A study of transcallosal inhibition in schizophrenia using transcranial magnetic stimulation

A considerable body of imaging research has demonstrated morphological changes in the corpus callosum (CC) of patients with schizophrenia. Transcranial magnetic stimulation (TMS) allows the possibility for the in vivo investigation of a variety of aspects of brain function including the spread of information across the CC. We aimed to investigate whether patients with schizophrenia demonstrate abnormalities of transcallosal inhibition (TCI), a TMS parameter measured with both single and paired pulse experiments. 25 patients with DSM-IV schizophrenia and 20 normal volunteers participated in the study. Electromyographic (EMG) recordings from the bilateral abductor pollicis brevis (APB) muscle were made during focal TMS stimulation to the motor cortex. Experimental paradigms were utilised to measure both the timing and degree of the effect of TCI. The patient group demonstrated a reduction in the degree of TCI at rest and during a sustained muscle contraction. TCI commenced at the same time in the patient and the control group but was of prolonged duration in the patient group although the length of TCI correlated with medication dose. Patients with schizophrenia demonstrate a reduction in the degree of TCI that appeared independent of medication dose. The latency of TCI is not altered in the patient group suggesting that cortical inhibitory mechanisms, rather than corpus callosal ones, are likely to be the cause of these TCI alterations.     

Measuring latency distribution of transcallosal fibers using transcranial magnetic stimulation

BackgroundNeuroimaging technology is being developed to enable non-invasive mapping of the latency distribution of cortical projection pathways in white matter, and correlative clinical neurophysiological techniques would be valuable for mutual verification. Interhemispheric interaction through the corpus callosum can be measured with interhemispheric facilitation and inhibition using transcranial magnetic stimulation.ObjectiveTo develop a method for determining the latency distribution of the transcallosal fibers with transcranial magnetic stimulation.MethodsWe measured the precise time courses of interhemispheric facilitation and inhibition with a conditioning-test paired-pulse magnetic stimulation paradigm. The conditioning stimulus was applied to the right primary motor cortex and the test stimulus was applied to the left primary motor cortex. The interstimulus interval was set at 0.1 ms resolution. The proportions of transcallosal fibers with different conduction velocities were calculated by measuring the changes in magnitudes of interhemispheric facilitation and inhibition with interstimulus interval.ResultsBoth interhemispheric facilitation and inhibition increased with increment in interstimulus interval. The magnitude of interhemispheric facilitation was correlated with that of interhemispheric inhibition. The latency distribution of transcallosal fibers measured with interhemispheric facilitation was also correlated with that measured with interhemispheric inhibition.ConclusionsThe data can be interpreted as latency distribution of transcallosal fibers. Interhemispheric interaction measured with transcranial magnetic stimulation is a promising technique to determine the latency distribution of the transcallosal fibers. Similar techniques could be developed for other cortical pathways.     

A transcranial magnetic stimulation study of abnormal cortical inhibition in schizophrenia

Previous research suggests that patients with schizophrenia demonstrate deficits in a range of parameters of motor cortical and cognitive inhibition. I-wave facilitation and long-interval cortical inhibition (LICI) are two paired pulse transcranial magnetic stimulation paradigms that appear to assess aspects of cortical inhibitory function that have not previously been assessed in this patient group. Eighteen patients with schizophrenia (nine medication-free) were compared with eight control subjects. We assessed resting motor threshold (RMT) levels, LICI and I-wave facilitation. RMT levels did not differ between the three groups. There was a significant overall difference in I-wave facilitation levels. Both patient groups as compared with the control group showed increased facilitation. There were no differences between the groups in the measure of LICI. Patients with schizophrenia appear to have increased I-wave facilitation. Increased I-wave facilitation suggests deficient function of cortical inhibitory GABAergic activity. This is consistent with previous research that has found deficient cortical inhibition in patients with schizophrenia.     

Interhemispheric transfer of information and schizophrenia

Summary The interhemispheric transfer of stereognostic information was investigated in four groups of subjects: paranoid schizophrenics, non-paranoid schizophrenics, non-schizophrenic psychiatric patients, and normals. Previous work has raised the possibility that schizophrenia is characterised by a dysfunction of the corpus callosum, but there are several methodological problems associated with this research. A comparison of inter-manual and same-hand conditions on the experimental task revealed no evidence for impaired transfer of information in the schizophrenic groups. However, the performance of the non-paranoid schizophrenic group was markedly inferior to all other groups on the right hand/right hand no transfer condition, consistent with a left hemisphere dysfunction. Possible reasons for the failure to replicate previous findings are discussed.     

重复经颅磁刺激用于精神分裂症中安全性及可行性

目的探讨重复经颅磁刺激用于精神分裂症中安全性及可行性。方法运用随机抽样方选取我院2013-01-2014-09收治的60例精神分裂症患者,依据治疗方法将患者分为研究组(n=30)和对照组(n=30)。对照组患者给予假刺激方案治疗,研究组给予重复经颅磁刺激治疗。结果研究组阳性和阴性症状评分均显著低于对照组(P0.05),精神症状改善时间和住院时间均显著短于对照组(P0.05),治疗的总有效率93.3%(28/30)显著高于对照组70.0%(21/30)(P0.05),不良反应发生率13.3%(4/30)显著低于对照组33.3%(10/30),P0.05。结论重复经颅磁刺激用于精神分裂症中安全可行,值得推广。     

Short- and intermediate-interval cortical inhibition and facilitation assessed by navigated transcranial magnetic stimulation

One of the most widely utilized in vitro models of ischemia or oxygen glucose deprivation (OGD) is the hippocampal organotypical culture (HOTC). The HOTC is used not only for the study of the mechanisms of cell death, but also has been the cornerstone of synaptic physiology. Although the intact nature of the HOTC is one of its primary advantages, some studies require a dissociated preparation in order to distinguish cell type specific responses. Typically, primary dissociated neuronal cultures are prepared from embryonic tissue. Since the HOTC is prepared from postnatal pups, we wanted to establish a primary culture of hippocampus from postnatal pups to parallel our studies in the HOTC preparation. Mixed cultures were prepared by enzymatic dissociation of hippocampus from 7-day-old mouse pups. These cultures responded to OGD with a time course of delayed cell death that was similar to that reported in HOTC. Dual label immunocytochemical staining revealed that neurons, but not astrocytes, were dying from apoptosis following OGD. To examine this vulnerability further, we also prepared neuronal enriched cultures by treating mixed cultures with cytosine-β-d-arabinofuranoside (CBA). These neuronal cultures appear to be even more sensitive to OGD. In addition, we have established primary astrocyte-enriched cultures from the same age pups to examine the vulnerability of astrocytes to OGD. These three culture preparations are useful for comparison of the responses of the two major cell types in the same culture, and the enriched cultures will allow biochemical, electrophysiological and molecular studies of homogenous cell populations.     

Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation

BACKGROUND: Cortical inhibition (CI) deficits have been proposed as a pathophysiologic mechanism in schizophrenia. This study employed 3 transcranial magnetic stimulation (TMS) paradigms to assess CI in patients with schizophrenia. Paired-pulse TMS involves stimulating with a lower-intensity pulse a few milliseconds before a higher-intensity pulse, thereby inhibiting the size of the motor evoked potential produced by the higher-intensity pulse. In the cortical silent period paradigm, inhibition is reflected by the silent period duration (ie, the duration of electromyographic activity cessation following a TMS-induced motor evoked potential). Transcallosal inhibition involves stimulation of the contralateral motor cortex several milliseconds prior to stimulation of the ipsilateral motor cortex, inhibiting the size of the motor evoked potential produced by ipsilateral stimulation. METHODS: We measured CI using these 3 paradigms in 15 unmedicated patients with schizophrenia (14 medication-naive and 1 medication-free for longer than 1 year) (13 were in the transcallosal inhibition paradigm), 15 medicated patients with schizophrenia (11 taking olanzapine, 1 risperidone, 1 quetiapine, 1 methotrimeprazine + perphenazine, 1 quetiapine + loxapine), and 15 healthy controls. RESULTS: Unmedicated patients demonstrated significant CI deficits compared with healthy controls across all inhibitory paradigms whereas medicated patients did not (at all inhibitory intervals, paired-pulse TMS: controls = 59.9%, medicated = 44.3%, unmedicated = 28.7%; cortical silent period: controls = 55.0 milliseconds, medicated = 60.4 milliseconds, unmedicated = 39.7 milliseconds; transcallosal inhibition: controls = 33.6%, medicated = 23.7%, unmedicated = 10.4%; P<.05). CONCLUSIONS: These results suggest that schizophrenia is associated with deficits in CI and that antipsychotic medications may increase CI.     

Intracortical inhibition and facilitation upon awakening from different sleep stages: a transcranial magnetic stimulation study

Intracortical facilitation and inhibition, as assessed by the paired-pulse transcranial magnetic stimulation technique with a subthreshold conditioning pulse followed by a suprathreshold test pulse, was studied upon awakening from REM and slow-wave sleep (SWS). Ten normal subjects were studied for four consecutive nights. Intracortical facilitation and inhibition were assessed upon awakening from SWS and REM sleep, and during a presleep baseline. Independently of sleep stage at awakening, intracortical inhibition was found at 1-3-ms interstimulus intervals and facilitation at 7-15-ms interstimulus intervals. Motor thresholds were higher in SWS awakenings, with no differences between REM awakenings and wakefulness, while motor evoked potential amplitude to unconditioned stimuli decreased upon REM awakening as compared to the other conditions. REM sleep awakenings showed a significant increase of intracortical facilitation at 10 and 15 ms, while intracortical inhibition was not affected by sleep stage at awakening. While the dissociation between motor thresholds and motor evoked potential amplitudes could be explained by the different excitability of the corticospinal system during SWS and REM sleep, the heightened cortical facilitation upon awakening from REM sleep points to a cortical motor activation during this stage.     

The effect of acute and chronic nicotine consumption on intra-cortical inhibition and facilitation: A transcranial magnetic stimulation study

ObjectiveThe aim of the present study was to explore the impact of acute and chronic nicotine consumption on measures of intracortical inhibition and facilitation.MethodsThis study involved 50 chronic heavy cigarette smokers and 40 healthy subjects matched for age, sex and educational level, with no history of chronic nicotine intake. Intracortical inhibition and facilitation were assessed using transcranial magnetic stimulation (TMS) measures of motor threshold (MT), short- and long-interval intra-cortical inhibition (SICI, LICI), cortical silent period (CSP) and intra-cortical facilitation (ICF). Basal serum levels of cotinine were measured in the healthy group and at ½ and 2 h after smoking a single cigarette in the chronic smokers.ResultsThere was enhanced SICI and reduced ICF in smokers (independent of time after smoking) compared with non-smokers. The former suggests a chronic effect of increased nicotine levels on GABA-A neurotransmission whereas the latter suggests an additional effect on glutamatergic transmission. There were no significant differences between smokers and non-smokers in other TMS parameters. There was a significant negative correlation between cotinine levels at ½ h after smoking and SICI at 3 ms ISI (P < 0.001). There were no significant differences in any of the neurophysiological measures between smokers at ½ h versus 2 h after smoking a single cigarette.ConclusionChronic nicotine consumption enhances SICI, and reduces ICF, supporting the hypothesis that nicotine acts as a neuromodulator of GABA-A and glutamate neurotransmission.     

Repetitive transcranial magnetic stimulation for treating the symptoms of schizophrenia: A PRISMA compliant meta-analysis

Objective

To explore the efficacies of 1-Hz (low frequency) and 10-Hz (high frequency) repetitive transcranial magnetic stimulation (rTMS) in treating auditory hallucinations and negative symptoms of schizophrenia, respectively.

The variability of intracortical inhibition and facilitation

OBJECTIVE: To assess the variability of transcranial magnetic stimulation paired pulse measurements of cortical excitability between subjects, between sessions and within subjects within sessions. METHODS: In experiment 1, intracortical inhibition and facilitation were assessed with a fixed conditioning stimulus intensity (CSI) of 80% of active motor threshold (AMT) whereas in experiment 2, the effect of different CSIs (60-110% of AMT) was investigated. RESULTS: Experiment 1 revealed that subjects differed significantly in the degree of inhibition and facilitation. Between sessions the variability was substantial as predicted by high within session variability. Experiment 2 allowed determination of individual thresholds for inhibition and facilitation. These thresholds were the best predictor of the amount of inhibition or facilitation at a given CSI. Across subjects we observed a high correlation of the threshold for inhibition (expressed in terms of maximum stimulator output) with AMT (r=0.93). Results for facilitation were more variable. CONCLUSIONS: The variability was high if a single CSI was used to compare the percent intracortical inhibition or facilitation between subjects, or between sessions. Much less variable was the threshold for intracortical inhibition/facilitation, which was highly correlated to AMT. We suggest that the ratio of CSI:AMT is a robust and useful additional measure of the integrity of neuronal circuits underlying intracortical inhibition/facilitation.     

Experience with transcranial magnetic stimulation in cortical mapping

Abstract

Seventeen subjects underwent transcranial magnetic stimulation (TMS) toward cortical mapping. Cortical mapping produced scalp representations of five upper extremity muscles and their spatial orientation tended to support an expected anatomic pattern. Muscle map locations and map areas showed trends across musical skill and hand dominance as well. No subject experienc.ed adverse effects during the study. TMS promises to be an effective tool for noninvasive cortical mapping. [Neural Res 1997; 19: 435-440]     

低频重复经颅磁刺激治疗精神分裂症慢性幻听的疗效及随访研究

目的研究低频重复经颅磁刺激（rTMS）对精神分裂症难治性慢性幻听症状的疗效。方法将46例精神分裂症伴慢性幻听患者随机分为研究组（23例）和对照组（23例）。研究组在原有抗精神病药物种类及剂量不变的同时给予经左侧颞顶叶的2周共10次低频（1Hz）rTMS刺激,对照组采用假rTMS刺激。治疗前后对两组分别进行AHRS听幻觉量表及临床疗效总评量表（CGI）评定幻听症状的变化,并对治疗有效者于3个月后随访。结果研究组治疗前、后AHRS评分分别为（8．1±2．5）和（3．5±1．5）;对照组为（7．8±2．6）和（6．5±2．1）,研究组疗效明显优于对照组（F=20．3,P〈0．05）。所有患者均完成试验,未见有严重的副反应出现。结论低频rTMS治疗精神分裂症难治性慢性幻听症状,疗效肯定且安全性好。     

Intracortical inhibition and facilitation of the response of the diaphragm to transcranial magnetic stimulation.

Respiratory muscles respond to a subcortical automatic command and to a neocortical voluntary command. In diseases such as stroke or motor neurone disease, an abnormal diaphragmatic response to single transcranial magnetic stimuli can identify a central source for respiratory disorders, but this is not likely to be the case in disorders affecting intracortical inhibitory and facilitatory mechanisms. This study describes the response of the diaphragm to paired transcranial magnetic stimulation. Thirteen normal subjects were studied (age range, 22 to 43 years; 7 men; phrenic conduction, <6.8 msec; latency of diaphragmatic motor evoked potential, <20.5 msec). Motor evoked potentials in response to paired stimulation were obtained in eight subjects only, with the motor threshold in the remaining five subjects too high to absorb the loss of power inherent in the double-stimulation montage. Interstimulus intervals less than 5 msec resulted in a statistically significant inhibition (p < 0.01 for interstimulus intervals of 1 and 3 ms), whereas intervals longer than 6 msec were facilitatory (maximal, 15 msec). The diaphragmatic pattern matched that of the biceps brachii. The authors conclude that it is possible to study intracortical inhibition and facilitation of diaphragmatic control, although not in all subjects. Technical improvement should alleviate current limitations and make paired transcranial magnetic stimulation a tool to study respiratory muscle abnormalities in settings in which intracortical interactions are important, such as movement disorders.     

Nonspecific facilitation of responses to transcranial magnetic stimulation.

We examined the effect of facial muscle contraction and eye movements on motor evoked potentials (MEPs) from the abductor pollicis brevis muscle (APB) evoked by transcranial magnetic stimulation (TMS). The hypothesis was that activity of large cortical regions (face) influences the excitability of spinal motoneurons via cortical or subcortical pathways. MEPs were recorded in 12 healthy subjects during the following conditions: (1) rest; (2) facial muscle contraction; (3) eye movements; (4) 10% precontraction of the target muscle; and (5) simultaneous target muscle precontraction and facial muscle contraction. In 9 subjects, spinal motoneuron excitability was assessed by measurements of F waves during the same facilitation maneuvers. Activation of eye and facial muscles clearly facilitated MEPs from the APB. The facilitation of MEP size during nonspecific maneuvers was almost similar to that obtained by target muscle precontraction, whereas shortening of latencies was significantly smaller. The occurrence and amplitude of F waves increased in parallel with MEP size during specific and nonspecific facilitation, pointing to spinal motoneuronal threshold changes as a potential facilitatory mechanism by facial and eye muscle activation. The different MEP latencies during specific and nonspecific facilitation were not explained by different spinal motoneuron excitability, but raise the possibility that supraspinal mechanisms contributed to nonspecific facilitation.     

重复经颅磁刺激治疗精神分裂症阴性症状的随机双盲研究

目的探讨重复经颅磁刺激（rTMS）治疗精神分裂症阴性症状的疗效。方法 30例精神分裂症患者被随机分为rTMS真刺激组（治疗组,15例）和rTMS伪刺激组（对照组,15例）,采用θ短阵快速脉冲刺激（TBS）模式刺激左侧前额叶背外侧皮质（DLPFC）,每周5次,共干预20次。于基线、治疗2周及治疗4周时应用阳性与阴性症状量表（PANSS）的阴性因子分和阴性症状量表（SANS）进行疗效评定。结果共有27例患者完成研究,对照组有3例脱落。经rTMS干预4周后,治疗组与对照组的PANSS阴性因子分减分值分别为（4.67±2.47）分和（2.33±1.87）分,两组比较有统计学差异（z=-2.41,P=0.016）;SANS总分减分值分别为（11.87±8.04）分和（5.92±6.47）分,两组比较有统计学差异（z=2.08,P=0.038）。根据PANSS阴性因子分评定,治疗组的有效率达到46.7%,对照组的有效率为16.7%;根据SANS总分评定治疗组的有效率达到46.7%,而对照组的有效率为8.3%;阴性症状的组间疗效差异有统计学意义（P〈0.05）。除了轻微的一过性头痛和入睡困难,未见有其他严重不良反应。结论 TBS模式可改善精神分裂症患者的阴性症状。     

重复经颅磁刺激治疗精神分裂症患者认知功能障碍的研究进展

认知功能障碍是精神分裂症患者的核心症状之一,与患者的预后和社会功能关系密切,使用抗精神病药物改善精神分裂症患者的认知损害效果尚不理想.重复经颅磁刺激(rTMS)作为一种将脉冲磁场作用于大脑皮质并产生感应电流,进而影响脑内神经电活动和基础代谢的电生理技术,目前已被用于精神分裂症患者的临床治疗中.本文综述了rTMS改善认知功能的可能机制,对rTMS治疗精神分裂症患者认知功能障碍的研究进展以及安全性等进行阐述.     

Left prefrontal repetitive transcranial magnetic stimulation in schizophrenia

In a double-blind, controlled study, we examined the therapeutic effects of high-frequency left prefrontal repetitive transcranial magnetic stimulation (rTMS) on schizophrenia symptoms. A total of 22 chronic hospitalized schizophrenia patients were randomly assigned to 2 weeks (10 sessions) of real or sham rTMS. rTMS was given with the following parameters: 20 trains of 5-second 10-Hz stimulation at 100 percent motor threshold, 30 seconds apart. Effects on positive and negative symptoms, self-reported symptoms, rough neuropsychological functioning, and hormones were assessed. Although there was a significant improvement in both groups in most of the symptom measures, no real differences were found between the groups. A decrease of more than 20 percent in the total PANSS score was found in 7 control subjects but only 1 subject from the real rTMS group. There was no change in hormone levels or neuropsychological functioning, measured by the MMSE, in either group. Left prefrontal rTMS (with the used parameters) seems to produce a significant nonspecific effect of the treatment procedure but no therapeutic effect in the most chronic and severely ill schizophrenia patients.     

Reduced motor cortical inhibition in migraine: A blinded transcranial magnetic stimulation study

Objective

To investigate motor cortical excitability, inhibition, and facilitation with navigated transcranial magnetic stimulation (TMS) in migraine in a blinded cross-sectional study.