Adjustments of prehension synergies in response to self-triggered and experimenter-triggered load and torque perturbations

Humans are known to show anticipatory adjustments in the grip force prior to a self-generated or predictable action or perturbation applied to a hand-held object. We investigated whether humans can also adjust covariation of individual finger forces (multi-finger synergies) prior to self-triggered perturbations. To address this issue, we studied adjustments in multi-digit synergies associated with applied load/torque perturbations while the subjects held a customized handle steadily. The main hypothesis was that the subjects would be able to demonstrate the phenomenon of anticipatory covariation, that is changes in covariation patterns among digit forces and moments of force in anticipation of a perturbation, but only when the perturbation was triggered by the subjects themselves. Based on the principle of superposition (decoupled grasping force and resultant torque control), we also expected to see different adjustments in indices of multi-digit synergies stabilizing the total gripping force and the total moment of force. The task for the subjects (n = 8) was to return the initial handle position as quickly as possible after a perturbation, which consisted of removing one of three loads hanging from the handle. There were six experimental conditions: two types of perturbations (self-triggered and experimenter-triggered) by three positions of the load (left, center, and right). Three-dimensional forces and moments of force recorded from each digit contact were used for the analysis. Indices of covariation among digit forces and among moments of force, previously employed for studying motor synergies, were computed across trials. Positive values of the indices reflected negative covariations of individual digit forces and moments of force (their inter-compensatory changes) to stabilize the total force and moment acting on the handle. In steady-state conditions, subjects showed strong positive indices for both digit forces and digit moments. Under the self-triggered conditions, changes in the indices of digit force and moment covariation were seen about 150 ms prior to the perturbation, while such changes were observed only after the perturbation under the experimenter-triggered conditions. Immediately following a perturbation, the indices of force and moment covariation rapidly changed to negative revealing the lack of inter-compensation among the individual digit forces and moments. Later, both indices showed a recovery to positive values; the recovery was faster in the self-triggered conditions than in the experimenter-triggered ones. During the steady-state phase after the perturbation, the indices of force and moment covariation decreased and increased, respectively, as compared to their values during the steady-state phase prior to the perturbation. We conclude that humans are able to adjust multi-digit synergies involved in prehensile tasks in anticipation of a self-triggered perturbation. These conclusions speak against hypotheses on the organization of multi-element actions based on optimal control principles. Different changes in the indices of force and moment covariation after a perturbation corroborate the principle of superposition. We discuss relations of anticipatory covariation to anticipatory postural adjustments.     

Treating anxious depression using repetitive transcranial magnetic stimulation

Background

A subset of patients given a clinical diagnosis of major depressive disorder (MDD) are described as having “anxious depression,” a presentation that, in some studies, has been an indicator of poor response to pharmacotherapy. The aim of this study was to determine if anxious depression is associated with attenuated response to repetitive transcranial magnetic stimulation (rTMS), an FDA-approved treatment for MDD.

Methods

Participants were 32 adult outpatients with treatment resistant MDD who were referred for rTMS. The Hamilton Rating Scale for Depression (HAMD) was administered to assess treatment response, and anxious depression was defined as a score of seven or above on the anxiety/somatization factor of the HAMD. A quarter of the sample met the anxious depression criterion at pretreatment.

Results

Both depression (total score) and anxiety symptoms improved from pre- to post-treatment with moderate to large treatment effects. Patients with and without anxious depression demonstrated similar rates of improvement in depression. Patients with versus without anxious depression demonstrated larger improvements in anxiety.

Limitations

The sample size was small, and assessments did not include structured diagnostic interview or independent measures of anxiety symptoms.

Conclusions

For the sample as a whole, there were significant improvements in both depression and anxiety. Anxious depression was not associated with attenuated treatment response to rTMS.     

Localising awareness of action with transcranial magnetic stimulation

 Seven subjects reacted to an auditory stimulus by pressing a response key and judged their reaction time (RT) by reporting the position of a rotating clock-hand at which they pressed the key. Transcranial magnetic stimulation (TMS) was delivered either over primary motor cortex (MI) or more anteriorly (with the centre of the coil over FCz) 75 ms before each subject’s median reaction time. TMS over MI produced substantial delays in actual RT, but much smaller delays in judged RT. TMS over FCz produced smaller delays in actual RT and relatively larger delays in judged RT. We conclude that awareness of responses is generated, at least in part, between premotor areas affected by stimulation over FCz and the primary motor cortex. Received: 3 June 1998 / Accepted: 4 February 1999     

经颅磁刺激对部位相关癫癎患者运动皮质功能的评估

目的:采用经颅磁刺激技术(TMS)探讨症状性运动部位相关癫癎患者发作间期运动皮质的兴奋性.方法:对诊断明确的34例癫癎患者(分治疗组和未治疗组)及20例年龄、性别匹配的正常对照组进行单脉冲经颅磁刺激,刺激部位头颅相应的运动手区和颈7棘突外侧,并于对侧小指外展肌记录运动诱发电位(MEP),分析其阈强度(TI)、周围潜伏期(PL)及皮质潜伏期(CL)、中枢传导时间(CCT)和静息期(SP).结果:所有癫癎患者PL、CL及CCT均在正常范围内,但TI和SP明显低于正常对照组(P< 0.01).在癫癎患者中,未治疗组TI及SP明显低于治疗组(P< 0.01),致癎灶侧TI及SP低于非致癎灶侧(P< 0.05),但非致癎灶侧SP亦缩短.结论:单脉冲低频TMS能有效地反映中枢运动皮质的功能状态,用于症状性运动部位相关癫癎患者发作间期运动皮质兴奋性研究具有重要的实用价值.     

跨颅磁刺激观察前额叶皮层在学习记忆中的作用

目的为了探讨前额叶皮层的功能。方法在被试进行联合搜索作业(conjunction search task)时,使用跨颅磁刺激干扰被试者右侧前额叶皮层的活动,观察被试者在训练前后反应时间的变化。结果发现磁刺激干扰前额叶的活动,明显地延长了被试者在训练前的反应时间,对训练之后的反应时间几乎没有变化。结论这说明右侧前额叶参与了记忆的编码,对记忆的提取没有作用。     

Short-term reduction of intracortical inhibition in the human motor cortex induced by repetitive transcranial magnetic stimulation

Ten healthy subjects and two patients who had an electrode implanted into the cervical epidural space underwent repetitive transcranial magnetic stimulation (rTMS; 50 stimuli at 5 Hz at active motor threshold intensity) of the hand motor area. We evaluated intracortical inhibition before and after rTMS. In healthy subjects, we also evaluated threshold and amplitude of motor evoked potentials (MEPs), duration of cortical silent period and short-latency intracortical facilitation. rTMS led to a short-lasting reduction in the amount of intracortical inhibition in control subjects with a high interindividual variability. There was no significant effect on other measures of motor cortex excitability. Direct recordings of descending corticospinal volleys from the patients were consistent with the idea that the effect of rTMS on intracortical inhibition occurred at the cortical level. Since the level of intracortical inhibition can be influenced by drugs that act on GABAergic systems, this may mean that low-intensity repetitive magnetic stimulation at 5 Hz can selectively modify the excitability of GABAergic networks in the human motor cortex. Electronic Publication     

Theta burst transcranial magnetic stimulation is associated with increased EEG synchronization in the stimulated relative to unstimulated cerebral hemisphere

Theta burst transcranial magnetic stimulation (TBS) may induce behavioural changes that outlast the stimulation period. The neurophysiological basis of these behavioural changes are currently under investigation. Given the evidence that cortical information processing relies on transient synchronization and desynchronization of neuronal assemblies, we set out to test whether TBS is associated with changes of neuronal synchronization as assessed by surface EEG. In four healthy subjects one TBS train of 600 pulses (200 bursts, each burst consisting of 3 pulses at 30 Hz, repeated at intervals of 100 ms) was applied over the right frontal eye field and EEG synchronization was assessed in a time-resolved manner over 60 min by using a non-overlapping moving window. For each time step the linear cross-correlation matrix for six EEG channels of the right and for the six homotopic EEG channels of the left hemisphere were computed and their largest eigenvalues used to assess changes of synchronization. Synchronization was computed for broadband EEG and for the delta, theta, alpha, beta and gamma frequency bands. In all subjects EEG synchronization of the stimulated hemisphere was significantly and persistently increased relative to EEG synchronization of the unstimulated hemisphere. This effect occurred immediately after TBS for the theta, alpha, beta and gamma frequency bands and 10-20 min after TBS for broadband and delta frequency band EEG. Our results demonstrate that TBS is associated with increased neuronal synchronization of the cerebral hemisphere ipsilateral to the stimulation site relative to the unstimulated hemisphere. We speculate that enhanced synchronization interferes with cortical information processing and thus may be a neurophysiological correlate of the impaired behavioural performance detected previously.     

Hierarchical control of static prehension: II. Multi-digit synergies

The purpose of this study was to explore the ability of the central nervous system (CNS) to organize synergies at two levels of a hypothetical control hierarchy involved in two-hand multi-finger prehension tasks with one or more persons participating in the task together. At the higher level of the hierarchy, the total force and moment of force produced on an object are distributed between the thumb and the virtual finger (an imagined finger with mechanical output equal to the involved fingers of the hand), while at the lower level the virtual finger action is distributed among the four fingers. We tested a hypothesis that the CNS is able to organize synergies at only one level of the hierarchy. The subjects held vertically one of the two handles, a narrow one and a wide one. They used the four fingers of the right hand opposed by the right hand thumb, the left hand thumb, the left hand index finger, the thumb of an experimenter, the index finger of an experimenter, or an inanimate object. Forces and moments of force produced by each digit were recorded. Indices of synergies stabilizing the mechanical output variables at each of the two levels were computed. Contrary to the expectations, force and moment of force stabilizing synergies were found at one or both levels of the hierarchy across all tasks. Unimanual tasks exhibited higher synergy indices compared to all tasks, while intrapersonal synergy indices were higher than those of interpersonal synergies. The results suggest that both feed-forward and feedback mechanisms may be used to create force and moment of force stabilizing synergies. We invoke the notion of chain effects and generalize it for relations among variance components related to stabilization of different mechanical variables. The reference configuration hypothesis offers a fruitful framework for analysis of prehension synergies.     

Motor control of the costal and crural diaphragm--insights from transcranial magnetic stimulation in man

The costal and crural parts of the diaphragm differ in their embryological development and physiological function. It is not known if this is reflected in differences in their motor cortical representation. We compared the response of the costal and crural diaphragms using varying intensities of transcranial magnetic stimulation of the motor cortex at rest and during submaximal and maximal inspiratory efforts. The costal and crural motor evoked potential recruitment curves during submaximal inspiratory efforts were similar. The response to stimulation before, during and at 10 and 30 min after 44 consecutive maximal inspiratory efforts was also the same. Using paired stimulations to investigate intra-cortical facilitatory and inhibitory circuits we found no difference between the costal and crural response with varying interstimulus intervals, or when conditioning and test stimulus intensity were varied. We conclude that supraspinal control of the costal and crural diaphragm is identical during inspiratory tasks.     

经颅磁刺激安全性的实验研究

目的 :探讨重复经颅磁刺激的安全性。方法 :选用 3 6只健康Wistar大鼠 ,随机分为对照组 ,低频刺激组和高频刺激组 ,对低频组和高频组分别给予不同频率和强度的经颅磁刺激 ,然后对各组大鼠的行为、组织病理形态学、血清髓鞘碱性蛋白 (MBP)及神经元特异性烯醇化酶 (NSE)含量进行观察。结果 :低频刺激组 (5Hz)和高频刺激组 (2 0Hz)在刺激过程中均未出现异常活动 ,无肢体强直、阵挛等 ,脑组织形态学包括大体观察、普通光镜及电镜改变不明显 ,其血清MBP和NSE含量与正常对照组比较 ,差异无显著性意义 (P >0 0 5 )。结论 :在一定强度和频率内经颅磁刺激是一种比较安全的方法     

Decreased susceptibility to pentylenetetrazol-induced seizures after low-frequency transcranial magnetic stimulation in rats

We studied the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure susceptibility in rats. rTMS of 1000 pulses at 0.5 Hz led to a prolonged latency for seizure development after an intraperitoneal injection of pentylenetetrazol. The rTMS effectively prevented the development of status epilepticus of pentylenetetrazol-induced convulsions. These findings indicate that low-frequency rTMS affects the neural excitability, in the direction of anticonvulsive, and therefore, suggest the possibility of therapeutic use of rTMS in epilepsy.     

Time course of the state-dependent effect of transcranial magnetic stimulation in the TMS-adaptation paradigm

The transcranial magnetic stimulation (TMS)-adaptation paradigm, based on the state-dependency of TMS effects, may become a useful tool for differential stimulation of functionally distinct neural populations within the stimulated region. Here we investigated, in the context of motion perception, the time course of state-dependent TMS effects in this paradigm. After adapting to a motion stimulus, subjects were asked to perform a motion direction discrimination task, with TMS applied over the motion selective area V5/MT prior to each experimental trial. Consistent with previous studies, TMS reversed the behavioral effect of adaptation; that is, detection of the adapted direction was enhanced and that of the unadapted direction was impaired. Importantly, this reversal was consistent over the whole block of trials carried out after adaptation: the state-dependent TMS effect was similar in the first and second halves of the post-adaptation discrimination block. This shows that while single-pulse TMS interacts with the effects of adaptation on a trial-by-trial basis to induce state-dependent effects, it does not abolish the effects of adaptation; rather, after each trial, the stimulated region returns to a state of adaptation.     

Short-latency subliminal effects of transcranial magnetic stimulation on forearm motoneurones

The H-reflex technique has been used to evaluate the time-course of the effects evoked by transcranial clockwise magnetic stimuli in flexor or extensor carpi radialis motoneurones. In six subjects, magnetic stimulation was applied over the scalp in the focus for the motor response of those muscles. At intensities below motor threshold, a facilitation of the H-reflex started at a conditioning-test interval of -4 ms (i.e. when the magnetic stimulus lagged the test stimulus by 4 ms), reached a peak at about -2 ms and rapidly decayed. At about -1 ms, the decay attained a local minimum, which in three subjects had values indicating the presence of an inhibition. Thereafter, a second facilitatory phase peaked at about +1 ms. By matching the time course with the latency of the cortical muscle action potential (CMAP) evoked by suprathreshold magnetic stimulation, it is inferred that the motoneuronal discharge coincides with the second peak of facilitation and is preceded by 3–4 ms of subliminal excitation. This early effect could be brought to threshold by convergence of a subliminal Ia EPSP, leading to a reduction of the CMAP latency. The early excitatory effects reported above are as fast as those described as following transcranial electrical stimulation, and should likewise be considered as monosynaptic.     

Manipulation of phosphene thresholds by transcranial direct current stimulation in man

Transcranial direct current stimulation (tDCS) can modulate the excitability of the human motor cortex, as revealed by the amplitude of the motor-evoked potentials (MEP). The aim of our study has been to produce localized changes of cerebral excitability of the visual cortex in the intact human by weak anodal and cathodal stimulation. For quantification of current-induced excitability changes, we measured phosphene threshold (PT) using short trains of 5-Hz transcranial magnetic stimulation (TMS) pulses in nine healthy subjects before, immediately after, 10 min, and 20 min after the end of tDCS. PTs are suggested as representative values of visual cortex excitability changes. Reduced PT was detected immediately and 10 min after the end of anodal stimulation, while cathodal stimulation resulted in an opposite effect. Our results show that tDCS elicits a transient, reversible excitability alteration of the visual cortex, thus representing a promising tool for neuroplasticity research. Electronic Publication     

Long-lasting depression of motor-evoked potentials to transcranial magnetic stimulation following exercise

We used transcranial magnetic stimulation to study the modulation of motor cortex excitability after rapid repetitive movements. Eleven healthy subjects aged 24–32 years were evaluated. Serial motor-evoked potential (MEP) recordings were performed from the right thenar eminence every 5 min for a period of 20 min at rest and for a period of 35 min after repetitive abduction-adduction of the thumb at maximal frequency for 1 min. All subjects presented distinct changes in MEP amplitude after exercise with an approximately 55% mean maximal decrease compared with basal conditions and complete recovery 35 min after the end of the exercise. The time course of MEP amplitude changes presented the following trend: (1) a rapid decrease phase within the first 5 min; (2) a maximal depression phase of 10 min duration (from the 5th to the 15th min); and (3) a slow recovery phase. No significant modifications in post-exercise MEP amplitude were found in ipsilateral non-exercised muscles. In order to determine the level where these changes take place, we recorded the M and F waves induced by median nerve stimulation at the wrist (all subjects) and MEPs in response to transcranial electrical stimulation (five subjects) at rest and during the decrease and maximal depression phases. None of these tests were significantly affected by exercise, indicating that the motor cortex was the site of change. Evaluation of maps of cortical outputs to the target muscle, performed in four subjects, showed an approximately 40% spatial reduction in stimulation sites evoking a motor response during the maximal depression phase. These data prove that exercise induces a reversible, long-standing depression of cortical excitability, probably related to intracortical presynaptic modulation, which transitorily reduces the motor representation area.     

Instrumentation for the measurement of electric brain responses to transcranial magnetic stimulation

There is described a 60-channel EEG acquisition system designed for the recording of scalp-potential distributions starting just 2.5ms after individual transcranial magnetic stimulation (TMS) pulses. The amplifier comprises gain-control and sample-and-hold circuits to prevent large artefacts from magnetically induced voltages in the leads. The maximum amplitude of the stimulus artefact during the 2.5ms gating period is 1.7 μV, and 5 ms after the TMS pulse it is only 0.9 μV. It is also shown that mechanical forces to the electrodes under the stimulator coil are a potential source of artefacts, even though, with chlorided silver wire and Ag/AgCl-pellet electrodes, the artefact is smaller than 1 μV. The TMS-compatible multichannel EEG system makes it possible to locate TMS-evoked electric activity in the brain.     

Instrumentation for the measurement of electric brain responses to transcranial magnetic stimulation

There is described a 60-channel EEG acquisition system designed for the recording of scalp-potential distributions starting just 2.5ms after individual transcranial magnetic stimulation (TMS) pulses. The amplifier comprises gain-control and sample-and-hold circuits to prevent large artefacts from magnetically induced voltages in the leads. The maximum amplitude of the stimulus artefact during the 2.5ms gating period is 1.7 μV, and 5 ms after the TMS pulse it is only 0.9 μV. It is also shown that mechanical forces to the electrodes under the stimulator coil are a potential source of artefacts, even though, with chlorided silver wire and Ag/AgCl-pellet electrodes, the artefact is smaller than 1 μV. The TMS-compatible multichannel EEG system makes it possible to locate TMS-evoked electric activity in the brain.     

The effect on corticospinal volleys of reversing the direction of current induced in the motor cortex by transcranial magnetic stimulation

Descending corticospinal volleys were recorded from a bipolar electrode inserted into the cervical epidural space of four conscious human subjects after monophasic transcranial magnetic stimulation over the motor cortex with a figure-of-eight coil. We examined the effect of reversing the direction of the induced current in the brain from the usual posterior-anterior (PA) direction to an anterior-posterior (AP) direction. The volleys were compared with D waves evoked by anodal electrical stimulation (two subjects) or medio-lateral magnetic stimulation (two subjects). As reported previously, PA stimulation preferentially recruited I1 waves, with later I waves appearing at higher stimulus intensities. AP stimulation tended to recruit later I waves (I3 waves) in one of the subjects, but, in the other three, I1 or D waves were seen. Unexpectedly, the descending volleys evoked by AP stimulation often had slightly different peak latencies and/or longer duration than those seen after PA stimulation. In addition the relationship between the size of the descending volleys and the subsequent EMG response was often different for AP and PA stimulation. These findings suggest that AP stimulation does not simply activate a subset of the sites activated by PA stimulation. Some sites or neurones that are relatively inaccessible to PA stimulation may be the low-threshold targets of AP stimulation.     

Intracortical inhibition of lower limb motor-evoked potentials after paired transcranial magnetic stimulation

The aim of the present study was to determine the characteristics of intracortical inhibition in the motor cortex areas representing lower limb muscles using paired transcranial magnetic (TMS) and transcranial electrical stimulation (TES) in healthy subjects. In the first paradigm (n=8), paired magnetic stimuli were delivered through a double cone coil and motor evoked potentials (MEPs) were recorded from quadriceps (Q) and tibialis anterior (TA) muscles during relaxation. The conditioning stimulus strength was 5% of the maximum stimulator output below the threshold MEP evoked during weak voluntary contraction of TA (33±5%). The test stimulus (67±2%) was 10% of the stimulator output above the MEP threshold in the relaxed TA. Interstimulus intervals (ISIs) from 1–15 ms were examined. Conditioned TA MEPs were significantly suppressed (P<0.01) at ISIs of less than 5 ms (relative amplitude from 20–50% of the control). TA MEPs tended to be only slightly facilitated at 9-ms and 10-ms ISIs. The degree of MEP suppression was not different between right and left TA muscles despite the significant difference in size of the control responses (P<0.001). Also, conditioned MEPs were not significantly different between Q and TA. The time course of TA MEP suppression, using electrical test stimuli, was similar to that found using TMS. In the second paradigm (n=2), the suppression of TA MEPs at 2, 3, and 4 ms ISIs was examined at three conditioning intensities with the test stimulation kept constant. For the pooled 2- to 4-ms ISI data, relative amplitudes were 34±6%, 61±5%, and 98±9% for conditioning intensities of 0.95, 0.90, and 0.85× active threshold, respectively (P<0.01). In conclusion, the suppression of lower limb MEPs following paired TMS showed similar characteristics to the intracortical inhibition previously described for the hand motor area. Received: 21 June 1996 / Accepted: 23 May 1997     

Transcranial magnetic stimulation in the rat

Transcranial magnetic stimulation (TMS) allows for quantification of motor system excitability. While routinely used in humans, application in other species is rare and little is known about the characteristics of animal TMS. The unique features of TMS, i.e., predominantly interneuronal stimulation at low intensity and non-invasiveness, are particularly useful in evaluating injury and recovery in animal models. This study was conducted to characterize the rodent motor evoked potential to TMS (MEP_TMS) and to develop a methodology for reproducible assessment of motor excitability in the rat. MEP_TMS were compared with responses evoked by electrical stimulation of cervical spinal cord (MEP_CES) and peripheral nerve. MEP were recorded by subcutaneous electrodes implanted bilaterally over the calf. Animals remained under propofol infusion and restrained in a stereotactic frame while TMS followed by CES measurements were obtained before and after 2 h of idle time. TMS was applied using a 5-cm-diameter figure-of-eight coil. MEP_TMS had onset latencies of 6.7±1.3 ms. Latencies decreased with higher stimulation intensity (r=–0.7, P<0.05). Two morphologies, MEP_{TMS, 1} and MEP_{TMS, 2}, were distinguished by latency of the first negative peak (N1), overall shape, and amplitude. MEP_{TMS, 2} were more frequent at higher stimulation intensity. While recruitment curves for MEP_{TMS, 1} followed a sigmoid course, no supramaximal response was reached for MEP_{TMS, 2}. Mid-cervical spinal transection completely abolished any response to TMS. MEP_CES showed a significantly shorter latency (5.29±0.24, P<0.0001). Two types of MEP_CES resembling MEP_{TMS, 1 and 2} were observed. Neither MEP_TMS nor MEP_CES changed on repeat assessment after 2 h. This study demonstrates the feasibility and reproducibility of TMS in the rat. Sigmoid recruitment curves for MEP_{TMS, 1} suggest input-output properties similar to those of the human corticospinal system. Latency differences between CES and TMS point to a supraspinal origin of the MEP_TMS. The two morphologies likely reflect different cortical or subcortical origins of MEP_TMS. Electronic Publication