Reflexive Pathway Research Articles

Navigating between Complexity and Control in Transdisciplinary Problem Framing: Meaning Making as an Approach to Reflexive Integration

ABSTRACT Referring to a problem-oriented research mode, transdisciplinarity faces the challenge of dealing with the complexity of real-world problems in a methodologically controlled manner. As the first step in transdisciplinary research, problem framing aims at identifying the problem that will serve as a common orientation point for the subsequent research process. Existing approaches to integrative problem framing seek collaboration of practical and scientific actors in order to develop a common definition of the problem. Such a strategy seems to rely on a unifying mode of integration that levels the diversity of perspectives of the involved actors. This paper presents an alternative approach to integrative problem framing in transdisciplinary research, which is based on a mode of reflexive integration. The corresponding approach of ‘meaning making’ intends to systematically grasp the plurality of perspectives involved and to relate them to an overarching theme. Substantiating and reflecting meaning making based on a research project on sustainability governance in Swiss cantons, the paper argues that meaning making enables a reflexive pathway between complexity and control in transdisciplinary problem framing.

Neural Control of Balance During Walking.

Neural control of standing balance has been extensively studied. However, most falls occur during walking rather than standing, and findings from standing balance research do not necessarily carry over to walking. This is primarily due to the constraints of the gait cycle: Body configuration changes dramatically over the gait cycle, necessitating different responses as this configuration changes. Notably, certain responses can only be initiated at specific points in the gait cycle, leading to onset times ranging from 350 to 600 ms, much longer than what is observed during standing (50–200 ms). Here, we investigated the neural control of upright balance during walking. Specifically, how the brain transforms sensory information related to upright balance into corrective motor responses. We used visual disturbances of 20 healthy young subjects walking in a virtual reality cave to induce the perception of a fall to the side and analyzed the muscular responses, changes in ground reaction forces and body kinematics. Our results showed changes in swing leg foot placement and stance leg ankle roll that accelerate the body in the direction opposite of the visually induced fall stimulus, consistent with previous results. Surprisingly, ankle musculature activity changed rapidly in response to the stimulus, suggesting the presence of a direct reflexive pathway from the visual system to the spinal cord, similar to the vestibulospinal pathway. We also observed systematic modulation of the ankle push-off, indicating the discovery of a previously unobserved balance mechanism. Such modulation has implications not only for balance but plays a role in modulation of step width and length as well as cadence. These results indicated a temporally-coordinated series of balance responses over the gait cycle that insures flexible control of upright balance during walking.

FEFsem neuronal response during combined volitional and reflexive pursuit.

Although much is known about volitional and reflexive smooth eye movements individually, much less is known about how they are coordinated. It is hypothesized that separate cortico-ponto-cerebellar loops subserve these different types of smooth eye movements. Specifically, the MT-MST-DLPN pathway is thought to be critical for ocular following eye movements, whereas the FEF-NRTP pathway is understood to be vital for volitional smooth pursuit. However, the role that these loops play in combined volitional and reflexive behavior is unknown. We used a large, textured background moving in conjunction with a small target spot to investigate the eye movements evoked by a combined volitional and reflexive pursuit task. We also assessed the activity of neurons in the smooth eye movement subregion of the frontal eye field (FEFsem). We hypothesized that the pursuit system would show less contribution from the volitional pathway in this task, owing to the increased involvement of the reflexive pathway. In accordance with this hypothesis, a majority of FEFsem neurons (63%) were less active during pursuit maintenance in a combined volitional and reflexive pursuit task than during purely volitional pursuit. Interestingly and surprisingly, the neuronal response to the addition of the large-field motion was highly correlated with the neuronal response to a target blink. This suggests that FEFsem neuronal responses to these different perturbations—whether the addition or subtraction of retinal input—may be related. We conjecture that these findings are due to changing weights of both the volitional and reflexive pathways, as well as retinal and extraretinal signals.

GJB1-associated X-linked Charcot-Marie-Tooth disease, a disorder affecting the central and peripheral nervous systems.

Charcot-Marie-Tooth disease (CMT) is a group of inherited diseases characterized by exclusive or predominant involvement of the peripheral nervous system. Mutations in GJB1, the gene encoding Connexin 32 (Cx32), a gap-junction channel forming protein, cause the most common X-linked form of CMT, CMT1X. Cx32 is expressed in Schwann cells and oligodendrocytes, the myelinating glia of the peripheral and central nervous systems, respectively. Thus, patients with CMT1X have both central and peripheral nervous system manifestations. Study of the genetics of CMT1X and the phenotypes of patients with this disorder suggest that the peripheral manifestations of CMT1X are likely to be due to loss of function, while in the CNS gain of function may contribute. Mice with targeted ablation of Gjb1 develop a peripheral neuropathy similar to that seen in patients with CMT1X, supporting loss of function as a mechanism for the peripheral manifestations of this disorder. Possible roles for Cx32 include the establishment of a reflexive gap junction pathway in the peripheral and central nervous system and of a panglial syncitium in the central nervous system.

Effect of emotional picture viewing on voluntary eyeblinks.

Eyeblinks, whether reflexive or voluntary, play an important role in protecting our vision. When viewing pictures, reflexive eyeblinks are known to be modulated by the emotional state induced thereby. More specifically, the hedonic valence (unpleasantness-pleasantness) induced by the picture has been shown to have a linear relationship with the amplitude of a startle blink elicited during picture viewing. This effect has been attributed to congruence between an ongoing state and task demands: an unpleasant emotional state is assumed to bias our attention towards potentially harmful stimuli, such as startle tones. However, recent research suggests that the valence-specific modulation may not be limited to the sensory parts of the reflexive pathway related to startle responses. Here, we examined the effect of emotional picture viewing on voluntary (in response to a written command) eyeblinks in adult humans. Emotional modulation of startle blinks was also evaluated. We found that when viewing unpleasant pictures, the amplitude of reflexive eyeblinks was augmented, but the amplitude of voluntary eyeblinks was unaffected. Nevertheless, the response latencies of voluntary eyeblinks were found to be delayed during the viewing of pleasant and unpleasant relative to neutral pictures. We conclude that these results support the theory that emotional experience augments sensory processing specific to potentially harmful stimuli. Further, the emotional state seems not to exert an effect on voluntarily elicited motor activity.

Cross‐talk and sensitization of bladder afferent nerves

The coordination of pelvic physiologic function requires complex integrative sensory pathways that may converge both peripherally and/or centrally. Following a focal, acute irritative or infectious pelvic insult, these same afferent pathways may produce generalized pelvic sensitization or cross-sensitization as we show bi-directionally for the bladder and bowel in an animal model. Single unit bladder afferent recordings following intracolonic irritation reveal direct sensitization to both chemical and mechanical stimuli that's dependent upon both intact bladder sensory (C-fiber) innervation and neuropeptide content. Concurrent mastocytosis (preponderantly neurogenic) likely plays a role in long-term pelvic organ sensitization via the release of nociceptive and afferent-modulating molecules. Prolonged pelvic sensitization as mediated by these convergent and antidromic reflexive pathway may likewise lead to chronic pelvic pain and thus the overlap of chronic pelvic pain disorders.

Neuromechanical models for insect locomotion: Stability, maneuverability, and proprioceptive feedback

We describe a hierarchy of models for legged locomotion, emphasizing relationships among feedforward (preflexive) stability, maneuverability, and reflexive feedback. We focus on a hexapedal geometry representative of insect locomotion in the ground plane that includes a neural central pattern generator circuit, nonlinear muscles, and a representative proprioceptive sensory pathway. Although these components of the model are rather complex, neglect of leg mass yields a neuromechanical system with only three degrees of freedom, and numerical simulations coupled with a Poincaré map analysis shows that the feedforward dynamics is strongly stable, apart from one relatively slow mode and a neutral mode in body yaw angle. These modes moderate high frequency perturbations, producing slow heading changes that can be corrected by a stride-to-stride steering strategy. We show that the model's response to a lateral impulsive perturbation closely matches that of a cockroach subject to a similar impulse. We also describe preliminary studies of proprioceptive leg force feedback, showing how a reflexive pathway can reinforce the preflexive stability inherent in the system.

Pathogenesis of X-Linked Charcot-Marie-Tooth Disease: Differential Effects of Two Mutations in Connexin 32

X-linked Charcot-Marie-Tooth disease is an inherited peripheral neuropathy arising in patients with mutations in the gene encoding connexin 32 (Cx32). Cx32 is expressed at the paranodes and Schmidt-Lantermann incisures of myelinating Schwann cells in which it is believed to form a reflexive pathway between the abaxonal and adaxonal cytoplasmic domains. Patients with the Val181Ala (V181A) mutation have a severe peripheral neuropathy. Experiments using a nude mouse xenograft system show that Schwann cells expressing only this mutant form of Cx32 are profoundly impaired in their ability to support the earliest stages of regeneration of myelinated fibers. Coupling between paired Xenopus oocytes expressing V181A is reduced compared with the coupling between oocytes expressing wild-type human Cx32 (32WT), and protein levels assayed by Western blot are substantially lower. Immunocytochemisty shows that Neuro2a cells expressing the V181A mutant have very few gap junction plaques compared with cells expressing 32WT; Cx32 protein levels are lower in these cells than in those expressing 32WT. Because failure of normal regeneration is evident before formation of myelin, loss of function of Cx32 may impact on the function of precursors of the myelinating Schwann cell before the formation of the hypothesized reflexive pathway. The Glu102Gly (E102G) mutation leads to a milder phenotype. Early regeneration is normal in grafts with Schwann cells expressing the E102G mutant. The only abnormality detected in the behavior of its channel is increased sensitivity to acidification-induced closure, a property that may lead to reduced gap junction coupling during periods of metabolic stress. This restricted functional abnormality may explain the relatively mild phenotype seen in the xenograft model and in E102G patients.

The role of chemical mediators and mucosal hyperreactivity in nasal hypersecretion in nasal allergy

This study was designed to elucidate, first, the degree of participation of direct effects of histamine on the nasal glands and the nasal vasculature in clinical manifestation of hyperrhinorrhea in nasal allergy and, second, the existence of hyperreactivity of the nasal glands to acetylcholine in nasal allergy. The study demonstrates that histamine released by degranulation of basophilic cells in the nasal mucosa causes nasal hypersecretion mostly by way of the reflexive pathway. Approximately 4% of the amount of nasal secretion induced by an antigen challenge in subjects with house-dust nasal allergy was due to a leakage of plasma. There were almost no direct effects of histamine on the nasal glands. Nasal secretion induced by nasal challenge with acetylcholine after vidian neurectomy comes from the nasal glands by its direct effects on the nasal glands, the amount of which indicates degree of reactivity of the nasal glands to acetylcholine independent of hypersensitivity of the mucosal sensory system. The nasal glands of vidian neurectomized subjects having nasal allergy reacted more excessively to extrinsic acetylcholine than nasal glands of subjects of the control group. This verifies the existence of hyperreactivity in the nasal glands to acetylcholine in nasal allergy. The nasal glands of nasal allergy patients may respond more excessively to a given amount of acetylcholine released from parasympathetic terminals.

Initiation of bilateral responses in a kinesthetic reaction time task.

Two experiments are presented in which different mechanisms controlling each limb in a bilateral arm response to a unilateral kinesthetic stimulus are postulated to occur. In Experiment 1, the limb serving as the stimulus are postulated to occur. In Experiment 1, the limb serving as the stimulus limb was described as operating with relative invariance by using a tightly coupled input-output reflexive pathway, whereas the nonstimulus limb appeared to be controlled by higher-order processing thought to be more susceptible to influences such as hemispheric specialization and stimulus expectancy. The differential control model was further tested in Experiment 2 by retaining the interhemispheric pathway of the unilateral kinesthetic stimulus but experimentally uncoupling the reflex mechanism from the stimulus side. Analyses of bilateral EMG premotor latencies under these conditions revealed that each response side can be controlled at separate levels-i.e., by a reflexive type mechanism or by higher-order processing when one of the response limbs is also the stimulus limb, both sides reflect behavior that is best described by an information processing type of voluntary control.