Ms Interstimulus Intervals Research Articles

Concurrent functional magnetic resonance imaging and electroencephalography assessment of sensory gating in schizophrenia

Schizophrenia is frequently accompanied by deficits in basic information processing, such as sensory gating. The sources behind deficient sensory gating in schizophrenia patients are, however, still largely unclear. The aim of the current study was to identify the brain structures involved in deficient sensory gating in schizophrenia patients. Twenty healthy male volunteers and 23 male schizophrenia patients were initially assessed in a somatosensory P50 suppression paradigm using concurrent electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) methodology. The trials consisted of single stimuli or pairs of identical stimuli with either 500 ms or 1,000 ms interstimulus intervals. Not all subjects showed a P50 waveform as a result of the somatosensory stimuli: It was detected in 13 schizophrenia patients and 15 control subjects. Significant P50 suppression was found in the 500 ms trials in controls only. Region of interest analyses were performed for a priori chosen regions. Significant negative correlations between P50 ratios and the BOLD response were found bilaterally in the hippocampus, thalamus, anterior and posterior superior temporal gyrus (STG), and in the left inferior frontal gyrus pars opercularis. However, significant group differences were found in the hippocampus and the thalamus only. This is the first study in which P50 suppression was assessed in schizophrenia patients with concurrent fMRI/EEG methodology. The data support that the STG, thalamus, inferior frontal gyrus, and the hippocampus are involved in P50 suppression. However, of these structures only the hippocampus and thalamus appeared involved in the altered sensory processing found in schizophrenia. Hum Brain Mapp 35:3578–3587, 2014. © 2013 Wiley Periodicals, Inc.

Individualized Brain Inhibition and Excitation Profile in Response to Paired-Pulse TMS

ABSTRACT Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are generated from paired-pulse transcranial magnetic stimulations (ppTMS) using certain interstimulus intervals (ISIs). ppTMS provides an accessible technique to evaluate inhibitory and facilitatory motor neural circuits. However, SICI and ICF are highly variable such that individual variability is not captured by any one static ISI. The authors hypothesized that individuals may have individualized and relatively stable pattern of SICI-ICF profiles. They tested SICI and ICF profiles using ISIs from 1 to 500 ms, on 2 occasions about 3 weeks apart, and the test-retest reliability, in 23 healthy controls. Moderate-to-good test-retest reliabilities were found at ppTMS with 1 and 3 ms ISIs (SICI) and with 12, 15, 18, and 21 ms ISIs (ICF), but not with other control ISIs. A similar pattern of results was obtained for men and women. Interestingly, the peak facilitation, peak inhibition, and maximum inhibition and facilitation ranges were individualized, such that they varied considerably across individuals but had high repeatability within individual (Cronbach's α = 0.76 to 0.85). Therefore, individuals appear to have unique inhibition-facilitation profiles that are relatively stable. Although the functional implications of individualized profiles are currently unknown, the relatively stable profiles may index underlying neural inhibition and excitation traits.

140. Effects of transcranial alternating current stimulation (tACS) on spontaneous motor tempo and sensorimotor synchronization: Preliminary data

We used transcranial alternating current stimulation (tACS) to modulate brain oscillations during spontaneous motor tempo and sensorimotor synchronization tasks to evaluate the effect of specific frequencies on motor performance. Six healthy subjects performed self-paced finger movements and auditory-paced finger tapping (synchronization–continuation task) with isochronous rhythmic sequences of 500 and 1500 ms interstimulus intervals (ISI). During each task, tACS was delivered to the left M1 (“reference” electrode on Pz) at an intensity of 1 mA in 5 randomized conditions: 5, 10, 20, 40 Hz, and sham. Baseline recordings (without tACS) were performed before and after each experimental session. In synchronization task with sequences of ISI 500 ms, 20 Hz tACS modified anticipatory mechanisms as revealed by a reduction of the negative mean asynchrony between the onset of the auditory cue and the motor response. However, this effect did not reach statistical significance due to the small sample. No effect emergent in the other conditions. We hypothesize that the reduction of the negative mean asynchrony may reflect a slowing of the motor output. These preliminary data are in line with previous studies in literature reporting specific effects of tACS at beta frequency on motor functions and cortical excitability.

P 216. Impairment of triad conditioned facilitation in amyotrophic lateral sclerosis

Triad conditioned facilitation induced by transcranial magnetic stimulation (TMS) in healthy individuals has been proposed to reflect the intrinsic 40 Hz piper rhythm of the motor cortex. However, it is unclear if triad conditioned facilitation is influenced by degeneration of the motor cortex. Amyotrophic lateral sclerosis (ALS) is characterized among others by degeneration of the motor cortex. We therefore hypothesized that triad conditioned facilitation may be impaired in ALS patients. Moreover, we hypothesized that this triad conditioning paradigm may be helpful to differentiate ALS from cervical myelopathy, an important differential diagnosis. In 10 patients with ALS and 9 patients with cervical myelopathy serving as disease control, we compared single pulse conditioned intracortical inhibition (ICI), intracortical facilitation (ICF) and also triad conditioned facilitation at various interstimulus intervals (ISI) between 3 ms and 50 ms. There were no differences in ICI and ICF between both groups. Both groups also showed similar triad conditioned facilitation at 10 ms ISI. Patients with cervical myelopathy showed normal triad conditioned facilitation at 25 ms ISI comparable to healthy subjects. In contrast ALS patients showed no triad conditioned facilitation at 25 ms. The absence of triad conditioned facilitation at 25 ms ISI in ALS patients may represent changes of the intrinsic rhythm of the motor cortex probably caused by cortical degeneration. Triad conditioned TMS may be a valuable tool to differentiate ALS patients from patients with cervical myelopathy.

Implementation of Integrated Mismatch Negativity in Differentiating Children with Specific Language Impairment

The study aimed to assess the use of Integrated Mismatch Negativity (MMNi) in differentiating children with specific language impairment (SLI) from a control group. Six conditions were created using a 1,000-Hz standard stimulus with three deviants of 1,020, 1,050, or 1,100 Hz and two interstimulus intervals of 400 and 200 ms. Recordings were processed offline using NeuroScan Edit (NeuroScan, Texas, United States). Four time analysis points were chosen and the magnitude of the integrated deviant was compared with the 100 standard subaverages. Mismatch negativity (MMN) presence was determined when 10 or less of the standard subaverages were less than the deviant subaverage magnitude. A total of 18 children with SLI and 35 typical development children participated in the study. Pearson chi-square test demonstrated that the proportion of MMN presence in the SLI group was not significantly different from the control group and it did not vary with condition. Two-way between-group analysis of variance confirmed that using 1,000 Hz standard, 1,050 Hz deviant, and 400 ms interstimulus interval was significantly different from the other conditions. MMNi does not serve as a tool for identifying children with SLI when using pure-tone stimuli. However, using different time analysis points with MMNi should be explored further, particularly with speech material.

Accessing, Integrating, and Inhibiting Word Meaning in Poor Comprehenders

This study examined three processes crucial to reading comprehension (semantic access, integration, and inhibition) to identify causes of comprehension impairment. Poor comprehenders were compared to chronological-age controls and vocabulary-age (VA) controls. When listening to homonym primes (“bank”) versus unrelated primes, controls were faster to name pictures related to dominant (money) and subordinate (river) meanings at 250 ms interstimulus interval (ISI) but only showed dominant priming at 1,000 ms ISI, whereas poor comprehenders only showed dominant priming. When listening to subordinately biased sentences ending in homonyms (“John fished from the bank”) versus control sentences, all groups showed priming when naming subordinate (appropriate) pictures at 250 ms ISI: VA controls and poor comprehenders also showed priming when naming dominant (inappropriate) pictures. At 1,000 ms ISI, controls showed appropriate priming, whereas poor comprehenders only showed inappropriate priming. These findings suggest that poor comprehenders have difficulties accessing subordinate word meanings, which can manifest as a failure to inhibit irrelevant information.

Refractory effects of the N1 event-related potential in experienced cochlear implant patients

Objective: To determine if cochlear implant (CI) patients exhibit a temporal processing deficit for auditory stimuli, by examining refractory effects of the N1 event-related potential (ERP) component. Design: CI patients and normally-hearing controls were tested in an auditory refractory period paradigm while ERP recordings were collected across the scalp. Participants were presented with brief 500-Hz tones that were separated by inter-stimulus intervals (ISIs) of 500, 1000, or 3000 ms. The amplitude of the N1 was examined as a function of ISI within each group. Study sample: Ten adult CI patients and 13 age-matched normally-hearing controls were tested. Patients had long-lasting severe or profound sensorineural hearing loss prior to implantation, and a minimum of two years experience with CI activation. Results: Unlike normally-hearing controls, CI users showed no refractory effect for tones at 500 ms ISIs compared to 1000 ms. However, similar to controls, recovery from refractoriness was observed in anterior locations at 3000 ms. Conclusion: The refractory period threshold, defined as the minimum ISI where different N1 amplitudes are elicited, is greater than 1000 ms in CI patients; at least double that of normally-hearing controls.

Intraoperative Neurophysiological Monitoring in Spinal Root Surgical Interventions

Background and Objective: Surgical interventions around spinal roots may result in rootlets injury and neurological deficits. Multimodal introperative neurophysiological monitoring (MIOM) can allow for early detection and then reversal of nerve roots potential injuries. These utilities have been currently used to evaluate spinal sensorimotor pathways and nerve root function during posterior spinal approches for transpedicular screw fixations in a rotine base in our setting (Vali-e ASR Hospital, Arak, Iran) since 1998. Methods: In three consecutive patients (1 male, 16 years old. and 2 female, 17 and 16 years old) kyphoscoliosis corrections, patient’s history, preoperative physical examination and MIOM were performed using a multimodal 40-channel electrophysiologic monitoring system (Nicolet Endeavor, VIASYS Healthcare, 2005, USA). In all cases somatosensory evoked potentials (SSEPs) and F-wave responses corresponding tothe related myotome, were recorded 2 days prior surgery. The SSEPs, bilateral EMGs of paravertebrals and related muscle, stimulus-evoked evoked EMGs by mid-dural spinal stimulation, stimulus-evoked EMGs through root stimulation (pre/post foraminal) were performed when required during different stages of operation procedure. The compound muscle action potentials (CMAPs) were recorded using a pair of 1 Cm2 golden cup surface electrode. A paired-pulse stimulation consisting of two pulses with 2 ms interstimulus interval (ISI), 100-300 µs duration and 10-40 mA intensity was applied through a surgical probe pair electrode touched to the intact dura, over the midline of dorsal column, 2 segments above the involved root, to evoke constant reproducible EMGs in paravertebrals and/or approperiate myotomes of the segment in both lower limbs. Latency of CMAPs were measured for dorsal culumn, foramen entrance and root exit site stimulations. Following the measurements of the F-wave latencies, the central root conduction time and foramenal segments were calculated and used for further monitoring.The SSEPs of ascending valleis from medial tibial nerve stimulation were recorded at C7 spine and C3´ or C4´of the operation side. A unilateral, sustained loss of 50% of the SSEP amplitude and/or increase by 10% of latency from average values after anesthesia, and SSEP/CMAP waveform change to an asynchronous polyphasic wave, were considered to be pathologic. Drilling and screw positionings were evaluated intraoperatively with standard posteroanterior and lateral radiographs.Results: None of the 3 patients showed significant change in the SSEPsor post-operative radiculopathies distinct from their preoperative presentations. One hour after the start of surgery, when the spinal column was exposed to the operating theatre temperature, a minimal prolongation of latencies as well as amplitude reduction of SSEPs was observed. The SSEP waveforms were not affected subsequently. A reverse change appeared again after paravertebral muscles stitching at the final hour of surgery.In our cases, latencies of different root segments were kept intact during the operation and also during the transfer to the recovery room. Propofol or Propofol/Ketamine mixture plus narcotic is suitable to obtain stable reproducible SSEPs and EMGs. Atracurium or other nondepolarizing skeletal muscle relaxants should be avoided. Muscle relaxants application or mean arterial pressure (MAP) below 70 mmHg may cause bilateral reduction or loss of SSEPs and EMGs. There was no postoperative clinically detectable complication.Conclusions: Findings of our study demonstrated that MIOM should be used in all patients undergoing surgery around spinal roots. Monitoring can practically reduce possibilities of neurological deficit. Futhermore, it can be concluded that the use of SSEPs to evaluate the pedicle screw placement or similar interventions is not an appropriate tool itself, since, , it could be practically limited to sensory fibers of root. In these settings and similar procedures, if IOM is required, alternative multimodal methods with greater sensitivity and efficacy should be explored. To aquire MIOM modalities, close collaboration of an anesthesioloist is nessesary.

Cocaine potentiates excitatory drive in the perifornical/lateral hypothalamus

The hypothalamus is a critical controller of homeostatic responses and plays a fundamental role in reward-seeking behaviour. Recently, hypothalamic neurones in the perifornical/lateral hypothalamic area (PF/LHA) have also been implicated in drug-seeking behaviour through projections to extra-hypothalamic sites such as the ventral tegmental area. For example, a population of neurones that expresses the peptide orexin has been strongly implicated in addiction-relevant behaviours. To date, the effect of addictive drugs on synaptic properties in the hypothalamus remains largely unexplored. Previous studies focusing on the PF/LHA neurones, however, have shown that the orexin system exhibits significant plasticity in response to food or sleep restriction. This neuroadaptive ability suggests that PF/LHA neurones could be highly susceptible to modifications by drug exposure. Here, we sought to determine whether cocaine produces synaptic plasticity in PF/LHA neurones. Whole-cell patch-clamp techniques were used to examine the effects of experimenter-administered (passive) or self-administered (SA) cocaine on glutamatergic synaptic transmission in PF/LHA neurones. These experiments demonstrate that both passive and SA cocaine exposure increases miniature excitatory postsynaptic current (mEPSC) frequency in PF/LHA neurones. In addition, SA cocaine reduced the paired-pulse ratio but the AMPA/NMDA ratio of evoked excitatory inputs was unchanged, indicative of a presynaptic locus for synaptic plasticity. Dual-labelling for orexin and excitatory inputs using the vesicular glutamate transporter (VGLUT2), showed that passive cocaine exposure increased VGLUT2-positive appositions onto orexin neurones. Further, a population of recorded neurones that were filled with neurobiotin and immunolabelled for orexin confirmed that increased excitatory drive occurs in this PF/LHA population. Given the importance of the PF/LHA and the orexin system in modulating drug addiction, we suggest that these cocaine-induced excitatory synapse-remodelling events within the hypothalamus may contribute to persistence in drug-seeking behaviour and relapse.

Heat-Evoked Experimental Pain Induces Long-Term Potentiation-Like Plasticity in Human Primary Motor Cortex

We designed a new paired associative stimulation (PAS) protocol that combines experimental pain evoked by laser stimuli and transcranial magnetic stimulation (TMS) (Laser-PAS) to primary motor cortex (M1). We tested in healthy subjects whether Laser-PAS elicits cortical plasticity as reflected by long-term changes in motor-evoked potentials (MEPs) (after-effects). In separate experiments, we examined numerous variables including changes induced by varying the interstimulus intervals (ISIs) and Laser-PAS-induced changes in target and non-target muscle MEPs. We measured MEPs after repetitive laser or TMS (rTMS) pulses, and compared magnetic- and electric (TES)-induced MEPs. We tested MEPs after applying Laser-PAS with laser pulses ipsilaterally to M1. Finally, we studied subjects receiving an N-methyl-D-aspartate (NMDA) receptor antagonist (memantine) or placebo (α-lipoic acid). During Laser-PAS at the 50 ms ISI MEPs decreased, thereafter they increased for 60 min; other ISIs induced no after-effects. The after-effects remained restricted to the target muscle. Repetitive laser pulses and rTMS induced no after-effects. After Laser-PAS, TMS-induced MEPs increased, whereas TES-induced MEPs did not. Laser-PAS with laser pulses ipsilaterally to M1 left MEPs unchanged. Memantine, but not α-lipoic acid, abolished the after-effects. In conclusion, Laser-PAS elicits NMDA-dependent cortical plasticity and provides new insights into human pain-motor integration.

Repetitive Paired-Pulse Transcranial Magnetic Stimulation Over the Visual Cortex Alters Visual Recovery Function

BackgroundSome repetitive transcranial magnetic stimulation (rTMS) techniques fail to facilitate cortical excitability in the human visual cortex. A more effective and facilitatory method is needed to increase the feasibility of rTMS to explore visual cortex function. ObjectiveThe present study aimed to develop a novel tool for modulating the visual cortex excitability and examined the influences of repetitive transcranial magnetic paired-pulse stimulation (rPPS) on the visual cortex. MethodsOptimal interstimulus intervals (ISIs) were determined to assess recovery function of visual evoked potentials (VEPs). Paired stimuli from checkerboard pattern reversals were presented at 11 ISIs from 50–200 ms. Each session consisted of control (S1) and paired (S1 + S2) epochs to extract the S2 response. The recovery function was calculated as the ratio of S2/S1 amplitudes. Subsequently, rPPS was utilized with a 1.5 ms ISI over the visual cortex at the stimulus intensity of the visual masking effect. Amplitudes and suppression ratios of the paired VEPs were compared before and after rPPS. The effect of single pulse TMS was also evaluated. ResultsPaired VEPs resulted in suppressive effects at ISIs up to 200 ms, with an optimal ISI of 90 ms due to small variability and moderate inhibitory effects. There was no significant effect of rPPS on N75-P100 with paired VEPs. Following rPPS, however, P100-N145 inhibition decreased up to 10 min. The single pulse protocol did not result in these effects. ConclusionsModulation of VEP recovery by rPPS suggested that rPPS exhibited a disinhibitory effect on the visual cortex.

Increased Cortical Excitability: A Mechanism for Alcohol Withdrawal Symptoms? (P07.145)

Objective: We used transcranial magnetic stimulation (TMS) to investigate whether motor cortical excitability changes in relation to the amount of chronic alcohol ingestion. Background Experimental data suggesting that chronic alcohol exposure induces brain neuroadaptative changes within the excitatory and inhibitory neuronal circuits but this has never been proven. This because of the lack until recently of measuring the excitatory/inhibitory balance non-invasively in humans. Design/Methods: 43 participants divided according to the amount of alcohol they regularly consumed within the preceding 12 months into high, moderate and low risk groups were studied twice, (i) during regular pattern of alcohol consumption and (ii) after abstaining from alcohol for at least 24 hours. Motor threshold, short intracortical inhibition ([SICI] paired pulse TMS at 2, 5 ms interstimulus intervals [ISIs]), intracortical facilitation ([ICF] 10, 15 ms ISIs) and long intracortical inhibition ([LICI] 100- 300 ms ISIs) were measured on both occasions. The results were compared to those of 20 controls with no history of exposure to alcohol. Results: During regular alcohol consumption, there was reduced ICF (p Conclusions: Chronic alcohol consumption is associated with alterations within the intracortical excitatory and inhibitory systems. These changes may be a mechanism underlying alcohol withdrawal symptoms. Disclosure: Dr. Badawy has nothing to disclose. Dr. Cook has received research support from UCB Pharma. Dr. Vogrin has nothing to disclose. Dr. Norman has nothing to disclose. Dr. Currie has nothing to disclose.

Parieto-motor functional connectivity is impaired in Parkinson's disease

BackgroundBradykinesia in Parkinson's disease is associated with a difficulty in selecting and executing motor actions, likely due to alterations in the functional connectivity of cortico-cortical circuits. Objective/HypothesisOur aims were to analyse the functional interplay between the posterior parietal cortex and the ipsilateral primary motor area in Parkinson's disease using bifocal transcranial magnetic stimulation, to evaluate its modulation by dopaminergic treatment and its relationship to a simple choice reaction task. MethodsWe studied 12 Parkinson's disease patients with and without dopaminergic treatment and 12 healthy controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right posterior parietal cortex and the right primary motor area using different conditioning stimulus intensities and interstimulus intervals. Reaction and movement times were studied by a simple choice reaction task. ResultsIn controls, we observed a significant facilitation of motor evoked potential amplitudes at 4 ms interstimulus interval when conditioning stimulus intensity was set to 90% of resting motor threshold. This functional interaction was not observed in Parkinson's disease patients without dopaminergic treatment and was not restored with treatment. Moreover, correlation analyses revealed that Parkinson's disease patients with less impaired parieto-motor interaction were faster in executing reaching movements in a choice reaction time task, suggesting that the functional parieto-motor impairment described here could be related to bradykinesia observed in Parkinson's disease patients. ConclusionsParieto-motor functional connectivity is impaired in Parkinson's disease. The reduced efficacy of this connection could be related to presence of bradykinesia previously observed in Parkinson's disease.

Recovery From Forward Masking in Elderly Cochlear Implant Users

To compare temporal aspects of peripheral neural responses and central auditory perception between groups of younger adult and elderly cochlear implant users. Cohort study. Academic hospital and cochlear implant center. Adult cochlear implant users aged 28 to 57 years in the younger group (n = 5) and 61 to 89 years (n = 9) in the elderly group. All subjects used Advanced Bionics devices. Diagnostic. Time constants of neural (i.e., electrically evoked compound action potentials [ECAPs]) and perceptual recovery from forward masking. Interstimulus intervals (ISIs) were varied in both experiments. ECAP recovery rates were equivalent between groups, and no correlation was found between ECAP recovery and age. No correlations were found between ECAP recovery and speech perception. Psychophysical recovery was significantly slower in the elderly compared with the younger subjects (p < 0.0005), with a significant effect of age (R2 = 0.70, p < 0.0005). At the longest ISI (240 ms), elderly subjects experienced a mean maximum threshold shift of 35.2% (relative to 1 ms ISI) versus 14.8% for younger subjects. There was a significant positive relationship between psychophysical recovery and consonant-nucleus-consonant word scores (R2 = 0.62, p < 0.001), although no relationship was found with Hearing in Noise Test sentences. These findings suggest that difficulties observed in speech perception by elderly CI users may be due to age-related changes in the central rather than peripheral auditory system. With further study, these results may provide information to allow clinicians to assess patients' temporal processing abilities and facilitate setting program parameters that will maximize their auditory perceptual experience with a cochlear implant.

Plasticity of motor threshold and motor-evoked potential amplitude – A model of intrinsic and synaptic plasticity in human motor cortex?

BackgroundNeuronal plasticity is the physiological correlate of learning and memory. In animal experiments, synaptic (i.e. long-term potentiation (LTP) and depression (LTD)) and intrinsic plasticity are distinguished. In human motor cortex, cortical plasticity can be demonstrated using transcranial magnetic stimulation (TMS). Changes in motor-evoked potential (MEP) amplitudes most likely represent synaptic plasticity and are thus termed LTP-like and LTD-like plasticity. Objective/hypothesisWe investigated the role of changes of motor threshold and their relation to changes of MEP amplitudes. MethodsWe induced plasticity by paired associative stimulation (PAS) with 25 ms or 10 ms inter-stimulus interval or by motor practice (MP) in 64 healthy subjects aged 18–31 years (median 24.0). ResultsWe observed changes of MEP amplitudes and motor threshold after PAS[25], PAS[10] and MP. In all three protocols, long-term individual changes in MEP amplitude were inversely correlated to changes in motor threshold (PAS[25]: P = .003, n = 36; PAS[10]: P = .038, n = 19; MP: P = .041, n = 19). ConclusionWe conclude that changes of MEP amplitudes and MT represent two indices of motor cortex plasticity. Whereas increases and decreases in MEP amplitude are assumed to represent LTP-like or LTD-like synaptic plasticity of motor cortex output neurons, changes of MT may be considered as a correlate of intrinsic plasticity.

Differences in excitability between median and superficial radial sensory axons

ObjectiveThe aim of this study was to investigate differences in excitability properties of human median and superficial radial sensory axons (e.g., axons innervating the glabrous and hairy skin in the hand). Previous studies have shown that excitability properties differ between motor and sensory axons, and even among sensory axons between median and sural sensory axons. MethodsIn 21 healthy subjects, threshold tracking was used to examine excitability indices such as strength–duration time constant, threshold electrotonus, supernormality, and threshold change at the 0.2ms inter-stimulus interval in latent addition. In addition, threshold changes induced by ischemia for 10min were compared between median and superficial radial sensory axons. ResultsCompared with radial sensory axons, median axons showed shorter strength–duration time constant, greater threshold changes in threshold electrotonus (fanning-out), greater supernormality, and smaller threshold changes in latent addition. Threshold changes in both during and after ischemia were greater for median axons. ConclusionsThese findings suggest that membrane potential in human median sensory axons is more negative than in superficial radial axons, possibly due to greater activity of electrogenic Na+/K+ pump. These results may reflect adaptation to impulses load carried by median axons that would be far greater with a higher frequency. SignificanceBiophysical properties are not identical in different human sensory axons, and therefore their responses to disease may differ.

Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex

Magnetic resonance spectroscopy (MRS) allows measurement of neurotransmitter concentrations within a region of interest in the brain. Inter-individual variation in MRS-measured GABA levels have been related to variation in task performance in a number of regions. However, it is not clear how MRS-assessed measures of GABA relate to cortical excitability or GABAergic synaptic activity. We therefore performed two studies investigating the relationship between neurotransmitter levels as assessed by MRS and transcranial magnetic stimulation (TMS) measures of cortical excitability and GABA synaptic activity in the primary motor cortex. We present uncorrected correlations, where the P value should therefore be considered with caution. We demonstrated a correlation between cortical excitability, as assessed by the slope of the TMS input-output curve and MRS-assessed glutamate levels (r = 0.803, P = 0.015) but no clear relationship between MRS-assessed GABA levels and TMS-assessed synaptic GABA(A) activity (2.5 ms inter-stimulus interval (ISI) short-interval intracortical inhibition (SICI); Experiment 1: r = 0.33, P = 0.31; Experiment 2: r = -0.23, P = 0.46) or GABA(B) activity (long-interval intracortical inhibition (LICI); Experiment 1: r = -0.47, P = 0.51; Experiment 2: r = 0.23, P = 0.47). We demonstrated a significant correlation between MRS-assessed GABA levels and an inhibitory TMS protocol (1 ms ISI SICI) with distinct physiological underpinnings from the 2.5 ms ISI SICI (r = -0.79, P = 0.018). Interpretation of this finding is challenging as the mechanisms of 1 ms ISI SICI are not well understood, but we speculate that our results support the possibility that 1 ms ISI SICI reflects a distinct GABAergic inhibitory process, possibly that of extrasynaptic GABA tone.

Nonretinotopic Exogenous Attention

Attention is crucial for visual perception because it allows the visual system to effectively use its limited resources by selecting behaviorally and cognitively relevant stimuli from the large amount of information impinging on the eyes. Reflexive, stimulus-driven attention is essential for successful interactions with the environment because it can, for example, speed up responses to life-threatening events. It is commonly believed that exogenous attention operates in the retinotopic coordinates of the early visual system. Here, using a novel experimental paradigm [1], we show that a nonretinotopic cue improves both accuracy and reaction times in a visual search task. Furthermore, the influence of the cue is limited both in space and time, a characteristic typical of exogenous cueing. These and other recent findings show that many more aspects of vision are processed nonretinotopically than previously thought.

Real-time feature extraction of P300 component using adaptive nonlinear principal component analysis

BackgroundThe electroencephalography (EEG) signals are known to involve the firings of neurons in the brain. The P300 wave is a high potential caused by an event-related stimulus. The detection of P300s included in the measured EEG signals is widely investigated. The difficulties in detecting them are that they are mixed with other signals generated over a large brain area and their amplitudes are very small due to the distance and resistivity differences in their transmittance.MethodsA novel real-time feature extraction method for detecting P300 waves by combining an adaptive nonlinear principal component analysis (ANPCA) and a multilayer neural network is proposed. The measured EEG signals are first filtered using a sixth-order band-pass filter with cut-off frequencies of 1 Hz and 12 Hz. The proposed ANPCA scheme consists of four steps: pre-separation, whitening, separation, and estimation. In the experiment, four different inter-stimulus intervals (ISIs) are utilized: 325 ms, 350 ms, 375 ms, and 400 ms.ResultsThe developed multi-stage principal component analysis method applied at the pre-separation step has reduced the external noises and artifacts significantly. The introduced adaptive law in the whitening step has made the subsequent algorithm in the separation step to converge fast. The separation performance index has varied from -20 dB to -33 dB due to randomness of source signals. The robustness of the ANPCA against background noises has been evaluated by comparing the separation performance indices of the ANPCA with four algorithms (NPCA, NSS-JD, JADE, and SOBI), in which the ANPCA algorithm demonstrated the shortest iteration time with performance index about 0.03. Upon this, it is asserted that the ANPCA algorithm successfully separates mixed source signals.ConclusionsThe independent components produced from the observed data using the proposed method illustrated that the extracted signals were clearly the P300 components elicited by task-related stimuli. The experiment using 350 ms ISI showed the best performance. Since the proposed method does not use down-sampling and averaging, it can be used as a viable tool for real-time clinical applications.

Effects of Long-Acting Methylphenidate in Adults with Attention Deficit Hyperactivity Disorder: A Study with Paired-Pulse Transcranial Magnetic Stimulation

Background: Methylphenidate improves attention deficits, hyperactivity and impulsivity in attention deficit hyperactivity disorder (ADHD). Recent investigations into motor cortex excitability with paired-pulse transcranial magnetic stimulation (ppTMS) technique have shown inhibition deficits in ADHD which correlate with clinical symptomatology. Therefore, we investigated the neurophysiological effects of long-acting methylphenidate (LA-Mph) with the ppTMS technique in adult patients with ADHD. Methods: Thirteen right-handed adult ADHD patients who were first diagnosed with ADHD were included in this ppTMS study. Measurements took place before and during treatment with LA-Mph (30–54 mg/day). Statistical analyses were performed to investigate treatment effects and correlations with clinical symptomatology. Results: LA-Mph significantly decreased the relative short intracortical motor inhibition (SICI) magnetically evoked potential (MEP) amplitude at 3-ms interstimulus interval (conditioned/unconditioned MEP amplitude: 0.83 ± 0.76 drug-free vs. 0.29 ± 0.19 with LA-Mph; p = 0.020). The relative intracortical facilitation MEP amplitude at 11 ms interstimulus interval (conditioned/unconditioned MEP amplitude: 1.51 ± 0.92 drug-free vs. 1.79 ± 0.95 with LA-Mph) was not significantly increased. The reduced relative SICI MEP amplitude with LA-Mph correlated significantly with the improvement of the psychopathological ADHD self-rating total scores (p = 0.046). Conclusion: These results show that in adult patients with ADHD, LA-Mph significantly improves motor disinhibition and might have differential stabilizing effects on motor hyperexcitability.