conclusions: The KD directly or indirectly alters the expression of several proteins involved in malignant progression and may be a useful tool for the treatment of gliomas.

Introduction: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC) is a nutritionally complete, commercially available 4∶1 (fat∶ carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas.

Methods: We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD) or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging.

Results: Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173) and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001). Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days.

Conclusions: KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.

Background: Malignant brain tumors affect people of all ages and are the second leading cause of cancer deaths in children. While current treatments are effective and improve survival, there remains a substantial need for more efficacious therapeutic modalities. The ketogenic diet (KD) - a high-fat, low-carbohydrate treatment for medically refractory epilepsy - has been suggested as an alternative strategy to inhibit tumor growth by altering intrinsic metabolism, especially by inducing glycopenia.

Methods: Here, we examined the effects of an experimental KD on a mouse model of glioma, and compared patterns of gene expression in tumors vs. normal brain from animals fed either a KD or a standard diet.

Results: Animals received intracranial injections of bioluminescent GL261-luc cells and tumor growth was followed in vivo. KD treatment significantly reduced the rate of tumor growth and prolonged survival. Further, the KD reduced reactive oxygen species (ROS) production in tumor cells. Gene expression profiling demonstrated that the KD induces an overall reversion to expression patterns seen in non-tumor specimens. Notably, genes involved in modulating ROS levels and oxidative stress were altered, including those encoding cyclooxygenase 2, glutathione peroxidases 3 and 7, and periredoxin 4.

Conclusions: Our data demonstrate that the KD improves survivability in our mouse model of glioma, and suggests that the mechanisms accounting for this protective effect likely involve complex alterations in cellular metabolism beyond simply a reduction in glucose.

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.

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.

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.