Multimodal morphometry and functional magnetic resonance imaging in schizophrenia and auditory hallucinations

AIM:To validate a multimodal[structural and functional magnetic resonance(MR)]approach as coincidence brain clusters are hypothesized to correlate with clinical severity of auditory hallucinations.METHODS:Twenty-two patients meeting Diagnostic and Statistical Manual of Mental Disorders(fourth edition,DSM-Ⅳ)criteria for schizophrenia and experiencing persistent hallucinations together with 28 healthy controls were evaluated with structural and functional MR imaging with an auditory paradigm designed to replicate those emotions related to the patients’hallucinatory experiences.Coincidence maps were obtained by combining structural maps of gray matter reduction with emotional functional increased activation.Abnormal areas were correlated with the brief psychiatric rating scale(BPRS)and the psychotic symptom rating scale(PSYRATS)scales.RESULTS:The coincidence analysis showed areas with coexistence gray matter reductions and emotional activation in bilateral middle temporal and superior temporal gyri.Significant negative correlations between BPRS and PSYRATS scales were observed.BPRS scores were negatively correlated in the middle temporal gyrus(right)(t=6.86,P=0.001),while negative PSYRATS correlation affected regions in both the superior temporal gyrus(left)(t=7.85,P=0.001)and middle temporal gyrus(left)(t=4.97,P=0.002).CONCLUSION:Our data identify left superior and middle temporal gyri as relevant areas for the understanding of auditory hallucinations in schizophrenia.The use of multimodal approaches,sharing structural and functional information,may demonstrate areas specifically linked to the severity of auditory hallucinations.     

MR and genetics in schizophrenia: focus on auditory hallucinations

Although many structural and functional abnormalities have been related to schizophrenia, until now, no single biological marker has been of diagnostic clinical utility. One way to obtain more valid findings is to focus on the symptoms instead of the syndrome. Auditory hallucinations (AHs) are one of the most frequent and reliable symptoms of psychosis. We present a review of our main findings, using a multidisciplinary approach, on auditory hallucinations. Firstly, by applying a new auditory emotional paradigm specific for psychosis, we found an enhanced activation of limbic and frontal brain areas in response to emotional words in these patients. Secondly, in a voxel-based morphometric study, we obtained a significant decreased gray matter concentration in the insula (bilateral), superior temporal gyrus (bilateral), and amygdala (left) in patients compared to healthy subjects. This gray matter loss was directly related to the intensity of AH. Thirdly, using a new method for looking at areas of coincidence between gray matter loss and functional activation, large coinciding brain clusters were found in the left and right middle temporal and superior temporal gyri. Finally, we summarized our main findings from our studies of the molecular genetics of auditory hallucinations. Taking these data together, an integrative model to explain the neurobiological basis of this psychotic symptom is presented.     

磁源性影像对初级听觉皮质定位的研究

目的：应用磁源性影像对健康受试者进行初级听觉皮质定位，研究磁源性影像对听觉皮质定位的价值。方法：使用306通道全头型生物磁仪（脑磁图，MEG）测量9例右利手健康受试者的听觉皮质磁诱发反应，其中男7例，女2例，年龄14－47岁，平均31岁。给予受试者双耳纯音刺激，声音频率2kHz，强度90dB声压级（SPL），声音持续时间为8ms，刺激时间间隔为1s.将MEG测得的磁反应信息叠加到MR源性影像（MSI），确定初级听觉皮质的位置。结果：所有受试者均出现M50、M100、M150及M200（给予双耳听觉刺激后，分别于50、100、150、200ms左右出现的听觉诱发磁场波峰）。将M50、M150叠加到MRI，其等电流偶极（ECD）位置均在双侧颞横回，为初级听觉皮质的位置。所有受试者中，M100左、右侧半球ECD位置最大差值x轴为19.1mm,y轴为20.7mm,z轴为7.1mm。M50左、右侧半球ECD位置最大差值x轴为20.0mm,y轴为21.2mm,z轴为7.6mm。同一受试者M50波峰ECD位置与相应半球的M100波峰ECD位置极为接近，在统计学上无显著性差异（P＞0．05），其最大差值x轴为3.3mm,y轴为2.0mm,z轴为1.2mm。经统计学处理，本组受试者左、右侧初级听觉皮质位置无显著性差异（P＞0．05）。结论：应用磁源性影像可对初级听觉皮质准确定位。     

Nervous system excitability and joint stiffness following short-term dynamic ankle immobilization

Joint immobilization has been demonstrated to modify neural excitability in subsets of healthy populations, leading to disinhibition of cortical and reflexive pathways. However, these findings may have limited clinical application as most models have investigated casting and rigid immobilization, while many musculoskeletal injuries often utilize dynamic immobilization devices such as boot immobilizers and pneumatic splints that allow for modified ambulation. We therefore aimed to determine the short-term effects of ambulation in ankle immobilization devices on nervous system excitability and stiffness in able-bodied individuals. A repeated-measures design was implemented where 12 healthy individuals were tested for cortical excitability to the ankle musculature using transcranial magnetic stimulation, reflexive excitability using the Hoffmann reflex, and ankle joint stiffness using arthrometry before and after 30 min of ambulation with a boot immobilizer, pneumatic leg splint, or barefoot. Motor evoked potential (MEP), cortical silent period (CSP), H_max to M_max ratio, and ankle joint displacement were extracted as dependent variables. Results indicated that despite the novel motor demands of walking in immobilization devices, no significant changes in cortical excitability (F ≥ 0.335, P ≥ 0.169), reflexive excitability (F ≥ 0.027, P ≥ 0.083), or joint stiffness (F ≥ 0.558, P ≥ 0.169) occurred. These findings indicate that short-term ambulation in dynamic immobilization devices does not modify neural excitability despite forced constraints on the sensorimotor system. We may therefore conclude that modifications to neural excitability in previous immobilization models are mediated by long-term nervous system plasticity rather than acute mechanisms, and there appear to be no robust changes in corticomotor or spinal excitability acutely posed by ambulation with immobilization devices.     

视觉和听觉记忆功能的MRI研究

目的 :研究视觉和听觉记忆过程中脑功能fMRI的差异。方法 :将 8个健康老人分为两组 ,分别参加视觉和听觉记忆过程 ,用 1.5TMRI采集图像。结果 :①视觉记忆和听觉记忆均激活了双侧 9区 ,且激活体积无显著性差异 (P >0 0 5 )。②两者在双侧 7区差异显著 ,视觉记忆明显大于听觉记忆 (P <0 .0 5 )。③在双侧颞叶 2 2区只有听觉记忆激活。④在双侧枕叶 17/ 18/ 19区只有视觉记忆激活。结论 :在记忆过程中 ,视觉和听觉任务呈现方法的差异对fMRI结果会产生不同的影响。     

Reliability of low-frequency auditory stimulation studies associated with technetium-99m hexamethylpropylene amine oxime single-photon emission tomography

Development of auditory stimulation tests associated with single-photon emission tomography (SPET) shows evidence of variations in perfusion related to the stimuli. Three brain SPET examinations with technetium-99m hexamethylpropylene amine oxime were performed on eight right-handed adults with normal hearing, the first one without stimulation and the other two associated with a 500-Hz/30-dB stimulation of the right ear. Temporal regions of interest covering auditory areas, as well as parietal ones (internal control), were drawn on three successive coronal slices. A cortico-cerebellar index R was calculated, and the variation in activity was defined for each subject using the ratio R _{poststlmulation} — R _{prestiunulation}/R _{prestimulation}. A significant increase in the temporal cortex count occurred in all subjects. This increase was bilateral, except for one subject in whom it was not significant on the right side. This result recurred during the second stimulation study. Overall the response of the left temporal cortex was stronger, although the asymmetry was not significant. The asymmetry repeated itself after each stimulation. The perfusion response is globally reliable in our study. We must ascertainhow sensitive this test is with regard to deaf adults and adults with normal hearing before extending its use to children. Correspondence to: Y.Le Scao     

Beat perception ability and instructions to synchronize influence gait when walking to music-based auditory cues

Synchronizing gait to music-based auditory cues (rhythmic auditory stimulation) is a strategy used to manage gait impairments in a variety of neurological conditions, including Parkinson’s disease. However, knowledge of how to individually optimize music-based cues is limited. The purpose of this study was to investigate how instructions to synchronize with auditory cues influences gait outcomes among healthy young adults with either good or poor beat perception ability. 65 healthy adults walked to metronome and musical stimuli with high and low levels of perceived groove (how much it induces desire to move) and familiarity at a tempo equivalent to their self-selected walking pace. Participants were randomized to instruction conditions: (i) synchronized: match footsteps with the beat, or (ii) free-walking: walk comfortably. Participants were classified as good or poor beat perceivers using the Beat Alignment Test. In this study, poor beat perceivers show better balance-related parameters (stride width and double-limb support time) when they are not instructed to synchronize their gait with cues (versus when synchronization was required). Good beat perceivers, in contrast, were better when instructed to synchronize gait (versus when no synchronization was required). Changes in stride length and velocity were influenced by musical properties, in particular the perceived ‘groove’ (greater stride length and velocity with high- versus low-groove cues) and, in some cases, this interacted with beat perception ability. The results indicate that beat perception ability and instructions to synchronize indeed influence spatiotemporal gait parameters when walking to music- and metronome-based rhythmic auditory stimuli. Importantly, these results suggest that both low groove cues and instructing poor beat perceivers to synchronize may interfere with performance while walking, thus potentially impacting both empirical and clinical outcomes.     

The effects of knee osteoarthritis on neural activity during a motor task: A scoping systematic review

ObjectiveTo examine the evidence of neural activation with functional magnetic resonance imaging (fMRI), corticospinal excitability, and other central nervous system measurement differences during motor tasks between those with and without knee osteoarthritis (KOA).MethodsA scoping review strategy was systematically performed. We searched PubMed, CINAHL, Embase, PsychInfo, SportDiscus, SCOPUS and Web of Science from database inception to April 2021. Any study investigating central nervous system measures during a motor task for individuals with KOA with or without a healthy control group for comparison was included. Two reviewers independently screened all studies in accordance with the Preferred Reported Items for Systematic Reviews and Meta-analyses extension for scoping reviews.ResultsThirteen studies met the inclusion criteria. KOA had reduced activation of the premotor cortex during a gait imagery task when examining the brain using fMRI. This hypoactivation was not significant when the task was combined with ankle movement. Individuals with KOA had decreased motor cortex activation during a force matching motor task. KOA was associated with gamma loop dysfunction of the quadriceps and increased responsiveness of the triceps surae muscles. Also, there was an increased soleus Hoffmann reflex during heel strike of gait cycle. The flexor withdrawal reflex was heighted for individuals with KOA with a lower threshold of the reflex occurring with increased joint compression, but this reflex was modulated with joint mobilizations.ConclusionIndividuals with KOA have motor deficits associated with decreased neural activation, central nervous system sensitization, decreased quadriceps muscle spindle responsiveness, and increased triceps surae muscle activity.     

Lateralization of functional magnetic resonance imaging (fMRI) activation in the auditory pathway of patients with lateralized tinnitus

Introduction Tinnitus is hypothesized to be an auditory phantom phenomenon resulting from spontaneous neuronal activity somewhere along the auditory pathway. We performed fMRI of the entire auditory pathway, including the inferior colliculus (IC), the medial geniculate body (MGB) and the auditory cortex (AC), in 42 patients with tinnitus and 10 healthy volunteers to assess lateralization of fMRI activation. Methods Subjects were scanned on a 3T MRI scanner. A T2*-weighted EPI silent gap sequence was used during the stimulation paradigm, which consisted of a blocked design of 12 epochs in which music presented binaurally through headphones, which was switched on and off for periods of 50 s. Using SPM2 software, single subject and group statistical parametric maps were calculated. Lateralization of activation was assessed qualitatively and quantitatively. Results Tinnitus was lateralized in 35 patients (83%, 13 right-sided and 22 left-sided). Significant signal change (P _corrected < 0.05) was found bilaterally in the primary and secondary AC, the IC and the MGB. Signal change was symmetrical in patients with bilateral tinnitus. In patients with lateralized tinnitus, fMRI activation was lateralized towards the side of perceived tinnitus in the primary AC and IC in patients with right-sided tinnitus, and in the MGB in patients with left-sided tinnitus. In healthy volunteers, activation in the primary AC was left-lateralized. Conclusion Our paradigm adequately visualized the auditory pathways in tinnitus patients. In lateralized tinnitus fMRI activation was also lateralized, supporting the hypothesis that tinnitus is an auditory phantom phenomenon.     

脑默认网络临床应用及研究进展

脑默认网络（DMN）已成为神经放射学、认知神经科学等相关领域研究的焦点,其在静息状态下表现出大脑中线和外侧皮质区域功能活动相对活跃的特征,与人类认知及神经精神疾病存在着密切的关系。对该系统主要解剖位置、功能和临床意义及研究方法进展予以简述,并重点介绍其在阿尔茨海默病所致的痴呆、精神分裂症以及情感障碍疾病中的研究进展。     

Image artifacts in concurrent transcranial magnetic stimulation (TMS) and fMRI caused by leakage currents: Modeling and compensation

Purpose

To characterize and eliminate a new type of image artifact in concurrent transcranial magnetic stimulation and functional MRI (TMS‐fMRI) caused by small leakage currents originating from the high‐voltage capacitors in the TMS stimulator system.

Materials and Methods

The artifacts in echo‐planar images (EPI) caused by leakage currents were characterized and quantified in numerical simulations and phantom studies with different phantom‐coil geometries. A relay‐diode combination was devised and inserted in the TMS circuit that shorts the leakage current. Its effectiveness for artifact reduction was assessed in a phantom scan resembling a realistic TMS‐fMRI experiment.

Results

The leakage‐current‐induced signal changes exhibited a multipolar spatial pattern and the maxima exceeded 1% at realistic coil‐cortex distances. The relay‐diode combination effectively reduced the artifact to a negligible level.

Conclusion

The leakage‐current artifacts potentially obscure effects of interest or lead to false‐positives. Since the artifact depends on the experimental setup and design (eg, amplitude of the leakage current, coil orientation, paradigm, EPI parameters), we recommend its assessment for each experiment. The relay‐diode combination can eliminate the artifacts if necessary. J. Magn. Reson. Imaging 2009;29:1211–1217. © 2009 Wiley‐Liss, Inc.     

The effects of 72 h of dynamic ankle immobilization on neural excitability and lower extremity kinematics

BackgroundAnkle injuries can foster maladaptive changes in nervous system function that predisposes patients to subsequent injury. Patients are often placed in a dynamic boot immobilizer (BI) following injury; however, little is known about the effects of this treatment on neuromechanical function.Research questionWe aimed to determine the effect of 72 h of BI-use on neural excitability and lower extremity joint motion in a healthy cohort.MethodsTwelve uninjured individuals (20.8 ± 1.4 yrs, 1.7 ± 0.1 m, 75.2 ± 9.9 kg) participated in this crossover study. Neural excitability and lower extremity kinematics were assessed before and after 72 h of BI or compression sock (CS) use. Neural excitability was assessed via the Hoffmann (H) reflex and transcranial magnetic stimulation of the motor cortex by measuring muscle activation at the tibialis anterior, peroneus longus, and soleus of the immobilized extremity. Three-dimensional lower extremity joint angles were assessed while participants walked on a treadmill. Repeated-measures analyses of variance detected changes in neural excitability and peak joint angles across time-points and testing conditions, while statistical parametric mapping (SPM) was implemented to determine continuous joint angle changes (α = 0.05).ResultsPre-BI to post-BI, H_Max:M_Max ratio (F = 6.496; p = 0.031) significantly decreased. The BI did not alter resting motor threshold (F = 0.601; p = 0.468), or motor evoked potential amplitudes (F > 2.82; p > 0.608). Significant changes in peak knee and hip angles in the frontal and transverse planes were observed (p < 0.05), with no changes at the ankle. SPM analyses revealed significant hip and knee changes in range of motion (p < 0.05).SignificanceDecreased measures of reflex but not corticospinal excitability suggest that BI-use for 72 h unloaded the joint enough to generate peripheral changes, but not the CNS, as has been described in casting models. Further, kinematic changes were observed in proximal lower extremity joints, likely due to swing-phase adaptations while wearing the BI.     

Increment of brain temporal perfusion during auditory stimulation

A study on the dynamic exploration of the auditory pathway is presented, in which technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPET) was used in volunteers with normal hearing. Changes in ^99mTc-HMPAO distribution were calculated using a region of interest/whole-brain count ratio. The results showed a temporal perfusion increment of 17% (right) and 19% (left) during tonal supraliminar stimulation, which was significantly different from the control ROI. Sensitivity tests for the method were requested before any clinical application. Offprint requests to: Y. Le Scao     

功能磁刺激中线圈的改进

目的：改进功能磁刺激中的线圈,解决影响线圈刺激特性的主要因素：兴奋点的确定和聚焦性,方法：用法拉第定律计算线圈的感应电场分布,结果：当神经和8字形线圈的手柄垂直,并且和线线圈边缘相切时,感应电场的一阶导数极大值点不随线圈的半径和刺激深度变化;用组合线圈可以减小目标点以上区域电场的一阶导数值。结论：对于8字形线圈,和传统的刺激方法相比,使用新方法易于确定兴奋点位置,所提出的组合线圈可以改善沿深度方向的聚焦性。     

Corticospinal adaptations and strength maintenance in the immobilized arm following 3 weeks unilateral strength training

Cross‐education strength training has being shown to retain strength and muscle thickness in the immobilized contralateral limb. Corticospinal mechanisms have been proposed to underpin this phenomenon; however, no transcranial magnetic stimulation (TMS) data has yet been presented. This study used TMS to measure corticospinal responses following 3 weeks of unilateral arm training on the contralateral, immobilize arm. Participants (n = 28) were randomly divided into either immobilized strength training (Immob + train) immobilized no training (Immob) or control. Participants in the immobilized groups had their nondominant arm rested in a sling, 15 h/day for 3 weeks. The Immob + train group completed unilateral arm curl strength training, while the Immob and control groups did not undertake training. All participants were tested for corticospinal excitability, strength, and muscle thickness of both arms. Immobilization resulted in a group x time significant reduction in strength, muscle thickness and corticospinal excitability for the untrained limb of the Immob group. Conversely, no significant change in strength, muscle thickness, or corticospinal excitability occurred in the untrained limb of the Immob + train group. These results provide the first evidence of corticospinal mechanisms, assessed by TMS, underpinning the use of unilateral strength training to retain strength and muscle thickness following immobilization of the contralateral limb.     

Examining changes in corticospinal excitability and balance performance in response to social-comparative feedback

BackgroundSocial-comparative feedback informs an individual that their performance was better or worse than the group. Previous studies have found that compared to knowledge of results alone, social-comparative feedback produces a valence response that results in larger improvements in balance performance. However, the neural processes contributing to these motor improvements have not yet been examined.Research questionDoes social-comparative feedback alter corticospinal excitability and consequently, balance performance?MethodsThirty-six healthy young adults stood and maintained their balance on a stabiliometer for eight trials. After three of the trials, the neutral (i.e., only knowledge of results) group received their performance feedback (i.e., time on balance) while the other two groups also received positive (i.e., performed better than the group) or negative (i.e., performed worse than the group) social-comparative feedback. To measure corticospinal excitability, soleus motor-evoked potentials were elicited using transcranial magnetic stimulation at the beginning of the experiment, after the presentation of feedback, and at the end of the experiment. Pre- and post- ratings of confidence, perceived skill, motivation, and anxiety were also collected.ResultsThe negative feedback group reported decreases in perceived skill (43 ± 29%) and balance confidence (26 ± 28%), while the positive group reported a 13 ± 17% increase in perceived skill. Despite these group differences in feedback perception, all three groups improved their balance performance by ≈35% (p < 0.001) by the eighth trial. However, this improvement in balance performance was not matched by any changes in corticospinal excitability over time (19.2 ± 55.9% change; p = 0.340) or between groups (p = 0.734).SignificanceOur findings suggest that social-comparative feedback, as presented in this study, does not affect corticospinal excitability and balance performance differently than knowledge of results (neutral feedback) alone. More arousing and more frequent forms of social-comparative feedback may be necessary for observing larger changes in the functional or neural control of balance.     

The role and interaction of visual and auditory afferents in postural stability

BackgroundMaintaining balance requires the integration of vestibular, proprioceptive and visual information and the translation of this input into appropriate motor responses. Although the role of the visual system has been widely investigated, there are no studies addressing the influence of non-specific distracting auditory inputs on postural stability.ObjectiveTo analyze the role of the visual and auditory systems in the maintenance of postural stability and to assess potential interaction between the two sensory systems.MethodsTwenty-three healthy subjects were examined by computerized dynamic posturography. Stability index scores were calculated under each of six conditions: three visual conditions (sway feedback, eyes open without feedback, eyes closed) were combined with two auditory conditions (exposure or no exposure to non-specific auditory input). Analysis of variance (ANOVA) was used to test for differences among groups in the six test conditions.ResultsPostural stability was much poorer in the eyes-closed (overall stability index (OSI): 6.8 ± 2.1°) than in the eyes-open condition (OSI: 2.2 ± 1.2°). Balance control significantly improved with visual feedback (OSI: 1.2 ± 0.5°). Exposure to non-specific auditory input (music through headphones) did not have a significant influence (OSI: 6.4 ± 2.3°/2.0 ± 0.9°/1.1 ± 0.5°).ConclusionsPostural stability depended not only on whether the subjects were tested with their eyes open or closed but also on the presence or absence of visual feedback. Non-specific auditory information did not influence postural control. Since postural stability is regulated by multiple senses such as the vestibular system and proprioception, auditory stimuli may play an increasing role if one of the systems involved is impaired.     

Isometric knee extensor fatigue following a Wingate test: peripheral and central mechanisms

Central and peripheral fatigue have been explored during and after running or cycling exercises. However, the fatigue mechanisms associated with a short maximal cycling exercise (30 s Wingate test) have not been investigated. In this study, 10 volunteer subjects performed several isometric voluntary contractions using the leg muscle extensors before and after two bouts of cycling at 25% of maximal power output and two bouts of Wingate tests. Transcranial magnetic stimulation (TMS) and electrical motor nerve stimulation (NM) were applied at rest and during the voluntary contractions. Maximal voluntary contraction (MVC), voluntary activation (VA), twitch amplitude evoked by electrical nerve stimulation, M wave and motor potential evoked by TMS (MEP) were recorded. MVC, VA and twitch amplitude evoked at rest by NM decreased significantly after the first and second Wingate tests, indicating central and peripheral fatigue. MVC and VA, but not the twitch amplitude evoked by NM, recovered before the second Wingate test. These results suggest that the Wingate test results in a decrease in MVC associated with peripheral and central fatigue. While the peripheral fatigue is associated with an intramuscular impairment, the central fatigue seems to be the main reason for the Wingate test‐induced impairment of MVC.     

正常人及突发性耳聋患者听觉功能性磁共振的初步研究

目的：用血氧水平依赖脑功能成像(blood-oxygen level dependent functional MRI，BOLD fMPI)对正常受试者及突发性耳聋患者听觉中枢进行定位并简单比较其异同。方法：健康志愿者10例，男6例，女4例，年龄24～51岁，平均36．4岁。以及突发性耳聋患者2例。所有正常志愿者刺激期，均接受单耳2000Hz纯音频刺激；基线期，无音频刺激。对于突发性耳聋患者，根据其电测听结果，给予相应听力下降频率的阈上及阈下刺激。实验数据均使用SPM99处理。结果：对于听力正常志愿者，fMRI结果显示双侧颞上回有较明显的激活，刺激对侧激活范围及强度均超过刺激同侧。对于突发性耳聋患者，给予阈下刺激时，脑内未发现明确的听觉激活区；给予阈上刺激时，可以发现双侧颞上回有较明显的激活，但双侧听觉中枢的激活程度及范围基本相近。结论：MRI可以显示正常人听觉中枢所在位置，因此当病变累及到听觉中枢时，可以用fMRI方法对突发性耳聋是中枢性的还是外周性的做出判断，若为中枢性的，则可显示听觉中枢的受累情况，对突发性耳聋的治疗给出指导性建议。     

Central and peripheral fatigue following non‐exhaustive and exhaustive exercise of disparate metabolic demands

The development of fatigue after non‐exhaustive and exhaustive exercise eliciting differing metabolic demands is poorly understood. Sixteen active males completed five cycling trials. The first trial established the lactate threshold (LT) and maximal oxygen uptake (VO_2max). Two of the remaining trials were completed at a severe intensity (halfway between LT and VO_2max, SI) and two at a moderate intensity (90% LT, MI). Each trial involved two non‐exhaustive bouts matched for work between intensities before cycling to exhaustion. Responses to stimulation of the femoral nerve and motor cortex were determined after each bout to determine peripheral and central fatigue. Corticospinal excitability, cortical silent period (cSP), short‐interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were also assessed. Non‐exhaustive cycling induced greater peripheral and central fatigue in the SI compared with the MI (P < 0.05). At exhaustion, there was no difference between intensities; however, peripheral fatigue tended to be greater in the SI vs MI (?31% vs ?17%, respectively, P = 0.051). Exhaustive cycling increased SICI (24%, P < 0.001) and reduced the cSP (?14%, P < 0.001) in the SI, whereas ICF was reduced in the MI (?16%, P < 0.001). These findings demonstrate exercise‐induced metabolic stress accelerates the development of peripheral and central fatigue, and differentially influences intracortical excitability.