Interstimulus Interval Research Articles

Altered motor cortical plasticity in patients with hepatic encephalopathy: A paired associative stimulation study

ObjectiveHepatic encephalopathy (HE) is a potentially reversible brain dysfunction caused by liver failure. Altered synaptic plasticity is supposed to play a major role in the pathophysiology of HE. Here, we used paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), a transcranial magnetic stimulation (TMS) protocol, to test synaptic plasticity of the motor cortex in patients with manifest HE. Methods23 HE-patients and 23 healthy controls were enrolled in the study. Motor evoked potential (MEP) amplitudes were assessed as measure for cortical excitability. Time courses of MEP amplitude changes after the PAS25 intervention were compared between both groups. ResultsMEP-amplitudes increased after PAS25 in the control group, indicating PAS25-induced synaptic plasticity in healthy controls, as expected. In contrast, MEP-amplitudes within the HE group did not change and were lower than in the control group, indicating no induction of plasticity. ConclusionsOur study revealed reduced synaptic plasticity of the primary motor cortex in HE. SignificanceReduced synaptic plasticity in HE provides a link between pathological changes on the molecular level and early clinical symptoms of the disease. This decrease may be caused by disturbances in the glutamatergic neurotransmission due to the known hyperammonemia in HE patients.

Body ownership, sensorimotor integration and motor cortical excitability: A TMS study about rubber hand illusion

ObjectiveThe Rubber Hand Illusion (RHI) manipulates body ownership experimentally and helps investigate the related neurophysiological processes. This study aimed to evaluate motor cortex excitability that hypothesized changed due to illusion. MethodTwenty-one healthy (twelve male, nine female), right-handed volunteers aged between 25 and 50 years were recruited to the study. Short-Latency Afferent Inhibition (SAI) was evaluated by transcranial magnetic stimulation (TMS) given with a figure-of-eight-shaped coil from the left motor cortex, 21 ms after peripheral electrical stimulation. Short-Interval Intracortical Inhibition (SICI) and Intracortical Facilitation (ICF) were investigated using a paired-pulse TMS at interstimulus intervals (ISI) of 1, 2.5, 3 ms and 15, 20, 25 ms, respectively. We used custom-made illusion setups for TMS paradigms. SAI, SICI and ICF was evaluated before, during and 15 min after the RHI. ResultsResults of the study revealed significantly high SAI during illusion compared to pre-illusion, but no difference was found between post-illusion 15th minutes and control measurements. Significantly reduced SICI at 2.5 and 3 ms ISI obtained during illusion, while RHI did not affect SICI at 1 ms ISI and ICF. SignificanceBody ownership illusion modulates the motor cortex excitability, possibly through altered sensory processing and sensorimotor integration.

‘I need a break’: the effect of choice of rest break duration on vigilance

Vigilance is the ability to sustain attention for an extended period of time and to respond to infrequently occurring critical signals. One of the most replicable findings within the vigilance literature is the performance decrement; the decline in performance as time on task increases. In an effort to attenuate the decrement, and decrease the workload and stress associated with vigilance, the present study investigated the role of choice of rest break duration on vigilance performance, perceived workload, and stress. Participants were assigned to one of three conditions: (1) choice condition, (2) no-choice condition (yoked-control), and (3) a no-break control condition. Participants completed a sensory vigilance task and common measures of workload and stress. A vigilance decrement was observed in all conditions. Participants in the choice condition exhibited more conservative responses and fewer false alarms than the no-choice condition. Across all conditions, task engagement and worry decreased, and distress increased. Practitioner Summary: This study shows the impact of rest breaks and autonomy on vigilance task performance. The findings suggest that resource theory is a plausible explanation for the vigilance decrement. Additionally, providing a choice in rest break length changes the operator’s criterion following the break. Abbreviations: TSA: transportation security administration; SART: sustained attention to response task; ERP: event-related potential; S-DT: self-determination theory; ISI: interstimulus interval; DSSQ: dundee stress state questionnaire; CFQ: cognitive failures questionnaire; BP: boredom proneness; NASA-TLX: NASA task load index; IMI: intrinsic motivation inventory

Pedunculopontine tegmental Nucleus-evoked prepulse inhibition of the blink reflex in Parkinson’s disease

ObjectiveTo investigate the effects on the blink reflex (BR) of single stimuli applied to the pedunculopontine tegmental nucleus (PPTg). MethodsThe BR was evoked by stimulating the supraorbital nerve (SON) in fifteen patients suffering from idiopathic Parkinson’s disease (PD) who had electrodes monolaterally or bilaterally implanted in the PPTg for deep brain stimulation (DBS). Single stimuli were delivered to the PPTg through externalized electrode connection wires 3–4 days following PPTg implantation. ResultsPPTg stimuli increased the latency and reduced duration, amplitude and area of the R2 component of the BR in comparison to the response recorded in the absence of PPTg stimulation. These effects were independent of the side of SON stimulation and were stable for interstimulus interval (ISI) between PPTg prepulse and SON stimulus from 0 to 110 ms. The PPTg-induced prepulse inhibition of the BR was bilaterally present in the brainstem. The R1 component was unaffected. ConclusionsThe prepulse inhibition of the R2 component may be modulated by the PPTg. SignificanceThese findings suggest that abnormalities of BR occurring in PD may be ascribed to a reduction of basal ganglia-mediated inhibition of brainstem excitability.

Sex-specific effects of psychedelics on prepulse inhibition of startle in 129S6/SvEv mice.

Prepulse inhibition (PPI) of startle is a sensorimotor gating phenomenon perturbed in a variety of neuropsychiatric conditions. Psychedelics disrupt PPI in rats and humans, but their effects and involvement of the serotonin 5-HT2A receptor (5-HT2AR) in mice remain unexplored. We tested the effect of the psychedelic 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.5 mg/kg, i.p.) on startle amplitude and %PPI in response to acoustic stimuli under up to four different experimental conditions that included changes in background and stimulus intensity, prepulse and pulse duration, and interstimulus interval in male and female 129S6/SvEv mice. We also evaluated the effect of the 5-HT2AR antagonist M100,907 (1 mg/kg, i.p.) on DOI-induced startle amplitude and %PPI, as well as the effect of the psychedelic LSD (0.24 mg/kg, i.p.) and the dopamine agonists apomorphine (5 mg/kg, s.c.) and SKF-82,958 (0.5 mg/kg, i.p.) in male 129S6/SvEv mice. DOI altered startle amplitude with either pulse alone or prepulse + pulse presentations in all PPI conditions, and increased %PPI in three out of four PPI conditions in male mice - an effect that was prevented by M100,907. In female mice, DOI increased %PPI without affecting startle amplitude. %PPI was positively correlated with startle amplitude in males while being negatively correlated in female mice. In male mice, LSD also increased %PPI, although it did not affect startle amplitude, whereas apomorphine and SKF-82,958 induced decreases in %PPI. Our findings highlight a distinct effect of the psychedelic DOI on PPI in 129S6/SvEv mice, suggesting 5-HT2AR-dependent PPI improvement in a paradigm-dependent and sex-dependent manner.

Intrinsically photosensitive retinal ganglion cell-driven pupil responses in patients with traumatic brain injury

Previous findings regarding intrinsically photosensitive retinal ganglion cell (ipRGC) function after traumatic brain injury (TBI) are conflicting. We examined ipRGC-driven pupil responses in civilian TBI and control participants using two pupillography protocols that assessed transient and adaptive properties: (1) a one second (s) long wavelength “red” stimulus (651 nm, 133 cd/m2) and 10 increasing intensities of 1 s short wavelength ”blue” stimuli (456 nm, 0.167 to 167 cd/m2) with a 60 s interstimulus interval, and (2) two minutes of 0.1 Hz red stimuli (33 cd/m2), followed by two minutes of 0.1 Hz blue stimuli (16 cd/m2). For Protocol 1, constriction amplitude and the 6 s post illumination pupil response (PIPR) were calculated. For Protocol 2, amplitudes and peak velocities of pupil constriction and redilation were calculated. For Protocol 1, constriction amplitude and the 6 s PIPR were not significantly different between TBI patients and control subjects for red or blue stimuli. For Protocol 2, pupil constriction amplitude attenuated over time for red stimuli and potentiated over time for blue stimuli across all subjects. Constriction and redilation velocities were similar between groups. Pupil constriction amplitude was significantly less in TBI patients compared to control subjects for red and blue stimuli, which can be attributed to age-related differences in baseline pupil size. While TBI, in addition to age, may have contributed to decreased baseline pupil diameter and constriction amplitude, responses to blue stimulation suggest no selective damage to ipRGCs.

Evidence for a general impairment of auditory and visual temporal order judgment in children with reading disabilities

Objectives: This study examined visual and auditory processing of children with reading disabilities (RD) to determine whether they show an impaired ability to judge a reading-related process such as temporal order of events and clarify whether or not this deficit is linked to rapid processing deficit. Method: The performance of 16 children with RD was compared with the performance of children in two control groups – one for chronological age (CA) and one for the same reading level –, doing visual and auditory temporal order tasks, both with linguistic and non-linguistic stimuli with inter-stimuli-intervals of 50, 150, or 300 ms. Results: The RD group performance was lower than the performance of the CA group in tasks requiring auditory temporal order processing for linguistic and non-linguistic stimuli. Regarding visual tasks, the RD group performed worse than both control groups in processing non-linguistic stimuli. In general, performance in every group decreased with decreasing inter-stimulus-interval (ISIs), suggesting that children with RD do not have impairments in the speed of perceptual processing. Conclusions: The perceptual problems of children with RD are better explained by temporal order processing problems than by difficulties in rapid processing. Inclusion of temporal order processing tasks in the evaluation of children with RD is recommended.

Test Re-test Reliability of Dual-site TMS Measures of SMA-M1 Connectivity Differs Across Inter-stimulus Intervals in Younger and Older Adults

Dual-site transcranial magnetic stimulation (TMS) is a promising tool to measure supplementary motor area and primary motor cortex (SMA-M1) connectivity in younger and older adults, and could be used to understand the pathophysiology of movement disorders. However, test re-test reliability of dual-site TMS measures of SMA-M1 connectivity has not been established. We examined the reliability of SMA-M1 connectivity using dual-site TMS in two sessions in 30 younger and 30 older adults. For dual-site TMS, a conditioning pulse delivered to SMA (140% of active motor threshold) preceded a test pulse delivered to M1 (intensity that elicited MEPs of ~1 mV) by inter-stimulus intervals (ISI) of 6 ms, 7 ms, and 8 ms. Moderate intraclass correlation coefficients (ICC) were found for SMA-M1 connectivity at an ISI of 7 ms in younger (ICC: 0.69) and older adults (ICC: 0.68). Poor ICCs were found for SMA-M1 connectivity at ISIs of 6 ms and 8 ms in both age groups (ICC range: 0.01–0.40). We report evidence for stable measures of SMA-M1 connectivity at an ISI of 7 ms in both age groups. These findings are foundational for future research developing evidence-based interventions to strengthen SMA-M1 connectivity to improve bilateral motor control in older adults and populations with movement disorders.

Cerebellar Brain Inhibition Is Associated With the Severity of Cervical Dystonia.

Cerebellar connectivity is thought to be abnormal in cervical dystonia (CD) and other dystonia subtypes, based on evidence from imaging studies and animal work. The authors investigated whether transcranial magnetic stimulation-induced cerebellar brain inhibition (CBI), a measure of cerebellar efficiency at inhibiting motor outflow, is abnormal in patients with CD and/or is associated with clinical features of CD. Because of methodological heterogeneity in CBI reporting, the authors deployed additional controls to reduce potential sources of variability in this study. Cerebellar brain inhibition was applied in 20 CD patients and 14 healthy control subjects. Cerebellar brain inhibition consisted of a cerebellar conditioning stimulus delivered at four different interstimulus intervals (ISIs) before a test stimulus delivered to hand muscle representation in the motor cortex. The average ratio of conditioned to unconditioned motor evoked potential was computed for each ISI. Cervical dystonia clinical severity was measured using the Toronto Western Spasmodic Torticollis Rating Scale. Control experiments involved neuronavigated transcranial magnetic stimulation, neck postural control in patients, and careful screening for noncerebellar pathway inhibition via cervicomedullary evoked potentials. There was no difference between CBI measured in healthy control subjects and CD patients at any of the four ISIs; however, CBI efficiency was significantly correlated with worsening CD clinical severity at the 5 ms ISI. Cerebellar brain inhibition is a variable measure in both healthy control subjects and CD patients; much of this variability may be attributed to experimental methodology. Yet, CD severity is significantly associated with reduced CBI at the 5 ms ISI, suggestive of cerebello-thalamo-cortical tract dysfunction in this disorder.

Computationally efficient model of myocardial electromechanics for multiscale simulations.

A model of myocardial electromechanics is suggested. It combines modified and simplified versions of previously published models of cardiac electrophysiology, excitation-contraction coupling, and mechanics. The mechano-calcium and mechano-electrical feedbacks, including the strain-dependence of the propagation velocity of the action potential, are also accounted for. The model reproduces changes in the twitch amplitude and Ca2+-transients upon changes in muscle strain including the slow response. The model also reproduces the Bowditch effect and changes in the twitch amplitude and duration upon changes in the interstimulus interval, including accelerated relaxation at high stimulation frequency. Special efforts were taken to reduce the stiffness of the differential equations of the model. As a result, the equations can be integrated numerically with a relatively high time step making the model suitable for multiscale simulation of the human heart and allowing one to study the impact of myocardial mechanics on arrhythmias.

Effect of intermittent high-frequency stimulation on muscle velocity recovery cycle recordings.

The technique of multifiber muscle velocity recovery cycle recordings was developed as a diagnostic tool to assess muscle membrane potential changes and ion channel function in vivo. This study was undertaken to assess the impact of intermittent high-frequency stimulation on muscle velocity recovery cycle components and to study whether the changes can be modified by endurance training. We recorded muscle velocity recovery cycles with 1 and 2 conditioning stimuli in the left tibialis anterior muscle in 15 healthy subjects during intermittent 37-Hz stimulation and analyzed its effects on the different phases of supernormality. Recordings were conducted before and after 2-wk endurance training. Training effect was assessed by measuring the difference in endurance time, peak force, and limb circumference. Muscle velocity recovery cycle recordings during intermittent high-frequency stimulation were successfully recorded in 12 subjects. Supernormality for interstimulus intervals shorter than 15 ms (early supernormality) was maximally reduced at the beginning of repetitive stimulation and recovered during stimulation. Supernormality for interstimulus intervals between 50 and 150 ms (late supernormality) showed a delayed decrease and stayed significantly reduced after high-frequency stimulation. Training had no significant effect on any of the measured parameters, but we found that training induced changes in peak force correlated positively with baseline changes of early supernormality. Our results support the hypothesis that early supernormality represents membrane potential, which depolarizes in the beginning of high-frequency stimulation. Late supernormality probably reflects transverse tubular function and shows progressive changes during high-frequency stimulation with delayed normalization.NEW & NOTEWORTHY A conditioning impulse in human muscle fibers induces a prolonged phase of increased velocity (also called supernormality) with two phases related to an early and late afterpotential. We investigated the effects of intermittent 37-Hz stimulation on muscle fiber supernormality and found that the early and late phases of supernormality changed differently, and that the late phase may reflect the ionic interactions responsible for the counter-regulation of muscle fatigue.

Stimulation of Myofascial Trigger Points in the Sternocleidomastoid Evokes Facial Thermal Response Correlated with the Referred Pain

The purpose of this research is to identify and correlate the referred pain evocated by myofascial trigger points (TrPs) pressure pain threshold (PPT) in the sternocleidomastoid muscle using thermal infrared imaging (IR). Facial IR images of 46 volunteers (21 male and 25 female, average age 32 ± 6.3) undergoing PPT of five TrPs locations on the sternocleidomastoid belly were recorded. Each PPT lasted 10 s, with an interstimulus interval of 2 min. Sixteen thermal IR images were recorded for each subject: at baseline (t0), 2 s before PPT (t1), 2 s (t2) and 60 s (t3) after PPT of each TrPs location. During the interstimulus interval, subjects were asked to draw over a head–neck template displayed on a computer screen the areas of referred pain eventually evoked by the stimulation and the referred pain intensity by means of a Visual Analogue Scale (VAS). The VAS template was then superimposed with the IR records. Two temperature (T) variations were calculated: ΔT1 = T(t2) − T(t1) and ΔT2 = T(t3) − T(t1). Differences in ∆T range ≥ 0.2 °C have been considered significant. In 77% of the superimpositions, the referred pain area corresponded to a ΔT2 ≥ 0.2 °C while only the 59% corresponded to a ΔT1 ≥ 0.2 °C. In 19% of superimpositions, a ΔT2 ≥ 0.2 °C did not correspond to a referred pain area indicated by the patient, and this percentage lowers to 4% for ΔT1 ≥ 0.2 °C. None of the areas that reported a VAS of 0 or 1 showed a ΔT1 ≥ 0.2 °C or a ΔT2 ≥ 0.2 °C. Considering the limitations of this pilot study, IR could be used to identify referred pain evocated by TrPs on sternocleidomastoid muscle.

Corticokinematic coherence is stronger to regular than irregular proprioceptive stimulation of the hand.

Proprioceptive afference can be investigated using corticokinematic coherence (CKC), which indicates coupling between limb kinematics and cortical activity. CKC has been quantified using proprioceptive stimulation (movement actuators) with fixed interstimulus interval (ISI). However, it is unclear how regularity of the stimulus sequence (jitter) affects CKC strength. Eighteen healthy volunteers (16 right-handed, 27.8 ± 5.0 yr, 7 females) participated in magnetoencephalography (MEG) session in which their right index finger was continuously moved at ∼3 Hz with Constant 333 ms ISI or with 20% Jitter (ISI 333 ± 66 ms) using a pneumatic-movement actuator. Three minutes of data per condition were collected. Finger kinematics were recorded with a three-axis accelerometer. CKC strength was defined as the peak coherence value in the Rolandic MEG gradiometer pair contralateral to the movement at 3 Hz. Both conditions resulted in significant coherence peaking in the gradiometers over the primary sensorimotor cortex. Constant stimulation yielded stronger CKC at 3 Hz (0.78 ± 0.11 vs. 0.66 ± 0.13, P < 0.001) and its first harmonic (0.60 ± 0.19 vs. 0.27 ± 0.11, P < 0.001) than irregular stimulation. Similarly, the respective sustained-movement evoked field was also stronger for constant stimulation. The results emphasize the importance of temporal stability of the proprioceptive stimulation sequence when quantifying CKC strength. The weaker CKC during irregular stimulation can be explained with temporal and thus spectral scattering of the paired peripheral and cortical events beyond the mean stimulation frequency. This impairs the signal-to-noise ratio of respective MEG signal and thus CKC strength. When accurately estimating and following changes in CKC strength, we suggest using precise movement actuators with constant stimulation sequence.NEW & NOTEWORTHY Cortical proprioceptive processing can be investigated using corticokinematic coherence (CKC). The findings show that CKC method is sensitive to temporal stability in the stimulation sequence. Although both regular and irregular sequences resulted in robust coherence, the regular stimulation sequence with pneumatic movement actuator is recommended to maximize coherence strength and reproducibility to allow better comparability between groups or populations.

Transcranial stimulation (TCS) O-TS002. Combining SICF and ICF with QPS boosts excitability increase in the primary motor cortex

Introduction . After-effects induced by repetitive transcranial magnetic stimulation (rTMS) at the primary motor cortex (M1) are usually indexed by the amplitude of the motor evoked potential (MEP). They depend on various parameters, in particular on the temporal pattern. Quadripulse stimulation (QPS; high-frequency train of four pulses delivered every-five seconds for 30 min) was originally invented based on a repetitive paired-pulse TMS (ppTMS) protocol, which utilized short-interval intracortical facilitation (SICF) as a building block. Here, we tried to test whether after-effects of QPS can be increased by integrating either SICF, intracortical facilitation (ICF) or long-interval intracortical inhibition (LICI). Methods . Three conditions were compared using a cross-over design in 23 healthy volunteers. The three conditions were SICF + ICF, SICF + LICI, and QPS-like. In SICF + ICF, two pulses with a 1.5 ms inter-stimulus interval (ISI) were repeated twice, separated by 10 ms (ICF). Likewise, in SICF + LICI two pulses with a 1.5 ms interval were repeated at 100-ms interval (LICI). In the QPS-like condition, the four pulses were evenly delivered at 5-ms intervals. In all three conditions the four pulses were repeated every-five seconds for 10 minutes. Amplitude of MEP elicited by single pulse TMS was measured before the intervention, and up to 60 minutes after it. The MEP amplitudes were normalized to the baseline and served as the main outcome. Results . The combination of two facilitatory ppTMS, SICF + ICF, resulted in significantly increased MEP amplitudes over time whereas combining the facilitatory SICF with the inhibitory LICI tended to decrease the MEP amplitude. QPS with 10-minute intervention time had no effect in contrast to the 3-times longer original QPS paradigm. Conclusion . The efficacy of the original QPS can be maintained with one third of stimulation time when differently organized in time along with optimal values for SICF + ICF.

SY1.8. Application of TMS in movement disorders

I will summarize several TMS applications in movement disorders. Function of supplementary motor area (SMA) and preSMA revealed by QPS (Shimzu T et al). We studied functional differences between the pre-SMA and SMA in sequence learning in humans. To induce LTP/LTD, we administered quadripulse transcranial magnetic stimulation (QPS) with an inter-stimulus interval of 5 or 50 ms (QPS-5/50) over the pre-SMA or SMA in healthy volunteers. QPS-5 over the pre-SMA increased the error rate without any changes in movement speed. When administered over the SMA, QPS affected the rate of reaction time reduction across trials without any changes in the error rate. Cerebellar involvement and cerebellar stimulation treatments. Essential tremor (Hanajima et al). Several lines of evidence suggested a cerebellar pathophysiology of essential tremor (ET). It was recently confirmed by human pathology, neuroimaging studies and others. This hypothesis was also confirmed by cerebellar TMS over cerebellum (cerebellar inhibition: CBI) and prism adaptation task in ET patients (Hanajima et al). Cerebellar stimulation treatments in movement disorders (Çan, M et al). Many researchers have been interested in cerebellar involvement in movement disorders and also cerebellar stimulation as one of treatment methods. However, our magnetic coil must activate cerebellum in some extent but not purely cerebellum alone, and always activate some other structures. The simulation study showed considerable amount of currents must be induced in the cerebellum even with a small coil. Cerebellar stimulation is one of future projects of TMS. Transcranial focused ultrasound stimulation (tFUS). Very low intensity tFUS makes reversible functional changes in human brain. This reversible modulation is used for functional studies of human brains. Its focality and ability to induce functional changes in deep brain structures, such as thalamus, must enable this method to be used in movement disorders. Alternative leg movements induction by lumbar rTMS (Nishimura et al). The lumbar gait center is known to produce gait-like alternative leg movements in animals. We made a system to voluntary induce a gait-like leg movement triggered by her/his own upper limb EMGs. This system induced alternative leg movements, gait like movements, in patients with paraplegia due to spinal cord injury.

P 23. Individualized I-waves adapted TMS – Preliminary results

Introduction. Synaptic plasticity is considered the neurophysiological correlate of learning processes in the human brain. It can be studied through transcranial magnetic stimulation (TMS). A TMS over the primary motor cortex (M1) generates descending volleys, so called I-waves (I1-I3). Their latencies can be detected with “short interval intracortical facilitation” (SICF). These latencies seem to play a pivotal role in the induction of synaptic plasticity. A paired pulse TMS, based on the defined (1.5 ms), as well as on the individual I-waves, lead to an increase in corticospinal excitability. The aim of this study was to investigate the effects of an individualized quadri-pulse theta burst stimulation (i-qTBS) with 4 bursts, based on each of the individual I1-I3- waves latencies for the first time. Methods. We studied the individual I-wave latencies through SICF in posterior-anterior (PA) and anterior-posterior (AP) current flow direction in the human M1-HAND of 12 healthy subjects (23-34 years, f=8). We used a newly engineered stimulator (MSB, Munich) to apply paired pulses with interstimulus interval of 0,1 ms to 6 ms in steps from 0,1 ms with a biphasic pulse configuration (pulse duration: 160 µs). The bursts of the qTBS consist of 4 pulses. We applied an (i)-qTBS adapted to the individual I-waves over the same hotspot (M1-HAND). Subsequently, the motor evoked potentials (MEP) and the resting motor threshold (RMT) were recorded over the period of one hour (post1-4). Results. The statistical analysis (rmANOVA) of the i-qTBS in PA direction did not show changes of the MEP-amplitude comparing the pre- to the 4 post-readings (F(4, 44) = 1.314, p = .280). The i-qTBS in AP direction also did not show any changes in MEP-amplitudes (F(4, 40) = .462, p = .763) over the course of an hour. Discussion. An i-qTBS adapted to the individual I-wave latencies did not result in any changes of corticospinal excitability. Possible reasons for this might be the high number (>200) of pre-stimuli due to the SICF, or extinction phenomena of different I1-/I3-effects. Further studies on individualized stimulation are necessary in order to analyse the neurophysiological mechanisms of the effects. This will enable a targeted individual therapeutical application of qTBS in a clinical context.

Large-scale analysis of interindividual variability in single and paired-pulse TMS data

ObjectiveThis study brought together over 60 transcranial magnetic stimulation (TMS) researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability. MethodsAuthors of previously published studies were contacted and asked to share deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to variability in response to single and paired-pulse TMS data. Results687 healthy participant’s data were pooled across 35 studies. Target muscle, pulse waveform, neuronavigation use, and TMS machine significantly predicted an individual’s single-pulse TMS amplitude. Baseline motor evoked potential amplitude, motor cortex hemisphere, and motor threshold (MT) significantly predicted short-interval intracortical inhibition response. Baseline motor evoked potential amplitude, test stimulus intensity, interstimulus interval, and MT significantly predicted intracortical facilitation response. Age, hemisphere, and TMS machine significantly predicted MT. ConclusionsThis large-scale analysis has identified a number of factors influencing participants’ responses to single and paired-pulse TMS. We provide specific recommendations to minimise interindividual variability in single and paired-pulse TMS data. SignificanceThis study has used large-scale analyses to give clarity to factors driving variance in TMS data. We hope that this ongoing collaborative approach will increase standardisation of methods and thus the utility of single and paired-pulse TMS.

Temporal preparation in adults with autistic spectrum disorder: The variable foreperiod effect.

Research suggested the possibility that temporal cognition may be different in autistic spectrum disorder (ASD). Although there are some empirical studies examining timing ability in these individuals, to our knowledge, no one directly assessed the ability to predict when an event will occur. Here, we report a study on implicit temporal preparation in individuals with ASD as indexed by the variable foreperiod (FP) effect. We compared a group of adult ASD participants to a group of typically-developed (TD) controls, for their respective abilities to utilize implicit temporal information in a simple detection task with three different preparatory intervals (FP, short, middle and long). Participants were given a warning tone to signal an imminent stimulus, and asked to press a key as quickly as they could upon detection of the stimulus. Both groups were able to use implicit temporal information, as revealed by both the variable-FP effect (i.e., faster response for targets appearing after a long FP) and asymmetric sequential effects (i.e., slower response in short-FP trials following a previous long-FP trial). The TD group exhibited a faster response in a long-FP trial that was preceded by short-FP one, whereas the ASD group did not, as reflected in their higher percentage of response omissions for a target that appeared later than in the previous trial. The reduced ability of ASD participants to modulate their responses under these conditions might reflect a difficulty in time-based monitoring of stimulus occurrence. LAY SUMMARY: Time-processing may be different in autistic spectrum disorder (ASD). This study addressed the ability to anticipate a relevant stimulus's onset according to predictable interstimulus intervals comparing adults with ASD and typically developed controls. We found that ASD participants did not benefit from temporal preparation when stimulus appeared later than previously attended. This suggests a reduced ability in detecting implicit temporal regularities between events.

Blink reflex recovery cycle distinguishes patients with idiopathic normal pressure hydrocephalus from elderly subjects.

The R2 component of blink reflex recovery cycle (R2BRrc) is a simple neurophysiological tool to detect the brainstem hyperexcitability commonly occurring in several neurological diseases such as Parkinson's disease and atypical parkinsonisms. In our study, we investigated for the first time the usefulness of R2BRrc to assess brainstem excitability in patients with idiopathic Normal Pressure Hydrocephalus (iNPH) in comparison with healthy subjects. Eighteen iNPH patients and 25 age-matched control subjects were enrolled. R2BRrc was bilaterally evaluated at interstimulus intervals (ISIs) of 100, 150, 200, 300, 400, 500 and 750ms in all participants. We investigated the diagnostic performance of R2BRrc in differentiating iNPH patients from control subjects using ROC analysis. Midbrain area and Magnetic Resonance Hydrocephalic Index (MRHI), an MRI biomarker for the diagnosis of iNPH, were measured on T1-weighted MR images, and correlations between R2BRrc values and MRI measurements were investigated. Fourteen (78%) of 18 iNPH patients showed an enhanced R2BRrc at ISIs 100-150-200ms, while no control subjects had abnormal R2BRrc. The mean amplitude of bilateral R2BRrc at the shortest ISIs (100-150-200ms) showed high accuracy in differentiating iNPH patients from controls (AUC = 0.89). R2BRrc values significantly correlated with midbrain area and MRHI values. This study represents the first evidence of brainstem hyperexcitability in iNPH patients. Given its low cost and wide availability, R2BRrc could be a useful tool for selecting elderly subjects with mild gait and urinary dysfunction who should undergo an extensive diagnostic workup for the diagnosis of NPH.

Temporal Factors Modulate Haloperidol-Induced Conditioned Catalepsy.

Repeated pairings of a neutral context and the effects of haloperidol give rise to conditioned catalepsy when the context is subsequently presented in a drug-free test. In order to confirm whether this response is based on Pavlovian processes, we conducted two experiments involving two manipulations that affect conditioning intensity in classical conditioning procedures: time of joint exposure to the conditioned and the unconditioned stimulus, and the length of the inter-stimulus interval (ISI). The results revealed that both an increase in the length of context-drug pairings during conditioning and a reduced ISI between drug administration and context exposure increased conditioned catalepsy. These results are discussed in terms of the temporal peculiarities of those procedures that involve drugs as the unconditioned stimulus along with the role of Pavlovian conditioning in context-dependent catalepsy.