Lemniscal Pathway Research Articles

Cortical region-specific recovery of auditory temporal processing following noise-induced hearing loss

Noise-induced hearing loss (NIHL) studies have focused on the lemniscal auditory pathway, but little is known about how NIHL impacts different cortical regions. Here we compared response recovery trajectories in the auditory and frontal cortices (AC, FC) of mice following NIHL. We recorded EEG responses from awake mice (male n = 15, female n = 14) before and following NIHL (longitudinal design) to quantify event related potentials and gap-in-noise temporal processing. Hearing loss was verified by measuring the auditory brainstem response (ABR) before and at 1-, 10-, 23–, and 45-days after noise-exposure. Resting EEG, event related potentials (ERP) and auditory steady state responses (ASSR) were recorded at the same time-points after NIHL. The inter-trial phase coherence (ITPC) of the ASSR was measured to quantify the ability of AC and FC to synchronize responses to short gaps embedded in noise. Despite the absence of click-evoked ABRs up to 90 dB SPL and up to 45-days post-exposure, ERPs from the AC and FC showed full recovery in ∼ 50 % of the mice to pre-NIHL levels in both AC and FC. The ASSR ITPC was reduced following NIHL in AC and FC in all the mice on day 1 after NIHL. The AC showed full recovery of ITPC over 45-days. Despite ERP amplitude recovery, the FC does not show recovery of ASSR ITPC. These results indicate post-NIHL plasticity with similar response amplitude recovery across AC and FC, but cortical region-specific trajectories in temporal processing recovery.

Sequential maturation of stimulus-specific adaptation in the mouse lemniscal auditory system.

Stimulus-specific adaptation (SSA), the reduction of neural activity to a common stimulus that does not generalize to other, rare stimuli, is an essential property of our brain. Although well characterized in adults, it is still unknown how it develops during adolescence and what neuronal circuits are involved. Using in vivo electrophysiology and optogenetics in the lemniscal pathway of the mouse auditory system, we observed SSA to be stable from postnatal day 20 (P20) in the inferior colliculus, to develop until P30 in the auditory thalamus and even later in the primary auditory cortex (A1). We found this maturation process to be experience-dependent in A1 but not in thalamus and to be related to alterations in deep but not input layers of A1. We also identified corticothalamic projections to be implicated in thalamic SSA development. Together, our results reveal different circuits underlying the sequential SSA maturation and provide a unique perspective to understand predictive coding and surprise across sensory systems.

Motor rehabilitation of aphasic stroke patient: the possibility of Rood's approach.

Motor rehabilitation of aphasic stroke patient: the possibility of Rood's approach.

Fibromyalgia-associated hyperalgesia is related to psychopathological alterations but not to gut microbiome changes.

Fibromyalgia-syndrome (FMS) is a complex disease characterized by chronic widespread pain and additional symptoms including depression, cognitive dysfunction (“fibro-fog”) and maldigestion. Our research team examined whether FMS-related pain parameters assessed by quantitative sensory testing (QST) and psychological disturbances are accompanied by alterations of the fecal microbiome. We recruited 25 patients with FMS and 26 age- and sex-matched healthy controls. Medical background, food habits, psychopathology and quality of life were assessed through questionnaires. Stool samples were analyzed by 16S rRNA gene amplification and sequencing. QST was performed according to the protocol of the German Network for Neuropathic Pain. QST showed that both lemniscal and spinothalamic afferent pathways are altered in FMS patients relative to healthy controls and that peripheral as well as central pain sensitization processes are manifest. Psychometric assessment revealed enhanced scores of depression, anxiety and stress. In contrast, neither the composition nor the alpha- and beta-diversity of the fecal microbiome was changed in FMS patients. FMS patients segregate from healthy controls in various parameters of QST and psychopathology, but not in terms of composition and diversity of the fecal microbiome. Despite consideration of several confounding factors, we conclude that the contribution of the gut microbiome to the pathophysiology of FMS is limited.

Impaired trigeminal control of ingestive behavior in the Prrxl1-/- mouse is associated with a lemniscal-biased orosensory deafferentation.

Although peripheral deafferentation studies have demonstrated a critical role for trigeminal afference in modulating the orosensorimotor control of eating and drinking, the central trigeminal pathways mediating that control, as well as the timescale of control, remain to be elucidated. In rodents, three ascending somatosensory pathways process and relay orofacial mechanosensory input: the lemniscal, paralemniscal, and extralemniscal. Two of these pathways (the lemniscal and extralemniscal) exhibit highly structured topographic representations of the orofacial sensory surface, as exemplified by the one-to-one somatotopic mapping between vibrissae on the animals’ face and barrelettes in brainstem, barreloids in thalamus, and barrels in cortex. Here we use the Prrxl1 knockout mouse model (also known as the DRG11 knockout) to investigate ingestive behavior deficits that may be associated with disruption of the lemniscal pathway. The Prrxl1 deletion disrupts somatotopic patterning and axonal projections throughout the lemniscal pathway but spares patterning in the extralemniscal nucleus. Our data reveal an imprecise and inefficient ingestive phenotype. Drinking behavior exhibits deficits on the timescales of milliseconds to seconds. Eating behavior shows deficits over an even broader range of timescales. An analysis of food acquisition and consummatory rate showed deficits on the timescale of seconds, and analysis of body weight suggested deficits on the scale of long term appetitive control. We suggest that ordered assembly of trigeminal sensory information along the lemniscal pathway is critical for the rapid and precise modulation of motor circuits driving eating and drinking action sequences.

A vibrissa pathway that activates the limbic system.

Vibrissa sensory inputs play a central role in driving rodent behavior. These inputs transit through the sensory trigeminal nuclei, which give rise to the ascending lemniscal and paralemniscal pathways. While lemniscal projections are somatotopically mapped from brainstem to cortex, those of the paralemniscal pathway are more widely distributed. Yet the extent and topography of paralemniscal projections are unknown, along with the potential role of these projections in controlling behavior. Here, we used viral tracers to map paralemniscal projections. We find that this pathway broadcasts vibrissa-based sensory signals to brainstem regions that are involved in the regulation of autonomic functions and to forebrain regions that are involved in the expression of emotional reactions. We further provide evidence that GABAergic cells of the Kölliker-Fuse nucleus gate trigeminal sensory input in the paralemniscal pathway via a mechanism of presynaptic or extrasynaptic inhibition.

Distinct integration of spectrally complex sounds in mouse primary auditory cortices

The standard hierarchical signal transmission along the lemniscal auditory pathway in mice changes in the cortex, where two tonotopically organized auditory regions receive thalamic inputs in parallel: the primary auditory cortex (A1) and the anterior auditory field (AAF). These fields show distinct properties of sound-evoked responses, where A1 responds robustly to sound onset and AAF exhibits faster and more transient responses following both sound onset and offset. Previous reports showed a strong involvement of AAF in temporal processing, revealing its particular role in encoding temporal information. A more regular tonotopy, narrower frequency response areas, and more robust direction selectivity to frequency modulated sweeps led to the speculation that A1 codes better the spectral composition of a sound than AAF. However, potential mechanisms explaining why A1 favors spectral processing have not been previously described. Using in vivo electrophysiological recordings in the mouse auditory cortex, we found that A1 neurons, unlike AAF neurons, respond stronger and faster to spectrally complex tones than to pure tones. Next, we show that both regular and putative fast-spiking neurons in A1, but not in AAF, display larger responses to spectrally complex tones than to pure tones. Finally, we use a laminar analysis to demonstrate that A1 neurons in layer 2/3 respond stronger to spectrally complex tones than neurons in layer 4, indicating an important transformation of the neural representation of spectral complexity between thalamo-recipient and supragranular layers in A1, but not in AAF. Our study reveals circuit features contributing to distinct processing of spectrally simple and complex sounds in the two primary auditory cortices and supports a dual-stream processing in the core auditory cortex.

Sequential Diffusion Tensor Imaging and Magnetic Resonance Spectroscopy in Patients Undergoing Reirradiation for Progressive Diffuse Intrinsic Pontine Glioma

PurposeDiffusion tensor imaging for evaluation of white matter tracts is used with magnetic resonance spectroscopy (MRS) to improve management of diffuse intrinsic pontine glioma (DIPG). Changes in the apparent diffusion coefficient (ADC), fractional anisotropy (FA), and tumor metabolite ratios have been reported after initial radiation for DIPG, but these markers have not been studied sequentially in patients undergoing reirradiation for progressive DIPG. Here, we report a case series of 4 patients who received reirradiation for progressive DIPG on a prospective clinical trial in which we evaluated quantitative changes in FA, ADC, and tumor metabolites and qualitative changes in white matter tracts. Methods and MaterialsThe median reirradiation dose was 25.2 Gy (24-30.8 Gy). Fiber tracking was performed using standard tractography analysis. The FA and ADC values for the corticospinal and medial lemniscus tracts were calculated before and after reirradiation. Multivoxel MRS was performed. Findings were correlated with clinical features and conventional MRI of tumors. ResultsAll patients had an initial response to reirradiation as shown by a decrease in tumor size. In general, FA increased with disease response and decreased with progression, whereas ADC decreased with disease response and increased with progression. At second progression, the FA fold change relative to values during disease response decreased in both patients with available imaging at second progression. Visualization of tracts demonstrated robust reconstitution of previously disrupted paths during tumor response; conversely, there was increased fiber tract disruption and infiltration during tumor progression. The MRS analysis revealed a decrease in choline:creatinine and choline:N-acetylaspartate ratios during tumor response and increase during progression. ConclusionsDistinct changes in white matter tracts and tumor metabolism were observed in patients with DIPG undergoing reirradiation on a prospective clinical trial. Changes related to tumor response and progression were observed after 24 to 30.8 Gy reirradiation.

Investigating the neuroanatomy underlying proprioception using a stroke model

Neuroanatomical investigations have associated cortical areas, beyond Primary Somatosensory Cortex (S1), with impaired proprioception. Cortical regions have included temporoparietal (TP) regions (supramarginal gyrus, superior temporal gyrus, Heschl's gyrus) and insula. Previous approaches have struggled to account for concurrent damage across multiple brain regions. Here, we used a targeted lesion analysis approach to examine the impact of specific combinations of cortical and sub-cortical lesions and quantified the prevalence of proprioceptive impairments when different regions are damaged or spared.Seventy-seven individuals with stroke (49 male; 28 female) were identified meeting prespecified lesion criteria based on MRI/CT imaging: 1) TP lesions without S1, 2) TP lesions with S1, 3) isolated S1 lesions, 4) isolated insula lesions, and 5) lesions not impacting these regions (other regions group). Initially, participants meeting these criteria (1–4) were grouped together into right or left lesion groups and compared to each other, and the other regions group (5), on a robotic Arm Position Matching (APM) task and a Kinesthesia (KIN) task. We then examined the behaviour of individuals that met each specific criteria (groups 1–5).Proprioceptive impairments were more prevalent following right hemisphere lesions than left hemisphere lesions. The extent of damage to TP regions correlated with performance on both robotic tasks. Even without concurrent S1 lesions, TP and insular lesions were associated with impairments on the APM and KIN tasks. Finally, lesions not impacting these regions were much less likely to result in impairments.This study highlights the critical importance of TP and insular regions for accurate proprioception. Significance statementThis work advances our understanding of the neuroanatomy of human proprioception. We validate the importance of regions, beyond the dorsal column medial lemniscal pathway and S1, for proprioception. Further, we provide additional evidence of the importance of the right hemisphere for human proprioception. Improved knowledge on the neuroanatomy of proprioception is crucial for advancing therapeutic approaches which target individuals with proprioceptive impairments following neurological injury or with neurological disorders.

Kv4.2-Positive Domains on Dendrites in the Mouse Medial Geniculate Body Receive Ascending Excitatory and Inhibitory Inputs Preferentially From the Inferior Colliculus.

The medial geniculate body (MGB) is the thalamic center of the auditory lemniscal pathway. The ventral division of MGB (MGV) receives excitatory and inhibitory inputs from the inferior colliculus (IC). MGV is involved in auditory attention by processing descending excitatory and inhibitory inputs from the auditory cortex (AC) and reticular thalamic nucleus (RTN), respectively. However, detailed mechanisms of the integration of different inputs in a single MGV neuron remain unclear. Kv4.2 is one of the isoforms of the Shal-related subfamily of potassium voltage-gated channels that are expressed in MGB. Since potassium channel is important for shaping synaptic current and spike waveforms, subcellular distribution of Kv4.2 is likely important for integration of various inputs. Here, we aimed to examine the detailed distribution of Kv4.2, in MGV neurons to understand its specific role in auditory attention. We found that Kv4.2 mRNA was expressed in most MGV neurons. At the protein level, Kv4.2-immunopositive patches were sparsely distributed in both the dendrites and the soma of neurons. The postsynaptic distribution of Kv4.2 protein was confirmed using electron microscopy (EM). The frequency of contact with Kv4.2-immunopositive puncta was higher in vesicular glutamate transporter 2 (VGluT2)-positive excitatory axon terminals, which are supposed to be extending from the IC, than in VGluT1-immunopositive terminals, which are expected to be originating from the AC. VGluT2-immunopositive terminals were significantly larger than VGluT1-immunopositive terminals. Furthermore, EM showed that the terminals forming asymmetric synapses with Kv4.2-immunopositive MGV dendritic domains were significantly larger than those forming synapses with Kv4.2-negative MGV dendritic domains. In inhibitory axons either from the IC or from the RTN, the frequency of terminals that were in contact with Kv4.2-positive puncta was higher in IC than in RTN. In summary, our study demonstrated that the Kv4.2-immunopositive domains of the MGV dendrites received excitatory and inhibitory ascending auditory inputs preferentially from the IC, and not from the RTN or cortex. Our findings imply that time course of synaptic current and spike waveforms elicited by IC inputs is modified in the Kv4.2 domains.

Structural Alterations in a Rat Model of Short-Term Conductive Hearing Loss Are Associated With Reduced Resting State Functional Connectivity.

Conductive hearing loss (CHL) results in attenuation of air conducted sound reaching the inner ear. How a change in air conducted sound alters the auditory system resulting in cortical alterations is not well understood. Here, we have assessed structural and functional magnetic resonance imaging (MRI) in an adult (P60) rat model of short-term conductive hearing loss (1 week). Diffusion tensor imaging (DTI) revealed fractional anisotropy (FA) and axial diffusivity alterations after hearing loss that circumscribed the auditory cortex (AC). Tractography found the lateral lemniscus tract leading to the bilateral inferior colliculus (IC) was reduced. For baseline comparison, DTI and tractography alterations were not found for the somatosensory cortex. To determine functional connectivity changes due to hearing loss, seed-based analysis (SBA) and independent component analysis (ICA) were performed. Short term conductive hearing loss altered functional connectivity in the AC and IC, but not the somatosensory cortex. The results present an exploratory neuroimaging assessment of structural alterations coupled to a change in functional connectivity after conductive hearing loss. The results and implications for humans consist of structural-functional brain alterations following short term hearing loss in adults.

Brain White Matter Abnormality Induced by Chronic Spinal Cord Injury in the Pediatric Population: A Preliminary Tract-based Spatial Statistic Study.

Objectives: Tract-based spatial statistics (TBSS) is a diffusion tensor imaging (DTI)-based processing technique that aims to improve the objectivity and interpretability of analysis of multisubject diffusion imaging studies. This study used TBSS to measure quantitative changes in brain white matter structures following spinal cord injury (SCI). Methods: Eighteen SCI subjects aged 8-20 years old (mean age, 16.5 years) were scanned using a conventional single-shot EPI DTI protocol using a 3.0T Siemens MR scanner. All participants underwent a complete International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination to determine the level and severity of injury. Five participants were classified as American Spinal Injury Association Impairment Scale (AIS) A, nine as AIS B, and four as AIS C/D. Imaging parameters used for data collection were as follows: 20 directions, b = 1000 s/mm2, voxel size = 1.8 mm x 1.8 mm, slice thickness = 5 mm, TE = 95 ms, TR = 4300 ms, slices = 30, TA = 4:45 min. To generate TBSS, nonparametric permutation tests were used for voxel-wise statistical analysis of the fractional anisotropy (FA) skeletons between AIS groups. A two-tailed t test was applied to extract voxels with significant differences at p < .05. Results: Notable significant changes occurred throughout the corticospinal, spinothalamic, and dorsal column/medial lemniscus tracts. Altered regions in the temporal, occipital, and parietal lobes were also identified. Conclusion: These results suggest that white matter structures are altered differently between people with different AIS classifications. TBSS has the potential to serve as a screening tool to identify white matter changes in regions of interest.

Loss of Calretinin in L5a impairs the formation of the barrel cortex leading to abnormal whisker-mediated behaviors

The rodent whisker-barrel cortex system has been established as an ideal model for studying sensory information integration. The barrel cortex consists of barrel and septa columns that receive information input from the lemniscal and paralemniscal pathways, respectively. Layer 5a is involved in both barrel and septa circuits and play a key role in information integration. However, the role of layer 5a in the development of the barrel cortex remains unclear. Previously, we found that calretinin is dynamically expressed in layer 5a. In this study, we analyzed calretinin KO mice and found that the dendritic complexity and length of layer 5a pyramidal neurons were significantly decreased after calretinin ablation. The membrane excitability and excitatory synaptic transmission of layer 5a neurons were increased. Consequently, the organization of the barrels was impaired. Moreover, layer 4 spiny stellate cells were not able to properly gather, leading to abnormal formation of barrel walls as the ratio of barrel/septum size obviously decreased. Calretinin KO mice exhibited deficits in exploratory and whisker-associated tactile behaviors as well as social novelty preference. Our study expands our knowledge of layer 5a pyramidal neurons in the formation of barrel walls and deepens the understanding of the development of the whisker-barrel cortex system.

Somatosensory evoked potentials in Hirayama disease: A Brazilian study.

Background: Hirayama’s disease (HD) is characterized by an insidious onset asymmetric weakness and atrophy of the forearm and hand. Taking as a premise, the etiopathogenesis of the disease is attributed to forward displacement of posterior wall of lower cervical dural canal in neck flexion causing marked compression and flattening of lower spinal cord. This may result in compression of the posterior column of the spinal cord and seems likely to result in somatosensory evoked potentials (SSEPs) abnormalities. In the present study, we studied the possible involvement of the lemniscal dorsal pathway in patients with HD.Methods: SSEPs in upper and lower extremities were prospectively performed in eight patients with HD. All the patients were recruited from the outpatient clinic of a neuromuscular disorder center from South Brazil. SSEPs were obtained by transcutaneous electrical stimulation of the median and posterior tibial nerves, on both sides. We collected the amplitude and the latency of the different components obtained in each channel. The interpretation was based on Brazilian study standards.Results: We evaluated seven men and one woman (mean age 27). The data obtained were compared to a control group consisting of eight patients with spondylotic cervical myelopathy, 6 men and 2 women with mean age of 59 years. The measurements of obtained by the SSEP were also compared between the groups and no significant difference was found for any of them.Conclusion: SSEP did not turn out to be an electrophysiological marker in our HD patients.

P.870Relationship between type of antipsychotic treatment and psychopathology in acute schizophrenia and schizoaffective patients

Much of what we know today about the molecular and cellular mechanisms underlying the development of the somatosensory cortex and patterning of the thalamocortical afferents comes from studies on the phenotypes of mice, in which a variety of genes have been altered using targeted mutations or other experimental means. Coupled with the recent advances in imaging of axons and dendrites in the cerebral cortex of living mice and rats, genetic loss of function and gain of function studies are likely to uncover many mysteries of the cortical development in general, and differentiation and patterning of the somatosensory cortex. This chapter provides an overview of the recent advances in mechanistic explanations of how the somatosensory cortex develops and the patterning of the thalamocortical axons which provide the primary sensory inputs from the sensory periphery via the dorsal column lemniscal and trigeminal pathways. Since the vast majority of the developmental studies use the mouse as a model, this species is the focus of the chapter.

Modification de la structuration des potentiels évoqués cérébraux sensoriels par stimulation périnéale lors d’une focalisation attentionnelle sur le besoin d’uriner

Cortical somatosensory evoked potentials (SEP) are usually used to test the integrity of lemniscal pathways and thus provide arguments for the neurogenic etiology of sensory symptoms. For example, PES by perineal stimulation (SEP-P) has been shown to be altered in incontinence or neurogenic sexual dysfunction. We wanted to verify the integrity, structure and amplitude of far-field responses of PES-P in two conditions, the first without feeling the need to urinate (S0), the second with urgency (US). SEP-P were recorded in ten patients without neurological pathology in both conditions S0and US after stimulation of the dorsal nerve of the penis/clitoris. Three consecutive responses each averaged over 1000passages at a frequency of 3Hz were recorded. Seven men and 3women were included. All patients had normal SEP-P in terms of amplitude and latency of the P40complex and fully reproducible especially for late responses. These early P40responses were identical in both S0and US states. Conversely, the far-field potentials, i.e. the late responses, were different in the two states, with a significant decrease (P<0.008paired T-test) in the amplitude of cortical responses in the US state. We observe that the late components of SEP-P were altered by the need to urinate urgently with sustained and selective attention to this need. These late components of SEP-P could be useful to better specify the attentional mechanisms involved in the continence-voiding cycle and to specify pathological sensory dysfunctions (urgency, painful bladder, frequency…). 4.

Tractography-based targeting of the ventral intermediate nucleus: accuracy and clinical utility in MRgFUS thalamotomy.

Tractography-based targeting of the thalamic ventral intermediate nucleus (T-VIM) is a novel method conferring patient-specific selection of VIM coordinates for tremor surgery; however, its accuracy and clinical utility in magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy compared to conventional indirect targeting has not been specifically addressed. This retrospective study sought to compare the treatment locations and potential adverse effect profiles of T-VIM with indirect targeting in a large cohort of MRgFUS thalamotomy patients. T-VIM was performed using diffusion tractography outlining the pyramidal and medial lemniscus tracts in 43 MRgFUS thalamotomy patients. T-VIM coordinates were compared with the indirect treatment coordinates used in the procedure. Thalamotomy lesions were delineated on postoperative T1-weighted images and displaced ("translated") by the anteroposterior and mediolateral difference between T-VIM and treatment coordinates. Both translated and actual lesions were normalized to standard space and subsequently overlaid with areas previously reported to be associated with an increased risk of motor and sensory adverse effects when lesioned during MRgFUS thalamotomy. T-VIM coordinates were 2.18 mm anterior and 1.82 mm medial to the "final" indirect treatment coordinates. Translated lesions lay more squarely within the boundaries of the VIM compared to nontranslated lesions and showed significantly less overlap with areas associated with sensory adverse effects. Translated lesions overlapped less with areas associated with motor adverse effects; however, this difference was not significant. T-VIM leads to the selection of more anterior and medial coordinates than the conventional indirect methods. Lesions moved toward these anteromedial coordinates avoid areas associated with an increased risk of motor and sensory adverse effects, suggesting that T-VIM may improve clinical outcomes.

P45-S Optimisation of the recording parameters of tibial somatosensory evoked potentials (SEPs)

Background Tibial SEPs assess the function of the dorsal columns and supraspinal medial lemniscal somatosensory pathways. Lumbar N22 responses (T12/L1) and cervical P30 (Cv7) allow topographic localisation but are challenging to obtain in routine clinical practice. Here, we studied technical parameters that affect spinal and cortical (P40) responses. Materials and methods In a sample of consecutively referred patients, spinal response amplitudes and latencies were studied simultaneously with cup or subdermal needle and different reference electrode montages and correlated with BMI. P30 recordings were trialled and P40 amplitude optimisation was studied with three different montages (Cz’-Fz, Cz’-Cc, Ci-Cc). Results Responses with subdermal needles were of equal or smaller amplitude in 22/37 compared to cup electrodes. Contralateral iliac crest reference (0.74 ± 0.62 μV) gave larger amplitudes than ipsilateral (0.59 ± 0.61 μV; P = 0.017). Spinal N22 responses (cup electrode, contralateral reference) were present in 33/37patients with BMI 25(0.58 ± 0.54 μV) and were not strongly correlated with BMI (Spearman = −0.32). 30/136 recordings had absent spinal responses with recordable P40. A P30 response was not recordable in 115/140 when P40 was present. Amplitudes of Cz’-Cc (3.09 ± 2.01 μV) were significantly greater than Cz’-Fz (2.42 ± 1.83 μV) in 117/150 of recordings (P = 0.001) and Ci-Cc (2.48 ± 1.55 μV) in 97/150 (P = 0.008). There were no significant differences in latencies. Conclusions Subdermal needle and cup electrodes produce comparable N20 recordings and contralateral iliac crest reference provides largest amplitudes. Interestingly, BMI does not significantly influence N22 amplitude. The Cv7 response was often absent when N22 and P40 were normal. P40 amplitude is maximal at Cz’-Cc derivation.

Microstructural integrity of corticospinal and medial lemniscus tracts: insights from diffusion tensor tractography of right-hand amputees

Reductions in sensory and motor activity following unilateral upper limb amputation during adulthood are associated with widespread, activity-dependent reorganization of the gray matter and white matter through the central nervous system. Likewise, in cases of congenital limb absence there is evidence that limited afferent or efferent activity affects the structural integrity of white matter pathways serving the affected side. Evidence that the structural integrity of mature sensory and motor tracts controlling the lost upper limb exhibits similar activity dependence is, however, sparse and inconsistent. Here we used diffusion tensor tractography to test whether amputation of the dominant right hand during adulthood (n = 16) alters the microstructural integrity of the major sensory (medial lemniscus, ML) and motor (corticospinal tract, CST) pathways controlling missing hand function. Consistent with prior findings, healthy control subjects (n = 27) exhibited higher fractional anisotropy (FA), an index of white matter microstructural integrity, within dominant left CST and nondominant right ML. Critically, in contrast to what might be expected if the microstructural organization of these tracts is activity dependent, these asymmetries persisted in amputees. Moreover, we failed to detect any differences in dominant left ML or CST between healthy control subjects and amputees. Our results are consistent with these white matter tracts being robust to changes in activity once mature or that continued use of the residual limb (in a compensatory fashion or with prosthesis) provides stimulation sufficient to maintain tract integrity. NEW & NOTEWORTHY We report that unilateral hand amputation in adults has no significant effects on the structure of major sensory or motor pathways contralateral to the amputation. Our results are consistent with the organization of these white matter tracts being robust to changes in activity once mature or that continued use of the residual limb (with or without a prosthesis) provides stimulation sufficient to maintain tract integrity.

Anodal Transcutaneous Spinal Direct Current Stimulation (tsDCS) Selectively Inhibits the Synaptic Efficacy of Nociceptive Transmission at Spinal Cord Level

Recently studies have aimed at developing transcutaneous spinal direct current stimulation (tsDCS) as a non-invasive technique to modulate spinal function in humans. Independent studies evaluating its after-effects on nociceptive or non-nociceptive somatosensory responses have reported comparable effects suggesting that tsDCS impairs axonal conduction of both the spino-thalamic and the medial lemniscus tracts. The present study aimed to better understand how tsDCS affects, in humans, the spinal transmission of nociceptive and non-nociceptive somatosensory inputs. We compared the after-effects of anodal low-thoracic, anodal cervical and sham tsDCS on the perception and brain responses elicited by laser stimuli selectively activating Aδ-thermonociceptors of the spinothalamic system and vibrotactile stimuli selectively activating low-threshold Aβ-mechanoreceptors of the lemniscal system, delivered to the hands and feet. Low-thoracic tsDCS selectively and significantly affected the LEP-N2 wave elicited by nociceptive stimulation of the lower limbs, without affecting the LEP-N2 wave elicited by nociceptive stimulation of the upper limbs, and without affecting the SEP-N2 wave elicited by vibrotactile stimulation of either limb. This selective and segmental effect indicates that the neuromodulatory after-effects of tsDCS cannot be explained by anodal blockade of axonal conduction and, instead, are most probably due to a segmental effect on the synaptic efficacy of the local processing and/or transmission of nociceptive inputs in the dorsal horn.