Motor and non-motor circuit disturbances in early Parkinson disease: which happens first?

For the last two decades, pathogenic concepts in Parkinson disease (PD) have revolved around the toxicity and spread of α-synuclein. Thus, α-synuclein would follow caudo-rostral propagation from the periphery to the central nervous system, first producing non-motor manifestations (such as constipation, sleep disorders and hyposmia), and subsequently impinging upon the mesencephalon to account for the cardinal motor features before reaching the neocortex as the disease evolves towards dementia. This model is the prevailing theory of the principal neurobiological mechanism of disease. Here, we scrutinize the temporal evolution of motor and non-motor manifestations in PD and suggest that, even though the postulated bottom-up mechanisms are likely to be involved, early involvement of the nigrostriatal system is a key and prominent pathophysiological mechanism. Upcoming studies of detailed clinical manifestations with newer neuroimaging techniques will allow us to more closely define, in vivo, the role of α-synuclein aggregates with respect to neuronal loss during the onset and progression of PD.

Efferent neurons control hearing sensitivity and protect hearing from noise through the regulation of gap junctions between cochlear supporting cells.

It is critical for hearing that the descending cochlear efferent system provides a negative feedback to hair cells to regulate hearing sensitivity and protect hearing from noise. The medial olivocochlear (MOC) efferent nerves project to outer hair cells (OHCs) to regulate OHC electromotility, which is an active cochlear amplifier and can increase hearing sensitivity. Here, we report that the MOC efferent nerves also could innervate supporting cells (SCs) in the vicinity of OHCs to regulate hearing sensitivity. MOC nerve fibers are cholinergic, and acetylcholine (ACh) is a primary neurotransmitter. Immunofluorescent staining showed that MOC nerve endings, presynaptic vesicular acetylcholine transporters (VAChTs), and postsynaptic ACh receptors were visible at SCs and in the SC area. Application of ACh in SCs could evoke a typical inward current and reduce gap junctions (GJs) between them, which consequently enhanced the direct effect of ACh on OHCs to shift but not eliminate OHC electromotility. This indirect, GJ-mediated inhibition had a long-lasting influence. In vivo experiments further demonstrated that deficiency of this GJ-mediated efferent pathway decreased the regulation of active cochlear amplification and compromised the protection against noise. In particular, distortion product otoacoustic emission (DPOAE) showed a delayed reduction after noise exposure. Our findings reveal a new pathway for the MOC efferent system via innervating SCs to control active cochlear amplification and hearing sensitivity. These data also suggest that this SC GJ-mediated efferent pathway may play a critical role in long-term efferent inhibition and is required for protection of hearing from noise trauma.NEW & NOTEWORTHY The cochlear efferent system provides a negative feedback to control hair cell activity and hearing sensitivity and plays a critical role in noise protection. We reveal a new efferent control pathway in which medial olivocochlear efferent fibers have innervations with cochlear supporting cells to control their gap junctions, therefore regulating outer hair cell electromotility and hearing sensitivity. This supporting cell gap junction-mediated efferent control pathway is required for the protection of hearing from noise.

Fluency shaping increases integration of the command-to-execution and the auditory-to-motor pathways in persistent developmental stuttering.

Fluency-shaping enhances the speech fluency of persons who stutter, yet underlying conditions and neuroplasticity-related mechanisms are largely unknown. While speech production-related brain activity in stuttering is well studied, it is unclear whether therapy repairs networks of altered sensorimotor integration, imprecise neural timing and sequencing, faulty error monitoring, or insufficient speech planning. Here, we tested the impact of one-year fluency-shaping therapy on resting-state fMRI connectivity within sets of brain regions subserving these speech functions. We analyzed resting-state data of 22 patients who participated in a fluency-shaping program, 18 patients not participating in therapy, and 28 fluent control participants, measured one year apart. Improved fluency was accompanied by an increased connectivity within the sensorimotor integration network. Specifically, two connections were strengthened; the left inferior frontal gyrus showed increased connectivity with the precentral gyrus at the representation of the left laryngeal motor cortex, and the left inferior frontal gyrus showed increased connectivity with the right superior temporal gyrus. Thus, therapy-associated neural remediation was based on a strengthened integration of the command-to-execution pathway together with an increased auditory-to-motor coupling. Since we investigated task-free brain activity, we assume that our findings are not biased to network activity involved in compensation but represent long-term focal neuroplasticity effects.

Dose-Dependent Pattern of Cochlear Synaptic Degeneration in C57BL/6J Mice Induced by Repeated Noise Exposure.

It is widely accepted that even a single acute noise exposure at moderate intensity that induces temporary threshold shift (TTS) can result in permanent loss of ribbon synapses between inner hair cells and afferents. However, effects of repeated or chronic noise exposures on the cochlear synapses especially medial olivocochlear (MOC) efferent synapses remain elusive. Based on a weeklong repeated exposure model of bandwidth noise over 2-20 kHz for 2 hours at seven intensities (88 to 106 dB SPL with 3 dB increment per gradient) on C57BL/6J mice, we attempted to explore the dose-response mechanism of prolonged noise-induced audiological dysfunction and cochlear synaptic degeneration. In our results, mice repeatedly exposed to relatively low-intensity noise (88, 91, and 94 dB SPL) showed few changes on auditory brainstem response (ABR), ribbon synapses, or MOC efferent synapses. Notably, repeated moderate-intensity noise exposures (97 and 100 dB SPL) not only caused hearing threshold shifts and the inner hair cell ribbon synaptopathy but also impaired MOC efferent synapses, which might contribute to complex patterns of damages on cochlear function and morphology. However, repeated high-intensity (103 and 106 dB SPL) noise exposures induced PTSs mainly accompanied by damages on cochlear amplifier function of outer hair cells and the inner hair cell ribbon synaptopathy, rather than the MOC efferent synaptic degeneration. Moreover, we observed a frequency-dependent vulnerability of the repeated acoustic trauma-induced cochlear synaptic degeneration. This study provides a sight into the hypothesis that noise-induced cochlear synaptic degeneration involves both afferent (ribbon synapses) and efferent (MOC terminals) pathology. The pattern of dose-dependent pathological changes induced by repeated noise exposure at various intensities provides a possible explanation for the complicated cochlear synaptic degeneration in humans. The underlying mechanisms remain to be studied in the future.

Low-frequency oscillations in cortical level to help diagnose task-specific dystonia.

Task-specific dystonia is a neurological movement disorder that abnormal contractions of muscles result in the twisting of fixed postures or muscle spasm during specific tasks. Due to the rareness and the pathophysiology of the disease, there is no test to confirm the diagnosis of task-specific dystonia, except comprehensive observations by the experts. Evidence from neural electrophysiological data suggests that enhanced low frequency (4-12 Hz) oscillations in the subcortical structure of the globus pallidus were associated with the pathological abnormalities concerning ß and γ rhythms in motor areas and motor cortical network in patients with task-specific dystonia. However, whether patients with task-specific dystonia have any low-frequency abnormalities in motor cortical areas remains unclear. In this study, we hypothesized that low-frequency abnormalities are present in core motor areas and motor cortical networks in patients with task-specific dystonia during performing the non-symptomatic movements and those low-frequency abnormalities can help the diagnosis of this disease. We tested this hypothesis by using EEG, effective connectivity analysis, and a machine learning method. Fifteen patients with task-specific dystonia and 15 healthy controls were recruited. The machine learning method identified 8 aberrant movement-related network connections concerning low frequency, ß and γ frequencies, which enabled the separation of the data of patients from those of controls with an accuracy of 90%. Importantly, 7 of the 8 aberrant connections engaged the premotor area contralateral to the affected hand, suggesting an important role of the premotor area in the pathological abnormities. The patients exhibited significantly lower low frequency activities during the movement preparation and significantly lower ß rhythms during movements compared with healthy controls in the core motor areas. Our findings of low frequency- and ß-related abnormalities at the cortical level and aberrant motor network could help diagnose task-specific dystonia in the clinical setting, and the importance of the contralesional premotor area suggests its diagnostic potential for task-specific dystonia.

Ipsilateral motor pathways to the lower limb after stroke: Insights and opportunities.

Stroke-related damage to the crossed lateral corticospinal tract causes motor deficits in the contralateral (paretic) limb. To restore functional movement in the paretic limb, the nervous system may increase its reliance on ipsilaterally descending motor pathways, including the uncrossed lateral corticospinal tract, the reticulospinal tract, the rubrospinal tract, and the vestibulospinal tract. Our knowledge about the role of these pathways for upper limb motor recovery is incomplete, and even less is known about the role of these pathways for lower limb motor recovery. Understanding the role of ipsilateral motor pathways to paretic lower limb movement and recovery after stroke may help improve our rehabilitative efforts and provide alternate solutions to address stroke-related impairments. These advances are important because walking and mobility impairments are major contributors to long-term disability after stroke, and improving walking is a high priority for individuals with stroke. This perspective highlights evidence regarding the contributions of ipsilateral motor pathways from the contralesional hemisphere and spinal interneuronal pathways for paretic lower limb movement and recovery. This perspective also identifies opportunities for future research to expand our knowledge about ipsilateral motor pathways and provides insights into how this information may be used to guide rehabilitation.

Acoustic Reflexes in Aural Atresia Patients: Evidence of an Intact Efferent System?

OBJECTIVE: To record crossed acoustic reflex thresholds (xART's) postoperatively from patients after surgical repair of unilateral congenital aural atresia (CAA). To seek explanations for when xARTs can and cannot be recorded. We hope to understand the implications for this central auditory reflex despite early afferent deprivation. METHODS: Patients who underwent surgery to correct unilateral CAA at a tertiary academic medical were prospectively enrolled to evaluate for the presence of xART. Preoperative ARTs in the normal (non-atretic) ear, and postoperative ipsilateral ARTs (stimulus in the normal ear) and contralateral ARTs (stimulus in the newly reconstructed atretic ear; record in the normal ear) were measured at 500, 1000, and 2000 Hz. RESULTS: Four of 11 patients with normal ipsilateral reflex thresholds preoperatively demonstrated crossed acoustic reflexes postoperatively (stimulus in reconstructed ear; record from normal ear). Four other patients demonstrated normal ipsilateral thresholds preoperatively but did not have crossed reflexes postoperatively. No reflexes (pre- or postoperatively) could be recorded in 3 patients. Crossed reflex threshold is significantly correlated with the postoperative audiometric threshold. There was no correlation between ipsilateral and contralateral reflex thresholds. CONCLUSION: Crossed acoustic reflexes can be recorded from some but not all postoperative atresia patients, and the thresholds for those reflexes correlate with the postoperative pure tone threshold. The presence of acoustic reflexes implies an intact CN VIII-to-opposite CN VII central reflex arc despite early unilateral sound deprivation.

Dynamic brain fluctuations outperform connectivity measures and mirror pathophysiological profiles across dementia subtypes: A multicenter study.

From molecular mechanisms to global brain networks, atypical fluctuations are the hallmark of neurodegeneration. Yet, traditional fMRI research on resting-state networks (RSNs) has favored static and average connectivity methods, which by overlooking the fluctuation dynamics triggered by neurodegeneration, have yielded inconsistent results. The present multicenter study introduces a data-driven machine learning pipeline based on dynamic connectivity fluctuation analysis (DCFA) on RS-fMRI data from 300 participants belonging to three groups: behavioral variant frontotemporal dementia (bvFTD) patients, Alzheimer's disease (AD) patients, and healthy controls. We considered non-linear oscillatory patterns across combined and individual resting-state networks (RSNs), namely: the salience network (SN), mostly affected in bvFTD; the default mode network (DMN), mostly affected in AD; the executive network (EN), partially compromised in both conditions; the motor network (MN); and the visual network (VN). These RSNs were entered as features for dementia classification using a recent robust machine learning approach (a Bayesian hyperparameter tuned Gradient Boosting Machines (GBM) algorithm), across four independent datasets with different MR scanners and recording parameters. The machine learning classification accuracy analysis revealed a systematic and unique tailored architecture of RSN disruption. The classification accuracy ranking showed that the most affected networks for bvFTD were the SN + EN network pair (mean accuracy = 86.43%, AUC = 0.91, sensitivity = 86.45%, specificity = 87.54%); for AD, the DMN + EN network pair (mean accuracy = 86.63%, AUC = 0.89, sensitivity = 88.37%, specificity = 84.62%); and for the bvFTD vs. AD classification, the DMN + SN network pair (mean accuracy = 82.67%, AUC = 0.86, sensitivity = 81.27%, specificity = 83.01%). Moreover, the DFCA classification systematically outperformed canonical connectivity approaches (including both static and linear dynamic connectivity). Our findings suggest that non-linear dynamical fluctuations surpass two traditional seed-based functional connectivity approaches and provide a pathophysiological characterization of global brain networks in neurodegenerative conditions (AD and bvFTD) across multicenter data.

Structural correlates of atypical visual and motor cortical oscillations in pediatric-onset multiple sclerosis.

We have previously demonstrated that pediatric-onset multiple sclerosis (POMS) negatively impacts the visual pathway as well as motor processing speed. Relationships between MS-related diffuse structural damage of gray and white matter (WM) tissue and cortical responses to visual and motor stimuli remain poorly understood. We used magnetoencephalography in 14 POMS patients and 15 age- and sex-matched healthy controls to assess visual gamma (30-80 Hz), motor gamma (60-90 Hz), and motor beta (15-30 Hz) cortical oscillatory responses to a visual-motor task. Then, 3T MRI was used to: (a) calculate fractional anisotropy (FA) of the posterior visual and corticospinal motor WM pathways and (b) quantify volume and thickness of the cuneus and primary motor cortex. Visual gamma band power was reduced in POMS and was associated with reduced FA of the optic radiations but not with loss of cuneus volume or thickness. Activity in the primary motor cortex, as measured by postmovement beta rebound amplitude associated with peak latency, was decreased in POMS, although this reduction was not predicted by structural metrics. Our findings implicate loss of WM integrity as a contributor to reduced electrical responses in the visual cortex in POMS. Future work in larger cohorts will inform on the cognitive implications of this finding in terms of visual processing function and will determine whether the progressive loss of brain volume known to occur in POMS ultimately contributes to both progressive dysfunction in such tasks as well as progressive reduction in cortical electrical responses in the visual cortex.

Neurophysiological impairments in multiple sclerosis-Central and peripheral motor pathways.

A systematic review of the literature was conducted comparing neurophysiological outcomes in persons with multiple sclerosis (PwMS) to healthy controls (HC), in studies of the central nervous system (CNS) function comprising motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) and in studies of the peripheral nervous system (PNS) function comprising electroneuronography (ENG) outcomes elicited by peripheral nerve stimulation. Studies comparing neuromuscular function, assessed during maximal voluntary contraction (MVC) of muscle, were included if they reported muscle strength along with muscle activation by use of electromyography (EMG) and/or interpolated twitch technique (ITT). Studies investigating CNS function showed prolonged central motor conduction times, asymmetry of nerve conduction motor pathways, and prolonged latencies in PwMS when compared to HC. Resting motor threshold, amplitude, and cortical silent periods showed conflicting results. CNS findings generally correlated with disabilities. Studies of PNS function showed near significant prolongation in motor latency of the median nerve, reduced nerve conduction velocities in the tibial and peroneal nerves, and decreased compound muscle action potential amplitudes of the tibial nerve in PwMS. ENG findings did not correlate with clinical severity of disabilities. Studies of neuromuscular function showed lower voluntary muscle activation and increased central fatigue in PwMS, whereas EMG showed divergent muscle activation (ie, EMG amplitude) during MVC. When comparing the existing literature on neurophysiological motor examinations in PwMS and HC, consistent and substantial impairments of CNS function were seen in PwMS, whereas impairments of the PNS were less pronounced and inconsistent. In addition, impairments in muscle activation were observed in PwMS.

Agent-dependent modulation of corticospinal excitability during painful transcutaneous electrical stimulation.

Pain has an inhibitory effect on the corticospinal excitability that has been interpreted as an evolutionary mechanism, directed to down-regulate cortical activity in order to facilitate rapid protective spinal reflexes. Here, we focused on the link between defensive mechanisms and motor system and we asked whether voluntary actions can modulate the corticospinal excitability during painful stimulations. To this aim, we manipulated the volition-related aspects of our paradigm by comparing conditions in which either the participant (self-generated action) or the experimenter (other-generated action) pressed the button to deliver painful high-intensity transcutaneous electric shocks to the right digit V. MEPs to TMS were recorded from the FDI and APB muscles of the stimulated hand. A compelling agent-dependent modulation of the corticospinal excitability was found, showing, in self-generated compared to other-generated actions, a significantly lower inhibitory effect, as measured by greater MEP amplitude. This finding suggests a top-down modulation of volitional actions on defensive mechanisms, promoting the view that predictive information from the motor system attenuates the responses to the foreseeable adverse events generated by one's own actions as compared to unpredictable events generated by someone else's actions.

Effects of injuries to descending motor pathways on restoration of gait in patients with pontine hemorrhage.

BACKGROUND AND PURPOSE: Gait disturbance due to injuries of the descending motor pathway, including corticospinal tract (CST), corticoreticular pathway (CRP), and medial and lateral vestibulospinal tracts (VSTs), are commonly encountered disabling sequelae of pontine hemorrhage. We investigated relations between changes in the CST, CRP, and medial and lateral VST and corresponding changes in gait function in patients with pontine hemorrhage. METHOD: Nine consecutive stroke patients with pontine hemorrhage, and 6 age-matched normal subjects were recruited. Four patients were allocated to group A (can't walk independently) and 5 to group B (can walk independently). Diffusion tensor imaging (DTI) data were acquired twice at acute to subacute stage and chronic stage after stroke onset. Diffusion tensor tractography (DTT) was used to reconstruct CST, CRP, medial and lateral VST. RESULT: The CRP shows a significantly different between groups A and B in both initial and follow up DTT (p > 0.05). In contrast, CST, medial VST and lateral VST did not show a significant difference (p > 0.05). Regarding DTI parameters of CRPs in group A, percentages of patients with fractional anisotropy (FA) and mean diffusivity (MD) values more than two standard deviation from normal were higher by follow up DTI than by initial DTI, however, the CRPs in group B only showed increased abnormal range of MD. CONCLUSIONS: The CST does not play an essential role in recovery of independent walking and vestibulospinal tracts may not crucially affect recovery of independent walking in patients with pontine hemorrhage. In contrast, and intact CRP or changes of the CRP integrity appear to be related to the recovery of gait function.

Neurophysiological and Biomechanical Evaluation of the Mechanisms Which Impair Safety of Swallow in Chronic Post-stroke Patients.

Oropharyngeal dysphagia (OD) is a common post-stroke complication and is associated with respiratory infections. The aim was to assess the biomechanical impairments in swallow function and the afferent and efferent swallowing pathways impairing swallow safety in chronic post-stroke patients. We studied 30 patients with unilateral stroke and chronic OD (> 3 months from stroke onset) with impaired safety of swallow (Penetration-Aspiration Scale [PAS] ≥ 2). We evaluated the efficacy, safety, and kinematics of the swallow response (residue, PAS, laryngeal vestibule closure time [LVCT]) with videofluoroscopy, sensory evoked potentials to pharyngeal electrical stimulation (pSEP), and pharyngeal motor evoked potentials (pMEP) to transcranial magnetic stimulation of both hemispheres. Mean age of patients was 70.1 ± 10.9 years (7 women). Stroke severity at onset was moderate (NIHSS median 10 [IQ range 3-11.5]), and modified Rankin Scale 2.8 ± 1.3. Mean PAS was 5.1 ± 1.9; prevalence of delayed LVCT was 86.7% and 30% presented aspirations. Pharyngeal hypoesthesia was present in 46.7% of patients and 92.3% showed abnormally asymmetrical pSEPs when comparing the ipsilesional with the contralesional hemisphere. Increased duration of swallow was associated with lower pSEP amplitude (P1-N2) in the contralesional hemisphere (p = 0.033). Patients with right hemispheric strokes showed greater reduction of pSEPs amplitude (N1-P1, p = 0.049). In contrast, pharyngeal resting motor threshold and pMEPs were symmetric in 73.3% patients without the physiologic hemispheric dominance. Mild-to-moderate disabled chronic post-stroke patients with OD presented severe impaired biomechanics of swallow response and high prevalence of aspirations. Initial results from the neurophysiological evaluation demonstrated prevalent impairments with disrupted integration of pharyngeal sensory inputs and reduced cortical excitability of efferent pathways. Patients with right hemispheric strokes showed poorer neurophysiological responses.

Novel method for restoration of anorectal function following spinal cord injury via nerve transfer in rats.

OBJECTIVES: Nerve transfer has been developed to restore partial function after serious nerve injuries, for example, restoring bladder control after spinal cord injury (SCI). Our aim here was to establish a preclinical proof-of-concept model using nerve transfer for restoring anorectal function after SCI. SETTING: We used laminectomy to model SCI, and bilateral spinal ventral and dorsal nerve root anastomosis to re-establish connectivity to the anorectal musculature. METHODS: Multidisciplinary methods were used to assess the anatomical and functional integrity of the alternative spinal-to-anorectal nerve circuit. Adult rats were used to establish the model. Bilateral anterior and posterior L5 nerve roots were surgically matched with anterior and posterior of S1 nerve roots by microscopic anastomosis to establish an artificial rectal reflex arc with complete sensory and motor pathways. Twelve weeks later, we used retrograde nerve tracing and neurohistomorphological analysis to assess anatomical integrity of the new artificial rectal reflex arc. Anorectal manometry was used to assess the function of the new nerve circuit. RESULTS: Retrograde tracing with recombinant attenuated pseudo rabies virus indicated that the new neural pathway was successfully established to the anorectal musculature after experimental SCI. Toluidine blue-stained sections of the anastomosis site revealed normal-appearing nerve fiber morphology and regeneration, and transmission electron microscopy revealed myelinated axons. Anorectal manometry revealed significant anorectal functional recovery. CONCLUSION: These results suggest that our model is a feasible first step in developing an alternative reflex pathway after laminectomy at L4 to S2 and shows promise for effective restoration of anorectal function.

Afferent-efferent connectivity between auditory brainstem and cortex accounts for poorer speech-in-noise comprehension in older adults.

Speech-in-noise (SIN) comprehension deficits in older adults have been linked to changes in both subcortical and cortical auditory evoked responses. However, older adults' difficulty understanding SIN may also be related to an imbalance in signal transmission (i.e., functional connectivity) between brainstem and auditory cortices. By modeling high-density scalp recordings of speech-evoked responses with sources in brainstem (BS) and bilateral primary auditory cortices (PAC), we show that beyond attenuating neural activity, hearing loss in older adults compromises the transmission of speech information between subcortical and early cortical hubs of the speech network. We found that the strength of afferent BS→PAC neural signaling (but not the reverse efferent flow; PAC→BS) varied with mild declines in hearing acuity and this "bottom-up" functional connectivity robustly predicted older adults' performance in a SIN identification task. Connectivity was also a better predictor of SIN processing than unitary subcortical or cortical responses alone. Our neuroimaging findings suggest that in older adults (i) mild hearing loss differentially reduces neural output at several stages of auditory processing (PAC > BS), (ii) subcortical-cortical connectivity is more sensitive to peripheral hearing loss than top-down (cortical-subcortical) control, and (iii) reduced functional connectivity in afferent auditory pathways plays a significant role in SIN comprehension problems.

Effects of type 1 diabetes mellitus on efferent auditory system in children and adolescents.

AIM: To investigate whether type 1 diabetes mellitus (T1DM) could affect the efferent auditory system by analyzing the relationship between the activation of the medial olivocochlear reflex with disease duration, metabolic control and age at time of diagnosis. METHOD: A total of 101 children and adolescents were evaluated. They were divided into two groups: 50 with T1DM and 51 without the disease. The participants answered a structured questionnaire containing questions about auditory complaints and were evaluated for tonal audiometry, tympanometry, acoustic reflex, otoacoustic emission by distortion product to evaluate the inhibitory effect of medial olivocochlear reflex (MOC). RESULTS: The participants with T1DM presented changed AR (increased or absent) at all the frequencies in both ears (p < 0.05) when compared with the group without the disease. No differences were found between the DPOAE amplitudes of the individuals with and without T1DM, in both ears at all the frequencies. There were significant differences in the activation of the MOC reflex between the groups with and without T1DM, the participants with T1DM presented the absence of the inhibitory effect of the DPOAE in the right and left ears, in the frequencies of 4000 Hz (p = 0.035/0.002respectively) and 6000 Hz (p = 0.033/0.031 respectively) and 8000 Hz (p = 0.007/0.001 respectively) when compared to the healthy group. Significant differences were also observed between the groups with and without T1DM (p < 0.05) for self-reported complaints of tinitus, difficulties with the perception of speech when there was noise and distraction with noise. No association was found between the hearing complaints and the audiological measurements obtained and disease time, metabolic control and age at the time of diagnosis. CONCLUSION: The findings suggest the presence of early auditory dysfunction of the efferent pathway in patients with T1DM.

Residual descending motor pathways influence spasticity after spinal cord injury.

OBJECTIVE: Spasticity is one of the most common symptoms manifested in humans with spinal cord injury (SCI). The neural mechanisms contributing to its development are not yet understood. Using neurophysiological and imaging techniques, we examined the influence of residual descending motor pathways on spasticity in humans with SCI. METHODS: We measured spasticity in 33 individuals with motor complete SCI (determined by clinical examination) without preservation of voluntary motor output in the quadriceps femoris muscle. To examine residual descending motor pathways, we used magnetic and electrical stimulation over the leg motor cortex to elicit motor evoked potentials (MEPs) in the quadriceps femoris muscle and structural magnetic resonance imaging to measure spinal cord atrophy. RESULTS: We found that 60% of participants showed symptoms of spasticity, whereas the other 40% showed no spasticity, demonstrating the presence of 2 clear subgroups of humans with motor complete SCI. MEPs were only present in individuals who had spasticity, and MEP size correlated with the severity of spasticity. Spinal cord atrophy was greater in nonspastic compared with spastic subjects. Notably, the degree of spared tissue in the lateral regions of the spinal cord was positively correlated with the severity of spasticity, indicating preservation of white matter related to motor tracts when spasticity was present. INTERPRETATION: These results support the hypothesis that preservation of descending motor pathways influences spasticity in humans with motor complete SCI; this knowledge might help the rehabilitation and assessment of people with SCI. ANN NEUROL 2019.

Gentle Perineal Skin Stimulation for Control of Nocturia.

One of the major causes of nocturia is overactive bladder (OAB). Somatic afferent nerve stimuli are used for treating OAB. However, clinical evidence for the efficacy of this treatment is insufficient due to the lack of appropriate control stimuli. Studies on anesthetized animals, which eliminate emotional factors and placebo effects, have demonstrated an influence of somatic stimuli on urinary bladder functions and elucidated the underlying mechanisms. In general, the effects of somatic stimuli are dependent on the modality, location, and physical characteristics of the stimulus. Recently we showed that gentle stimuli applied to the perineal skin using a soft elastomer roller inhibited micturition contractions to a greater extent than a roller with a hard surface. Studies aiming to elucidate the neural mechanisms of gentle stimulation-induced inhibition reported that 1-10 Hz discharges of low-threshold cutaneous mechanoreceptive Aß, Aδ, and C fibers evoked during stimulation with an elastomer roller inhibited the micturition reflex by activating the spinal cord opioid system, thereby reducing both ascending and descending transmission between bladder and pontine micturition center. The present review will provide a brief summary of (1) the effect of somatic electrical stimulation on the micturition reflex, (2) the effect of gentle mechanical skin stimulation on the micturition reflex, (3) the afferent, efferent, and central mechanisms underlying the effects of gentle stimulation, and (4) a translational clinical study demonstrating the efficacy of gentle skin stimuli for treating nocturia in the elderly with OAB by using the two roller types inducing distinct effects on rat micturition contractions. Anat Rec, 302:1824-1836, 2019. © 2019 American Association for Anatomy.

Assessment of the efferent auditory system in children with suspected auditory processing disorder: the Middle ear muscle reflex and contralateral inhibition of OAEs.

OBJECTIVE: To determine whether children aged 7 to 12 years with listening difficulties show objective evidence for efferent auditory function based on measurements of medial olivo-cochlear and middle ear muscle reflexes. DESIGN: Click-evoked otoacoustic emissions recorded with and without contralateral broadband noise and ipsilateral and contralateral tonal (1000, 2000 Hz) middle ear muscle reflex thresholds were examined. STUDY SAMPLE: 29 children diagnosed with suspected auditory processing disorder (APD) and a control group of 34 typically developing children participated in this study. RESULTS: Children with suspected APD had poorer performance on auditory processing tests than the control group. Middle ear muscle reflex thresholds were significantly higher at 2000 Hz in the suspected APD group for contralateral stimulation. MOC inhibition effects did not differ between APD and control groups. CONCLUSIONS: This research supports earlier studies showing altered acoustic reflexes in children with APD. No group differences were found for the MOC reflex measures, consistent with some earlier studies in children with APD.