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Context: More studies are needed to compare the effect of voluntary contraction, electrical stimulation, and electrical stimulation superimposed onto voluntary contraction in improving trained and untrained homolog muscle strength and lower-extremity endurance. Design: Seventy-six healthy young adults (age = 20.41 [3.07] y, 61 females and 15 males) were included in the study. Subjects were randomly divided into 3 groups as voluntary isometric contraction (IC) group, Russian current (RC) group, and superimposed Russian current (SRC) group. Methods: All training regimens were performed under physiotherapist supervision for a total of 18 sessions (3 times per week for 6 wk). In each session, 10 ICs were achieved with voluntary isometric exercise only, RC only, or RC superimposed onto ICs. Main outcome measures were trained and untrained quadriceps strength (maximal voluntary isometric contraction [MVIC]) and lower-extremity endurance (sit-to-stand test). Results: After 6 weeks of training, all outcome measures improved in all groups (P P = .562). The trained quadriceps MVIC score (P η2 = .478), untrained quadriceps MVIC score (P = .011, η2 = .115), and sit-to-stand test score (P η2 = .357) differed significantly among the 3 groups; post hoc analysis revealed that the trained quadriceps MVIC score was higher in SRC and RC groups than in the IC group, untrained quadriceps MVIC score was higher in SRC group than in the RC group, and sit-to-stand test score was higher in SRC group than in the RC group and IC group. Conclusions: RC and RC superimposed onto IC are superior to IC in improving quadriceps muscle strength, and RC superimposed onto IC is superior to RC and IC in improving lower-extremity endurance. RC superimposed onto IC and voluntary IC created cross-education effect on untrained quadriceps.

We describe a scalp-recorded measure of tonotopic selectivity, the "cortical onset response" (COR) and compare the results between humans and cats. The COR results, in turn, were compared with psychophysical masked-detection thresholds obtained using similar stimuli and obtained from both species. The COR consisted of averaged responses elicited by 50-ms tone-burst probes presented at 1-s intervals against a continuous noise masker. The noise masker had a bandwidth of 1 or 1/8th octave, geometrically centred on 4000 Hz for humans and on 8000 Hz for cats. The probe frequency was either - 0.5, - 0.25, 0, 0.25 or 0.5 octaves re the masker centre frequency. The COR was larger for probe frequencies more distant from the centre frequency of the masker, and this effect was greater for the 1/8th-octave than for the 1-octave masker. This pattern broadly reflected the masked excitation patterns obtained psychophysically with similar stimuli in both species. However, the positive signal-to-noise ratio used to obtain reliable COR measures meant that some aspects of the data differed from those obtained psychophysically, in a way that could be partly explained by the upward spread of the probe's excitation pattern. Our psychophysical measurements also showed that the auditory filter width obtained at 8000 Hz using notched-noise maskers was slightly wider in cat than previous measures from humans. We argue that although conclusions from COR measures differ in some ways from conclusions based on psychophysics, the COR measures provide an objective, noninvasive, valid measure of tonotopic selectivity that does not require training and that may be applied to acoustic and cochlear-implant experiments in humans and laboratory animals. ispartof: JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY vol:23 issue:4 pages:513-534 ispartof: location:United States status: published

Introduction Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Neuropsychological assessment contributes to DBS treatment in several ways: it monitors the cognitive safety of the treatment, identifies beneficial or detrimental cognitive side effects and it could aid to explain variability in treatment outcome, and possibly the treatment's working mechanism(s). Background This systematic review assessed the cognitive safety of DBS for OCD and explored whether changes in cognitive function may help explain its working mechanism(s). Materials and Methods EMBASE, PubMed/Medline, Psycinfo, and the Cochrane Library were systematically searched for studies reporting cognitive outcomes following DBS for OCD. Searches were completed in November 2020. Included studies were appraised for study design and quality according to National Heart, Lung and Blood Institute (NHLBI) quality assessment tools. Results Five randomized controlled trials and ten observational studies comprising a total of 178 patients were analyzed collectively. Variable outcomes of DBS were observed in the domains of attention, memory, executive functioning, and in particular cognitive flexibility. Conclusion Although individual studies generally do not report cognitive deterioration after DBS for OCD, the variability of study designs and the multitude of cognitive measures used, precluded a meta-analysis to confirm its safety, and recognition of a cognitive pattern through which the efficacy of DBS for OCD might be explained. In future, prospective studies should preferably include a standardized neuropsychological assessment battery specifically addressing executive functioning and have a longer-term follow-up in order to demonstrate the cognitive safety of the procedure. Such prospective and more uniform data collection may also contribute to our understanding of the working mechanisms of DBS in OCD.

Alzheimer's disease (AD) is the most common type of dementia that causes disabilities in memory formation and activities of daily living. Unfortunately, pharmacologic treatments have minimal and short-lasting effects on AD. With the increasing aging population, investigations into therapeutic strategies for AD that lead to a delay in disease progression would significantly reduce the global burden of AD. Deep brain stimulation (DBS) is considered therapeutic for several conditions, such as movement disorders and some psychiatric diseases. Preclinical and clinical studies that used DBS as a treatment modality demonstrate the safety of DBS in AD and suggest potential memory improvements after surgery. Nevertheless, more studies are needed to understand the therapeutic mechanism of DBS. In this review, we summarize studies on DBS in various targets for AD and discuss DBS-induced changes in neurogenesis and pathological markers in AD.

Obsessive-compulsive disorder is among the most disabling psychiatric disorders. Although deep brain stimulation is considered an effective treatment, its use in clinical practice is not fully established. This is, at least in part, due to ambiguity about the best suited target and insufficient knowledge about underlying mechanisms. Recent advances suggest that changes in broader brain networks are responsible for improvement of obsessions and compulsions, rather than local impact at the stimulation site. These findings were fueled by innovative methodological approaches using brain connectivity analyses in combination with neuromodulatory interventions. Such a connectomic approach for neuromodulation constitutes an integrative account that aims to characterize optimal target networks. In this critical review, we integrate findings from connectomic studies and deep brain stimulation interventions to characterize a neural network presumably effective in reducing obsessions and compulsions. To this end, we scrutinize methodologies and seemingly conflicting findings with the aim to merge observations to identify common and diverse pathways for treating obsessive-compulsive disorder. Ultimately, we propose a unified network that-when modulated by means of cortical or subcortical interventions-alleviates obsessive-compulsive symptoms. https://doi.org/10.1016/j.biopsych.2021.07.010

Obsessive-compulsive disorder is among the most disabling psychiatric disorders. Although deep brain stimulation is considered an effective treatment, its use in clinical practice is not fully established. This is, at least in part, due to ambiguity about the best suited target and insufficient knowledge about underlying mechanisms. Recent advances suggest that changes in broader brain networks are responsible for improvement of obsessions and compulsions, rather than local impact at the stimulation site. These findings were fueled by innovative methodological approaches using brain connectivity analyses in combination with neuromodulatory interventions. Such a connectomic approach for neuromodulation constitutes an integrative account that aims to characterize optimal target networks. In this critical review, we integrate findings from connectomic studies and deep brain stimulation interventions to characterize a neural network presumably effective in reducing obsessions and compulsions. To this end, we scrutinize methodologies and seemingly conflicting findings with the aim to merge observations to identify common and diverse pathways for treating obsessive-compulsive disorder. Ultimately, we propose a unified network that-when modulated by means of cortical or subcortical interventions-alleviates obsessive-compulsive symptoms. https://doi.org/10.1016/j.biopsych.2021.07.010

We report a novel forward-model implementation of the full reference tissue model (fFTRM) that addresses the fast-exchange approximation employed by the simplified reference tissue model (SRTM) by incorporating a non-zero dissociation time constant from the specifically bound compartment. The forward computational approach avoided errors associated with noisy and nonorthogonal basis functions using an inverse linear model. Compared to analysis by a multilinear single-compartment reference tissue model (MRTM), fFTRM provided improved accuracy for estimation of binding potentials at early times in the scan, with no worse reproducibility across sessions. To test the model's ability to identify small focal changes in binding potential using a within-scan challenge, we employed a nonhuman primate model of focal dopamine release elicited by deep brain microstimulation remote to ventral striatum (VST) during imaging by simultaneous PET and fMRI. The new model reported an unambiguously lateralized response in VST consistent with fMRI, whereas the MRTM-derived response was not lateralized and was consistent with simulations of model bias. The proposed model enabled better accuracy in PET [11C]raclopride displacement studies and may also facilitate challenges sooner after injection, thereby recovering some sensitivity lost to radioactive decay of the PET tracer. ispartof: JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM vol:42 issue:6 pages:1007-1019 ispartof: location:United States status: published

The amygdala is a key region in emotional regulation, which is often impaired in psychosis. However, it is unclear if amygdala dysfunction directly contributes to psychosis, or whether it contributes to psychosis through symptoms of emotional dysregulation. We studied the functional connectivity of amygdala subdivisions in patients with 22q11.2DS, a known genetic model for psychosis susceptibility. We investigated how dysmaturation of each subdivision’s connectivity contributes to positive psychotic symptoms and impaired tolerance to stress in deletion carriers.Longitudinally-repeated MRI scans from 105 patients with 22q11.2DS (64 at high-risk for psychosis and 37 with impaired tolerance to stress) and 120 healthy controls between the ages of 5 to 30 years were included. We calculated seed-based whole-brain functional connectivity for amygdalar subdivisions and employed a longitudinal multivariate approach to evaluate the developmental trajectory of functional connectivity across groups.Patients with 22q11.2DS presented a multivariate pattern of decreased basolateral amygdala (BLA)-frontal connectivity alongside increased BLA-hippocampal connectivity. Moreover, associations between developmental drops in centro-medial amygdala (CMA)-frontal connectivity to both impaired tolerance to stress and positive psychotic symptoms in deletion carriers were detected. SFA hyperconnectivity to the striatum was revealed as a specific pattern arising in patients who develop mild to moderate positive psychotic symptoms.Overall, CMA-frontal dysconnectivity was found as a mutual neurobiological substrate in both impaired tolerance to stress and psychosis, suggesting a role in prodromal dysregulation of emotions in psychosis. While BLA dysconnectivity was presented as an early finding in patients with 22q11.2DS, contributing to impaired tolerance to stress.

Objective. Meralgia paresthetica (MP) is a mononeuropathy of the exclusively sensory lateral femoral cutaneous nerve (LFCN) that is difficult to treat with conservative treatments. Afferents from the LFCN enter the spinal cord through the dorsal root entry zones (DREZs) innervating L2 and L3 spinal segments. We previously showed that epidural electrical stimulation of the spinal cord can be configured to steer electrical currents laterally in order to target afferents within individual DREZs. Therefore, we hypothesized that this neuromodulation strategy is suitable to target the L2 and L3 DREZs that convey afferents from the painful territory, and thus alleviates MP related pain. Approach. A patient in her mid-30s presented with a four year history of dysesthesia and burning pain in the anterolateral aspect of the left thigh due to MP that was refractory to medical treatments. We combined neuroimaging and intraoperative neuromonitoring to guide the surgical placement of a paddle lead over the left DREZs innervating L2 and L3 spinal segments. Main results. Optimized electrode configurations targeting the left L2 and L3 DREZs mediated immediate and sustained alleviation of pain. The patient ceased all other medical management, reported improved quality of life, and resumed recreational physical activities. Significance. We introduced a new treatment option to alleviate pain due to MP, and demonstrated how neuromodulation strategies targeting specific DREZs is effective to reduce pain confined to specific regions of the body while avoiding disconfort.

Alzheimer’s disease (AD) is the most common form of dementia. Although previous studies have selectively investigated the localization of amyloid-beta (Aβ) deposition in certain brain regions, a comprehensive characterization of the rostro-caudal distribution of Aβ plaques in the brain and their inter-regional correlation remain unexplored. Our results demonstrated remarkable working and spatial memory deficits in 9-month-old 5xFAD mice compared to wildtype mice. High Aβ plaque load was detected in the somatosensory cortex, piriform cortex, thalamus, and dorsal/ventral hippocampus; moderate levels of Aβ plaques were observed in the motor cortex, orbital cortex, visual cortex, and retrosplenial dysgranular cortex; and low levels of Aβ plaques were located in the amygdala, and the cerebellum; but no Aβ plaques were found in the hypothalamus, raphe nuclei, vestibular nucleus, and cuneate nucleus. Interestingly, the deposition of Aβ plaques was positively associated with brain inter-regions including the prefrontal cortex, somatosensory cortex, medial amygdala, thalamus, and the hippocampus. In conclusion, this study provides a comprehensive morphological profile of Aβ deposition in the brain and its inter-regional correlation. This suggests an association between Aβ plaque deposition and specific brain regions in AD pathogenesis.

In the last two decades, the focus of neurogenic dysphagia management has moved from passive compensatory strategies to evidence-based rehabilitative approaches. Advances in technology have enabled the development of novel treatment approaches such as neuromodulation techniques, which target the promotion of neurological reorganization for functional recovery of swallowing. Given the rapid pace of development in the field, this review aims to summarize the current findings on the effects of neuromodulation techniques on the human swallowing system and evaluate their therapeutic potential for neurogenic dysphagia. Implications for future clinical research and practical considerations for using neuromodulation in clinical practice will also be discussed. ispartof: DYSPHAGIA vol:38 issue:4 ispartof: location:United States status: published

This paper describes high-frequency nerve block experiments carried out on rat sciatic nerves to measure the speed of recovery of A fibres from block carryover. Block carryover is the process by which nerve excitability remains suppressed temporarily after High Frequency Alternative (HFAC) block is turned off following its application. In this series of experiments 5 rat sciatic nerves were extracted and prepared for ex-vivo stimulation and recording in a specially designed perfusion chamber. For each nerve repeated HFAC block and concurrent stimulation trials were carried out to observe block carryover after signal shutoff. The nerve was allowed to recover fully between each trial. Time to recovery from block was measured by monitoring for when relative nerve activity returned to within 90% of baseline levels measured at the start of each trial. HFAC block carryover duration was found to be dependent on accumulated dose by statistical test for two different HFAC durations. The carryover property of HFAC block on A fibres could enable selective stimulation of autonomic nerve fibres such as C fibres for the duration of carryover. Block carryover is particularly relevant to potential chronic clinical applications of block as it reduces power requirements for stimulation to provide the blocking effect. This work characterizes this process toward the creation of a model describing its behavior.

The noradrenergic locus coeruleus (LC) is a controller of brain and behavioral states. Activating LC neurons en masse by electrical or optogenetic stimulation promotes a stereotypical "activated" cortical state of high-frequency oscillations. However, it has been recently reported that spontaneous activity of LC cell pairs has sparse yet structured time-averaged cross-correlations, which is unlike the highly synchronous neuronal activity evoked by stimulation. Therefore, LC population activity could consist of distinct multicell ensembles each with unique temporal evolution of activity. We used nonnegative matrix factorization (NMF) to analyze large populations of simultaneously recorded LC single units in the rat LC. NMF identified ensembles of spontaneously coactive LC neurons and their activation time courses. Since LC neurons selectively project to specific forebrain regions, we hypothesized that distinct ensembles activate during different cortical states. To test this hypothesis, we calculated band-limited power and spectrograms of local field potentials in cortical area 24a aligned to spontaneous activations of distinct LC ensembles. A diversity of state modulations occurred around activation of different LC ensembles, including a typical activated state with increased highfrequency power as well as other states including decreased high-frequency power. Thus-in contrast to the stereotypical activated brain state evoked by en masse LC stimulation-spontaneous activation of distinct LC ensembles is associated with a multitude of cortical states.

Objective To evaluate the efficacy of magnetic stimulation (MStim) added to bladder training (BT) on incontinence-related quality of life (QoL) and clinical parameters in women with idiopathic overactive bladder (OAB). Material and Methods Seventy-six women with idiopathic OAB were randomized into two groups using the random numbers generator as follows: Group 1 received BT alone (n: 38), and Group 2 received BT + MStim (n: 38). MStim was performed with MStim therapy armchair (Novamag NT60), 2 days a week, 20 min a day, a total of 12 sessions for 6 weeks. Women were evaluated in terms of incontinence severity (24-h pad test), 3-day voiding diary (frequency of voiding, incontinence episodes, nocturia, and number of pads), symptom severity (OAB-V8), QoL (IIQ-7), positive response and cure-improvement rates, and treatment satisfaction (Likert scale) at the baseline and the end of treatment (sixth week). Results A statistically significant improvement was found in incontinence severity, frequency of voiding, incontinence episodes, nocturia, number of pads, symptom severity, and QoL parameters for two groups at the end of the treatment compared to the baseline values (p < 0.05). At the end of treatment; incontinence severity, incontinence episodes, nocturia, number of pads, symptom severity, and QoL were significantly improved in Group 2 compared to Group 1 (p < 0.05). No difference was found between the two groups in terms of frequency of voiding (p > 0.05). The positive response and cure-improvement rates, and treatment satisfaction were significantly higher in Group 2 than in Group 1 (p < 0.05). Conclusion MStim added to BT is more effective than BT alone in women with idiopathic OAB.

BackgroundTo date, the burden and severity of the full spectrum of bilateral vestibulopathy (BVP) symptoms has not yet been measured in a standardized manner. Since therapeutic interventions aiming to improve BVP symptoms are emerging, the need for a new standardized assessment tool that encompasses the specific aspects of BVP arises. Therefore, the aim of this study was to develop a multi-item Patient Reported Outcome Measure (PROM) that captures the clinically important symptoms of BVP and assesses its impact on daily life.MethodsThe development of the Bilateral Vestibulopathy Questionnaire (BVQ) consisted of two phases: (I) initial item generation and (II) face and content validity testing. Items were derived from a literature review and individual semi-structured interviews focusing on the full spectrum of reported BVP symptoms (I). Subsequently (IIa), individual patient interviews were conducted using “thinking aloud” and concurrent verbal probing techniques to assess the comprehensibility of the instructions, questions and response options, and the relevance, missing domains, or missing items. Interviews continued until saturation of input was reached. Finally, international experts with experience in the field of the physical, emotional, and cognitive symptoms of BVP participated in an online focus group to assess the relevance and comprehensiveness of the BVQ (IIb).ResultsThe BVQ consisted of two sections. The first section included 50 items scored on a six-point Likert scale arranged into seven constructs (i.e., imbalance, oscillopsia, other physical symptoms, cognitive symptoms, emotional symptoms, limitations and behavioral changes and social life). The second section consisted of four items, scored on a visual analog scale from 0 to 100, to inquire about limitations in daily life, perceived health and expectations regarding future recovery. Interviews with BVP patients [n= 8, 50% female, mean age 56 years (range 24–88 years)] and the expert meeting confirmed face and content validity of the developed BVQ.ConclusionThe BVQ, which was developed to assess the spectrum of BVP symptoms and its impact on daily life, proved to have good face and content validity. It can be used to characterize current self-reported symptoms and disability and to evaluate symptom burden before and after therapeutic interventions in future research and clinical practice.

Tinnitus is an auditory sensation in the absence of actual external stimulation. Different clinical interventions are used in tinnitus treatment, but only few patients respond to available options. The lack of successful tinnitus treatment is partly due to the limited knowledge about the mechanisms underlying tinnitus. Recently, the auditory part of the thalamus has gained attention as a central structure in the neuropathophysiology of tinnitus. Increased thalamic spontaneous firing rate, bursting activity and oscillations, alongside an increase of GABAergic tonic inhibition have been shown in the auditory thalamus in animal models of tinnitus. In addition, clinical neuroimaging studies have shown structural and functional thalamic changes with tinnitus. This review provides a systematic overview and discussion of these observations that support a central role of the auditory thalamus in tinnitus. Based on this approach, a neuromodulative treatment option for tinnitus is proposed.

Tinnitus is an auditory sensation in the absence of actual external stimulation. Different clinical interventions are used in tinnitus treatment, but only few patients respond to available options. The lack of successful tinnitus treatment is partly due to the limited knowledge about the mechanisms underlying tinnitus. Recently, the auditory part of the thalamus has gained attention as a central structure in the neuropathophysiology of tinnitus. Increased thalamic spontaneous firing rate, bursting activity and oscillations, alongside an increase of GABAergic tonic inhibition have been shown in the auditory thalamus in animal models of tinnitus. In addition, clinical neuroimaging studies have shown structural and functional thalamic changes with tinnitus. This review provides a systematic overview and discussion of these observations that support a central role of the auditory thalamus in tinnitus. Based on this approach, a neuromodulative treatment option for tinnitus is proposed.

Objective. Several lumped and distributed parameter models of the inner ear have been proposed to improve vestibular implant stimulation. The models should account for all significant physical phenomena that influence the current propagation, such as the electrical double layer (EDL) and medium polarization. The electrical properties of the medium are reflected in the electrical impedance; therefore, the study aimed to measure the impedance in the guinea pig inner ear and construct its equivalent circuit. Approach. The electrical impedance was measured from 100 Hz to 50 kHz between a pair of platinum electrodes immersed in 0.9% NaCl saline solution using sinusoidal voltage signals. The Randles circuit was fitted to the measured impedance in the saline solution in order to estimate the EDL parameters ( C , W , a n d R c t ) of the electrode interface in saline. Then, the electrical impedance was measured between all combinations of the electrodes located in the semicircular canal ampullae and the vestibular nerve in the guinea pig in vitro. The extended Randles circuit considering the medium polarization ( R i , R e , C m ) together with EDL parameters ( C , R c t ) obtained from the saline solution was fitted to the measured impedance of the guinea pig inner ear. The Warburg element was assumed negligible and was not considered in the guinea pig model. Main results. For the set-up used, the obtained EDL parameters were: C = 27.09 * 10 − 8 F , R c t = 18.75 k Ω . The average values of intra-, extracellular resistances, and membrane capacitance were R i = 4.74 k Ω , R e = 45.05 k Ω , C m = 9.69 * 10 − 8 F , respectively. Significance. The obtained values of the model parameters can serve as a good estimation of the EDL for modelling work. The EDL, together with medium polarization, plays a significant role in the electrical impedance of the guinea pig inner ear, therefore, they should be considered in electrical conductivity models to increase the credibility of the simulations.

Deep brain stimulation is used to alleviate symptoms of neurological and psychiatric disorders including Parkinson's disease, epilepsy, and obsessive-compulsive-disorder. Electrically stimulating limbic structures has been of great interest, and in particular, the region of the fornix. We conducted a systematic search for studies that reported clinical and preclinical outcomes of deep brain stimulation within the fornix up to July 2019. We identified 13 studies (7 clinical, 6 preclinical) that examined the effects of fornix stimulation in Alzheimer's disease (n = 9), traumatic brain injury (n = 2), Rett syndrome (n = 1), and temporal lobe epilepsy (n = 1). Overall, fornix stimulation can lead to decreased rates of cognitive decline (in humans), enhanced memory (in humans and animals), visuo-spatial memorization (in humans and animals), and improving verbal recollection (in humans). While the exact mechanisms of action are not completely understood, studies suggest fornix DBS to be involved with increased functional connectivity and neurotransmitter levels, as well as enhanced neuroplasticity.

Neuropathic pain is a complex, heterogeneous disorder that affects approximately 8% of the total adult human population and comes with significant burden for both the patient and health care system.13 The international association for the study of pain defines neuropathic pain as “pain caused by a lesion or disease of the somatosensory nervous system” and classifies chronic neuropathic pain as a disease under International Classification of Diseases 11th Revision (ICD-11).89 Despite the development and use of many pharmacological drugs and guidelines for the treatment of chronic neuropathic pain over the years,8 a substantial amount of neuropathic pain patients remain undertreated or untreated, with less than 50% of patients responding to pharmacological treatment.30 The development of novel, last-resort interventional treatment therapies is crucial to also relief pain in these refractory patients. Over the years, spinal cord stimulation (SCS) has proven to be a valuable last-resort treatment option (approximately 50% pain reduction in 50%-70% of patients) for a wide variety of refractory pain disorders, such as painful diabetic peripheral neuropathy (PDPN),22,94 complex regional pain syndrome (CRPS),42,43 and failed back surgery syndrome (FBSS).53,77 The mechanism underlying Tonic SCS (see section 2) is partly understood, and evidence has been provided for a mechanism of action through both spinal (section 2.1) and supraspinal levels (section 2.2). Recently, new physiological targets for stimulation as well as novel SCS paradigms were introduced to bridge the gap between currently achieved pain relief (as obtained with Tonic SCS) and the desired pain relief. Literature on the effect of stimulation at new anatomical locations, such as dorsal root ganglion stimulation (DRGS) (see section 3), and the use of new subsensory SCS paradigms such as high-frequency (HF) SCS (see section 4.2) and Burst SCS (see section 4.3) are discussed. This review ends with concluding remarks and future directions for research.

The objective is to review the literature related to lower urinary tract (LUT) conditions in children to conceptualize general practice guidelines for the general practitioner, pediatrician, pediatric urologist, and urologist. PubMed was searched for the last 15-year literature by the committee. All articles in peer-review journal-related LUT conditions (343) have been retrieved and 76 have been reviewed extensively. Prospective trials were few and the level of evidence was low. Most of the recommendations have been done by committee consensus after extensive discussion of literature reports. History taking is an integral part of evaluation assessing day- and nighttime urine and bowel control, urgency, and frequency symptoms. Exclusion of any neurogenic and organic cause is essential. Uroflowmetry and residual urine determination are recommended in all patients to evaluate bladder emptying. Urodynamic studies are reserved for refractory or complicated cases. Urotherapy that aims to educate the child and family about bladder and bowel function and guides them to achieve normal voiding and bowel habits should initially be employed in all cases except those who have urinary tract infections (UTI) and constipation. Specific medical treatment is added in the case of refractory overactive bladder symptoms and recurrent UTIs.Conclusion: Producing recommendations for managing LUTS in children based on high-quality studies is not possible. LUTS in children should be evaluated in a multimodal way by minimal invasive diagnostic procedures. Urotherapy is the mainstay of treatment and specific medical treatment is added in refractory cases.What is Known:• Symptoms of the lower urinary tract may have significant social consequences and sometimes clinical morbidities like urinary tract infections and vesicoureteral reflux. In many children, however, there is no such obvious cause for the incontinence, and they are referred to as having functional bladder problems.What is New:• This review aims to construct a practical recommendation strategy for the general practitioner, pediatrician, pediatric urologist, and urologist for LUTS in children. Producing recommendations for managing LUTS in children based on high-quality studies is not possible. LUTS in children should be evaluated in a multimodal way by minimal invasive diagnostic procedures. Urotherapy is the mainstay of treatment and specific medical treatment is added in refractory cases.

Primary Sjogren's syndrome is a complex systemic autoimmune disorder that primarily affects exocrine glands such as the lacrimal glands. Dry eye disease is one of the most prevalent complications of Sjogren's syndrome, affecting most patients. It significantly impairs quality of life and management is often difficult and unsatisfactory, in part due to weak correlation between symptoms and signs and poor recognition of the three main subtypes aqueous-deficient, evaporative and neuropathic dry eye. This review provides an overview of key aspects of dry eye disease, such as its multifactorial aetiology and recent insights into pathophysiology. The uses and pitfalls of commonly-used diagnostic tests for dry eye are reviewed, as well as the increasing number of new imaging technologies and biomarkers to refine diagnosis. There are many current and emerging treatment options for dry eye in Sjogren's syndrome, but high-level evidence of efficacy is mostly lacking, as are evidence-based treatment algorithms. All these aspects make the management of dry eye in Sjogren's syndrome challenging.

Primary Sjogren's syndrome is a complex systemic autoimmune disorder that primarily affects exocrine glands such as the lacrimal glands. Dry eye disease is one of the most prevalent complications of Sjogren's syndrome, affecting most patients. It significantly impairs quality of life and management is often difficult and unsatisfactory, in part due to weak correlation between symptoms and signs and poor recognition of the three main subtypes aqueous-deficient, evaporative and neuropathic dry eye. This review provides an overview of key aspects of dry eye disease, such as its multifactorial aetiology and recent insights into pathophysiology. The uses and pitfalls of commonly-used diagnostic tests for dry eye are reviewed, as well as the increasing number of new imaging technologies and biomarkers to refine diagnosis. There are many current and emerging treatment options for dry eye in Sjogren's syndrome, but high-level evidence of efficacy is mostly lacking, as are evidence-based treatment algorithms. All these aspects make the management of dry eye in Sjogren's syndrome challenging.

A milestone in vertebrate evolution, the transition from water to land, owes its success to the development of a sprawling body plan that enabled an amphibious lifestyle. The body, originally adapted for swimming, evolved to benefit from limbs that enhanced its locomotion capabilities on submerged and dry ground. The first terrestrial animals used sprawling locomotion, a type of legged locomotion in which limbs extend laterally from the body (as opposed to erect locomotion, in which limbs extend vertically below the body). This type of locomotion—exhibited, for instance, by salamanders, lizards, and crocodiles—has been studied in a variety of fields, including neuroscience, biomechanics, evolution, and paleontology. Robotics can benefit from these studies to design amphibious robots capable of swimming and walking, with interesting applications in field robotics, in particular for search and rescue, inspection, and environmental monitoring. In return, robotics can provide useful scientific tools to test hypotheses in neuroscience, biomechanics, and paleontology. For instance, robots have been used to test hypotheses about the organization of neural circuits that can switch between swimming and walking under the control of simple modulation signals, as well as to identify the most likely gaits of extinct sprawling animals. Here, I review different aspects of amphibious and sprawling locomotion, namely gait characteristics, neurobiology, numerical models, and sprawling robots, and discuss fruitful interactions between robotics and other scientific fields.

The cerebellum is recognised to bilaterally modulate sensorimotor function and has recently been shown to play a role in swallowing. Unilateral cerebellar repetitive trans-cranial magnetic stimulation (rTMS) excites corticobulbar motor pathways to the pharynx but the effects of bilateral versus unilateral cerebellar rTMS on these pathways are unknown. In this three-part cross-over study, healthy participants (n = 13) were randomly allocated to receive unilateral or bilateral 10 Hz cerebellar rTMS. Participants were intubated with pharyngeal electromyography and/or manometry catheters for motor evoked potentials (MEPs) and pressure recordings. In part 1 of the study, single pulse TMS was used to measure baseline motor cortical pharyngeal MEP (PMEP) and hemispheric cerebellar MEP (CMEP) amplitudes, before cerebellar rTMS was administered. Repeat measures of PMEP amplitude were performed at 15-min intervals for an hour post unilateral and bilateral rTMS. Thereafter, in two further studies, a cortical ‘virtual lesion’ (V/L) was applied prior to cerebellar rTMS with pre and post PMEPs (part 2) and measurements of swallowing accuracy (part 3) using a behavioural task. Compared to baseline, unilateral and bilateral cerebellar rTMS provoked increases in pharyngeal cortical excitation (P = 0.028, 0.0005, respectively). Bilateral rTMS was significantly more effective than unilateral in causing cortical excitation (P = 0.0005) and in reversing the suppressive neurological (P = 0.0005) and behavioural (P = 0.0005) effects of a cortical V/L. Our findings suggest bilateral cerebellar rTMS has greater facilitatory effects on corticobulbar motor pathways to the pharynx than unilateral stimulation with the potential to be a more effective clinical therapy if its effects are reproduced in populations with neurogenic dysphagia.

Background and Aim Standardizing evaluative outcomes and their assessment facilitates comparisons between clinical studies and provides a basis for comparing direct effects of different treatment options. The aim of this study was to systematically review types of outcomes and measurement instruments used in studies regarding treatment options for slow-transit constipation (STC) in adults. Methods In this systematic review of the literature, we searched MEDLINE, Embase, and PsycINFO from inception through February 2018, for papers assessing any STC treatment in adult patients. Outcomes were systematically extracted and categorized in domains using the conceptual framework of the Outcome Measures in Rheumatology filter 2.0. Outcome reporting was stratified by decade of publication, intervention, and study type. Results Forty-seven studies were included in this systematic review. Fifty-nine different types of outcomes were identified. The outcomes were structured in three core areas and 18 domains. The most commonly reported domains were defecation functions (94%), gastrointestinal transit (53%), and health-care service use (51%). The most frequently reported outcomes were defecation frequency (83%), health-related quality of life (43%), and adverse events and complications (43%). In 62% of the studies, no primary outcome was defined, whereas in two studies, more than one primary outcomes were selected. A wide diversity of measurement instruments was used to assess the reported outcomes. Conclusion Outcomes reported in studies on STC in adults are heterogeneous. A lack of standardization complicates comparisons between studies. Developing a core outcome set for STC in adults could contribute to standardization of outcome reporting in (future) studies.

Recent research has shown promising results for the development of a clinically feasible vestibular implant in the near future. However, correct electrode placement remains a challenge. It was shown that fluoroscopy was able to visualize the semicircular canal ampullae and electrodes, and guide electrode insertion in real time. Ninety-four percent of the 18 electrodes were implanted correctly (

Short-term muscle disuse has been reported to lower both postabsorptive and postprandial myofibrillar protein synthesis rates. This study assessed the impact of disuse on daily myofibrillar protein synthesis rates following short-term (2 and 7 days) muscle disuse under free living conditions. Thirteen healthy young men (age: 20 ± 1 yr; BMI: 23 ± 1 kg/m−2) underwent 7 days of unilateral leg immobilization via a knee brace, with the nonimmobilized leg acting as a control. Four days before immobilization participants ingested 400 mL of 70% deuterated water, with 50-mL doses consumed daily thereafter. Upper leg bilateral MRI scans and muscle biopsies were collected before and after 2 and 7 days of immobilization to determine quadriceps volume and daily myofibrillar protein synthesis rates. Immobilization reduced quadriceps volume in the immobilized leg by 1.7 ± 0.3 and 6.7 ± 0.6% after 2 and 7 days, respectively, with no changes in the control leg. Over the 1-wk immobilization period, myofibrillar protein synthesis rates were 36 ± 4% lower in the immobilized (0.81 ± 0.04%/day) compared with the control (1.26 ± 0.04%/day) leg ( P < 0.001). Myofibrillar protein synthesis rates in the control leg did not change over time ( P = 0.775), but in the immobilized leg they were numerically lower during the 0- to 2-day period (16 ± 6%, 1.11 ± 0.09%/day, P = 0.153) and were significantly lower during the 2- to 7-day period (44 ± 5%, 0.70 ± 0.06%/day, P < 0.001) when compared with the control leg. We conclude that 1 wk of muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates in healthy young men.

The objective is to review the literature related to lower urinary tract (LUT) conditions in children to conceptualize general practice guidelines for the general practitioner, pediatrician, pediatric urologist, and urologist. PubMed was searched for the last 15-year literature by the committee. All articles in peer-review journal-related LUT conditions (343) have been retrieved and 76 have been reviewed extensively. Prospective trials were few and the level of evidence was low. Most of the recommendations have been done by committee consensus after extensive discussion of literature reports. History taking is an integral part of evaluation assessing day- and nighttime urine and bowel control, urgency, and frequency symptoms. Exclusion of any neurogenic and organic cause is essential. Uroflowmetry and residual urine determination are recommended in all patients to evaluate bladder emptying. Urodynamic studies are reserved for refractory or complicated cases. Urotherapy that aims to educate the child and family about bladder and bowel function and guides them to achieve normal voiding and bowel habits should initially be employed in all cases except those who have urinary tract infections (UTI) and constipation. Specific medical treatment is added in the case of refractory overactive bladder symptoms and recurrent UTIs.Conclusion: Producing recommendations for managing LUTS in children based on high-quality studies is not possible. LUTS in children should be evaluated in a multimodal way by minimal invasive diagnostic procedures. Urotherapy is the mainstay of treatment and specific medical treatment is added in refractory cases.What is Known:• Symptoms of the lower urinary tract may have significant social consequences and sometimes clinical morbidities like urinary tract infections and vesicoureteral reflux. In many children, however, there is no such obvious cause for the incontinence, and they are referred to as having functional bladder problems.What is New:• This review aims to construct a practical recommendation strategy for the general practitioner, pediatrician, pediatric urologist, and urologist for LUTS in children. Producing recommendations for managing LUTS in children based on high-quality studies is not possible. LUTS in children should be evaluated in a multimodal way by minimal invasive diagnostic procedures. Urotherapy is the mainstay of treatment and specific medical treatment is added in refractory cases.

This opinion statement proposes a set of candidacy criteria for vestibular implantation of adult patients with bilateral vestibulopathy (BVP) in a research setting. The criteria include disabling chronic symptoms like postural imbalance, unsteadiness of gait and/or head movement-induced oscillopsia, combined with objective signs of reduced or absent vestibular function in both ears. These signs include abnormal test results recorded during head impulses (video head impulse test or scleral coil technique), bithermal caloric testing and rotatory chair testing (sinusoidal stimulation of 0.1 Hz). Vestibular implant (VI) implantation criteria are not the same as diagnostic criteria for bilateral vestibulopathy. The major difference between VI-implantation criteria and the approved diagnostic criteria for BVP are that all included vestibular tests of semicircular canal function (head impulse test, caloric test, and rotatory chair test) need to show significant impairments of vestibular function in the implantation criteria. For this, a two-step paradigm was developed. First, at least one of the vestibular tests needs to fulfill stringent criteria, close to those for BVP. If this is applicable, then the other vestibular tests have to fulfill a second set of criteria which are less stringent than the original criteria for BVP. If the VI-implantation is intended to excite the utricle and/or saccule (otolith stimulation), responses to cervical and ocular vestibular evoked myogenic potentials must be absent in addition to the above mentioned abnormalities of semicircular canal function. Finally, requirements for safe and potentially effective stimulation should be met, including implanting patients with BVP of peripheral origin only, and assessing possible medical and psychiatric contraindications.

ObjectiveThis study aimed to investigate (1) the patterns of vestibular impairment in bilateral vestibulopathy (BVP) and subsequently, the implications regarding patient eligibility for vestibular implantation, and (2) whether this pattern and severity of vestibular impairment is etiology dependent.MethodsA total of one hundred and seventy-three subjects from three tertiary referral centers in Europe were diagnosed with BVP according to the Bárány Society diagnostic criteria. The subjects underwent vestibular testing such as the caloric test, torsion swing test, video Head Impulse Test (vHIT) in horizontal and vertical planes, and cervical and/or ocular vestibular evoked myogenic potentials (c- and oVEMPs). The etiologies were split into idiopathic, genetic, ototoxicity, infectious, Menière's Disease, (head)trauma, auto-immune, neurodegenerative, congenital, and mixed etiology.ResultsThe caloric test and horizontal vHIT more often indicated horizontal semicircular canal impairment than the torsion swing test. The vHIT results showed significantly higher gains for both anterior canals compared with the horizontal and posterior canals (p < 0.001). The rates of bilaterally absent oVEMP responses were higher compared to the bilaterally absent cVEMP responses (p = 0.010). A total of fifty-four percent of the patients diagnosed with BVP without missing data met all three Bárány Society diagnostic test criteria, whereas 76% of the patients were eligible for implantation according to the vestibular implantation criteria. Regarding etiology, only horizontal vHIT results were significantly lower for trauma, neurodegenerative, and genetic disorders, whereas the horizontal vHIT results were significantly higher for Menière's Disease, infectious and idiopathic BVP. The exploration with hierarchical cluster analysis showed no significant association between etiology and patterns of vestibular impairment.ConclusionThis study showed that caloric testing and vHIT seem to be more sensitive for measuring vestibular impairment, whereas the torsion swing test is more suited for measuring residual vestibular function. In addition, no striking patterns of vestibular impairment in relation to etiology were found. Nevertheless, it was demonstrated that although the implantation criteria are stricter compared with the Bárány Society diagnostic criteria, still, 76% of patients with BVP were eligible for implantation based on the vestibular test criteria. It is advised to carefully examine every patient for their overall pattern of vestibular impairment in order to make well-informed and personalized therapeutic decisions.

The nervous system poses a grand challenge for integration with modern electronics and the subsequent advances in neurobiology, neuroprosthetics, and therapy which would become possible upon such integration. Due to its extreme complexity, multifaceted signaling pathways, and similar to 1 kHz operating frequency, modern complementary metal oxide semiconductor (CMOS) based electronics appear to be the only technology platform at hand for such integration. However, conventional CMOS-based electronics rely exclusively on electronic signaling and therefore require an additional technology platform to translate electronic signals into the language of neurobiology. Organic electronics are just such a technology platform, capable of converting electronic addressing into a variety of signals matching the endogenous signaling of the nervous system while simultaneously possessing favorable material similarities with nervous tissue. In this review, we introduce a variety of organic material platforms and signaling modalities specifically designed for this role as "translator" , focusing especially on recent implementation in in vivo neuromodulation. We hope that this review serves both as an informational resource and as an encouragement and challenge to the field. Funding Agencies|Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research; Swedish Research CouncilSwedish Research CouncilEuropean Commission; European Research Council (ERC)European Research Council (ERC)European Commission; Onnesjo Foundation; ERC under the European Union [949191]; Swedish Government Strategic Research Area in Materials Science on Advanced Functional Materials at Linkoping University [2009-00971]

Modulation of neuronal activity for seizure control using various methods of neurostimulation is a rapidly developing field in epileptology, especially in treatment of refractory epilepsy. Promising results in human clinical practice, such as diminished seizure burden, reduced incidence of sudden unexplained death in epilepsy, and improved quality of life has brought neurostimulation into the focus of veterinary medicine as a therapeutic option. This article provides a comprehensive review of available neurostimulation methods for seizure management in drug-resistant epilepsy in canine patients. Recent progress in non-invasive modalities, such as repetitive transcranial magnetic stimulation and transcutaneous vagus nerve stimulation is highlighted. We further discuss potential future advances and their plausible application as means for preventing epileptogenesis in dogs.

Dysphagia is a common and devastating complication following brain damage. Over the last 2 decades, dysphagia treatments have shifted from compensatory to rehabilitative strategies that facilitate neuroplasticity, which is the reorganization of neural networks that is essential for functional recovery. Moreover, there is growing interest in the application of cortical and peripheral neurostimulation to promote such neuroplasticity. Despite some preliminary positive findings, the variability in responsiveness toward these treatments remains substantial. The purpose of this review is to summarize findings on the effects of neurostimulation in promoting neuroplasticity for dysphagia rehabilitation and highlight the need to develop more effective treatment strategies. We then discuss the role of metaplasticity, a homeostatic mechanism of the brain to regulate plasticity changes, in helping to drive neurorehabilitation. Finally, a hypothesis on how metaplasticity could be applied in dysphagia rehabilitation to enhance treatment outcomes is proposed. ispartof: NEUROLOGICAL SCIENCES vol:43 issue:1 pages:199-209 ispartof: location:Italy status: published

Contains fulltext : 288348.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Neuropsychological assessment contributes to DBS treatment in several ways: it monitors the cognitive safety of the treatment, identifies beneficial or detrimental cognitive side effects, and it could aid to explain variability in treatment outcome, and possibly the treatment's working mechanism(s). BACKGROUND: This systematic review assessed the cognitive safety of DBS for OCD and explored whether changes in cognitive function may help explain its working mechanism(s). MATERIALS AND METHODS: EMBASE, PubMed/Medline, Psycinfo, and the Cochrane Library were systematically searched for studies reporting cognitive outcomes following DBS for OCD. Searches were completed in November 2020. Included studies were appraised for study design and quality according to National Heart, Lung, and Blood Institute (NHLBI) quality assessment tools. RESULTS: Five randomized controlled trials and ten observational studies comprising a total of 178 patients were analyzed collectively. Variable outcomes of DBS were observed in the domains of attention, memory, executive functioning, and in particular, cognitive flexibility. CONCLUSION: Although individual studies generally do not report cognitive deterioration after DBS for OCD, the variability of study designs and the multitude of cognitive measures used precluded a meta-analysis to confirm its safety and recognition of a cognitive pattern through which the efficacy of DBS for OCD might be explained. In the future, prospective studies should preferably include a standardized neuropsychological assessment battery specifically addressing executive functioning and have a longer-term follow-up in order to demonstrate the cognitive safety of the procedure. Such prospective and more uniform data collection may also contribute to our understanding of the working mechanisms of DBS in OCD.

The ideal treatment for overactive bladder is still elusive. In those where medication fails to improve symptoms options include invasive treatments such as botulinum toxin-A, sacral neural stimulation or posterior tibial nerve stimulation. Scientific professional society guidelines advise percutaneous posterior tibial nerve stimulation as a third line treatment option only after multi-disciplinary team review as well as failure of both conservative and pharmacological management. The aim of this article is to review all techniques for tibial nerve stimulation and their efficacy.

Objective: The increase in voluntary force of an untrained limb (i.e. Cross-education) after unilateral resistance training (RT) is believed to be a consequence of cortical adaptations. However, studies measuring neurophysiological adaptations with transcranial magnetic stimulation (TMS) found inconsistent results. One unexamined factor contributing to the conflicting data is the variation in the type and intensity of muscle contractions, fatigue, and the strategies of pacing the movement. Therefore, the purpose was to analyse how those unilateral RT variables affect the adaptations in ipsilateral M1 (iM1) and cross-education.Methods: We performed a systematic literature review, with the following search terms with Boolean conjunctions: "Transcranial magnetic stimulation" AND "Ipsilateral cortex" AND "Resistance training".Results: The 11 acute and 12 chronic studies included partially support the idea of increased cortical excitability and reduced intracortical inhibition in iM1, but the inconsistency between studies was high.Conclusions: Differences in type and intensity of contraction, fatigue, and strategies of pacing the movement contributed to the inconsistencies. The tentative conclusion is that high intensity eccentric or externally paced contractions are effective to increase iM1 excitability but cross-education can occur in the absence of such changes. Thus, the mechanism of the cross-education examined with TMS remains unclear. (C) 2019 Elsevier Ltd. All rights reserved.

Objective: The increase in voluntary force of an untrained limb (i.e. Cross-education) after unilateral resistance training (RT) is believed to be a consequence of cortical adaptations. However, studies measuring neurophysiological adaptations with transcranial magnetic stimulation (TMS) found inconsistent results. One unexamined factor contributing to the conflicting data is the variation in the type and intensity of muscle contractions, fatigue, and the strategies of pacing the movement. Therefore, the purpose was to analyse how those unilateral RT variables affect the adaptations in ipsilateral M1 (iM1) and cross-education. Methods: We performed a systematic literature review, with the following search terms with Boolean conjunctions: "Transcranial magnetic stimulation" AND "Ipsilateral cortex" AND "Resistance training". Results: The 11 acute and 12 chronic studies included partially support the idea of increased cortical excitability and reduced intracortical inhibition in iM1, but the inconsistency between studies was high. Conclusions: Differences in type and intensity of contraction, fatigue, and strategies of pacing the movement contributed to the inconsistencies. The tentative conclusion is that high intensity eccentric or externally paced contractions are effective to increase iM1 excitability but cross-education can occur in the absence of such changes. Thus, the mechanism of the cross-education examined with TMS remains unclear. (C) 2019 Elsevier Ltd. All rights reserved.

Electroresponsive hydrogels possess a conducting material component and respond to electric stimulation through reversible absorption and expulsion of water. The high level of hydration, soft elastomeric compliance, biocompatibility, and enhanced electrochemical properties render these hydrogels suitable for implantation in the brain to enhance the transmission of neural electric signals and ion transport. This review provides an overview of critical electroresponsive hydrogel properties for augmenting electric stimulation in the brain. A background on electric stimulation in the brain through electroresponsive hydrogels is provided. Common conducting materials and general techniques to integrate them into hydrogels are briefly discussed. This review focuses on and summarizes advances in electric stimulation of electroconductive hydrogels for therapeutic applications in the brain, such as for controlling delivery of drugs, directing neural stem cell differentiation and neurogenesis, improving neural biosensor capabilities, and enhancing neural electrode-tissue interfaces. The key challenges in each of these applications are discussed and recommendations for future research are also provided. Accepted version