Phonological, orthographic and morphological skills are related to structural properties of ventral and motor white matter pathways in skilled and impaired readers.

Using diffusion tensor imaging (DTI), we assessed the extent to which fractional anisotropy values in the dorsal (i.e., arcuate fasciculus; AF) versus ventral (i.e., inferior fronto-occipital fasciculus; IFOF) distinction of structural white matter pathways associated with selected reading processes, could be replicated in skilled adult readers (N = 17) and extended to adults with reading impairments (N = 13). In addition to the AF and IFOF, motor-based tracts (i.e., posterior limb of the internal capsule (PLIC) and the frontal aslant tract (FAT)) were isolated to explore their role in reading performance. Several interesting relationships with reading performance emerged. First, orthographic awareness was related to the left IFOF in skilled readers, whereas orthographic awareness was related to left PLIC for impaired readers. Morphological awareness was related to left FAT for skilled readers, whereas morphological awareness was related to right AF, right IFOF and left PLIC for impaired readers. Overall, these findings support the notion that adult reading performance (both skilled and impaired) is related to the structural properties of the ventral white matter pathways. More consideration should be paid to motor pathways, particularly the PLIC, and their role in compensatory reading strategies in individuals with reading impairments.

Activity in the pontine reticular nuclei scales with handgrip force in humans.

The neural pathways that contribute to force production in humans are currently poorly understood, as the relative roles of the corticospinal tract and brainstem pathways, such as the reticulospinal tract (RST), vary substantially across species. Using functional magnetic resonance imaging (fMRI), we aimed to measure activation in the pontine reticular nuclei (PRN) during different submaximal handgrip contractions to determine the potential role of the PRN in force modulation. Thirteen neurologically intact participants (age: 28 ± 6 yr) performed unilateral handgrip contractions at 25%, 50%, 75% of maximum voluntary contraction during brain scans. We quantified the magnitude of PRN activation from the contralateral and ipsilateral sides during each of the three contraction intensities. A repeated-measures ANOVA demonstrated a significant main effect of force (P = 0.012, [Formula: see text] = 0.307) for PRN activation, independent of side (i.e., activation increased with force for both contralateral and ipsilateral nuclei). Further analyses of these data involved calculating the linear slope between the magnitude of activation and handgrip force for each region of interest (ROI) at the individual-level. One-sample t tests on the slopes revealed significant group-level scaling for the PRN bilaterally, but only the ipsilateral PRN remained significant after correcting for multiple comparisons. We show evidence of task-dependent activation in the PRN that was positively related to handgrip force. These data build on a growing body of literature that highlights the RST as a functionally relevant motor pathway for force modulation in humans.NEW & NOTEWORTHY In this study, we used a task-based functional magnetic resonance imaging (fMRI) paradigm to show that activity in the pontine reticular nuclei scales linearly with increasing force during a handgrip task. These findings directly support recently proposed hypotheses that the reticulospinal tract may play an important role in modulating force production in humans.

Moving toward elucidating alternative motor pathway structures post-stroke: the value of spinal cord neuroimaging.

Stroke results in varying levels of motor and sensory disability that have been linked to the neurodegeneration and neuroinflammation that occur in the infarct and peri-infarct regions within the brain. Specifically, previous research has identified a key role of the corticospinal tract in motor dysfunction and motor recovery post-stroke. Of note, neuroimaging studies have utilized magnetic resonance imaging (MRI) of the brain to describe the timeline of neurodegeneration of the corticospinal tract in tandem with motor function following a stroke. However, research has suggested that alternate motor pathways may also underlie disease progression and the degree of functional recovery post-stroke. Here, we assert that expanding neuroimaging techniques beyond the brain could expand our knowledge of alternate motor pathway structure post-stroke. In the present work, we will highlight findings that suggest that alternate motor pathways contribute to post-stroke motor dysfunction and recovery, such as the reticulospinal and rubrospinal tract. Then we review imaging and electrophysiological techniques that evaluate alternate motor pathways in populations of stroke and other neurodegenerative disorders. We will then outline and describe spinal cord neuroimaging techniques being used in other neurodegenerative disorders that may provide insight into alternate motor pathways post-stroke.

Evidence of mirror therapy for recruitment of ipsilateral motor pathways in stroke recovery: A resting fMRI study.

Mirror therapy (MT) has been proposed to promote motor recovery post-stroke through activation of mirror neuron system, recruitment of ipsilateral motor pathways, or/and increasing attention toward the affected limb. However, neuroimaging evidence for these mechanisms is still lacking. To uncover the underlying mechanisms, we designed a randomized controlled study and used a voxel-based whole-brain analysis of resting-state fMRI to explore the brain reorganizations induced by MT. Thirty-five stroke patients were randomized to an MT group (n â€‹= â€‹16) and a conventional therapy (CT) group (n â€‹= â€‹19) for a 4-week intervention. Before and after the intervention, the Fugl-Meyer Assessment Upper Limb subscale (FMA-UL) and resting-state fMRI were collected. A healthy cohort (n â€‹= â€‹16) was established for fMRI comparison. The changes in fractional amplitude of low-frequency fluctuation (fALFF) and seed-based functional connectivity were analyzed to investigate the impact of intervention. Results showed that greater FMA-UL improvement in the MT group was associated with the compensatory increase of fALFF in the contralesional precentral gyrus (M1) region and the re-establishment of functional connectivity between the bilateral M1 regions, which facilitate motor signals transmission via the ipsilateral motor pathways from the ipsilesional M1, contralesional M1, to the affected limb. A step-wise linear regression model revealed these two brain reorganization patterns collaboratively contributed to FMA-UL improvement. In conclusion, MT achieved motor rehabilitation primarily by recruitment of the ipsilateral motor pathways. Trial Registration Information: http://www.chictr.org.cn. Unique Identifier. ChiCTR-INR-17013644, submitted on December 2, 2017.

Abnormal synergies and associated reactions post-hemiparetic stroke reflect muscle activation patterns of brainstem motor pathways.

Individuals with moderate-to-severe post-stroke hemiparesis cannot control proximal and distal joints of the arm independently because they are constrained to stereotypical movement patterns called flexion and extension synergies. Accumulating evidence indicates that these synergies emerge because of upregulation of diffusely projecting brainstem motor pathways following stroke-induced damage to corticofugal pathways. During our recent work on differences in synergy expression among proximal and distal joints, we serendipitously observed some notable characteristics of synergy-driven muscle activation. It seemed that: paretic wrist/finger muscles were activated maximally during contractions of muscles at a different joint; differences in the magnitude of synergy expression occurred when elicited via contraction of proximal vs. distal muscles; and associated reactions in the paretic limb occurred during maximal efforts with the non-paretic limb, the strength of which seemed to vary depending on which muscles in the non-paretic limb were contracting. Here we formally investigated these observations and interpreted them within the context of the neural mechanisms thought to underlie stereotypical movement patterns. If upregulation of brainstem motor pathways occurs following stroke-induced corticofugal tract damage, then we would expect a pattern of muscle dependency in the observed behaviors consistent with such neural reorganization. Twelve participants with moderate-to-severe hemiparetic stroke and six without stroke performed maximal isometric torque generation in eight directions: shoulder abduction/adduction and elbow, wrist, and finger flexion/extension. Isometric joint torques and surface EMG were recorded from shoulder, elbow, wrist, and finger joints and muscles. For some participants, joint torque and muscle activation generated during maximal voluntary contractions were lower than during maximal synergy-induced contractions (i.e., contractions about a different joint), particularly for wrist and fingers. Synergy-driven contractions were strongest when elicited via proximal joints and weakest when elicited via distal joints. Associated reactions in the wrist/finger flexors were stronger than those of other paretic muscles and were the only ones whose response depended on whether the non-paretic contraction was at a proximal or distal joint. Results provide indirect evidence linking the influence of brainstem motor pathways to abnormal motor behaviors post-stroke, and they demonstrate the need to examine whole-limb behavior when studying or seeking to rehabilitate the paretic upper limb.

White Matter Microstructural Damage Associated With Gait Abnormalities in Idiopathic Normal Pressure Hydrocephalus.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a common disease in elderly adults. Patients with iNPH are generally characterized by progressive gait impairment, cognitive deficits, and urinary urgency and/or incontinence. A number of radiographic studies have shown that iNPH patients have enlarged ventricles and altered brain morphology; however, few studies have focused on the relationships between altered brain structure and gait dysfunction due to iNPH. Thus, this study aimed to evaluate the abnormalities of white matter (WM) correlated with gait impairment in iNPH patients and to gain a better understanding of its underlying pathology. Methods: Fifteen iNPH patients (five women, 10 men) were enrolled in this study, and each patient's demographic and gait indices were collected. First, we performed a correlation analysis between the demographic and gait indices. Then, all gait indices were grouped according to the number of WM hyperintensities (WMH) among each WM tract (JHU WM tractography atlas), to perform comparative analysis. Results: Considering sex and illness duration as covariates, correlation analysis showed a significantly negative correlation between step length (r = -0.80, p = 0.001), pace (r = -0.84, p = 2.96e-4), and age. After removing the effects of age, sex, and illness duration, correlation analysis showed negative correlation between step length (r = -0.73, p = 0.007), pace (r = -0.74, p = 0.005), and clinical-grade score and positive correlation between 3-m round trip time (r = 0.66, p = 0.021), rising time (r = 0.76, p = 0.004), and clinical-grade score. Based on WMH of each white matter tract, gait indices showed significant differences (p < 0.05/48, corrected by Bonferroni) between fewer WMH patients and more WMH in the middle cerebellar peduncle, left medial lemniscus, left posterior limb of the internal capsule (IC), and right posterior limb of the IC. Conclusions: Our results indicated that iNPH patients exhibited gait-related WM abnormalities located in motor and sensory pathways around the ventricle, which is beneficial to understand the underlying pathology of iNPH.

Abnormal cerebral microstructures revealed by diffusion kurtosis imaging in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which cerebral structural impairment is a consistent feature. PURPOSE: To investigate cerebral microstructural changes in ALS using diffusion kurtosis imaging (DKI) for the first time. STUDY TYPE: Prospective. SUBJECTS: Eighteen ALS patients and 20 healthy controls. FIELD STRENGTH/SEQUENCE: DKI images were obtained by a spin-echo echo-planar imaging sequence on a 3T MRI scanner, with three b-values (0, 1000, and 2000 s/mm2 ) and 64 diffusion encoding directions. ASSESSMENT: The revised ALS Functional Rating Scale (ALSFRS-R) was administered to assess disease severity, and the symptom duration and disease progression rate were also recorded. Voxel-based analysis was applied to examine the alteration of DKI metrics (ie, mean kurtosis metrics [MK], axial kurtosis [AK], and radial kurtosis [RK]) and the conventional diffusion metrics (ie, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity). STATISTICAL TESTS: Student's t-test, chi-square test, and Pearson correlation analysis. RESULTS: ALS patients showed MK reductions in gray matter areas, including the bilateral precentral gyrus, bilateral paracentral lobule, and left anterior cingulate gyrus; they also showed decreased MK values in white matter (WM) in the bilateral precentral gyrus, bilateral corona radiata, bilateral middle corpus callosum, left occipital lobe, and right superior parietal lobule. The spatial distribution of the regions with reduced RK was similar to those with decreased MK. No significant AK difference was found between groups. The correlation analysis revealed significant associations between DKI metrics and clinical assessments such as ALSFRS-R score and disease duration. Additionally, several WM regions showed between-group differences in conventional diffusion metrics; but the spatial extent was smaller than that with reduced DKI metrics. DATA CONCLUSION: The reduction in DKI metrics indicates decreased microstructural complexity in ALS, involving both motor-related areas and extramotor regions. DKI metrics can serve as potential biomarkers for assessing disease severity. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:554-562.

The descending motor tracts are different in dancers and musicians.

Long-term motor training, such as dance or gymnastics, has been associated with increased diffusivity and reduced fiber coherence in regions including the corticospinal tract. Comparisons between different types of motor experts suggest that experience might result in specific structural changes related to the trained effectors (e.g., hands or feet). However, previous studies have not segregated the descending motor pathways from different body-part representations in motor cortex (M1). Further, most previous diffusion tensor imaging studies used whole-brain analyses based on a single tensor, which provide poor information about regions where multiple white matter (WM) tracts cross. Here, we used multi-tensor probabilistic tractography to investigate the specific components of the descending motor pathways in well-matched groups of dancers, musicians and controls. To this aim, we developed a procedure to identify the WM regions below the motor representations of the head, hand, trunk and leg that served as seeds for tractography. Dancers showed increased radial diffusivity (RD) in comparison with musicians, in descending motor pathways from all the regions, particularly in the right hemisphere, whereas musicians had increased fractional anisotropy (FA) in the hand and the trunk/arm motor tracts. Further, dancers showed larger volumes compared to both other groups. Finally, we found negative correlations between RD and FA with the age of start of dance or music training, respectively, and between RD and performance on a melody task, and positive correlations between RD and volume with performance on a whole-body dance task. These findings suggest that different types of training might have different effects on brain structure, likely because dancers must coordinate movements of the entire body, whereas musicians focus on fewer effectors.

Ipsilateral motor evoked potentials in a patient with unihemispheric cortical atrophy due to Rasmussen encephalitis.

The role of the ipsilaterally descending motor pathways in the recovery mechanisms after unilateral hemispheric damage is still poorly understood. Motor output reorganization was investigated in a 56-year-old male patient with acquired unilateral hemispheric atrophy due to Rasmussen encephalitis. In particular, the ipsilateral corticospinal pathways were explored using focal transcranial magnetic stimulation. In the first dorsal interosseous and wrist extensors muscles, the median amplitudes of the ipsilateral motor evoked potentials induced by transcranial magnetic stimulation in the patient were higher than those of 10 age-matched healthy control subjects. In the biceps brachii muscle, the median amplitudes of the ipsilateral motor evoked potentials were the second largest in the patient compared to the controls. This study demonstrated a reinforcement of ipsilateral motor projections from the unaffected motor cortex to the hemiparetic hand in a subject with acquired unihemispheric cortical damage.

Cross-Frequency Coupling in Descending Motor Pathways: Theory and Simulation.

Coupling of neural oscillations is essential for the transmission of cortical motor commands to motoneuron pools through direct and indirect descending motor pathways. Most studies focus on iso-frequency coupling between brain and muscle activities, i.e., cortico-muscular coherence, which is thought to reflect motor command transmission in the mono-synaptic corticospinal pathway. Compared to this direct pathway, indirect corticobulbospinal motor pathways involve multiple intermediate synaptic connections via spinal interneurons. Neuronal processing of synaptic inputs can lead to modulation of inter-spike intervals which produces cross-frequency coupling. This theoretical study aims to evaluate the effect of the number of synaptic layers in descending pathways on the expression of cross-frequency coupling between supraspinal input and the cumulative output of the motoneuron pool using a computer simulation. We simulated descending pathways as various layers of interneurons with a terminal motoneuron pool using Hogdkin-Huxley styled neuron models. Both cross- and iso-frequency coupling between the supraspinal input and the motorneuron pool output were computed using a novel generalized coherence measure, i.e., n:m coherence. We found that the iso-frequency coupling is only dominant in the mono-synaptic corticospinal tract, while the cross-frequency coupling is dominant in multi-synaptic indirect motor pathways. Furthermore, simulations incorporating both mono-synaptic direct and multi-synaptic indirect descending pathways showed that increased reliance on a multi-synaptic indirect pathway over a mono-synaptic direct pathway enhances the dominance of cross-frequency coupling between the supraspinal input and the motorneuron pool output. These results provide the theoretical basis for future human subject study quantitatively assessing motor command transmission in indirect vs. direct pathways and its changes after neurological disorders such as unilateral brain injury.

Cerebral blood flow features in chronic subcortical stroke: Lesion location-dependent study.

We investigated the influence of lesion location on cerebral blood flow (CBF) in chronic subcortical stroke patients. Three-dimensional pseudocontinuous arterial spin labeling was employed to obtain CBF images in normal controls (NC) and patients with left hemisphere subcortical infarctions involving motor pathways. Stroke patients were divided into two subgroups based on the infarction location (basal ganglia (BS) or pontine (PS). We mapped CBF alterations in a voxel-wise manner and compared them to detect differences among groups with height-level false discovery rate correction. Regions with significant group differences were extracted to perform post hoc analyses among the BS, PS and NC groups using a general linear model with age, gender, years of education, and interval after stroke as covariates. The BS group displayed significantly increased CBF in the contralesional putamen relative to NC and significantly decreased CBF in the ipsilesional sensorimotor cortex, ipsilesional thalamus and contralesional cerebellum. The PS group displayed significantly increased CBF in the contralesional inferior frontal gyrus relative to both the NC and BS groups. Nevertheless, the PS group showed significantly decreased CBF mainly in the cerebellum. Our results suggest different alteration patterns of CBF in chronic stroke patients with different infarct locations within subcortical motor pathways, potentially providing important information for the initiation of individualized rehabilitation strategies for subcortical stroke patients involving different infarct types.

A comparison between threshold criterion and amplitude criterion in transcranial motor evoked potentials during surgery for supratentorial lesions.

OBJECTIVE: The aim of this study was to compare sensitivity and specificity between the novel threshold and amplitude criteria for motor evoked potentials (MEPs) monitoring after transcranial electrical stimulation (TES) during surgery for supratentorial lesions in the same patient cohort. METHODS: One hundred twenty-six patients were included. All procedures were performed under general anesthesia. Craniotomies did not expose motor cortex, so that direct mapping was less suitable. After TES, MEPs were recorded bilaterally from abductor pollicis brevis (APB), from orbicularis oris (OO), and/or from tibialis anterior (TA). The percentage increase in the threshold level was assessed and considered significant if it exceeded by more than 20% on the affected side the percentage increase on the unaffected side. Amplitude on the affected side was measured with a stimulus intensity of 150% of the threshold level set for each muscle. RESULTS: Eighteen of 126 patients showed a significant change in the threshold level as well as an amplitude reduction of more than 50% in MEPs recorded from APB, and 15 of the patients had postoperative deterioration of motor function of the arm (temporary in 8 cases and permanent in 7 [true-positive and false-negative results]). Recording from TA was performed in 66 patients; 4 developed postoperative deterioration of motor function of the leg (temporary in 3 cases and permanent in 1), and showed a significant change in the threshold level, and an amplitude reduction of more than 50% occurred in 1 patient. An amplitude reduction of more than 50% occurred in another 10 patients, without a significant change in the threshold level or postoperative deterioration. Recording from OO was performed in 61 patients; 3 developed postoperative deterioration of motor function of facial muscles (temporary in 2 cases and permanent in 1) and had a significant change in the threshold level, and 2 of the patients had an amplitude reduction of more than 50%. Another 6 patients had an amplitude reduction of more than 50% but no significant change in the threshold level or postoperative deterioration.Sensitivity of the threshold criterion was 100% when MEPs were recorded from APB, OO, or TA, and its specificity was 97%, 100%, and 100%, respectively. Sensitivity of the amplitude criterion was 100%, 67%, and 25%, with a specificity of 97%, 90%, and 84%, respectively. CONCLUSIONS: The threshold criterion was comparable to the amplitude criterion with a stimulus intensity set at 150% of the threshold level regarding sensitivity and specificity when recording MEPs from APB, and superior to it when recording from TA or OO.

Clonidine administration during intraoperative monitoring for pediatric scoliosis surgery: Effects on central and peripheral motor responses.

OBJECTIVE: To study the effect of clonidine administrated as a co-analgesic during scoliosis surgery, on the neuromonitoring of spinal motor pathways. METHODS: Using standardized intraoperative monitoring, we compared the time course of peripherally and transcranially electrically evoked motor potentials (TcEMEPs) before and after injection of a single bolus of clonidine in children under total intravenous anesthesia (TIVA). MEP data were obtained from 9 patients and somatosensory evoked potentials (SSEPs) were obtained from 2 patients. The potential effect of clonidine on mean blood pressure (BP) was controlled. RESULTS: TcEMEPs from upper and lower limbs rapidly showed significant drops in amplitude after the injection of clonidine. Amplitudes reached minimal values within five minutes and remained very weak for at least 10-20minutes during which monitoring of the central motor pathways was severely compromised. SSEPs were not altered during maximal amplitude depression of the TcEMEPS. CONCLUSIONS: This is the first report showing that clonidine severely interferes with neuromonitoring of the spinal cord motor pathways. The results are discussed in light of the literature describing the effects of dexmedetomidine, another α-2 adrenergic agonist. The experimental and literature data point to central mechanisms taking place at both the spinal and cerebral levels. Therefore, clonidine as well as other α-2 adrenergic agonists should be used with extreme caution in patients for whom neuromonitoring of the motor pathways is required during surgery.

Combined Strategy for a Reliable Evaluation of Spinal Cord Injury Using an in vivo Model.

BACKGROUND: A complete neurological exam contributes in establishing spinal cord injury severity and its extent by identifying the damage to the sensory and motor pathways involved in order to address a more case-specific and precise pharmacological therapy. However, assessment of neurologic function in spinal cord injury models is usually reported by using sensory or motor tests independently. METHODS: A reliable integral method is needed to precisely evaluate location and severity of the injury at baseline and, in further assessments, to establish the degree of spontaneous recovery. A combination of sensation-based tests and motor-based tests was used to evaluate impaired neurologic function after spinal cord injury and the degree of spontaneous recovery, in different stages, on an in vivo model. RESULTS: Combined neurologic evaluation was useful to establish location and severity of the injury in all animals and also to detect degrees of spontaneous recovery at different stages after the injury. Comparisons of neurological function were assessed in time-days and groups between BBB motor score, latency maintenance of posture, locomotion and latency presentation of grooming before and after the injury. Our results suggest that a combined assessment strategy, including sensory and motor tests, can lead to better evaluation of spinal cord injury severity and location, and documentation of the extent of spontaneous recovery following SCI and identify specific motor and sensory pathway integrity. CONCLUSION: In conclusion, a combined assessment strategy provides a concise method for evaluating the impact of interventions in experimental models of SCI.

Increase in gray matter volume and white matter fractional anisotropy in the motor pathways of patients with secondarily generalized neocortical seizures.

PURPOSE: Convulsive motor activity is a clinical manifestation of secondarily generalized seizures evolving from different focal regions. The way in which the motor seizures present themselves is not very different from most of the generalized seizures in and between epilepsy patients. This might point towards the involvement of motor-related cortices and corticospinal pathway for wide spread propagation of epileptic activity. Our aim was to identify changes in the cerebral structures and to correlate clinical variables with structural changes particularly in the motor-related cortices and pathway of patients with generalized convulsions from different seizure foci. METHODS: Sixteen patients with focal onset and secondarily generalized seizures were included, along with sixteen healthy volunteers. Structural differences were analysed by measuring grey matter (GM) volume and thickness via T1-weighted MRI, and white matter (WM) fractional anisotropy (FA) via diffusion tensor imaging. GM and WM microstructural properties were compared between patients and controls by voxel- and surface- based analyses. Next, morphometric findings were correlated with seizure severity and disease duration to identify the pathologic process. KEY FINDINGS: In addition to widely reduced GM and WM properties, increased GM volume in the bilateral precentral gyri and paracentral lobules, and elevated regional FA in the bilateral corticospinal tracts adjacent to these motor -related GM were observed in patients and with higher statistical difference in the sub-patient group with drug-resistance. SIGNIFICANCE: The increment of GM volume and WM FA in the motor pathway positively correlated with severity and duration of epilepsy. The demonstrated microstructural changes of motor pathways imply a plastic process of motor networks in the patients with frequent generalization of focal seizures.

Circuit Homology between Decussating Pathways in the Ciona Larval CNS and the Vertebrate Startle-Response Pathway.

Comparing synaptic circuits and networks between brains of different animal groups helps us derive an understanding of how nervous systems might have evolved. The circuits of the startle response pathway in the brains of tailed vertebrates are known from electrophysiological studies on the giant reticulospinal Mauthner cells (M-cells). To identify morphological counterparts in chordate tunicates, a sister group of vertebrates [1, 2], we have compiled a densely reconstructed connectome (defined in [3]) for the CNS in the tadpole larva of Ciona intestinalis (L.), using ssEM [4]. The dorsal, tubular CNS of the ∼1-mm tadpole larva is built on a similar plan to vertebrates, its neurons distributed rostrocaudally in three centers, a brain vesicle, motor ganglion, and caudal nerve cord [5]. A single pair of descending decussating neurons, ddNs, found in the motor ganglion, have similarities to reticulospinal neurons descending from the vertebrate hindbrain to the spinal cord. The pre- and postsynaptic connections and circuits of these ddNs support their homology with decussating vertebrate M-cells. Network analysis reveals that, like M-cells, ddNs receive mechanosensory input from the peripheral nervous system and provide input to motoneurons, premotor interneurons, and ascending commissural inhibitory neurons (ACINs). These circuits uncover a putative homologous startle network in the Ciona tadpole. However, differences in circuits, including a lack of bilateral symmetry in their network, and convergence of inputs from left and right sides, raise questions about the relationship between form and function, and are a possible outcome of the tiny number of neurons in ascidian larvae.

A novel threshold criterion in transcranial motor evoked potentials during surgery for gliomas close to the motor pathway.

OBJECTIVE Warning criteria for monitoring of motor evoked potentials (MEP) after direct cortical stimulation during surgery for supratentorial tumors have been well described. However, little is known about the value of MEP after transcranial electrical stimulation (TES) in predicting postoperative motor deficit when monitoring threshold level. The authors aimed to evaluate the feasibility and value of this method in glioma surgery by using a new approach for interpreting changes in threshold level involving contra- and ipsilateral MEP. METHODS Between November 2013 and December 2014, 93 patients underwent TES-MEP monitoring during resection of gliomas located close to central motor pathways but not involving the primary motor cortex. The MEP were elicited by transcranial repetitive anodal train stimulation. Bilateral MEP were continuously evaluated to assess percentage increase of threshold level (minimum voltage needed to evoke a stable motor response from each of the muscles being monitored) from the baseline set before dural opening. An increase in threshold level on the contralateral side (facial, arm, or leg muscles contralateral to the affected hemisphere) of more than 20% beyond the percentage increase on the ipsilateral side (facial, arm, or leg muscles ipsilateral to the affected hemisphere) was considered a significant alteration. Recorded alterations were subsequently correlated with postoperative neurological deterioration and MRI findings. RESULTS TES-MEP could be elicited in all patients, including those with recurrent glioma (31 patients) and preoperative paresis (20 patients). Five of 73 patients without preoperative paresis showed a significant increase in threshold level, and all of them developed new paresis postoperatively (transient in 4 patients and permanent in 1 patient). Eight of 20 patients with preoperative paresis showed a significant increase in threshold level, and all of them developed postoperative neurological deterioration (transient in 4 patients and permanent in 4 patients). In 80 patients no significant change in threshold level was detected, and none of them showed postoperative neurological deterioration. The specificity and sensitivity in this series were estimated at 100%. Postoperative MRI revealed gross-total tumor resection in 56 of 82 patients (68%) in whom complete tumor resection was attainable; territorial ischemia was detected in 4 patients. CONCLUSIONS The novel threshold criterion has made TES-MEP a useful method for predicting postoperative motor deficit in patients who undergo glioma surgery, and has been feasible in patients with preoperative paresis as well as in patients with recurrent glioma. Including contra- and ipsilateral changes in threshold level has led to a high sensitivity and specificity.

Segmental organization of vestibulospinal inputs to spinal interneurons mediating crossed activation of thoracolumbar motoneurons in the neonatal mouse.

Vestibulospinal pathways activate contralateral motoneurons (MNs) in the thoracolumbar spinal cord of the neonatal mouse exclusively via axons descending ipsilaterally from the vestibular nuclei via the lateral vestibulospinal tract (LVST; Kasumacic et al., 2010). Here we investigate how transmission from the LVST to contralateral MNs is mediated by descending commissural interneurons (dCINs) in different spinal segments. We test the polysynaptic nature of this crossed projection by assessing LVST-mediated ventral root (VR) response latencies, manipulating synaptic responses pharmacologically, and tracing the pathway transynaptically from hindlimb extensor muscles using rabies virus (RV). Longer response latencies in contralateral than ipsilateral VRs, near-complete abolition of LVST-mediated calcium responses in contralateral MNs by mephenesin, and the absence of transsynaptic RV labeling of contralateral LVST neurons within a monosynaptic time window all indicate an overwhelmingly polysynaptic pathway from the LVST to contralateral MNs. Optical recording of synaptically mediated calcium responses identifies LVST-responsive ipsilateral dCINs that exhibit segmental differences in proportion and dorsoventral distribution. In contrast to thoracic and lower lumbar segments, in which most dCINs are LVST responsive, upper lumbar segments stand out because they contain a much smaller and more ventrally restricted subpopulation of LVST-responsive dCINs. A large proportion of these upper lumbar LVST-responsive dCINs project to contralateral L5, which contains many of the hindlimb extensor MNs activated by the LVST. A selective channeling of LVST inputs through segmentally and dorsoventrally restricted subsets of dCINs provides a mechanism for targeting vestibulospinal signals differentially to contralateral trunk and hindlimb MNs in the mammalian spinal cord.

A note on the mapping and quantification of the human brain corticospinal tract.

Several diffusion tensor imaging tractography (DTT) have been adopted to construct the living human brain corticospinal tract. In this Note, we applied method "A" as recently described and used by "Lin CC, Tsai MY, Lo YC, et al. Reproducibility of corticospinal diffusion tensor tractography innormal subjects and hemiparetic stroke patients. Eur J Radiol 2013;82: e610-6." We compared the results obtained with method "A" with those obtained using an anatomy-guided method "B" on two healthy adults. We also quantified the results using tract volume, and corresponding fractional anisotropy, mean, and radial diffusivities. We demonstrate that accurate mapping and quantification of CST requires at least two regions of interest one at the level of the medulla oblongata, a second at the level of pons, this assures termination at the motor spine and contamination with cerebellar and sensory pathways.

Tailoring neurophysiological strategies with clinical context enhances resection and safety and expands indications in gliomas involving motor pathways.

BACKGROUND: Resection of motor pathway gliomas requires the intraoperative recognition of essential cortical-subcortical motor structures. The degree of involvement of motor structures is variable, and increases as result of treatments patients are submitted to. Intraoperative neurophysiology offers various stimulation modalities, which efficiency is based on the ability to recognize essential sites with the highest possible resolution in most clinical conditions. Two stimulation paradigms evolved for intraoperative guidance of motor tumors removal: the 60 Hz-technique [low frequency (LF)] and the pulse-technique [high frequency-(HF)], delivered by bipolar or monopolar probe respectively. Most surgical teams rely on to either of the 2 techniques. The key point is the integration of the choice of the stimulation modality with the clinical context. METHODS: In 591 tumors involving the corticospinal tract, the use of HF and LF was tailored to the clinical context defined by patient clinical history and tumor features (by imaging). The effect was evaluated on the feasibility of mapping, the impact on immediate and permanent morbidity, the extent of resection, and the number of patients treated. RESULTS: By integrating the choice of the probe and the stimulation protocol with patient clinical history and tumor characteristics, the best probe-frequency match was identified for the different sets of clinical conditions. This integrative approach allows increasing the extent of resection and patient functional integrity, and greatly expands the number of patients who could benefit from surgery. CONCLUSIONS: The integration of stimulation modalities with clinical context enhances the extent and safety of resection and expands the population of patients who could benefit from surgical treatment.