Ventral Stimulation Research Articles

Ventral tegmental area deep brain stimulation for chronic cluster headache: Effects on cognition, mood, pain report behaviour and quality of life.

Deep brain stimulation in the ventral tegmental area (VTA-DBS) has provided remarkable therapeutic benefits in decreasing headache frequency and severity in patients with medically refractory chronic cluster headache (CH). However, to date the effects of VTA-DBS on cognition, mood and quality of life have not been examined in detail. The aim of the present study was to do so in a case series of 18 consecutive patients with cluster headache who underwent implantation of deep brain stimulation electrodes in the ventral tegmental area. The patients were evaluated preoperatively and after a mean of 14 months of VTA-DBS on tests of global cognition (Mini Mental State Examination), intelligence (Wechsler Abbreviated Scale of Intelligence), verbal memory (California Verbal Learning Test-II), executive function (Delis-Kaplan Executive Function System), and attention (Paced Auditory Serial Addition Test). Depression (Beck Depression Inventory and Hospital Anxiety and Depression Rating Scale-D), anxiety (Hospital Anxiety and Depression Rating Scale-A), apathy (Starkstein Apathy Scale), and hopelessness (Beck Hopelessness Scale) were also assessed. Subjective pain experience (McGill Pain Questionnaire), behaviour (Pain Behaviour Checklist) and quality of life (Short Form-36) were also evaluated at the same time points. VTA-DBS resulted in significant improvement of headache frequency (from a mean of five to two attacks daily, p < .001) and severity (from mean Verbal Rating Scale [VRS] of 10 to 7, p < .001) which was associated with significant reduction of anxiety (from mean HADS-A of 11.94 to 8.00, p < .001) and help-seeking behaviours (from mean PBC of 4.00 to 2.61, p < .001). VTA-DBS did not produce any significant change to any tests of cognitive function and any other outcome measures (BDI, HADS-D, SAS, BHS, McGill Pain Questionnaire, Short Form-36). We confirm the efficacy of VTA-DBS in the treatment of medically refractory chronic cluster headache. The reduction of headache frequency and severity was associated with a significant reduction of anxiety. Furthermore, the result suggests that VTA-DBS for chronic cluster headache improves pain-related help-seeking behaviours and does not produce any change in cognition.

A direct comparison of ventral capsule and anteromedial subthalamic nucleus stimulation in obsessive compulsive disorder: clinical and imaging evidence for dissociable Effects

A direct comparison of ventral capsule and anteromedial subthalamic nucleus stimulation in obsessive compulsive disorder: clinical and imaging evidence for dissociable Effects

Orthostatic Tremor: Pathophysiology Guiding Treatment.

Orthostatic tremor (OT) is a rare disorder characterized by tremor and a feeling of unsteadiness while standing that resolve upon walking or sitting. A pathognomonic 13-18Hz tremor is seen on surface EMG while standing. Though its clinical features have been better defined over time, much of its pathophysiology remains unknown and treatment options are limited. We review here recent developments in both of these areas. Several recent studies have furthered our understanding of the central oscillatory network involved in OT. fMRI and 18F-FDG-PET studies have identified a ponto-cerebello-thalamo-cortical network underlying OT, though the nature of its dysfunction remains unknown. Randomized trials of treatments for OT are few, so most data are from case reports or small case series. Clonazepam and gabapentin are likely the most effective medical therapies, while bilateral ventral intermediate nucleus deep brain stimulation shows promise for refractory cases. Though much about OT remains unknown, our understanding of its pathophysiology has improved through recent studies. Treatment benefit is overall modest and inconsistent, though better understanding of the disease could lead to new avenues for treatment.

Physiological mechanisms of thalamic ventral intermediate nucleus stimulation for tremor suppression.

Ventral intermediate thalamic deep brain stimulation is a standard therapy for the treatment of medically refractory essential tremor and tremor-dominant Parkinson's disease. Despite the therapeutic benefits, the mechanisms of action are varied and complex, and the pathophysiology and genesis of tremor remain unsubstantiated. This intraoperative study investigated the effects of high frequency microstimulation on both neuronal firing and tremor suppression simultaneously. In each of nine essential tremor and two Parkinson's disease patients who underwent stereotactic neurosurgery, two closely spaced (600 µm) microelectrodes were advanced into the ventral intermediate nucleus. One microelectrode recorded action potential firing while the adjacent electrode delivered stimulation trains at 100 Hz and 200 Hz (2-5 s, 100 µA, 150 µs). A triaxial accelerometer was used to measure postural tremor of the contralateral hand. At 200 Hz, stimulation led to 68 ± 8% (P < 0.001) inhibition of neuronal firing and a 53 ± 5% (P < 0.001) reduction in tremor, while 100 Hz reduced firing by 26 ± 12% (not significant) with a 17 ± 6% (P < 0.05) tremor reduction. The degree of cell inhibition and tremor suppression were significantly correlated (P < 0.001). We also found that the most ventroposterior stimulation sites, closest to the border of the ventral caudal nucleus, had the best effect on tremor. Finally, prior to the inhibition of neuronal firing, microstimulation caused a transient driving of neuronal activity at stimulus onset (61% of sites), which gave rise to a tremor phase reset (73% of these sites). This was likely due to activation of the excitatory glutamatergic cortical and cerebellar afferents to the ventral intermediate nucleus. Temporal characteristics of the driving responses (duration, number of spikes, and onset latency) significantly differed between 100 Hz and 200 Hz stimulation trains. The subsequent inhibition of neuronal activity was likely due to synaptic fatigue. Thalamic neuronal inhibition seems necessary for tremor reduction and may function in effect as a thalamic filter to uncouple thalamo-cortical from cortico-spinal reflex loops. Additionally, our findings shed light on the gating properties of the ventral intermediate nucleus within the cerebello-thalamo-cortical tremor network, provide insight for the optimization of deep brain stimulation technologies, and may inform controlled clinical studies for assessing optimal target locations for the treatment of tremor.

Activation of the rat olfactory bulb by direct ventral stimulation after nerve transection.

The aim of this study was to demonstrate how direct electrical stimulation can activate the olfactory bulb after denervation of the olfactory nerve input. Sprague-Dawley rats (n = 5) were anesthetized and olfactory bulbs exposed. Olfactory nerves were transected by passing a Teflon blade between the cribriform plate and ventral surface of the bulb. A cochlear implant electrode array was used to stimulate 6 different positions along the ventral surface of the olfactory bulb. Biphasic constant-current pulses were used (50-1000 μA, 50-1000 μs) to stimulate the bulb, and a 16-electrode paddle array was used to record localized negative field potential responses at the dorsal surface of the bulb. Localized negative field potentials were reliably obtained using biphasic, 500-μA, 200-μs pulses. A shift in stimulating position by 1 mm resulted in a significant change in the dorsal field potential. Direct stimulation of the deafferented olfactory bulb was effective in generating localized field potential responses. These findings support the potential use of direct electrical stimulation for the treatment of anosmia.

Electrophysiologic Mapping of Cortical Networks Activated by Dorsal vs. Ventral Subthalamic Nucleus Deep Brain Stimulation (P4.054)

Electrophysiologic Mapping of Cortical Networks Activated by Dorsal vs. Ventral Subthalamic Nucleus Deep Brain Stimulation (P4.054)

Holmes' Tremor with Shoulder Pain Treated by Deep Brain Stimulation of Unilateral Ventral Intermediate Thalamic Nucleus and Globus Pallidus Internus.

A 21-year-old male was admitted with severe right arm and hand tremors after a thalamic hemorrhage caused by a traffic accident. He was also suffering from agonizing pain in his right shoulder that manifested after the tremor. Neurologic examination revealed a disabling, severe, and irregular kinetic and postural tremor in the right arm during target-directed movements. There was also an irregular ipsilateral rest tremor and dystonic movements in the distal part of the right arm. The amplitude was moderate at rest and extremely high during kinetic and intentional movements. The patient underwent left globus pallidum internus and ventral intermediate thalamic nucleus deep brain stimulation. The patient improved by more than 80% as rated by the Fahn-Tolosa-Marin Tremor Rating Scale and Visual Analog Scale six months after surgery.

Ventral tegmental area deep brain stimulation in refractory short-lasting unilateral neuralgiform headache attacks.

SEE LEONE AND PROIETTI CECCHINI DOI101093/AWW233 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Short-lasting unilateral neuralgiform headache attacks are primary headache disorders characterized by short-lasting attacks of unilateral pain accompanied by autonomic features. A small minority are refractory to medical treatment. Neuroimaging studies have suggested a role of the posterior hypothalamic region in their pathogenesis. Previous case reports on deep brain stimulation of this region, now understood to be the ventral tegmental area, for this disorder are limited to a total of three patients. We present a case series of 11 new patients treated with ventral tegmental area deep brain stimulation in an uncontrolled, open-label prospective observational study. Eleven patients with refractory short-lasting unilateral neuralgiform headache attacks underwent ipsilateral ventral tegmental area deep brain stimulation in a specialist unit. All patients had failed, or been denied access to, occipital nerve stimulation within the UK's National Health Service. Primary endpoint was change in mean daily attack frequency at final follow-up. Secondary outcomes included attack severity, attack duration, headache load (a composite score of attack frequency, severity and duration), quality of life measures, disability and affective scores. Information was also collected on adverse events. Eleven patients (six male) with a median age of 50 years (range 26-67) were implanted between 2009 and 2014. Median follow-up was 29 months (range 7-63). At final follow-up the median improvement in daily attack frequency was 78% (interquartile range 33%). Response rate (defined as at least a 50% improvement in daily attack frequency) was 82% and four patients were rendered pain-free for prolonged periods of time. Headache load improved by 99% (interquartile range 52%). Improvements were observed in a number of quality of life, disability and affect measures. Adverse events included mild incision site pain, subcutaneous displacement of the implantable pulse generator, transient oscillopsia and minor wound infection. One patient required removal of the system due to wound infection. Ventral tegmental area deep brain stimulation may be an effective treatment option for refractory short-lasting unilateral neuralgiform headache attack patients who have failed other therapies.

A systematic investigation of the differential roles for ventral tegmentum serotonin 1- and 2-type receptors on food intake in the rat

Central serotonin (5-HT) pathways are known to influence feeding and other ingestive behaviors. Although the ventral tegmentum is important for promoting the seeking and consumption of food and drugs of abuse, the roles of 5-HT receptor subtypes in this region on food intake have yet to be comprehensively examined. In these experiments, food restricted rats were given 2-h access to rat chow; separate groups of non-restricted animals had similar access to a sweetened fat diet. Feeding and locomotor activity were monitored following ventral tegmentum stimulation or blockade of 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, or 5-HT2C receptors. 5-HT1A receptor stimulation transiently inhibited rearing behavior and chow intake in food-restricted rats, and had a biphasic effect on non-restricted rats offered the palatable diet. 5-HT1B receptor agonism transiently inhibited feeding in restricted animals, but did not affect intake of non-restricted rats. In contrast, 5-HT1B receptor antagonism decreased palatable feeding. Although stimulation of ventral tegmental 5-HT2B receptors with BW723C86 did not affect hunger-driven food intake, it significantly affected palatable feeding, with a trend for an increasing intake at 2.0µg/side but not at 5.0µg/side. Antagonism of the same receptor modestly but significantly inhibited feeding of the palatable diet at 5.0µg/side ketanserin. Neither stimulation nor blockade of 5-HT2A or 5-HT2C receptors caused prolonged effects on intake or locomotion. These data suggest that serotonin's effects on feeding within the ventral tegmentum depend upon the specific receptor targeted, as well as whether intake is motivated by food restriction or the palatable nature of the offered diet.

STN-DBS Reduces Saccadic Hypometria but Not Visuospatial Bias in Parkinson's Disease Patients.

In contrast to its well-established role in alleviating skeleto-motor symptoms in Parkinson's disease, little is known about the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on oculomotor control and attention. Eye-tracking data of 17 patients with left-hemibody symptom onset was compared with 17 age-matched control subjects. Free-viewing of natural images was assessed without stimulation as baseline and during bilateral DBS. To examine the involvement of ventral STN territories in oculomotion and spatial attention, we employed unilateral stimulation via the left and right ventralmost contacts respectively. When DBS was off, patients showed shorter saccades and a rightward viewing bias compared with controls. Bilateral stimulation in therapeutic settings improved saccadic hypometria but not the visuospatial bias. At a group level, unilateral ventral stimulation yielded no consistent effects. However, the evaluation of electrode position within normalized MNI coordinate space revealed that the extent of early exploration bias correlated with the precise stimulation site within the left subthalamic area. These results suggest that oculomotor impairments “but not higher-level exploration patterns” are effectively ameliorable by DBS in therapeutic settings. Our findings highlight the relevance of the STN topography in selecting contacts for chronic stimulation especially upon appearance of visuospatial attention deficits.

Bilateral Ventral Intermediate Nucleus Thalamic Deep Brain Stimulation in Orthostatic Tremor

Background: Orthostatic tremor (OT) is characterized by high-frequency leg tremor when standing still, resulting in a sense of imbalance, with limited treatment options. Ventral intermediate (Vim) nucleus thalamic deep brain stimulation (DBS) has been reported as beneficial in a few cases. Objective: To report clinical outcomes, lead locations, and stimulation parameters in 2 patients with severe medication-refractory OT treated with Vim DBS. Methods: The patients underwent surface electromyography (EMG) to confirm the OT diagnosis. Outcomes were measured as change in tolerated standing time at the last follow-up. Lead locations were quantified using postoperative MRI. Results: Vim DBS was well tolerated and resulted in improvement in standing time (patient 1: 50 s at baseline to 15 min 16 months after surgery; patient 2: 34 s at baseline to 4.2 min 7 months after surgery). Postoperative surface EMG for patient 1 demonstrated a delayed onset of tremor, lower-amplitude tremor, and periods of quiescence, but an unchanged tremor frequency. Conclusion: These cases provide further support for Vim DBS to improve standing time in severe medication-refractory OT. The location of the effective thalamic target for OT does not differ from the effective target for essential tremor.

The Allure of Transcutaneous Vagus Nerve Stimulation as a Novel Therapeutic Modality

The vagus nerve, running from the brainstem through the neck to many peripheral organs, functions as a bidirectional communication pathway between the brain and the body. Its name is a reflection of its widespread distribution throughout the body, as vagus means “wandering” in Latin. The vagus nerve regulates the function of the autonomic nervous system from its efferent projections from the brain to its innervated organs. The brain receives information from these organs by the afferent projections of the vagus. It has been estimated that about 80% of the fibers in the vagus nerve are afferent fibers. This estimation concerning afferent fibers provides the rationale for how stimulating the vagus nerve in the periphery can influence brain function and possibly diseases of the brain. Although afferent projections terminate in the nucleus tractus solitarius in the brainstem, there are direct and indirect ascending projections from the nucleus tractus solitarius to many areas of the brain involved in central autonomic regulation (e.g., midbrain, hypothalamus, and cortex). The nucleus tractus solitarius also sends projections to brain areas involved in mood and emotion, such as the amygdala and hippocampus, as well as the soma for noradrenergic and serotoninergic neurons (1). Human imaging studies show ventral nerve stimulation (VNS) to cause effects in both subcortical and cortical areas (2). Consistent with such results, long-term stimulation of the vagus nerve in rats, using clinically appropriate stimulating parameters, revealed widespread activation throughout the brain (3,4). There is evidence for the efficacy of VNS in several diseases of the brain. The US Food and Drug Administration approved the use of VNS for treatment-resistant epilepsy in 1997 and for treatment-resistant depression in 2005. VNS Therapy (Cyberonics, Inc., Houston, Texas) consists of surgically implanted coiled electrodes to the left vagus nerve. The electrodes are connected to a stimulator pack subcutaneously implanted in the chest area near the clavicle. The device is controlled via a handheld personal computer and can deliver specific intermittent electrical signals from the left vagus nerve to the brain. However, the necessity of surgery with the possibility of perioperative risks as well as the cost of the procedure has limited the widespread use of VNS. For these reasons, its approved use is limited to treatment-resistant depression. By contrast, transcutaneous vagus nerve stimulation (tVNS) makes use of the fact that the vagus nerve is distributed on the surface of the ear such that stimulation can be carried out without surgery. If effective, tVNS has the potential to increase greatly the use of VNS for patients with diseases such as depression, including patients who are not treatment resistant. Hein et al. (5) previously reported on a randomized shamcontrolled add-on study of short-term tVNS in 37 patients with depression, with all but one being treated with some

Dorsal periaqueductal gray simultaneously modulates ventral subiculum induced-plasticity in the basolateral amygdala and the nucleus accumbens.

The ventral subiculum of the hippocampus projects both to the basolateral amygdala (BLA), which is typically, associated with a response to aversive stimuli, as well as to the nucleus accumbens (NAcc), which is typically associated with a response to appetitive stimuli. Traditionally, studies of the responses to emotional events focus on either negative or positive affect-related processes, however, emotional experiences often affect both. The ability of high-level processing brain regions (e.g., medial prefrontal cortex) to modulate the balance between negative and positive affect-related regions was examined extensively. In contrast, the ability of low-level processing areas (e.g., periaqueductal gray—PAG) to do so, has not been sufficiently studied. To address whether midbrain structures have the ability to modulate limbic regions, we first examined the ventral subiculum stimulation’s (vSub) ability to induce plasticity in the BLA and NAcc simultaneously in rats. Further, dorsal PAG (dPAG) priming ability to differentially modulate vSub stimulation induced plasticity in the BLA and the NAcc was subsequently examined. vSub stimulation resulted in plasticity in both the BLA and the NAcc simultaneously. Moreover, depending on stimulus intensity, differential dPAG priming effects on LTP in these two regions were observed. The results demonstrate that negative and positive affect-related processes may be simultaneously modulated. Furthermore, under some conditions lower-level processing areas, such as the dPAG, may differentially modulate plasticity in these regions and thus affect the long-term emotional outcome of the experience.

Dopamine and glutamate interaction mediates reinstatement of drug-seeking behavior by stimulation of the ventral subiculum.

Background:Drug addiction is a chronic brain disease characterized by recurrent episodes of relapse to drug-seeking/-taking behaviors. The ventral subiculum, the primary output of the hippocampus, plays a critical role in mediating drug-seeking behavior.Methods:A d-amphetamine intravenous self-administration rat model was employed along with focal electrical stimulation of the ventral subiculum (20 Hz/200 pulses) to examine its role in reinstatement of drug-seeking behavior. Dopamine efflux in the nucleus accumbens was measured by in vivo microdialysis and subsequent HPLC-ED analyses. Pharmacological antagonism of dopamine and ionotropic glutamate receptors locally within the nucleus accumbens was employed to assess the role of glutamate and dopamine in reinstatement of drug-seeking behavior induced by stimulation of the ventral subiculum.Results:Here, we demonstrate that reinstatement of drug-seeking behavior following extinction of d-amphetamine self-administration by rats was induced by electrical stimulation in the ventral subiculum but not the cortex. This reinstatement was accompanied by a significant increase in dopamine efflux in the nucleus accumbens and was disrupted by microinfusion of a dopamine D1 or D2 antagonist into the nucleus accumbens. Inhibition of N-methyl-D-aspartate or non- N-methyl-D-aspartate receptors had no effect on the reinstatement induced by ventral subiculum stimulation, whereas co-infusion of D1 and N-methyl-D-aspartate antagonists at formerly ineffective doses prevented drug-seeking behavior.Conclusions:These data support the hypothesis that dopamine/glutamate interactions within the ventral striatum related to memory processes are involved in relapse to addictive behavior.

Frequency-dependent functional neuromodulatory effects on the motor network by ventral lateral thalamic deep brain stimulation in swine

Thalamic deep brain stimulation (DBS) is an FDA-approved neurosurgical treatment for medication-refractory essential tremor. Its therapeutic benefit is highly dependent upon stimulation frequency and voltage parameters. We investigated these stimulation parameter-dependent effects on neural network activation by performing functional magnetic resonance imaging (fMRI) during DBS of the ventral lateral (VL) thalamus and comparing the blood oxygenation level-dependent (BOLD) signals induced by multiple stimulation parameter combinations in a within-subject study of swine. Low (10Hz) and high (130Hz) frequency stimulation was applied at 3, 5, and 7V in the VL thalamus of normal swine (n=5). We found that stimulation frequency and voltage combinations differentially modulated the brain network activity in the sensorimotor cortex, the basal ganglia, and the cerebellum in a parameter-dependent manner. Notably, in the motor cortex, high frequency stimulation generated a negative BOLD response, while low frequency stimulation increased the positive BOLD response. These frequency-dependent differential effects suggest that the VL thalamus is an exemplary target for investigating functional network connectivity associated with therapeutic DBS.

Differences in Neural Circuitry Guiding Behavioral Responses to Polarized light Presented to Either the Dorsal or Ventral Retina in Drosophila

Linearly polarized light (POL) serves as an important cue for many animals, providing navigational information, as well as directing them toward food sources and reproduction sites. Many insects detect the celestial polarization pattern, or the linearly polarized reflections off of surfaces, such as water. Much progress has been made toward characterizing both retinal detectors and downstream circuit elements responsible for celestial POL vision in different insect species, yet much less is known about the neural basis of how polarized reflections are detected. We previously established a novel, fully automated behavioral assay for studying the spontaneous orientation response of Drosophila melanogaster populations to POL stimuli presented to either the dorsal, or the ventral halves of the retina. We identified separate retinal detectors mediating these responses: the ‘Dorsal Rim Area’ (DRA), which had long been implicated in celestial POL vision, as well as a previously uncharacterized ‘ventral polarization area’ (VPA). In this study, we investigate whether DRA and VPA use the same or different downstream circuitry, for mediating spontaneous behavioral responses. We use homozygous mutants, or molecular genetic circuit-breaking tools (silencing, as well as rescue of synaptic activity), in combination with our behavioral paradigm. We show that responses to dorsal versus ventral stimulation involve previously characterized optic lobe neurons, like lamina monopolar cell L2 and medulla cell types Dm8/Tm5c. However, using different experimental conditions, we show that important differences exist between the requirement of these cell types downstream of DRA versus VPA. Therefore, while the neural circuits underlying behavioral responses to celestial and reflected POL cues share important building blocks, these elements play different functional roles within the network.

Effect of Dorsal and Ventral Subthalamic Nucleus Deep Brain Stimulation on Actual and Perceived Sense of Postural Balance (P7.059)

Effect of Dorsal and Ventral Subthalamic Nucleus Deep Brain Stimulation on Actual and Perceived Sense of Postural Balance (P7.059)

Spinal Cord Stimulation for Visceral Pain—A Novel Approach

Spinal cord stimulation and dorsal column stimulation have been used successfully in the management of visceral pain for many years. A novel technique of ventral column stimulation has been used in our institute with good outcomes since 2007. We describe a retrospective series of 26 patients with visceral neuropathic pain who were treated with neuromodulation. Patients with either dermatomal hyperalgesia or sympathetically mediated neuropathic abdominal pain who had been treated with spinal cord stimulation were assessed. An independent observer conducted a face-to-face interview with each patient to collect data including demography, electrode placement, electrode mapping, and outcomes. There was significant reduction in visual analog pain scores from a median 9 at baseline to 4 at 26 months (p ≤ 0.05). Reduction in opioid consumption was very significant from a baseline median oral morphine equivalent of 160 mg to 26 mg (p < 0.001). In addition, quality of life, activities of daily living, and patient global impression of change improved. There is a need to further investigate the use of ventral stimulation for visceral pain syndromes. This would need multicenter trials to collect adequate numbers of patients to allow hypothesis testing to underpin recommendations for future evidence-based therapies.

Upper-limb muscle responses to epidural, subdural and intraspinal stimulation of the cervical spinal cord

Objective. Electrical stimulation of the spinal cord has potential applications following spinal cord injury for reanimating paralysed limbs and promoting neuroplastic changes that may facilitate motor rehabilitation. Here we systematically compare the efficacy, selectivity and frequency-dependence of different stimulation methods in the cervical enlargement of anaesthetized monkeys. Approach. Stimulating electrodes were positioned at multiple epidural and subdural sites on both dorsal and ventral surfaces, as well as at different depths within the spinal cord. Motor responses were recorded from arm, forearm and hand muscles. Main results. Stimulation efficacy increased from dorsal to ventral stimulation sites, with the exception of ventral epidural electrodes which had the highest recruitment thresholds. Compared to epidural and intraspinal methods, responses to subdural stimulation were more selective but also more similar between adjacent sites. Trains of stimuli delivered to ventral sites elicited consistent responses at all frequencies whereas from dorsal sites we observed a mixture of short-latency facilitation and long-latency suppression. Finally, paired stimuli delivered to dorsal surface and intraspinal sites exhibited symmetric facilitatory interactions at interstimulus intervals between 2–5 ms whereas on the ventral side interactions tended to be suppressive for near-simultaneous stimuli. Significance. We interpret these results in the context of differential activation of afferent and efferent roots and intraspinal circuit elements. In particular, we propose that distinct direct and indirect actions of spinal cord stimulation on motoneurons may be advantageous for different applications, and this should be taken into consideration when designing neuroprostheses for upper-limb function.

Biotechnology and Bioengineering: Volume 110, Number 12, December 2013

Cover Legend Myoblast align and differentiate preferentially upon dorsal and ventral stimulation in materials‐based sandwich‐like microenvironments. See related article by Salmerón‐Sánchez et. al., Biotechnology and Bioengineering, Volume 110, Number 11 (November 2013), pages 3048‐3058. (Image courtesy of José Ballester‐Beltrán and Prof. Manuel Salmerón‐Sánchez.) image