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Background: Temporal summation and conditioned pain modulation (CPM) can be measured using a thermode and cold pressor test (CPTest). Unfortunately, these complex and expensive tools are ill-suited for routine clinical assessments. Aims: We aimed to compare the temporal summation and CPM obtained with the thermode + CPTest paradigm to those obtained with a novel paradigm using transcutaneous electrical nerve stimulation (TENS). Methods: We assessed temporal summation and CPM in 29 healthy participants, using two paradigms (random order): TENS, and thermode + CPTest. In the TENS paradigm, both the conditioning stimulus (CS) and the test stimulus (TS) were delivered using TENS; in the thermode + CPTest paradigm, the CS consisted of a CPTest and the TS was delivered using a thermode. We compared the average temporal summation and CPM evoked by the two paradigms. Results: Average temporal summation was similar for both modalities (P = 0.90), and the number of participants showing temporal summation was similar in both paradigms (19 with thermode vs. 18 with TENS; P = 1.00). Average CPM response was larger following the thermode + CPTest than following the TENS (P = 0.005), and more participants showed CPM with the thermode + CPTest paradigm compared to the TENS paradigm (24 vs. 14; P = 0.01). Conclusions: Both paradigms were roughly equivalent in the ability to evoke temporal summation (although response to one modality did not predict response to the other), but the TENS paradigm appeared to be less apt to induce a CPM response than the thermode + CPTest paradigm.

Motor imagery (MI) is known to improve motor function through enhancement of motor cortex activity. Spinal reciprocal inhibition (RI) is modulated by motor cortex activity, and, therefore, MI may change RI. The aim of this study was to examine the changes in RI during MI involving the lower extremity. Spinal RI was measured from the tibialis anterior (TA) to the soleus (SOL). Eleven healthy adults participated in experiment 1. All participants performed the following three conditions, and RI was assessed during each condition: (1) resting condition; (2) MI of ankle dorsiflexion condition (MI-DF); and (3) MI of ankle plantarflexion condition (MI-PF). Twelve healthy adults participated in experiment 2. All participants performed the following two conditions, and RI was assessed before and after MI practice for 10 min: (1) resting condition and (2) MI-DF. The interval between the conditioning and test stimulus (inter-stimulus interval; ISI) was set at 0, 1, 2, or 3 ms and 20 ms. In experiment 1, RI during MI-PF was significantly decreased compared with that during resting with both stimulus intervals. RI during MI-DF showed no significant change compared with that during resting with both ISIs. In experiment 2, the difference between the rest condition and the MI-DF condition after the MI task with ISI of 20 ms was significantly higher than before the MI task. Our findings suggest that real-time changes in RI during MI involving the lower extremity may vary depending on the direction of motion and MI practice.

Conditioning transcranial magnetic stimulation (TMS) with subthreshold conditioning stimulus followed by supra-threshold test stimulus at inter-stimulus intervals (ISI) of 1–5 ms results in inhibition (SICI), while ISI at 10–15 ms results in facilitation (ICF). One concerning issue, applying ICF/SICI protocols on patients is the substantial protocol variability. Here, we hypothesized that increasing the number of CS could result in more robust ICF/SICI protocols. Twenty healthy subjects participated in the study. Motor-evoked potentials (MEP) were obtained from conditioning TMS with a varying number of conditioning stimuli in 3, 4, 10, and 15 ms ISI over the primary motor cortex. MEP amplitudes were then compared to examine excitability. TMS with 3, 5, and 7 conditioning stimuli but not with one conditioning stimulus induced ICF. Moreover, 10 ms ISI produced stronger ICF than 15 ms ISI. Significant SICI was only induced with one conditioning stimulus. Besides, 3 ms ISI resulted in stronger SICI than 4 ms ISI. Only a train of conditioning stimuli induced stable ICF and may be more advantageous than the classical paired pulse ICF paradigm. Supplementary Information The online version contains supplementary material available at 10.1007/s00221-020-06010-7.

OBJECTIVE To compare spatial pain modulation capabilities between adolescents with and without migraine. BACKGROUND Conditioned pain modulation (CPM) responses at the leg are similar in adolescents with versus without migraine. However, the anatomical region of testing may affect spatial pain modulation capabilities as differences in nociceptive processing between patients with migraine and healthy controls are found in local areas that are near the site of clinical pain but not in nonlocal areas. This study aimed to examine spatial pain modulation capabilities tested by the CPM paradigm using test stimulus applied to a local body area. METHODS Nineteen adolescents with migraine (age 14.9 ± 2.3, mean ± SD; 16 female) and 20 healthy adolescents (age 13.8 ± 2.5, mean ± SD; 16 female) completed this case-control study at Cincinnati Children's Hospital Medical Center. Pressure pain thresholds (PPT) were assessed at the trapezius before and during immersion of the foot in a cold water bath (8°C). RESULTS In the migraine group (146.0 ± 79.1, mean ± SD), compared to healthy controls (248.0 ± 145.5, mean ± SD), significantly lower PPT (kilopascal) values were found (estimate = 124.28, 95% CI: 58.98, 189.59, p

Interhemispheric inhibition (IHI) is a dual-site TMS protocol measuring inhibitory interactions between the primary motor cortices (M1). IHI is performed by applying an initial conditioning stimulus followed by a test stimulus to the contralateral M1. Conventionally, the response in the contralateral hand to the conditioning TMS pulse is either not measured, or discarded. The aim of this experiment was to investigate whether MEPs evoked from these conditioning stimuli can be utilised as non-conditioned, or ‘baseline’, responses, and therefore expedite IHI data collection. We evaluated short-latency (10 ms) and long-latency (40 ms) IHI bidirectionally in 14 healthy participants. There was no difference in MEP amplitudes evoked by conventional single TMS pulses randomly inserted into IHI blocks, and those evoked by the conditioning stimulus. Nor was there any significant difference in IHI magnitude when using single pulse MEPs or conditioning stimulus MEPs as baseline responses. The utilisation of conditioning stimuli dispenses with the need to insert dedicated single TMS pulses into IHI blocks, allowing for additional IHI data to be collected in the same amount of time.

Repetitive passive movement (RPM) is a rehabilitation technique that increases spinal reciprocal inhibition (RI) as movement speed increases. However, characterization of the RPM number, frequency and range relative to the afferent impulses of muscle spindles and RI modulation has not been performed. In this study, we attempted to clarify these factors and evaluate their relationship to RI. We used 20 healthy adults for our first experiment (Experiment 1) and 16 healthy adults for our second experiment (Experiment 2). In Experiment 1, the RPM task was performed in the 80°-120° range for the ankle joint for 618 times at 80°/s (80°/s_618 times), 309 times at 160°/s (160°/s_309 times) and 618 times at 160°/s (160°/s_618 times). In Experiment 2, the RPM task focused on two ranges for the ankle joint (80°-100° and 100°-120°) and was performed at 160°/s with a movement time of 10 min. To measure RI, electrical stimulation was used to evoke a conditioning stimulus in the common peroneal nerve and the test stimulus in the tibial nerve. Conditions included the test stimulus only and conditioning stimulation-test stimulation intervals (CTI) of 2 and 20 ms. RI was measured before (Pre); immediately after; and 5, 10, 15 and 20 min after the task. Our findings suggest that the faster the movement speed of the RPM and the wider the movement range, the greater the increase in Ia firing. This may have enhanced RI by activating the inhibitory interneurons of RI.

Objective: To compare the application time of the Automated Auditory Brainstem Response (A-ABR) between the click and CE-Chirp® stimuli. Methods: Forty-six newborns were evaluated without risk indicators for hearing loss and presenting transient evoked otoacoustic emissions (TEOAE). The A-ABR was performed with Interacoustics® Titan equipment in a hospital, with the click and CE-Chirp® stimuli at the same time. Descriptive statistical analyses and inferential statistics analyses (Student's t-test calculation for mean comparisons among independent samples) were used for the variables age, gender, examination time, laterality and test stimulus used. Results: Of the 46 neonates in the sample, 23 were male and 23 female. The mean age of the sample was 23.1 days. The mean procedure time using the Click stimulus was 85.9 seconds for the right ear and 86.1 seconds for the left ear, whereas for the use of the CE-Chirp® stimulus the results obtained for the right and left ear were28.4 seconds and 27.9 seconds, respectively. There was a statistically significant difference between the mean times obtained through the CE-Chirp® and Click stimuli for both ears (p=0.000). There was no statistically significant difference in the comparison between the right and left ears or between females and males. Conclusion: It was found that the mean duration of the A-ABR procedure using the CE- Chirp® stimulus is three times lower than with the Click stimulus.

Cortical facilitation assessed with triad conditioning transcranial magnetic stimulation has been termed triad-conditioned facilitation (TCF). TCF has been supposed to reflect increased intracortical facilitation (ICF) at short interstimulus intervals (ISI) around 10 ms and an intrinsic rhythm of the motor cortex at longer ISI around 25 ms. To gain further insight into the pathophysiological mechanism of TCF, we systematically studied the effect of suprathreshold conditioning stimulus (CS) and test stimulus (TS) intensity on TCF. Various CS intensities and TS intensities were used in a triad-conditioning paradigm that was applied to 11 healthy subjects. ISI between pulses were studied between 5 and 200 ms. TCF at 10 ms ISI enhanced with increasing CS intensity but decreased with increasing TS intensity. The duration of facilitation was longer with higher CS intensity. However, TCF at 25 ms ISI could not be elicited with none of the CS and TS intensities addressed here. Our results are consistent with the notion of TCF at short ISI reflecting ICF. The enhanced and prolonged facilitation with increase of CS without additional isolated facilitation at longer ISI suggest a prolongation of ICF. Electronic supplementary material The online version of this article (10.1007/s00221-020-05812-z) contains supplementary material, which is available to authorized users.

Adaptive psychophysical methods are widely used for the quick estimation of percentage points (thresholds) on psychometric functions for two-alternative forced-choice (2AFC) tasks. The use of adaptive methods is supported by numerous simulation studies documenting their performance, which have shown that thresholds can be reasonably estimated with them when their founding assumptions hold. One of these assumptions is that the psychometric function is invariant, but empirical evidence is mounting that human performance in 2AFC tasks needs to be described by two different psychometric functions, one that holds when the test stimulus is presented first in the 2AFC trial and a different one that holds when the test is presented second. The same holds when presentations are instead simultaneous at two spatial locations rather than sequential. We re-evaluated the performance of adaptive methods in the presence of these order effects via simulation studies and an empirical study with human observers. The simulation study showed that thresholds are severely overestimated by adaptive methods in these conditions, and the empirical study corroborated these findings. These results question the validity of threshold estimates obtained with adaptive methods that incorrectly assume the psychometric function to be invariant with presentation order. Alternative ways in which thresholds can be accurately estimated in the presence of order effects are discussed.

The lateral prefrontal cortex of primates (lPFC) plays a central role in complex cognitive behavior, in decision-making as well as in guiding top-down attention. However, how and where in lPFC such behaviorally relevant signals are computed is poorly understood. We analyzed neural recordings from chronic microelectrode arrays implanted in lPFC region 8Av/45 of two rhesus macaques. The animals performed a feature match-to-sample task requiring them to match both motion and color information in a test stimulus. This task allowed to separate the encoding of stimulus motion and color from their current behavioral relevance on a trial-by-trial basis. We found that upcoming motor behavior can be robustly predicted from lPFC activity. In addition, we show that 8Av/45 encodes the color of a visual stimulus, regardless of its behavioral relevance. Most notably, whether a color matches the searched-for color can be decoded independent of a trial’s motor outcome and while subjects detect unique feature conjunctions of color and motion. Thus, macaque area 8Av/45 computes, among other task-relevant information, the behavioral relevance of visual color features. Such a signal is most critical for both the selection of responses as well as the deployment of top-down modulatory signals, like feature-based attention.