Interstimulus Interval Research Articles

Morphine Consumption During Lactation Impairs Short-Term Neuronal Plasticity in Rat Offspring CA1 Neurons

Background: Facing environmental factors during early postnatal life, directly or indirectly via mother-infant relationships, profoundly affects the structure and function of the mammals’ Central Nervous System (CNS). Objectives: This study aimed to evaluate the effect of morphine consumption during the lactation period on short-term synaptic plasticity of the hippocampal Cornu Ammonis 1 (CA1) neurons in rat offspring. Materials & Methods: In addition to a group of control mother rats (CO), three groups subcutaneously received 5 (M5), 10 (M10), or 20 (M20) mg/kg morphine every 12 hours during the lactation period. At 45 days old, following the stimulation of the Schaffers’ collaterals, basic field Excitatory Post-Synaptic Potentials (fEPSPs) were recorded in their offspring’s hippocampal CA1 neuronal circuits. After the construction input/output curve, paired-pulse stimulations with the inter-stimulus intervals of 20, 80, and 200 ms were applied to determine the short-term synaptic plasticity, and the paired-pulse ratio was evaluated. Results: The baseline synaptic responses of the rats CA1 neurons whose mothers received 10 and 20 mg/kg morphine twice daily during the lactation period decreased compared to the CO animals (P<0.01 & P<0.001, respectively). Furthermore, compared to the controls, the Paired-Pulse Ratio (PPR) of the CA1 neural circuits of M10 and M20 rats at 20 and 80 ms Inter-Stimulus Intervals (ISI) decreased (P<0.01). Conclusion: Morphine exposure during the lactation period has a detrimental impact on the primary synaptic activity and short-term synaptic plasticity of the hippocampal CA1 neuronal circuits of rats’ offspring.

Auditory perception dominates in motor rhythm reproduction.

It is commonly agreed that vision is more sensitive to spatial information, while audition is more sensitive to temporal information. When both visual and auditory information are available simultaneously, the modality appropriateness hypothesis predicts that, depending on the task, the most appropriate (i.e., reliable) modality dominates perception. While previous research mainly focused on discrepant information from different sensory inputs to scrutinize the modality appropriateness hypothesis, the current study aimed at investigating the modality appropriateness hypothesis when multimodal information was provided in a nondiscrepant and simultaneous manner. To this end, participants performed a temporal rhythm reproduction task for which the auditory modality is known to be the most appropriate. The experiment comprised an auditory (i.e., beeps), a visual (i.e., flashing dots), and an audiovisual condition (i.e., beeps and dots simultaneously). Moreover, constant as well as variable interstimulus intervals were implemented. Results revealed higher accuracy and lower variability in the auditory condition for both interstimulus interval types when compared to the visual condition. More importantly, there were no differences between the auditory and the audiovisual condition across both interstimulus interval types. This indicates that the auditory modality dominated multimodal perception in the task, whereas the visual modality was disregarded and hence did not add to reproduction performance.

P 85 Impaired pain processing on a brainstem level in patients with complex regional pain syndrome

Introduction: The complex regional pain syndrome (CRPS) is a chronic pain condition, which can follow limb trauma and is accompanied with sensorimotor dysfunction 1 . Current pathophysiological concepts assume local inflammatory processes that lead to peripheral and central sensitization of the nociceptive system 2 . Secondary maladaptive alterations of cortical sensorimotor excitability and disinhibition are well-established but little is known about the contribution of the brainstem. Preliminary evidence for altered brainstem excitability to trigeminal afferent stimulation was recently provided 3,4 . This study uses a more comprehensive assessment of the nociceptive blink reflex (NBR) to assess the interaction of brainstem excitability and habituation to painful stimuli. Methods : 14 CRPS patients (10 female, 53 ± 17.6 years) and 10 controls (HCs; 9 female, 52±18.3) received assessments of pain and the NBR (R2 component, 2 trials, 10 stimuli/trial, interstimulus interval 3-5s). The R2 area (R2a) and habituation (R2h; gradient of R2a against stimulus order) were measured for the stimulated/non-stimulated side (_s/_ns). Results : Pain levels were 5,0±1,5/10 at rest and 7,2±2,1/10 during movements. ANOVA revealed a significant group effect for patients vs. controls (F=4.0; p=0.015). Post hoc tests were corrected for multiple comparisons and showed exceeding excitability (R2a_s: t=2.42, p=0.048; R2a_ns: t=2.98, p= 0.028) and impaired habituation (R2h_s: t=2.45, p=0.044; R2h_ns t=2.60, p=0.036). No significant associations of both disease duration and pain levels with NBR measurements could be obtained. Discussion : We here provide first evidence of altered NBR excitability and habituation indicating altered pain processing on a brainstem level. These results complement previous findings by demonstrating disinhibition as a source of increased brainstem excitability to painful stimulation remote from the limb directly affected by CRPS 4 . Future investigations are needed for a better understanding of the brainstem and its role in the pathophysiology of CRPS. The potential of the NBR as clinical biomarker, as it has been demonstrated in other pain diseases, should also be clarified in further investigation 5 . Literature: 1 Veldman PH et al. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet 1993. 2 Eldufani J et al. A medical mystery of CRPS. Heliyon. 2020. 3 Thiele A, et al. Treatment with calcitonin gene-related peptide antibodies modifies brainstem excitability and habituation to nociceptive trigeminal stimulation in migraineurs. CEPHALALGIA. 2021. 4 Drummond P et al. The Source of Hemisensory Disturbances in CRPS, The Clinical Journal of Pain: 2021. 5 De Marinis M et al. Decreased habituation of the R2component of the blink reflex in migraine patients. Clinical neurophysiology. 2003.

Human auditory frequency discrimination and inter-stimulus interval

The goal of this study was to determine how human performance in discriminating between similar frequencies in the auditory spectrum was influenced by modifying the interstimulus interval (ISI). The ISI is defined as the time elapsed from the end of the first stimulus and the beginning of the second stimulus. The relationship between ISI and auditory discrimination was explored using an auditory file comprised of 40 tests that each contained two tones with a frequency difference of 1%. For each test, 44 participants were asked to select the tone they perceived as being a higher frequency. The two frequencies used in each test were centered around one of five base frequencies, and the ISI used in each test was one of eight predetermined intervals. Results from previous auditory frequency discrimination studies regarding the just-noticeable difference (JND) and Weber’s law were used in the selection of the frequency difference of 1% that was used in this experiment. This frequency difference was kept constant across all the tests in order to ensure that the ISI was the main factor influencing participant performance. Participant performance was greatest at an ISI of 1000 ms when results were averaged by frequency. Additionally, as the base frequency increased, average performance generally improved. The findings from this experiment promote further investigation into the effects of varying ISI on the integration of auditory information by the auditory cortex.

Time Delay Affects Thermal Discrimination.

Time order errors have been investigated in several fields, and the time delay between subsequent stimuli in discrimination tasks is one example of such errors. However, the effect of these types of errors in thermal discrimination tasks is understudied. To evaluate the effect of inter-stimulus interval (ISI) on thermal perception, we used a discrimination task with a staircase method between two non-zero thermal stimuli. We found that JND ISI=0s was 3.10 and increased by 11.9% and 21.2% at JND ISI=3s and JND ISI=9s, respectively. Statistical analysis revealed that ISI was a statistically significant effect ( ) on thermal perception in our task. Future studies on thermal perception should keep the ISI consistent and report the time.

Regulated Monosyllabic Talk Test vs. Counting Talk Test During Incremental Cardiorespiratory Exercise: Determining the Implications of the Utterance Rate on Exercise Intensity Estimation.

PurposeWhen utilizing breathing for speech, the rate and volume of inhalation, as well as the rate of exhalation during the utterance, seem to be largely governed by the speech-controlling system and its requirements with respect to phrasing, loudness, and articulation. However, since the Talk Test represents a non-standardized form of assessment of exercise intensity estimation, this study aimed to compare the utterance rate and the estimated exercise intensity using a newly introduced time-controlled monosyllabic Talk Test (tMTT) versus a self-paced Counting Talk Test (CTT) across incremental exercise stages and examined their associations with the exercise physiological measures.MethodsTwenty-four participants, 10 males and 14 females (25 ± 4.0 yr; 160 ± 10 cm; 62 ± 14.5 kg) performed two sessions of submaximal cardiorespiratory exercise at incremental heart rate reserve (HRR) stages ranging from 40 to 85% of HRR: one session was performed with a currently available CTT that was affixed to a wall in front of the participants, and the other session was conducted with a tMTT with a 1-s inter-stimulus interval that was displayed from a tablet. In each session, the participants performed six stages of exercise at 40, 50, 60, 70, 80, and 85% HRR on a treadmill and were also asked to rate their perceived exertion based on Borg’s 6 to 20 Rating of Perceived Exertion (RPE) at each exercise stage.ResultsThe newly designed tMTT significantly delineated all the six stages of incremental exercise (p ≤ 0.017), while CTT could only delineate exercise stages at 60, 80, and 85% HRR. However, in estimations of exercise intensity, the tMTT demonstrated only moderate associations with HRR and Borg’s RPE, similarly to the CTT.ConclusionIf the purpose of exercise monitoring is to detect the intensity of light, moderate, and vigorous exercise intensity, the tMTT could be more universally applicable. However, due to its larger variability of speech rate across exercise intensities, the time-regulated approach may alter the speech breathing characteristics of the exercising individuals in other ways that should be investigated in future research.

A novel tablet-based application for assessment of manual dexterity and its components: a reliability and validity study in healthy subjects

BackgroundWe developed five tablet-based tasks (applications) to measure multiple components of manual dexterity. Aim: to test reliability and validity of tablet-based dexterity measures in healthy participants.MethodsTasks included: (1) Finger recognition to assess mental rotation capacity. The subject taps with the finger indicated on a virtual hand in three orientations (reaction time, correct trials). (2) Rhythm tapping to evaluate timing of finger movements performed with, and subsequently without, an auditory cue (inter-stimulus interval). (3) Multi-finger tapping to assess independent finger movements (reaction time, correct trials, unwanted finger movements). (4) Sequence tapping to assess production and memorization of visually cued finger sequences (successful taps). (5) Line-tracking to assess movement speed and accuracy while tracking an unpredictably moving line on the screen with the fingertip (duration, error). To study inter-rater reliability, 34 healthy subjects (mean age 35 years) performed the tablet tasks twice with two raters. Relative reliability (Intra-class correlation, ICC) and absolute reliability (Standard error of measurement, SEM) were established. Task validity was evaluated in 54 healthy subjects (mean age 49 years, range: 20–78 years) by correlating tablet measures with age, clinical dexterity assessments (time taken to pick-up objects in Box and Block Test, BBT and Moberg Pick Up Test, MPUT) and with measures obtained using a finger force-sensor device.ResultsMost timing measures showed excellent reliability. Poor to excellent reliability was found for correct trials across tasks, and reliability was poor for unwanted movements. Inter-session learning occurred in some measures. Age correlated with slower and more variable reaction times in finger recognition, less correct trials in multi-finger tapping, and slower line-tracking. Reaction times correlated with those obtained using a finger force-sensor device. No significant correlations between tablet measures and BBT or MPUT were found. Inter-task correlation among tablet-derived measures was weak.ConclusionsMost tablet-based dexterity measures showed good-to-excellent reliability (ICC ≥ 0.60) except for unwanted movements during multi-finger tapping. Age-related decline in performance and association with finger force-sensor measures support validity of tablet measures. Tablet-based components of dexterity complement conventional clinical dexterity assessments. Future work is required to establish measurement properties in patients with neurological and psychiatric disorders.

Processing time affects sequential memory performance beginning at the level of visual encoding.

Electrophysiological studies have demonstrated that theta-band activity is useful for investigating neural mechanisms of memory. However, mechanisms specifically driving memory performance remain poorly understood. In sequential memory, performance can be artificially attenuated by shortening the inter-stimulus interval (ISI) between memory item presentations. Therefore, we sought to clarify the mechanisms of sequential memory performance by analyzing theta-band (4–8 Hz) activity recorded via magnetoencephalogram in 33 participants during performance of a sequential memory task where memory items were presented at either slow or fast rates in accordance with longer or shorter ISIs, respectively. Particularly in the slow task, theta activity clearly modulated in accordance with the presentation of memory items. Common cortical target regions in the occipital and frontal cortex were identified in both tasks and related to visual encoding and memory maintenance, respectively. Compared to the slow task, occipital-theta activity was significantly lower in the fast task from the midterm until the ending of encoding, in correspondence with significantly lower recall for memory items in this same period. Meanwhile, despite a loss of clarity in responsiveness to individual memory items in the fast task, frontal-theta activity was not different between tasks and exhibited particularly strong responses in both tasks during the holding period prior to recall. Our results indicate that shorter processing time erodes sequential memory performance beginning at the level of visual encoding.

Early visual processing and adaptation as markers of disease, not vulnerability: EEG evidence from 22q11.2 deletion syndrome, a population at high risk for schizophrenia

We investigated visual processing and adaptation in 22q11.2 deletion syndrome (22q11.2DS), a condition characterized by an increased risk for schizophrenia. Visual processing differences have been described in schizophrenia but remain understudied early in the disease course. Electrophysiology was recorded during a visual adaptation task with different interstimulus intervals to investigate visual processing and adaptation in 22q11.2DS (with (22q+) and without (22q−) psychotic symptoms), compared to control and idiopathic schizophrenia groups. Analyses focused on early windows of visual processing. While increased amplitudes were observed in 22q11.2DS in an earlier time window (90–140 ms), decreased responses were seen later (165–205 ms) in schizophrenia and 22q+. 22q11.2DS, and particularly 22q−, presented increased adaptation effects. We argue that while amplitude and adaptation in the earlier time window may reflect specific neurogenetic aspects associated with a deletion in chromosome 22, amplitude in the later window may be a marker of the presence of psychosis and/or of its chronicity/severity.

Common and independent processing of visual motion perception and oculomotor response.

Visual motion signals are used not only to drive motion perception but also to elicit oculomotor responses. A fundamental question is whether perceptual and oculomotor processing of motion signals shares a common mechanism. This study aimed to address this question using visual motion priming, in which the perceived direction of a directionally ambiguous stimulus is biased in the same (positive priming) or opposite (negative priming) direction as that of a priming stimulus. The priming effect depends on the duration of the priming stimulus. It is assumed that positive and negative priming are mediated by high- and low-level motion systems, respectively. Participants were asked to judge the perceived direction of a π-phase-shifted test grating after a smoothly drifting priming grating during varied durations. Their eye movements were measured while the test grating was presented. The perception and eye movements were discrepant under positive priming and correlated under negative priming on a trial-by-trial basis when an interstimulus interval was inserted between the priming and test stimuli, indicating that the eye movements were evoked by the test stimulus per se. These findings suggest that perceptual and oculomotor responses are induced by a common mechanism at a low level of motion processing but by independent mechanisms at a high level of motion processing.

Investigating the Effect of Stimulus Type on Electroencephalogram Signal in a Brain-Computer Interface System with Interaction Error

Purpose: Brain-Computer Interface (BCI) systems are a new channel of communication between human thoughts and machines without the aid of neuromuscular systems. Although BCI systems exhibit several advantages, they yet have a long road ahead to reach a flawless state. For example, error occurrence is one of the problems in these systems, leading to Error-Related Potentials (ErRP) in the brain signal. In this study, Electroencephalogram (EEG) signals in the condition of system error occurrence are investigated. Since local information on the EEG signal channels alone cannot reveal the secrets of the brain, functional connectivity was used as a feature in this research.
 Materials and Methods: In this research, 32 channel EEG signals with a sampling frequency of 256 Hz were recorded from 18 participants while interacting with a BCI system which has an interaction error. Two types of stimulus were used, including visual and tactile ones. Moreover, the Inter-Stimulus-Interval (ISI) was changed during the task. After pre-processing, brain functional connectivity was calculated between all channel pairs in four groups (visual, tactile, combined visual-tactile (ISI=3.5), and combined visual-tactile (ISI=2)) using Magnitude-Squared Coherence (MSC) measure.
 Results: The results showed a significant difference in frontal-right temporal connectivity between correct and error classes in tactile stimulation, in visual stimulation significant differences in frontal-occipital connectivity, in visual-tactile (ISI=3.5) stimulation significant differences in left temporal-occipital connectivity (P-value< 0.001), and in visual-tactile (ISI=2) stimulation significant differences in central-occipital connectivity were seen (P-value< 0.01).
 Conclusion: This study shows that using brain functional connectivity features along with local features can improve the performance of BCI systems.

Morphine Consumption During Lactation Impairs Short-Term Neuronal Plasticity in Rat Offspring CA1 Neurons

Background: Facing environmental factors during early postnatal life, directly or indirectly via mother-infant relationships, profoundly affects the structure and function of the mammals’ Central Nervous System (CNS). Objectives: This study aimed to evaluate the effect of morphine consumption during the lactation period on short-term synaptic plasticity of the hippocampal Cornu Ammonis 1 (CA1) neurons in rat offspring. Methods: In addition to a group of control mother rats (CO), three groups subcutaneously received 5 (M5), 10 (M10), or 20 (M20) mg/kg morphine every 12 hours during the lactation period. At 45 days old, following the stimulation of the Schaffers’ collaterals, basic field Excitatory Post-Synaptic Potentials (fEPSPs) were recorded in their offspring's hippocampal CA1 neuronal circuits. After the construction input/output curve, paired-pulse stimulations with the inter-stimulus intervals of 20, 80, and 200 ms were applied to determine the short-term synaptic plasticity, and the paired-pulse ratio was evaluated. Results: The baseline synaptic responses of the rats CA1 neurons whose mothers received 10 and 20 mg/kg morphine twice daily during the lactation period decreased compared to the CO animals (P<0.01 & P<0.001, respectively). Furthermore, compared to the controls, the Paired-Pulse Ratio (PPR) of the CA1 neural circuits of M10 and M20 rats at 20 and 80 ms Inter-Stimulus Intervals (ISI) decreased (P<0.01). Conclusions: Morphine exposure during the lactation period has a detrimental impact on the primary synaptic activity and short-term synaptic plasticity of the hippocampal CA1 neuronal circuits of rats’ offspring.

Effects of inter-stimulus intervals on concurrent P300 and SSVEP features for hybrid brain-computer interfaces

BackgroundRecently, we have implemented a high-speed brain-computer interface (BCI) system with a large instruction set using the concurrent P300 and steady-state visual evoked potential (SSVEP) features (also known as hybrid features). However, it remains unclear how to select inter-stimulus interval (ISI) for the proposed BCI system to balance the encoding efficiency and decoding performance. New methodThis study developed a 6 * 9 hybrid P300-SSVEP BCI system and investigated a series of ISIs ranged from −175–0 ms with a step of 25 ms. The influence of ISI on the hybrid features was analyzed from several aspects, including the amplitude of the induced features, classification accuracy, information transfer rate (ITR). Twelve naive subjects were recruited for the experiment. ResultsThe results showed the ISI factor had a significant impact on the hybrid features. Specifically, as the values of ISI decreased, the amplitudes of the induced features and accuracies decreased gradually, while the ITRs increased rapidly. It’s achieved the highest ITR of 158.50 bits/min when ISI equal to − 175 ms. Comparison with Existing MethodThe optimal ISI in this study achieved superior performance in comparison with the one we used in the previous study. ConclusionsThe ISI can exert an important influence on the P300-SSVEP BCI system and its optimal value is − 175 ms in this study, which is significant for developing the high-speed BCI system with larger instruction sets in the future.

Short latency afferent inhibition: comparison between threshold-tracking and conventional amplitude recording methods.

Short-latency afferent inhibition (SAI), which is conventionally measured as a reduction in motor evoked potential amplitude (A-SAI), is of clinical interest as a potential biomarker for cognitive impairment. Since threshold-tracking has some advantages for clinical studies of short-interval cortical inhibition, we have compared A-SAI with a threshold-tracking alternative method (T-SAI). In the T-SAI method, inhibition was calculated by tracking the required TMS intensity for the targeted MEP amplitude (200 uV) both for the test (TMS only) and paired (TMS and peripheral stimulation) stimuli. A-SAI and T-SAI were recorded from 31 healthy subjects using ten stimuli at each of 12 inter-stimulus intervals, once in the morning and again in the afternoon. There were no differences between morning and afternoon recordings. When A-SAI was normalized by log conversion it was closely related to T-SAI. Between subjects, variability was similar for the two techniques, but within-subject variability was significantly smaller for normalized A-SAI. Conventional amplitude measurements appear more sensitive for detecting changes within-subjects, such as in interventional studies, but threshold-tracking may be as sensitive as detecting abnormal SAI in a patient.

Individual resting-state alpha peak frequency and within-trial changes in alpha peak frequency both predict visual dual-pulse segregation performance.

Although sensory input is continuous, information must be combined over time to guide action and cognition, leading to the proposal of temporal sampling windows. A number of studies have suggested that a 10-Hz sampling window might be involved in the "frame rate" of visual processing. To investigate this, we tested the ability of participants to localize and enumerate 1 or 2 visual flashes presented either at near-threshold or full-contrast intensities, while recording magnetoencephalography. The inter-stimulus interval (ISI) between the 2 flashes was varied across trials. Performance in distinguishing between 1 and 2 flashes was linked to the alpha frequency, both at the individual level and trial-by-trial. Participants with a higher resting-state alpha peak frequency showed the greatest improvement in performance as a function of ISI within a 100-ms time window, while those with slower alpha improved more when ISI exceeded 100ms. On each trial, correct enumeration (1 vs. 2) performance was paired with faster pre-stimulus instantaneous alpha frequency. Our results suggest that visual sampling/processing speed, linked to peak alpha frequency, is both an individual trait and can vary in a state-dependent manner.

Transcranial magnetic stimulation as biomarker of excitability in drug development: A randomized, double-blind, placebo-controlled, cross-over study.

AimsThe purpose of this study was to investigate pharmacodynamic effects of drugs targeting cortical excitability using transcranial magnetic stimulation (TMS) combined with electromyography (EMG) and electroencephalography (EEG) in healthy subjects, to further develop TMS outcomes as biomarkers for proof‐of‐mechanism in early‐phase clinical drug development. Antiepileptic drugs presumably modulate cortical excitability. Therefore, we studied effects of levetiracetam, valproic acid and lorazepam on cortical excitability in a double‐blind, placebo‐controlled, 4‐way cross‐over study.MethodsIn 16 healthy male subjects, single‐ and paired‐pulse TMS‐EMG–EEG measurements were performed predose and 1.5, 7 and 24 hours postdose. Treatment effects on motor‐evoked potential, short and long intracortical inhibition and TMS‐evoked potential amplitudes, were analysed using a mixed model ANCOVA and cluster‐based permutation analysis.ResultsWe show that motor‐evoked potential amplitudes decreased after administration of levetiracetam (estimated difference [ED] −378.4 μV; 95%CI: −644.3, −112.5 μV; P < .01), valproic acid (ED −268.8 μV; 95%CI: −532.9, −4.6 μV; P = .047) and lorazepam (ED −330.7 μV; 95%CI: −595.6, −65.8 μV; P = .02) when compared with placebo. Long intracortical inhibition was enhanced by levetiracetam (ED −60.3%; 95%CI: −87.1%, −33.5%; P < .001) and lorazepam (ED −68.2%; 95%CI: −94.7%, −41.7%; P < .001) at a 50‐ms interstimulus interval. Levetiracetam increased TMS‐evoked potential component N45 (P = .004) in a central cluster and decreased N100 (P < .001) in a contralateral cluster.ConclusionThis study shows that levetiracetam, valproic acid and lorazepam decrease cortical excitability, which can be detected using TMS‐EMG–EEG in healthy subjects. These findings provide support for the use of TMS excitability measures as biomarkers to demonstrate pharmacodynamic effects of drugs that influence cortical excitability.

Handling EEG artifacts and searching individually optimal experimental parameter in real time: a system development and demonstration

Objective. Neuroadaptive paradigms that systematically assess event-related potential (ERP) features across many different experimental parameters have the potential to improve the generalizability of ERP findings and may help to accelerate ERP-based biomarker discovery by identifying the exact experimental conditions for which ERPs differ most for a certain clinical population. Obtaining robust and reliable ERPs online is a prerequisite for ERP-based neuroadaptive research. One of the key steps involved is to correctly isolate electroencephalography artifacts in real time because they contribute a large amount of variance that, if not removed, will greatly distort the ERP obtained. Another key factor of concern is the computational cost of the online artifact handling method. This work aims to develop and validate a cost-efficient system to support ERP-based neuroadaptive research. Approach. We developed a simple online artifact handling method, single trial PCA-based artifact removal (SPA), based on variance distribution dichotomies to distinguish between artifacts and neural activity. We then applied this method in an ERP-based neuroadaptive paradigm in which Bayesian optimization was used to search individually optimal inter-stimulus-interval (ISI) that generates ERP with the highest signal-to-noise ratio. Main results. SPA was compared to other offline and online algorithms. The results showed that SPA exhibited good performance in both computational efficiency and preservation of ERP pattern. Based on SPA, the Bayesian optimization procedure was able to quickly find individually optimal ISI. Significance. The current work presents a simple yet highly cost-efficient method that has been validated in its ability to extract ERP, preserve ERP effects, and better support ERP-based neuroadaptive paradigm.

Subthalamic nucleus conditioning reduces premotor-motor interaction in Parkinson's disease

BackgroundDeep brain stimulation of the subthalamic nucleus is effective to alleviate motor symptoms in advanced Parkinson's disease. Using a novel conditioning paradigm, it has been shown that deep brain stimulation pulses from electrodes in the subthalamic nucleus modulate corticospinal excitability as determined with transcranial magnetic stimulation applied to the motor cortex. The mechanism of action is unclear. ObjectiveTo investigate the effects of subthalamic nucleus and dorsal premotor cortex conditioning on corticospinal excitability as a function of interstimulus intervals between target areas and deep brain stimulation frequencies. MethodsIn 19 patients with Parkinson's disease with subthalamic nucleus deep brain stimulation, the premotor-motor interaction was investigated in four different deep brain stimulation conditions (off, clinically used settings, 3 Hz, 20 Hz). Transcranial magnetic pulses were applied to the premotor and motor cortex and paired at certain intervals with deep brain stimulation pulses. The volume of tissue activated by deep brain stimulation was correlated with neurophysiological findings. ResultsThere was distinct motor cortex inhibition by premotor cortex conditioning at an interstimulus interval of 1 ms before the motor cortex stimulation. Subthalamic nucleus conditioning with deep brain stimulation frequencies of 3 and 20 Hz at an interstimulus interval of 10 ms between subthalamic nucleus and primary motor cortex reduced premotor-motor inhibition. The volume of tissue activated by deep brain stimulation correlated positively with this effect. Corticospinal excitability was not affected by subthalamic nucleus conditioning as used here. ConclusionsPremotor-motor inhibition is modulated by subthalamic nucleus conditioning, presumably through the monosynaptic hyperdirect pathway.

Maladaptive motor cortical excitability and connectivity in polyneuropathy with neuropathic pain.

Sensory symptoms, especially neuropathic pain, are common in polyneuropathy. Conventional diagnostic tools can evaluate structural or functional impairment of nerves but cannot reveal mechanisms of neuropathic pain. Changes in the brain after polyneuropathy may play roles in the genesis of neuropathic pain. This cross-sectional study investigated changes of cortical excitability within left primary motor cortex (M1) by measuring resting motor thresholds, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and afferent inhibition between polyneuropathy patients and controls, and investigated the correlates of these parameters with neuropathic pain and M1 structural and functional connectivity assessed by diffusion tractography imaging and functional magnetic resonance imaging. Thirty-three painful and 15 nonpainful neuropathic patients and 21 controls were enrolled. There were no differences in intraepidermal nerve fiber density, nerve conduction studies, thermal thresholds, or autonomic functional tests between patients with and without neuropathic pain. Compared to controls, neuropathic patients exhibited similar resting motor thresholds or afferent inhibition, but attenuated SICI and augmented ICF, especially in painful patients. Changes of intracortical excitability in neuropathic patients were correlated with intensities of neuropathic pain, and different presentations of SICI and ICF were noted between patients with and without thermal paresthesia. Additionally, short-latency afferent inhibition at an interstimulus interval of 20ms was associated with structural connectivity of left M1 with brain areas associated with pain perception. Maladaptive cortical excitability with altered structural connectivity in left M1 developed after peripheral nerve degeneration and was associated with neuropathic pain and sensory symptoms in polyneuropathy.

The subsequent interruptive effects of pain on attention.

Pain is known to interrupt attentional performance selectively. In a previous study, we showed that the interruptive effect of thermal pain on attention could persist up to 1500ms after painful stimulus offset, but whether the pain modality affects this subsequent interruptive effect remains unclear. The present study was conducted to determine the time course of the interruptive effect of electrically induced pain on orienting and executive attention using various intervals between electric stimulation and attentional tasks (0, 250, 500, 750, 1000, 1250 and 1500ms) and three study groups (pain, non-pain and control). We performed two separate experiments in which participants performed a spatial cue task (Experiment 1) and the Stroop task (Experiment 2). Participants in the pain and non-pain groups received brief electric somatosensory stimulation, and those in the control group received no physical stimulus. We compared the performance of the three groups under the interstimulus interval (ISI) conditions. The impairment of orienting attention prevailed under the first six ISI conditions in the pain and non-pain groups (F2, 63 =5.72, p<0.01); executive attention was not affected (F1,66 =1.64, p=0.20), confirming the persistence of the interruptive effect after stimulus offset. This study demonstrated the interruptive effect of somatic stimulation on subsequent orienting attention performance, with no effect on executive attention. These findings suggest that pain has differential effects on the components of attention, depending on its modality and salience. This study confirmed that pain had a selective subsequent interruptive effect on attention and found that the time course of the interruption depended on the modality of pain and the component of attention.