Cortical Magnetic Stimulation Research Articles

Neural representations of self-perception of voice: An intracortical evoked potential analysis based on an adolescent with right temporal lobe epilepsy

IntroductionThe neural bases for language perception have been studied elsewhere using Transcranial Magnetic Stimulation, functional Magnetic Resonance Imaging and Direct Cortical Stimulation. However, to our knowledge, there is no previous report about a patient identifying the change in his voice tone, speed, and prosody because of right temporal cortical stimulation. Nor has there been a cortico-cortical evoked potential (CCEP) assessment of the network underlying this process. Case reportWe present CCEP from a patient with right focal refractory temporal lobe epilepsy of tumoral etiology who reported changes in the perception of his own speech prosody during stimulation. This report will serve as a complement to the understanding of the neural networks of language and prosody. ConclusionThe present report shows that right superior temporal gyrus, transverse temporal gyrus, right amygdala, hippocampus, and fusiform gyrus (FG) are part of the neural network subjacent to own human voice perception.

Modulation of spontaneous motor unit potentials by a new motor cortical magnetic stimulation method in amyotrophic lateral sclerosis

Patients with amyotrophic lateral sclerosis (ALS) show altered cortical excitability. In this study, we measure modulation of spontaneous motor unit potentials (sMUPs) in hand muscles by multifocal cortical stimulation with a newly developed wearable transcranial rotating permanent magnet stimulator (TRPMS). We conducted cross-sectional and longitudinal electromyographic assessments in 40 and 20 ALS patients, respectively, of the stimulation-induced peak increase in the count of sMUPs in two hand muscles modulated by unilateral TRPMS stimulation of the primary motor cortex. We measured peak sMUP counts during several short sessions consisting of 10 stimuli over 60s and 30s post-stimulation periods. The longitudinal component involved an initial assessment at an early stage of the disease and up to five follow-up assessments at least 3months apart. TRPMS stimulation produced no device-related adverse effects. It showed an inverted V-shaped modulation of the peak sMUP counts as a function of ALS functional rating scale revised scores. The ratios of ALS subjects showing peak sMUP count increases between early and intermediate stages (χ2 = 4.086, df = 1, p = 0.043) and intermediate and late stages (χ2 = 4.29, df = 1, p = 0.038) in cross-sectional data were significantly different. Longitudinal assessment also produced a significant (z = 2.31, p = 0.021) result, with all subjects showing a post-initial visit increase in peak sMUP counts. These results are consistent with delayed onset of upper motor neuronal dysfunction with respect to onset of clinical features. However, the above results need to be confirmed in a larger sample of patients and with multiple lines of evidence.

Evaluation of spinal and cortical magnetic stimulation together with MScan MUNE in the early stages of the disease in the diagnosis of ALS

Electrophysiological methods are still the leading investigations in the diagnosis of ALS. Although needle EMG is the main finding in demonstrating lower motor neuron involvement, the search continues for a method that supports the diagnosis as high as EMG in the electrophysiological evaluation of upper motor neuron involvement. But it would be valuable to try to develop the standards of the classical transcranial cortical stimulation methods.

Repetitive transcranial magnetic cortical stimulation for resistance diabetic neuropathic pain

No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Although medical treatment are useful, they produce a diversity of side effects and are occasionally ineffective. Repetitive transcranial magnetic stimulation (rTMS) safe, non-invasive and effective therapeutic opportunities for many neurogenic disorders. This study was designed to assess the efficacy rTMS for treatment resistance neuropathic pain (NP) in diabetic patients.

Electrodiagnosis of Amyotrophic Lateral Sclerosis: A Review of Existing Guidelines.

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper motor neurons in the motor cortex and lower motor neurons (LMN) in the brainstem and spinal cord, resulting in a progressive functional impairment. Neurophysiology is a diagnostic tool to detect dysfunction of upper motor neurons and LMN, even when the changes are subclinical. Electromyography is the standard neurophysiological investigation to detect LMN changes, which is essential to exclude mimicking disorders and attain early diagnosis. Recently, Awaji criteria was proposed to support ALS diagnosis, in these criteria fasciculation potentials associated with neurogenic motor unit potentials represents a sufficient marker of LMN involvement, in each muscle. Many studies have confirmed that Awaji criteria are more sensitive, permitting earlier diagnosis without loss of specificity when compared with the revised El Escorial criteria. Fasciculations are easily detected by ultrasound; increasingly, this technique has been used to diagnose ALS, combined with electromyography. This combination can increase diagnostic accuracy. Many techniques for estimating the number of motor units have been proposed, they are useful to quantify LMN loss. Electrical impedance myography is an emerging technique with great potential to monitor ALS progression. Neurophysiological investigation of upper motor neuron dysfunction is difficult in ALS, detecting decreased cortical inhibition by threshold tracking cortical magnetic stimulation is a promising method, which needs to be validated in different centers.

Plasma Circular RNA DYM Related to Major Depressive Disorder and Rapid Antidepressant Effect Treated by Visual Cortical Repetitive Transcranial Magnetic Stimulation

BackgroundReduced plasma circular RNA DYM (circDYM) has been detected in patients with major depressive disorder (MDD). Mechanism research has demonstrated that circDYM, acting as a microRNA-9 sponge, suppressed microglial activation by increasing Heat Shock Protein 90 ubiquitination, indicating that circDYM could be a potential biomarker of MDD. MethodsThirty-two normal controls (NCs) and 60 MDD patients were recruited. Enrolled patients were randomly allocated to the real or sham repetitive transcranial magnetic stimulation (rTMS) group, followed by continuous five-day visual cortical rTMS or sham treatment. All participants underwent multidimensional neuropsychological assessments and detection of circDYM levels. ResultsInitial scores on all emotional and psychosocial assessments in MDD were significantly different from those of NCs. As compared with the NC group, baseline plasma circDYM levels in MDD patients decreased remarkably (p=0.030) and showed significant positive correlations with the scores of the 24-item Hamilton Depression Rating Scale (r=0.318, p=0.031) and retardation subscale (r=0.323, p=0.029). The increase in circDYM was noteworthy after rTMS (p=0.006), while downregulation with no statistical significance was observed after sham treatment (p=0.170). LimitationsIt was not estimated on the correlation between plasma circDYM levels and long-term efficacy of rTMS. The mechanism of upregulated circDYM expression in response to visual cortical rTMS remained unrevealed, and the sample size was relatively small. ConclusionsThis study verified the reduced circDYM levels in MDD patients, and further determined the upregulated circDYM expression after rTMS treatment, revealing the potential of circDYM as a biomarker for MDD diagnosis and antidepressant effect of visual cortical rTMS.

Determination of Differences in Seed-Based Resting State Functional Magnetic Resonance Imaging Language Networks in Pediatric Patients with Left- and Right-Lateralized Language: A Pilot Study.

Background and PurposeThe current tools available for localization of expressive language, including functional magnetic resonance imaging (fMRI) and cortical stimulation mapping (CSM), require that the patient remain stationary and follow language commands with precise timing. Many pediatric epilepsy patients, however, have intact language skills but are unable to participate in these tasks due to cognitive impairments or young age. In adult subjects, there is evidence that language laterality can be determined by resting state (RS) fMRI activity, however there are few studies on the use of RS to accurately predict language laterality in children.MethodsA retrospective review of pediatric patients at Texas Children’s Hospital was performed to identify patients who have undergone epilepsy surgical planning over 3 years with language localization using traditional methods of Wada testing, CSM, or task-based fMRI with calculated laterality index, as well as a 7-minute RS scan available without excessive motion or noise. We found the correlation between each subject’s left and right Broca’s region activity and each of 68 cortical regions.ResultsA group of nine patients with left-lateralized language were found to have greater voxel-wise correlations than a group of six patients with right-lateralized language between a left hemispheric Broca’s region seed and the following six cortical regions: left inferior temporal, left lateral orbitofrontal, left pars triangularis, right lateral orbitofrontal, right pars orbitalis and right superior frontal regions.ConclusionsIn a cohort of children with epilepsy, we found that patients with left- and right-hemispheric language lateralization have different RS networks.

The effect of cortical versus sacral repetitive magnetic stimulation on lower urinary tract dysfunction in patients with multiple sclerosis.

75% of multiple sclerosis (MS) patients have lower urinary tract symptoms. Moreover, up to 80% of asymptomatic patients show abnormalities on urodynamic examination. The objective of this study is to assess the effect of repetitive magnetic stimulation on the motor cortex versus sacral roots in MS patients with lower urinary tract dysfunction (LUTD). 40 MS patients with LUTD were divided according to urodynamic studies (UDS) into two groups (20 patients each): Group A (overactive bladder) and Group B (underactive bladder). Each group was further subdivided into Subgroup (A-I) and (B-I) which received cortical magnetic stimulation and Subgroup (A-II) and (B-II) which received sacral magnetic stimulation. UDS, pelvic ultrasound as well as Incontinence Quality of Life (I-QOL) questionnaire were compared before and after magnetic stimulation sessions in each group as well as between groups. UDS showed significant reduction in bladder capacity, improvement in bladder contractility in all groups and subgroups. Moreover, it showed improvement of urine flow rate only in Group B. Reduction of post-void residual urine was noted in all subgroups except in (Group A-II). I-QOL questionnaire showed improvement in patients with underactive bladder only. Intergroup comparison between A and B showed no difference. Cortical as well as sacral magnetic stimulation showed significant effect on lower urinary tract dysfunction that led to improvement in symptoms in MS patients with underactive bladder, rather than those with overactive bladder.

Characteristics of respiratory muscle involvement in myotonic dystrophy type 1

The pathophysiology of respiratory muscle weakness in myotonic dystrophy type 1 (DM1) remains incompletely understood. 21 adult patients with DM1 (11 men, 42 ± 13 years) and 21 healthy matched controls underwent spirometry, manometry, and diaphragm ultrasound. In addition, surface electromyography of the diaphragm and the obliquus abdominis muscle was performed following cortical and posterior cervical magnetic stimulation (CMS) of the phrenic nerves or magnetic stimulation of the lower thoracic nerve roots. Magnetic stimulation was combined with invasive recording of the twitch transdiaphragmatic and gastric pressure (twPdi and twPgas) in 10 subjects per group. The following parameters were reduced in DM1 patients compared to control subjects: maximum inspiratory pressure (MIP; 40.3 ± 19.2 vs. 95.8 ± 28.5 cmH2O, p < 0.01), diaphragm thickening ratio (DTR; 2.0 ± 0.4 vs. 2.7 ± 0.6, p < 0.01), twPdi following CMS (10.8 ± 8.3 vs. 21.4 ± 10.1 cmH2O, p = 0.03), and amplitude of diaphragm compound muscle action potentials (0.10 ± 0.25 vs. 0.46 ± 0.35 mV; p = 0.04). MIP and DTR were significantly correlated with the muscular impairment rating scale (MIRS) score. Maximum expiratory pressure (MEP) was reduced in DM1 patients compared to controls (41.3 ± 13.4 vs. 133.8 ± 28.0 cmH2O, p < 0.01) and showed negative correlation with the MIRS score. Pgas following a maximum cough was markedly lower in patients than in controls (71.9 ± 43.2 vs. 102.4 ± 35.5 cmH2O) but without statistical significance (p = 0.06). In DM1, respiratory muscle weakness relates to clinical disease severity and involves inspiratory and probably expiratory muscle strength. Axonal phrenic nerve pathology may contribute to diaphragm dysfunction.

P2625Pathophysiology of diaphragm involvement in systolic heart failure: insights from diaphragm ultrasound and phrenic nerve stimulation studies

Abstract Background Diaphragm ultrasound allows for assessment of both diaphragm excursion and thickness. Cervical and cortical magnetic stimulation (CEMS and COMS) with recording of the diaphragmatic compound motor action potential (CMAP) is diagnostically useful to evaluate the conductive properties of the inspiratory pathway. Systolic heart failure (HF) is characterized by a loss of systolic pump function. Diaphragm weakness in HF has been reported to potentially contribute to exercise intolerance Methods 14 patients with systolic HF (11 men, 3 women; 64±12 years, NYHA 2±0.9, LVEF 36.1±5.6%) and 12 healthy controls matched for age and gender (4 men, 8 women; 56±8 years) underwent spirometric lung function testing and assessment of diaphragm excursion (during tidal breathing, TB, voluntary sniff, VS and deep breathing, DB) and thickness of the right hemidiaphragm by ultrasound. COMS and CEMS of the phrenic nerves with simultaneous bilateral recording of the diaphragm CMAP using surface electrodes was performed in 9 patients. Results Compared to controls, HF patients showed reduced forced vital capacity (75.46±18.05% vs. 107.62±17.13%, p&lt;0.05). Diaphragm excursion amplitude was significantly reduced in HF patients (4.29±1.35 cm vs. 7.34±2.10 cm, p&lt;0.05). Diaphragm contractility was impaired too, as reflected by the diaphragm thickening ratio (DTR; 2.01±0.46 vs. 2.53±0.74, p&lt;0.05). Diaphragm CMAP following COMS and CEMS of the phrenic nerves revealed normal latencies in HF patients compared to controls (COMS Latency; 19.05±2.37 msec vs. 18.97±3.59 msec, p= n. s.). Conclusions Diaphragm involvement in systolic HF is reflected by reduced FVC and impaired ultrasound parameters of diaphragm function. Diaphragmatic pathology is likely to be myopathic because magnetic phrenic nerve conduction studies show no abnormalities. Diaphragm ultrasound may be useful as a diagnostic tool for assessment of diaphragm function in systolic HF. Acknowledgement/Funding This study was supported by Sanofi-Genzyme, Neu-Isenburg, Germany. The funders had no role in study design, data collection and analysis, preparation.

Electrophysiological Properties of the Human Diaphragm Assessed by Magnetic Phrenic Nerve Stimulation: Normal Values and Theoretical Considerations in Healthy Adults

This study determined normal values for motor evoked potentials (MEPs) and compound muscle action potentials (CMAPs) of the diaphragm following cortical and cervical magnetic stimulation (COMS and CEMS) of the phrenic nerves in healthy adults. Using surface electrodes, diaphragmatic MEP and CMAP were recorded in 70 subjects (34 ± 13 years, 25 men) following supramaximal cortical magnetic stimulation and CEMS at functional residual capacity and using a standardized inspiratory pressure trigger (-0.5 kPa). All healthy volunteers underwent standard spirometry and measurement of maximum inspiratory and expiratory pressure. At functional residual capacity, upper limit of normal for MEP latency was 25 ms in men and 23 ms in women (p < 0.05), and upper limit of normal for CMAP latency was 6 ms. In contrast to MEP and CMAP amplitude, corresponding latencies showed little interindividual and intraindividual variability. Use of an inspiratory pressure trigger enhanced reproducibility and amplitude of diaphragm MEP. Diaphragm responses to both cortical and cervical magnetic stimulation were symmetrical and independent of age (in our cohort), with higher values for latency and amplitude in men (each p < 0.05). Diaphragm CMAP amplitude showed weak-moderate correlations with forced vital capacity (r = 0.47; p < 0.01), maximum inspiratory pressure (r = 0.39; p < 0.01), and maximum expiratory pressure (r = 0.32; p < 0.01). Combination of cortical magnetic stimulation and CEMS of the phrenic nerves is feasible and allows noninvasive assessment of both central and peripheral conductivity of the diaphragm and the inspiratory pathway.

Phrenic nerve involvement and respiratory muscle weakness in patients with Charcot-Marie-Tooth disease 1A.

Diaphragm weakness in Charcot-Marie-Tooth disease 1A (CMT1A) is usually associated with severe disease manifestation. This study comprehensively investigated phrenic nerve conductivity, inspiratory and expiratory muscle function in ambulatory CMT1A patients. Nineteen adults with CMT1A (13 females, 47 ± 12 years) underwent spiromanometry, diaphragm ultrasound, and magnetic stimulation of the phrenic nerves and the lower thoracic nerve roots, with recording of diaphragm compound muscle action potentials (dCMAP, n = 15), transdiaphragmatic and gastric pressures (twPdi and twPgas, n = 12). Diaphragm motor evoked potentials (dMEP, n = 15) were recorded following cortical magnetic stimulation. Patients had not been selected for respiratory complaints. Disease severity was assessed using the CMT Neuropathy Scale version 2 (CMT-NSv2). Healthy control subjects were matched for age, sex, and body mass index. The following parameters were significantly lower in CMT1A patients than in controls (all P < .05): forced vital capacity (91 ± 16 vs 110 ± 15% predicted), maximum inspiratory pressure (68 ± 22 vs 88 ± 29 cmH2 O), maximum expiratory pressure (91 ± 23 vs 123 ± 24 cmH2 O), and peak cough flow (377 ± 135 vs 492 ± 130 L/min). In CMT1A patients, dMEP and dCMAP were delayed. Patients vs controls showed lower diaphragm excursion (5 ± 2 vs 8 ± 2 cm), diaphragm thickening ratio (DTR, 1.9 [1.6-2.2] vs 2.5 [2.1-3.1]), and twPdi (8 ± 6 vs 19 ± 7 cmH2 O; all P < .05). DTR inversely correlated with the CMT-NSv2 score (r = -.59, P = .02). There was no group difference in twPgas following abdominal muscle stimulation. Ambulatory CMT1A patients may show phrenic nerve involvement and reduced respiratory muscle strength. Respiratory muscle weakness can be attributed to diaphragm dysfunction alone. It relates to neurological impairment and likely reflects a disease continuum.

The nature of respiratory muscle weakness in patients with late-onset Pompe disease

Late-onset Pompe disease (LOPD) causes myopathy of skeletal and respiratory muscles, and phrenic nerve pathology putatively contributes to diaphragm weakness. The aim of this study was to investigate neural contributions to diaphragm dysfunction, usefulness of diaphragm ultrasound, and involvement of expiratory abdominal muscles in LOPD. Thirteen patients with LOPD (7 male, 51±17 years) and 13 age- and gender-matched controls underwent respiratory muscle strength testing, ultrasound evaluation of diaphragm excursion and thickness, cortical and cervical magnetic stimulation (MS) of the diaphragm with simultaneous recording of surface electromyogram and twitch transdiaphragmatic pressure (twPdi; n = 6), and MS of the abdominal muscles with recording of twitch gastric pressure (twPgas; n = 6). The following parameters were significantly reduced in LOPD patients versus controls: forced vital capacity (p<0.01), maximum inspiratory and expiratory pressure (both p<0.001), diaphragm excursion velocity (p<0.05), diaphragm thickening ratio (1.8 ± 0.4 vs. 2.6 ± 0.6, p<0.01), twPdi following cervical MS (12.0 ± 6.2 vs. 19.4 ± 4.8 cmH2O, p<0.05), and twPgas following abdominal muscle stimulation (8.8 ± 8.1 vs. 34.6 ± 17.1 cmH2O, p<0.01). Diaphragm motor evoked potentials and compound muscle action potentials showed no between-group differences. In conclusion, phrenic nerve involvement in LOPD could not be electrophysiologically confirmed. Ultrasound supports assessment of diaphragm function. Abdominal expiratory muscles are functionally involved in LOPD.

P55-F Neurophysiological assessment of rTMS effectiveness in patients with schizophrenia using cortical and cutaneous silent period

Background At this moment there is not a definite consensus on the effectiveness of the rTMS treatment and parameters to be used for the AVH drug resistant patients (Slotema et al., 2012). We aimed to identify changes of intracortical and spinal motoneuronal inhibition measured before and after 10 sessions of 15 min 1 Hz rTMS. Methods In 6 healthy subjects and 10 patients we assessed the APB silent period (SP) to cortical magnetic single pulse stimulation at 140% RMT applied on motor primary cortex region while the participants performed submaximal isometric contraction. Cutaneous SP was recorded after 2nd finger dermatome electrical stimulation using ring electrodes. We compared CSP/CuSP ratio of a healthy subjects group (HS) with pretreatment and after rTMS treatment conditions for a control patients group (CG) receiving sham treatment and a treatment patients group (TG) receiving treatment on T3-P3 scalp location at the beginning of the study, within one week after, one month after and 3 months after the treatment. Results In HS the CSP showed the average duration of 160 ms (SD 20) larger than CuSP duration of 44 ms (SD 4). The average CSP/CuSP ratio was 3,64:1 in HS. CG ratio analyzed in 3 patients increased from 3,92:1 to 4,4:1. TG and CG ratio at one month and 3 months post rTMS analyses are in progress. Conclusion Intracortical inhibition showed larger duration than spinal motoneuronal inhibition in HS, CG and TG. In CG, preliminary data showed slight increment of CSP:CuSP after rTMS.

P44-S Sensorimotor integration in fibromyalgia

Background Fibromyalgia, is a chronic pain disorder, especially common in women, characterised by widespread pain, fatigue, sleep disorders and cognitive dysfunction. Recently prolonged somatosensory temporal discrimination values was shown in fibromyalgia patients compatible with impaired central sensory processing. However knowledge about sensorimotor integration in fibromyalgia is still lacking. Short latency afferent inhibition (SAI) is a phenomenon in which sensory stimulus modulates motor response. SAI is associated with cholinergic system, cognitive functions and sensorimotor integrity. In this study, sensorimotor integration is assessed with SAI paradigm in fibromyalgia patients for the first time. Methods 15 fibromyalgia patients and age-gender matched 15 healthy subjects were included in the study. Severity of pain and other symptoms were evaluated with visual analogue-scale and symptom severity scale respectively, cognitive functions were assessed with neuropsychological tests. Basal motor evoked potential (MEP) was recorded from right abductor pollicis brevis muscle at rest. SAI was obtained by right median nerve direct electrical current stimulation at twice the intensity of sensory threshold, 21 ms in advance of left motor cortical magnetic stimulation. Mean MEP amplitude ratio, recorded after single and conditioned stimulations, were calculated as SAI. Results No significant difference was found between the groups in terms of SAI values (Control group: 40.3 ± 23.4% inhibition; fibromyalgia group: 34.3 ± 25.6% inhibition, p = 0.51). There was no correlation between SAI values and severity of pain and other symptoms and cognitive function scores in the fibromyalgia group. Conclusion Even though sensory processing is impaired, sensorimotor integration and neural pathways that generate and modulate SAI remain intact in fibromyalgia.

Reduced Short-Latency Afferent Inhibition Indicates Impaired Sensorimotor Integrity During Migraine Attacks.

Migraine attacks disrupt sensory information processing and may also disturb sensorimotor integration. This prospective pilot study aimed to assess the sensorimotor integration and inhibitory circuitry in the sensorimotor cortex using short-latency afferent inhibition (SAI) paradigm in migraine. Twenty-five migraine without aura patients (10 interictal, 5 preictal, 10 ictal) and 16 healthy controls were enrolled. SAI was elicited by combining the right median nerve electrical stimulation and left motor cortical magnetic stimulation at the 21-millisecond interval. Mean motor evoked potential (MEP) amplitude ratio, recorded from right abductor pollicis muscle after single and conditioned stimulations, was calculated as SAI. Average MEP inhibition ratio after single and conditioned stimuli in healthy controls was not significantly different from interictal patients (45.1%±20.3% vs 44.5%±14.75% [P = .93]). However, SAI was significantly reduced during preictal/prodromal (-14.6%±42.8% [P = .002]) and ictal/headache (-7.4%±31.1% [P = .0001]) periods of migraine compared to healthy controls. Pronounced decrease in SAI during preictal and ictal periods in migraine was shown for the first time. Instead of inhibition to a conditioned stimulus, facilitation in the sensorimotor cortex was detected both ictally and preictally. Preictal SAI results suggest the presence of increased excitability state several hours prior to the headache phase. This phenomenon could be related to the cortical hyperresponsivity to sensory stimuli and cognitive disturbances accompanying migraine attacks as SAI is modulated by cholinergic activity.

Transdiapragmatic pressure and contractile properties of the diaphragm following magnetic stimulation

Insufficient normal values exist regarding twitch transdiaphragmatic pressure (twPdi) derived from standardized cervical and cortical magnetic stimulation (MS) of the diaphragm.Therefore, 63 subjects (24 men, 39 women; 34 ± 13 years) underwent transcortical and posterior cervical MS of the diaphragm with simultaneous recording of twitch oesophageal and gastric pressures (twPes, twPgas).Following cortical MS at functional residual capacity, twPdi amplitudes showed high intra-individual variability which was markedly reduced when an inspiratory pressure trigger was applied. Lower limit of the 95% confidence interval computed around the mean value (LLN) was 12 cmH2O, independent of gender or age. Following cervical MS of the phrenic nerves, twPdi amplitudes were well reproducible and unaffected by gender, but age-dependent (age 18–30: LLN 23 cmH2O; age ≥ 30: LLN 16 cmH2O; p < 0.05).The inspiratory pathway can be assessed using cervical MS of the phrenic nerves. If transcranial motor cortex stimulation of the diaphragm is also applied, a standardized inspiratory pressure trigger is recommended. Dynamics of diaphragm contraction appear to be age-dependent.

Effects of Acoustic Paired Associative Stimulation on Late Auditory Evoked Potentials

Paired associative stimulation (PAS), a form of non-invasive cortical stimulation pairing transcranial magnetic stimulation (TMS) with a peripheral sensory stimulus, has been shown to induce neuroplastic effects in the human motor, somatosensory and auditory cortex. The current study investigated the effects of acoustic PAS on late auditory evoked potentials (LAEP) and the influence of tone duration and placebo stimulation. In two experiments, 18 participants underwent a PAS with a 4 kHz paired tone of 400 ms duration using 200 pairs of stimuli (TMS-pulse over the left auditory cortex 45 ms after tone-onset) presented at 0.1 Hz. In Experiment 1 this protocol was contrasted with a protocol using a short paired tone of 23 ms duration (PAS-23 ms vs. PAS-400 ms). In Experiment 2 this PAS protocol was contrasted with sham stimulation (PAS-400 ms-sham vs. PAS-400 ms). Before and after PAS, LAEP were recorded for tones of 4 kHz (same carrier frequency as the paired tone) and 1 kHz as control tone. In Experiment 1, there was a significant difference between LAEP amplitudes of the 4 kHz tone after PAS-23 ms and PAS-400 ms with higher LAEP amplitudes after PAS-23 ms. Before both conditions, no difference could be detected. In Experiment 2 we observed a significant overall decrease in LAEP amplitudes pre to post PAS. Unspecific decreases of LAEP following PAS with a long paired tone (PAS-400 ms) might be related to habituation effects due to repeated presentation of sound stimuli which are not evident for PAS with a short paired tone (PAS-23 ms). Interpreting this result using the concept of temporal integration time allows us to discuss it in the context of spike-timing dependent plasticity.

Modulation of motor excitability by cortical optogenetic theta burst stimulation

Intermittent theta burst stimulation (iTBS) and continuous theta burst stimulation (cTBS) are protocols used in repetitive transcranial magnetic stimulation (rTMS) or cortical electrical stimulation (CES) to facilitate or suppress corticospinal excitability. However, rTMS and CES excite all types of neuron in the target cortex probed by the coil or electrode, making it difficult to differentiate the effect of TBS on specific neural circuits involved in motor plasticity. In this study, TBS protocols were converted into an optogenetic model to achieve focalized and cell-type-specific cortical modulation. Light-sensitive channelrhodopsin-2 (ChR2) was expressed in the glutamatergic neuron in the primary motor cortex (M1) driven by the CaMKIIα promoter. A custom-made optrode comprising an optical fiber and a metal cannula electrode was fabricated to achieve optogenetic stimulation and simultaneous local field potential (LFP) recording. Single-pulse CES was delivered into M1 to elicit motor-evoked potential (MEP), which served as an indicator of motor excitability, before and after TBS intervention. Results show that both CES-iTBS and optogenetic iTBS (Opto-iTBS) can potentiate MEP activity. However, CES-cTBS suppressed MEP activity whereas Opto-cTBS enhanced it. This discrepancy may have resulted from the different neural networks targeted by the two TBS modalities, with CES-cTBS exciting all types of neuron and Opto-cTBS targeting excitatory neuron specifically. The results support the idea that intra-cortical networks determine the variation of TBS-induced neuroplasticity. This study shows that focalized and cell-type-specific brain stimulation using the optogenetic approach is viable and can be extended for further exploration of neuroplasticity.

P32. Improved reliabilty of intraoperative language mapping through preoperative nTMS and baseline linguistic scores

Objective Repetitive navigated transcranial magnetic stimulation (rnTMS) and direct cortical stimulation (DCS) during awake surgery are complementary tools to locate speech functional areas of the brain. However, patients show inter-individual differences in their preoperative linguistic capabilities, which can impact the validity of intraoperative DSC mapping. We developed a standardized approach which utilizes preoperative aphasia scores and rnTMS to screen patients for their capability to perform reliable object naming during awake surgery. Methods We prospectively included 18 patients with language-eloquent brain tumors, scheduled for awake surgery. Aachen Aphasia Score (AAS), Demtect Score (DS) and Berlin Aphasia Score (BAS) were used to evaluate linguistic eloquence of each patient preoperatively. Moreover, all patients underwent 3 runs of naming all objects without rnTMS (baseline run), from which only promptly and correctly named objects were retained for later rnTMS mapping. These selected objects were also used for the intraoperative baseline testing and DCS mapping under level 2 of Ramsay Sedation Score. Results The degree of preoperative language impairment significantly correlated with the incidence of errors during preoperative as well as intraoperative baseline errors (AAT p = 0.01, BAS p = 0.001, DS = 0.001). Patients with significant aphasia (BAS >=2, AAT >=1) and cognitive impairment (DS >=2) committed over 50% of incorrect or delayed namings in the preoperative baseline (p = 0.001). Despite utilizing only the images retained after preoperative baseline naming, these patients still made significantly more mistakes during intraoperative baseline naming than patients with less severe aphasia. Moreover, the dosage of anaesthetic medication significantly correlated with the incidence of errors during intraoperative baseline naming (propofol p = 0.028, remifentanil p = 0.036), despite stopping all systemic analgetic and sedative medication at least 8 min before testing. Conclusion Patients with significant aphasia (BAS >=2, AAT >=2) and cognitive impairment (DS >=2) are not able to perform reliable intraoperative object naming and are therefore not suited for this procedure. In addition, dosages of analgetic and sedative medication during craniotomy should be kept as low as possible to allow for reliable intraoperative cognitive testing.