Reducing the Soleus Stretch Reflex With Conditioning: Exploring Game- and Impedance-Based Biofeedback

People with spasticity, i.e., stretch hyperreflexia, have a limited functional independence and mobility. While a broad range of spasticity treatments is available, many treatments are invasive, non-specific, or temporary and might have negative side effects. Operant conditioning of the stretch reflex is a promising non-invasive paradigm with potential long-term sustained effects. Within this conditioning paradigm, seated participants have to reduce the mechanically elicited reflex response using biofeedback of reflex magnitude quantified using electromyography (EMG). Before clinical application of the conditioning paradigm, improvements are needed regarding the time-intensiveness and slow learning curve. Previous studies have shown that gamification of biofeedback can improve participant motivation and long-term engagement. Moreover, quantification of reflex magnitude for biofeedback using reflexive joint impedance may obtain similar effectiveness within fewer sessions. Nine healthy volunteers participated in the study, split in three groups. First, as a reference the “Conventional” group received EMG- and bar-based biofeedback similar to previous research. Second, we explored feasibility of game-based biofeedback with the “Gaming” group receiving EMG- and game-based biofeedback. Third, we explored feasibility of game- and impedance-based biofeedback with the “Impedance” group receiving impedance and game-based biofeedback. Participants completed five baseline sessions (without reflex biofeedback) and six conditioning sessions (with reflex biofeedback). Participants were instructed to reduce reflex magnitude without modulating background activity. The Conventional and Gaming groups showed feasibility of the protocol in 2 and 3 out of 3 participants, respectively. These participants achieved a significant Soleus short-latency (M1) within-session reduction in at least –15% in the 4th–6th conditioning session. None of the Impedance group participants showed any within-session decrease in Soleus reflex magnitude. The feasibility in the EMG- and game-based biofeedback calls for further research on gamification of the conditioning paradigm to obtain improved participant motivation and engagement, while achieving long-term conditioning effects. Before clinical application, the time-intensiveness and slow learning curve of the conditioning paradigm remain an open challenge.

Underlying hemodynamic differences are associated with responses to tilt testing

Aim of this study was to explore whether differences in resting hemodynamic parameters may be associated with tilt test results in unexplained syncope. We analyzed age, gender, systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) by merging three large databases of patients considered likely to be of vasovagal reflex etiology, comparing patients who had tilt-induced reflex response with those who did not. Tilt-induced reflex response was defined as spontaneous symptom reproduction with characteristic hypotension and bradycardia. Relationship of demographics and baseline supine BP to tilt-test were assessed using logistic regression models. Individual records of 5236 patients (45% males; mean age: 60 ± 22 years; 32% prescribed antihypertensive therapy) were analyzed. Tilt-positive (n = 3129, 60%) vs tilt-negative patients had lower SBP (127.2 ± 17.9 vs 129.7 ± 18.0 mmHg, p < 0.001), DBP (76.2 ± 11.5 vs 77.7 ± 11.7 mmHg, p < 0.001) and HR (68.0 ± 11.5 vs 70.5 ± 12.5 bpm, p < 0.001). In multivariable analyses, tilt-test positivity was independently associated with younger age (Odds ratio (OR) per 10 years:1.04; 95% confidence interval (CI), 1.01–1.07, p = 0.014), SBP ≤ 128 mmHg (OR:1.27; 95%CI, 1.11–1.44, p < 0.001), HR ≤ 69 bpm (OR:1.32; 95%CI, 1.17–1.50, p < 0.001), and absence of hypertension (OR:1.58; 95%CI, 1.38–1.81, p < 0.001). In conclusion, among patients with suspected reflex syncope, younger age, lower blood pressure and lower heart rate are associated with positive tilt-test result.

Case of anterolateral migration of herniated cervical disc fragment mimicking a spinal meningioma

Background: Before the introduction of high-resolution MR, few disc fragments were misdiagnosed as meningiomas. Case Description: A 63-year-old female presented with a 6-month history of mild to moderate pain in the left arm, weakness 4/5 in the left arm C5-C6 distribution, and a loss of the left biceps reflex response. Although the MR study was read as showing a C5-C6 level probable spinal meningioma, this proved to be a sequestrated disc fragment at surgery. Conclusion: Rarely, cervical disc herniations may be misdiagnosed on MR studies as spinal meningiomas.

Sleep and conditioning of the siphon withdrawal reflex in Aplysia

Sleep is essential for memory consolidation after learning as shown in mammals and invertebrates such as bees and flies. Aplysia californica displays sleep and sleep in this mollusk was also found to support memory for an operant conditioning task. Here, we investigated whether sleep in Aplysia is also required for memory consolidation in a simpler type of learning, i.e., the conditioning of the siphon withdrawal reflex. Two groups of animals (Wake, Sleep, each n=11) were conditioned on the siphon withdrawal reflex with the training following a classical conditioning procedure where an electrical tail shock served as unconditioned stimulus (US) and a tactile stimulus to the siphon as conditioned stimulus (CS). Responses to the CS were tested before (Pre-test), 24 and 48 hours after training. While Wake animals remained awake for 6 hours after training, Sleep animals had undisturbed sleep. The 24h-test in both groups was combined with extinction training, i.e., the extended presentation of the CS alone over two blocks. At the 24h-test, siphon withdrawal durations to the CS were distinctly enhanced in both Sleep and Wake groups with no significant difference between groups, consistent with the view that consolidation of a simple conditioned reflex response does not require post-training sleep. Surprisingly, extinction training did not reverse the enhancement of responses to the CS. On the contrary, at the 48h-test, withdrawal durations to the CS were even further enhanced across both groups. This suggests that processes of sensitization, an even simpler non-associative type of learning, contributed to the withdrawal responses. Our study provides evidence for the hypothesis that sleep preferentially benefits consolidation of more complex learning paradigms than conditioning of simple reflexes.

The 2021 Carl Ludwig Lecture. Unsympathetic autonomic regulation in heart failure: patient-inspired insights

Defined as a structural or functional cardiac abnormality accompanied by symptoms, signs or biomarkers of altered ventricular pressures or volumes, heart failure also is a state of autonomic disequilibrium. A large body of evidence affirms that autonomic disturbances are intrinsic to heart failure; that basal or stimulated sympathetic nerve firing or neural norepinephrine (NE) release more often than not exceed homeostatic need, such that an initially adaptive adrenergic or vagal reflex response, becomes maladaptive; and, that the magnitude of such maladaptation predicts prognosis. This Ludwig lecture develops two theses: that the elucidation and judiciously targeted amelioration of maladaptive autonomic disturbances offers opportunities to complement contemporary guideline-based heart failure therapy; and, that serendipitous single-participant insights, acquired in the course of experimental protocols with entirely different intent, can generate novel insight, inform mechanisms, and launch entirely new research directions. I précis 6 elements of our current synthesis of the causes and consequences of maladaptive sympathetic disequilibrium in heart failure, shaped by patient-inspired epiphanies: arterial baroreceptor reflex modulation; excitation stimulated by increased cardiac filling pressure; paradoxical muscle sympathetic activation as a peripheral neurogenic constraint on exercise capacity; renal sympathetic restraint of natriuresis; co-existing sleep apnea; and, augmented chemoreceptor reflex sensitivity, then conclude by envisaging translational therapeutic opportunities.

Tempo-spatial integration of nociceptive stimuli assessed via the nociceptive withdrawal reflex in healthy humans.

Spatial information of nociceptive stimuli applied in the skin of healthy humans is integrated in the spinal cord to determine the appropriate withdrawal reflex response. Double-simultaneous stimulus applied in different skin sites are integrated, eliciting a larger reflex response. The temporal characteristics of the stimuli also modulate the reflex e.g. by temporal summation. The primary aim of this study was to investigate how the combined tempo-spatial aspects of two stimuli are integrated in the nociceptive system. This was investigated by delivering single and double simultaneous stimulation, and sequential stimulation with different inter-stimulus intervals (ISIs ranging 30-500 ms.) to the sole of the foot of fifteen healthy subjects. The primary outcome measure was the size of the nociceptive withdrawal reflex (NWR) recorded from the Tibialis Anterior (TA) and Biceps Femoris (BF) muscles. Pain intensity was measured using an NRS scale. Results showed spatial summation in both TA and BF when delivering simultaneous stimulation. Simultaneous stimulation provoked larger reflexes than sequential stimulation in TA, but not in BF. Larger ISIs elicited significantly larger reflexes in TA, while the opposite pattern occurred in BF. This differential modulation between proximal and distal muscles suggests the presence of spinal circuits eliciting a functional reflex response based on the specific tempo-spatial characteristics of a noxious stimulus. No modulation was observed in pain intensity ratings across ISIs. Absence of modulation in the pain intensity ratings argues for an integrative mechanism located within the spinal cord governed by a need for efficient withdrawal from a potentially harmful stimulus.

COVID-19 Pandemic; Anxiety and Depression among frontline healthcare workers: Rising from the Ashes

This chapter gives an insight into the psychological journey of the essential healthcare workers (HCWs) during the COVID-19 pandemic. The catastrophe which started off with uncertainty, provoked fear-related behaviors among the frontline doctors, nurses and paramedical staff. With meager resources and lack of a disaster plan, fire-fighting was a reflex response of healthcare institutions. Though the whole world seemed to be unprepared for the calamity, developing countries with fragile healthcare systems were more vulnerable to collapse. The negative aura was complicated by mistrust among the general population, regarding healthcare workers, institutions and government. Furthermore, with economic downfall; balancing work and protecting the family was a challenge for HCWs, especially during the pandemic peak. The psychological distress translated to rising incidence of depression and anxiety among them. As institutions gained insight into psychosocial issues of HCWs; support and therapies were offered to them. Positive messages labelling HCWs as “Heroes of the Pandemic” were circulated and structured programs developed to address their needs. With the advent of COVID-19 vaccine, a ray of hope emerged, although there are still apprehensions about its efficacy and side-effects. The whole world now eagerly awaits the calamity to perish while normality can rise from ashes.

Deep Tendon Reflex: The Tools and Techniques. What Surgical Neurology Residents Should Know

The deep tendon reflex (DTR) is a key component of the neurological examination. However, interpretation of the results is a challenge since there is a lack of knowledge on the important features of reflex responses such as the amount of hammer force, the strength of contraction, duration of the contraction and relaxation. The tools used to elicit the reflexes also play a role in the quality of the reflex contraction. Furthermore, improper execution techniques during the DTR assessment may alter the findings and cloud the true assessment of the nervous system. Therefore, understanding the basic principles and the key features of DTR allows for better interpretation of the reflex responses. This paper discusses the brief history of reflexes, the development of the reflex hammer, and also the key features of a reflex response encompassing the amplitude of force needed to elicit a reflex response, the velocity of contraction, the strength of contraction, and the duration of contraction and relaxation phases. The final section encloses the techniques of eliciting DTR in the upper extremities, trunk, and lower extremities, and the interpretation of these reflexes.