Changes In Cortical Excitability Research Articles

Biological and Neurobiological Mechanisms of Transcranial Direct Current Stimulation.

Objective: Changes in cortical excitability and neuroplasticity are important parts of the neuropathology and pathophysiology of many neuropsychiatric disorders. Noninvasive brain stimulation is a high-potential therapeutic approach to modify cortical activities. One of the most popular of these techniques is transcranial direct current stimulation (tDCS). However, the biological and neurobiological effects of tDCS should be better clarified to enable its optimal use in clinical and therapeutic practices. In this paper, we summarize the neurophysiological and physiological effects and mechanisms of action of tDCS. Method : An update literature review was conducted on the biological responses of tDCS reported in human, in vitro and in vivo studies, with a focus on cellular cascades related to neuroplasticity, neuronal reorganization and inflammation caused by applied direct current electric fields. Results: The regulatory mechanisms of tDCS on motor and cognitive functions can be described by membrane polarization and transmembrane potential with a main subsequent effect on neurotransmission systems, neuronal excitability, synaptic microenvironment and neuronal connectivity to neuronal reorganization and neurogenesis in association with synaptic plasticity as well as inflammatory processes. In general, the effects of tDCS may include acute- or after-effects and direct or indirect effects and can be examined at different levels including the neurochemical, the neuroelectrical and the brain oscillatory levels. Conclusion: A deep understanding of the molecular and cellular responses to tDCS is very important and crucial. This therapeutic technique can be utilized in various clinical trials with a perspective of being routinely suggested and presented to patients with different pathological conditions influencing the central or peripheral nervous system.

Age-related Changes in Cortical Excitability Linked to Decreased Attentional and Inhibitory Control

Understanding age-related changes in cortical excitability and their relation to cognitive functions will help to improve interventions based on non-invasive brain stimulation that aim to support cognitive function in older adults. Here, we investigate the relationship between cortical excitability, executive function, and underlying neural activity in samples of healthy young and older adults. These participants performed a Simon task during electroencephalogram (EEG) recording. During the task, participants had to respond to the colour of a lateralized stimulus while ignoring its spatial location. We studied event-related brain potential correlates of attentional and inhibitory control [i.e., the posterior contralateral negativity (N2pc) and central contralateral negativity (N2cc), respectively] related to the Simon task performance. We also used transcranial magnetic stimulation (TMS) EEG coregistration. In detail, we applied single-pulse TMS during EEG recording in order to analyse global mean field power (GMFP) and TMS-evoked potentials (TEPs) as correlates of cortical excitability. We found lower GMFP amplitude within 101–200 ms in older compared to young adults. Moreover, older adults showed smaller N45 amplitude and slower P180 latency. These findings suggest cortical excitability alterations related to ageing. Older adults also exhibited longer reaction times and N2pc and N2cc latencies, indicating that it took them longer to allocate attention to the target stimulus and inhibit the tendency to respond to the attended location. Finally, in older adults, cortical excitability alterations correlated with longer reaction times and N2pc latencies. These results suggest that age-related alterations in cortical excitability represent a dysfunctional change associated with physiological ageing.

Static magnetic field stimulation over motor cortex modulates resting functional connectivity in humans

Focal application of transcranial static magnetic field stimulation (tSMS) over the human motor cortex induces local changes in cortical excitability. Whether tSMS can also induce distant network effects, and how these local and distant effects may vary over time, is currently unknown. In this study, we applied 10 min tSMS over the left motor cortex of healthy subjects using a real/sham parallel design. To measure tSMS effects at the sensori-motor network level, we used resting-state fMRI. Real tSMS, but not sham, reduced functional connectivity within the stimulated sensori-motor network. This effect of tSMS showed time-dependency, returning to sham levels after the first 5 min of fMRI scanning. With 10 min real tSMS over the motor cortex we did not observe effects in other functional networks examined (default mode and visual system networks). In conclusion, 10 min of tSMS over a location within the sensori-motor network reduces functional connectivity within the same functional network.

Tracking cortical excitability dynamics with transcranial magnetic stimulation in focal epilepsy.

IntroductionThe lack of reliable biomarkers constrain epilepsy management. We assessed the potential of repeated transcranial magnetic stimulation with electromyography (TMS‐EMG) to track dynamical changes in cortical excitability on a within‐subject basis.MethodsWe recruited people with refractory focal epilepsy who underwent video‐EEG monitoring and drug tapering as part of the presurgical evaluation. We performed daily TMS‐EMG measurements with additional postictal assessments 1–6 h following seizures to assess resting motor threshold (rMT), and motor evoked potentials (MEPs) with single‐ and paired‐pulse protocols. Anti‐seizure medication (ASM) regimens were recorded for the day before each measurement and expressed in proportion to the dosage before tapering. Additional measurements were performed in healthy controls to evaluate day‐to‐day rMT variability.ResultsWe performed 77 (58 baseline, 19 postictal) measurements in 16 people with focal epilepsy and 35 in seven healthy controls. Controls showed minimal day‐to‐day rMT variation. Withdrawal of ASMs was associated with a lower rMT without affecting MEPs of single‐ and paired‐pulse TMS‐EMG paradigms. Postictal measurements following focal to bilateral tonic–clonic seizures demonstrated unaltered rMT and increased short interval intracortical inhibition, while measurements following focal seizures with impaired awareness showed decreased rMT's and reduced short and long interval intracortical inhibition.ConclusionSerial within‐subject rMT measurements yielded reproducible, stable results in healthy controls. ASM tapering and seizures had distinct effects on TMS‐EMG excitability indices in people with epilepsy. Drug tapering decreased rMT, indicating increased overall corticospinal excitability, whereas seizures affected intracortical inhibition with contrasting effects between seizure types.

Relationship Between Cortical Excitability Changes and Cortical Thickness in Subcortical Chronic Stroke.

Ischemic stroke leads to excitability changes of the motor network as probed by means of transcranial magnetic stimulation (TMS). There is still limited data that shows to what extent structural alterations of the motor network might be linked to excitability changes. Previous results argue that the microstructural state of specific corticofugal motor tracts such as the corticospinal tract associate with cortical excitability in chronic stroke patients. The relationship between changes of cortical anatomy after stroke, as operationalized by means of decreases or increases in local cortical thickness (CT), has scarcely been addressed. In the present study, we re-analyzed TMS data and recruitment curve properties of motor evoked potentials and CT data in a group of 14 well-recovered chronic stroke patients with isolated supratentorial subcortical lesions. CT data of the stroke patients were compared to CT data of 17 healthy controls. Whole-brain and region-of-interest based analyses were conducted to relate CT data to measures of motor cortical excitability and clinical data. We found that stroke patients exhibited significantly reduced CT not only in the ipsilesional primary motor cortex but also in numerous secondary motor and non-motor brain regions, particularly in the ipsilesional hemisphere including areas along the central sulcus, the inferior frontal sulcus, the intraparietal sulcus, and cingulate cortices. We could not detect any significant relationship between the extent of CT reduction and stroke-related excitability changes of the motor network or clinical scores.

Prefrontal theta phase-dependent rTMS-induced plasticity of cortical and behavioral responses in human cortex

BackgroundPrefrontal theta oscillations are involved in neuronal information transfer and retention. Phases along the theta cycle represent varied excitability states, whereby high-excitability states correspond to high-frequency neuronal activity and heightened capacity for plasticity induction, as demonstrated in animal studies. Human studies corroborate this model and suggest a core role of prefrontal theta activity in working memory (WM).Objective/Hypothesis: We aimed at modulating prefrontal neuronal excitability and WM performance in healthy humans, using real-time EEG analysis for triggering repetitive transcranial magnetic stimulation (rTMS) theta-phase synchronized to the left dorsomedial prefrontal cortex. Methods16 subjects underwent 3 different rTMS interventions on separate days, with pulses triggered according to the individual's real-time EEG activity: 400 rTMS gamma-frequency (100 Hz) triplet bursts applied during either the negative peak of the prefrontal theta oscillation, the positive peak, or at random phase. Changes in cortical excitability were assessed with EEG responses following single-pulse TMS, and behavioral effects by using a WM task. ResultsNegative-peak rTMS increased single-pulse TMS-induced prefrontal theta power and theta-gamma phase-amplitude coupling, and decreased WM response time. In contrast, positive-peak rTMS decreased prefrontal theta power, while no changes were observed after random-phase rTMS. ConclusionFindings point to the feasibility of EEG-TMS technology in a theta–gamma phase–amplitude coupling mode for effectively modifying WM networks in human prefrontal cortex, with potential for therapeutic applications.

"Tricking the Brain" Using Immersive Virtual Reality: Modifying the Self-Perception Over Embodied Avatar Influences Motor Cortical Excitability and Action Initiation.

To offer engaging neurorehabilitation training to neurologic patients, motor tasks are often visualized in virtual reality (VR). Recently introduced head-mounted displays (HMDs) allow to realistically mimic the body of the user from a first-person perspective (i.e., avatar) in a highly immersive VR environment. In this immersive environment, users may embody avatars with different body characteristics. Importantly, body characteristics impact how people perform actions. Therefore, alternating body perceptions using immersive VR may be a powerful tool to promote motor activity in neurologic patients. However, the ability of the brain to adapt motor commands based on a perceived modified reality has not yet been fully explored. To fill this gap, we “tricked the brain” using immersive VR and investigated if multisensory feedback modulating the physical properties of an embodied avatar influences motor brain networks and control. Ten healthy participants were immersed in a virtual environment using an HMD, where they saw an avatar from first-person perspective. We slowly transformed the surface of the avatar (i.e., the “skin material”) from human to stone. We enforced this visual change by repetitively touching the real arm of the participant and the arm of the avatar with a (virtual) hammer, while progressively replacing the sound of the hammer against skin with stone hitting sound via loudspeaker. We applied single-pulse transcranial magnetic simulation (TMS) to evaluate changes in motor cortical excitability associated with the illusion. Further, to investigate if the “stone illusion” affected motor control, participants performed a reaching task with the human and stone avatar. Questionnaires assessed the subjectively reported strength of embodiment and illusion. Our results show that participants experienced the “stone arm illusion.” Particularly, they rated their arm as heavier, colder, stiffer, and more insensitive when immersed with the stone than human avatar, without the illusion affecting their experienced feeling of body ownership. Further, the reported illusion strength was associated with enhanced motor cortical excitability and faster movement initiations, indicating that participants may have physically mirrored and compensated for the embodied body characteristics of the stone avatar. Together, immersive VR has the potential to influence motor brain networks by subtly modifying the perception of reality, opening new perspectives for the motor recovery of patients.

Prolonged Continuous Theta Burst Stimulation to Demonstrate a Larger Analgesia as Well as Cortical Excitability Changes Dependent on the Context of a Pain Episode.

A series of neuropathic pain conditions have a prevalence in older adults potentially associated with declined functioning of the peripheral and/or central nervous system. Neuropathic pain conditions demonstrate defective cortical excitability and intermissions, which raises questions of the impact of pain on cortical excitability changes and when to deliver repetitive transcranial magnetic stimulation (rTMS) to maximize the analgesic effects. Using prolonged continuous theta-burst stimulation (pcTBS), a relatively new rTMS protocol to increase excitability, this study was designed to investigate pcTBS analgesia and cortical excitability in the context of pain. With capsaicin application, twenty-nine healthy participants received pcTBS or Sham stimulation either in the phase of pain initialization (capsaicin applied) or pain ascending (20 min after capsaicin application). Pain intensity was measured with a visual-analogic scale (VAS). Cortical excitability was assessed by motor-evoked potential (MEP) and cortical silent period (CSP) which evaluates corticospinal excitability and GABAergic intracortical inhibition, respectively. Our data on pain dynamics demonstrated that pcTBS produced a consistent analgesic effect regardless of the time frame of pcTBS. More importantly, pcTBS delivered at pain initialization induced a larger pain reduction and a higher response rate compared to the stimulation during pain ascending. We further provide novel findings indicating distinct mechanisms of pcTBS analgesia dependent on the context of pain, in which pcTBS delivered at pain initialization was able to reverse depressed MEP, whereby pcTBS during pain ascending was associated with increased CSP. Overall, our data indicate pcTBS to be a potential protocol in pain management that could be delivered before the initialization of a pain episode to improve rTMS analgesia, potentially through inducing early corticospinal excitability changes that would be suppressed by nociceptive transmission.

Age-dependent non-linear neuroplastic effects of cathodal tDCS in the elderly population: a titration study

BackgroundNeuromodulatory effects of transcranial direct current stimulation (tDCS) in older humans have shown heterogeneous results, possibly due to sub-optimal stimulation protocols associated with limited knowledge about optimized stimulation parameters in this age group. We systematically explored the association between the stimulation dosage of cathodal tDCS and induced after-effects on motor cortex excitability in the elderly. MethodThirty-nine healthy volunteers in two age groups, namely Pre-Elderly (50–65 years) and Elderly (66–80 years), participated in the study. Ten sessions of cathodal tDCS, with a combination of four intensities (1, 2, 3 mA and sham) and three durations (15, 20, 30 min) were conducted over the M1 in each participant. Cortical excitability changes were monitored with TMS-induced motor evoked potentials (MEPs) for up to 2 h after stimulation. ResultsMotor cortex excitability was reduced by cathodal stimulation intensities of 1 and 3 mA in both age groups, in accordance with results observed in the younger age groups of previous studies. For the 2 mA stimulation condition, an age-dependent conversion of plasticity into a stimulation duration-dependent excitability enhancement was observed in the Pre-Elderly group, whereas in the Elderly group, LTD-like plasticity was preserved, or abolished, depending on stimulation duration. ConclusionThe LTD-like plasticity effects induced by cathodal tDCS originally described in young adults are also observable in older humans, but non-linearities of the resulting plasticity were partially preserved only in the Pre-Elderly, but not the Elderly group. These results aid in understanding age-dependent plasticity dynamics in humans, and to define more efficient tDCS protocols in the aging brain.

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 Safety, Clinical, and Neurophysiological Effects of Intranasal Ketamine in Patients Who Do Not Respond to Electroconvulsive Therapy: Protocol for a Pilot, Open-Label Clinical Trial.

BackgroundMajor depressive disorder is among the most disabling illnesses worldwide, with a lifetime prevalence of 16.2%. Research suggests that 20% to 40% of patients with depression do not respond to pharmacotherapy, developing treatment-resistant depression. Electroconvulsive therapy is the gold standard for treating individuals with treatment-resistant depression, with remission rates of approximately 75% to 90%. However, 10% to 25% of patients do not respond to electroconvulsive therapy, and many are unable to tolerate it due to the side effects. Both groups are considered to be patients who do not respond to electroconvulsive therapy, because both groups continue to exhibit symptoms of severe depression, have a limited number of treatment options available, and are in need of rapid treatment. Ketamine, an N-methyl-D-aspartate receptor antagonist, has been shown to exert rapid antidepressant effects in patients with treatment-resistant depression when administered in subanesthetic doses through 40-minute intravenous infusions. Recently, a ketamine compound, esketamine (Spravato), that is administered through the intranasal route received regulatory approval by the US Food and Drug Administration and Health Canada to treat depression. However, esketamine is challenging to access due to high costs and limited availability. Racemic ketamine (rketamine) is cheap and easy to access; however, the effects in patients who have not responded to electroconvulsive therapy have yet to be understood or tested. This study will use transcranial magnetic stimulation to study mechanisms of human brain cortical physiology at the systemic level to identify neurobiomarkers of response.ObjectiveThe objective of this open-label pilot clinical trial is to test the feasibility and safety of intranasal ketamine in patients who have not responded to electroconvulsive therapy. The primary outcome is to determine the feasibility of a larger randomized controlled trial to test the efficacy of intranasal ketamine for patients who have not responded to electroconvulsive therapy for clinical indicators in unipolar depression. The secondary outcome is to determine the preliminary effects of an intervention on clinical outcomes, such as depressive symptoms, suicidal ideation, and quality of living. The third outcome is to explore neurophysiological changes as measured by transcranial magnetic stimulation electromyography and electroencephalography to measure changes in cortical excitability as potential predictors of clinical response.MethodsA sterile solution of racemic ketamine hydrochloride will be administered twice per week for 4 weeks (8 sessions) intranasally to patients with treatment-resistant depression who did not respond to or could not tolerate an acute course of electroconvulsive therapy. We will recruit 25 adults (24-65 years old) over the course of 2 years from an academic psychiatric hospital in Toronto, Canada.ResultsThis study has received ethics approval, and funding has been secured. The study is currently active.ConclusionsThis is the first study to test repeated doses of intranasal rketamine in patients who have not responded to electroconvulsive therapy for depression. Results from this study will (1) inform the development of a larger adequately powered randomized controlled trial to test the efficacy of intranasal ketamine for depression and (2) determine potential neurophysiological markers of clinical response.Trial RegistrationClinical Trials.gov NCT05137938; http://clinicaltrials.gov/ct2/show/NCT05137938International Registered Report Identifier (IRRID)PRR1-10.2196/30163

Cortical excitability changes as a marker of cognitive impairment in Parkinson’s disease

Cognitive impairment of different severity with eventual progression to dementia in Parkinson’s disease (PD) appears during the course of the disease. In this study, transcranial magnetic stimulation (TMS) was used to assess cortical excitability changes in PD patients with varying cognitive impairment. We aimed to identify the TMS parameters that could serve as a non-invasive marker of cognitive impairment in patients with PD. Consecutive PD patients were recruited in the study. Detailed neuropsychological assessment was carried out to identify PD without cognitive impairment (PD-nC), PD with mild cognitive impairment (PD-MCI) and PD with dementia (PDD). Twenty patients of PDD (2 females and 18 males), 20 PD-MCI (4 females and 16 males), 18 PD-nC (5 females, 13 males) and 18 healthy controls (4 females, and 14 males) were included in the study. All the participants underwent TMS with recording of resting motor threshold, central motor conduction time, silent period, short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). All the groups were age matched. The SICI was present in all; however, significantly greater inhibition was noted in PDD (Mean±SD; 0.11 ± 0.08) followed by PD-MCI (0.31 ± 0.17), PD-nC (0.49 ± 0.26) and controls (0.61 ± 0.23; p < 0.001). The ICF was significantly reduced in PDD (Mean±SD; 0.15 ± 0.18), PD-MCI (0.55 ± 0.31), PD-nC (0.96 ± 0.59), when compared to healthy controls (1.81 ± 0.83; p < 0.001). Patients with PD-nC, PD-MCI and PDD had graded reduction in ICF and increasing intracortical inhibition as the disease progressed from PD-nC through PD-MCI to PDD. This suggests progressive overactivity of GABAergic transmission, glutaminergic deficiency with consequent reduction of cholinergic transmission leading to dementia.

Response to “Negative Results Call for More Delicate Experimental Design in Cortical Excitability Change of taVNS Intervention”

First of all, we would like to thank Gu et al. for their interest in our paper and critical reflection of the experimental design. As the mechanism of action and optimal stimulation paradigm of taVNS have not been elucidated, taVNS research is associated with several challenges. Therefore, we encourage the collaboration between taVNS research groups, critical reflections, and the implementation of transparent study designs. However, we would like to respond to the concerns raised by Gu et al. as, in our opinion, these concerns have been addressed in our paper.

The Immediate Effects of Intermittent Theta Burst Stimulation of the Cerebellar Vermis on Cerebral Cortical Excitability During a Balance Task in Healthy Individuals: A Pilot Study.

Objective: This pilot study aimed to investigate the immediate effects of single-session intermittent theta-burst stimulation (iTBS) on the cerebellar vermis during a balance task, which could unveil the changes of cerebral cortical excitability in healthy individuals.Subjects: A total of seven right-handed healthy subjects (26.86 ± 5.30 years) were included in this study.Interventions: Each subject received single-session iTBS on cerebellar vermis in a sitting position.Main Measures: Before and after the intervention, all subjects were asked to repeat the balance task of standing on the left leg three times. Each task consisted of 15 s of standing and 20 s of resting. Real-time changes in cerebral cortex oxygen concentrations were monitored with functional near-infrared spectroscopy (fNIRS). During the task, changes in blood oxygen concentration were recorded and converted into the mean HbO2 for statistical analysis.Results: After stimulation, the mean HbO2 in the left SMA (P = 0.029) and right SMA (P = 0.043) significantly increased compared with baseline. However, no significant changes of mean HbO2 were found in the bilateral dorsolateral prefrontal lobe (P > 0.05).Conclusion: Single-session iTBS on the cerebellar vermis in healthy adults can increase the excitability of the cerebral cortex in the bilateral supplementary motor areas during balance tasks.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2100048915].

Combining Optogenetic Stimulation and Motor Training Improves Functional Recovery and Perilesional Cortical Activity

Background. An ischemic stroke is followed by the remapping of motor representation and extensive changes in cortical excitability involving both hemispheres. Although stimulation of the ipsilesional motor cortex, especially when paired with motor training, facilitates plasticity and functional restoration, the remapping of motor representation of the single and combined treatments is largely unexplored. Objective. We investigated if spatio-temporal features of motor-related cortical activity and the new motor representations are related to the rehabilitative treatment or if they can be specifically associated to functional recovery. Methods. We designed a novel rehabilitative treatment that combines neuro-plasticizing intervention with motor training. In detail, optogenetic stimulation of peri-infarct excitatory neurons expressing Channelrhodopsin 2 was associated with daily motor training on a robotic device. The effectiveness of the combined therapy was compared with spontaneous recovery and with the single treatments (ie optogenetic stimulation or motor training). Results. We found that the extension and localization of the new motor representations are specific to the treatment, where most treatments promote segregation of the motor representation to the peri-infarct region. Interestingly, only the combined therapy promotes both the recovery of forelimb functionality and the rescue of spatio-temporal features of motor-related activity. Functional recovery results from a new excitatory/inhibitory balance between hemispheres as revealed by the augmented motor response flanked by the increased expression of parvalbumin positive neurons in the peri-infarct area. Conclusions. Our findings highlight that functional recovery and restoration of motor-related neuronal activity are not necessarily coupled during post-stroke recovery. Indeed the reestablishment of cortical activation features of calcium transient is distinctive of the most effective therapeutic approach, the combined therapy.

Neural and behavioral effects of theta burst stimulation priming on processing of affective and neutral information in working memory

Abstract Theta-burst stimulation (TBS) has been increasingly used to target prefrontal brain regions, such as the dorsolateral prefrontal cortex (DLPFC), to improve neurocognitive and emotional functioning. However, despite the promising outcomes, there is still a lot of variability in responses and the clinical efficacy remains rather modest. Interestingly, fundamental research targeting the motor cortex has suggested the use of priming techniques to enhance TBS-related changes in cortical excitability. Hence, TBS priming - using a prime TBS protocol to enhance the effects of a subsequent test TBS protocol - can yield improved TBS efficacy when applied over the prefrontal cortex. Moreover, recent developments in the field indicate that stimulation priming can be highly efficacious in reducing depressive symptoms. In this within-subjects, sham-controlled study, we investigated how different TBS priming protocols over the left DLPFC affect cognitive performance and task-related brain activity in a sample of fifty healthy adults. Participants performed a verbal working memory task, consisting of affective and neutral word stimuli, during functional magnetic resonance imaging (fMRI) after receiving one of four TBS priming combinations (i.e., a prime followed by a test protocol); (1) sham TBS + sham TBS, (2) sham TBS + intermittent TBS, (3) intermittent TBS + intermittent TBS, (4) continuous TBS + intermittent TBS. Each prime and test protocol was separated by a 15-minute break and there was one week in between each experimental session. Task performance and participants’ activation patterns elicited by the task following the different TBS priming conditions were assessed. During this talk, the behavioral and neural findings will be presented. Moreover, implications of the study findings for further studies evaluating the neurobehavioral effects of TBS priming on emotional working memory, in healthy and neuropsychiatric samples, will be discussed. Keywords: Theta Burst Stimulation (TBS), functional magnetic resonance imaging (fMRI), Stimulation Priming, Working Memory

Repetitive magnetic stimulation induces synaptic plasticity through cooperative pre- and postsynaptic activation

Abstract Repetitive TMS (rTMS) induces changes in cortical excitability. However, the cellular and molecular mechanisms which underlie rTMS-induced plasticity remain incompletely understood. Using a combination of functional optical imaging, electrophysiological recordings, and multi-scale computational modeling we study how the physical input parameters of rTMS affect the ability of neurons to express synaptic plasticity. Our experiments in pyramidal neurons of mouse organotypic tissue cultures show that a cooperative pre- and postsynaptic activation during stimulation asserts metaplastic effects, which result in robust LTP-induction. At the molecular level we demonstrate that these effects depend on the activation of NMDA receptors, L-type voltage gated calcium channels and functional intracellular calcium stores. Finally, a computational model that is based on a voltage-dependent STDP rule with fast BCM-like metaplasticity reproduces our findings, and predicts biological differences between 10 Hz and iTBS protocols. These results confirm and expand upon our previous work on rTMS-induced synaptic plasticity in animal models. They provide a framework towards the development of multi-scale computational models that can predict biological effects of rTMS. Keywords: LTP, STDP, Metaplasticity, Multi-scale computational modeling

Cyclic changes of visual cortical excitability across migraine phases: A study with sound induced flash illusions

Abnormal cortical excitability has a role in migraine but the link with beginning and stop of migraine attacks remains unclear. Critical insight could come by excitability changes across the migraine cycle. Here we explore it through sound induced flash illusions (SIFI). SIFI are cross-modal illusory percepts critically dependent on visual cortical excitability (less illusions = increased excitability) that have been found to be altered in episodic and chronic migraine(1–2).

Visual cortical excitability in chronic migraineurs treated with erenumab: Preliminary results of a study with sound induced flash illusions

Surrounding environment perception can be studied using sound-induced flash illusions (SIFI): single flashes presented with two or more beeps are perceived as multiple flashes (fission illusion); the extent of such illusions is associated to changes in visual cortical excitability, known to be altered in migraineurs. We aim to evaluate SIFI changes in migraineurs after three months erenumab therapy.

Changes in Cortical Excitability and Parkinson Tremor After Botulinum Toxin Therapy.

To investigate the relationship between botulinum toxin type A (BoNT-A) administration, tremor amplitude, and modulation of intracortical excitability and sensorimotor processing using paired-pulse transcranial magnetic stimulation (pp-TMS) in patients with early, tremor-dominant Parkinson disease (PD). Twelve de novo (naive to anti-PD medications) and 7 l-dopa (optimized on levodopa) participants with PD with tremor affecting one arm were recruited. All participants received 4 serial BoNT-A treatments for tremor every 12 weeks and peak effect was assessed 6 weeks posttreatment, totaling 8 visits over 42 weeks. Injection measures were based on kinematic tremor analysis. Short interval intracortical inhibition (SICI), intracortical facilitation (ICF), long interval intracortical inhibition (LICI), and measures of sensorimotor interaction (short-latency afferent [SAI] and long-latency afferent [LAI] stimulation) were assessed in both hemispheres using pp-TMS paradigms at each time point. Linear mixed models analyzed the effect of each pp-TMS measure and tremor severity within each cohort and the association between pp-TMS and tremor severity in the de novo cohort over 42 weeks. t Tests compared pp-TMS measures between hemispheres per time point. Baseline SICI, LICI, and SAI was reduced (higher motor evoked potential [MEP] ratio) on the tremulous/treated side compared to the nontremulous side in de novo participants. On the treated side in the de novo cohort, BoNT-A treatment significantly reduced ICF and increased LICI, SAI, and LAI (lower MEP ratio) at peak BoNT-A time points. The change in tremor severity was significantly associated with changes in SICI, LICI, and LAI. Our findings suggest that tremor severity in early PD may be related to impaired intracortical inhibition and defective sensorimotor integration.