14 research outputs found
Modulation of human corticospinal excitability by paired associative stimulation in patients with amyotrophic lateral sclerosis and effects of Riluzole
BACKGROUND Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes an impairment in both the upper and lower motor neurons. The recent description of numerous non-motor signs points to an involvement of the neocortex networks that is more complex than was previously believed. Paired associative stimulation (PAS), a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation, can enhance motor output in the contralateral hand through an NMDA-mediated sensorimotor mechanism.
OBJECTIVE To describe the effects of PAS on ALS patients before and after Riluzole intake compared with healthy subjects.
METHODS PAS was used to detect differences between 24 newly-diagnosed ALS patients and 25 age-matched healthy controls. MEP amplitude from the abductor pollicis brevis was considered before PAS, immediately after (T0) and after 10 (T10), 20 (T20), 30 (T30) and 60 (T60) minutes. Statistical significance was calculated using RM-ANOVA.
RESULTS In healthy controls, PAS significantly increased MEP amplitude at T10, T20 and T30 (pâŻ<âŻ0.05). In ALS patients, a significant increase in MEP amplitude was also observed after 60âŻmin (pâŻ<âŻ0.05), thus demonstrating NMDA-mediated enhanced facilitatory plasticity. After two weeks of riluzole intake, no MEP amplitude increase was evident after PAS at any time point. In three monomelic-onset ALS patients, sensorimotor facilitation was evident only in the hemisphere corresponding to the affected side and appeared in the opposite hemisphere when the patients manifested contralateral symptoms.
CONCLUSIONS PAS may be considered a useful tool when investigating NMDA-mediated neocortical networks in ALS patients and the modulation of such networks after anti-glutamatergic drug intake
Priming Pharyngeal Motor Cortex by Repeated Paired Associative Stimulation: Implications for Dysphagia Neurorehabilitation
Background. Several stimulation parameters can influence the neurophysiological and behavioral effects of paired associative stimulation (PAS), a neurostimulation paradigm that repeatedly pairs a peripheral electrical with a central cortical (transcranial magnetic stimulation [TMS]) stimulus. This also appears to be the case when PAS is applied to the pharyngeal motor cortex (MI), with some variability in excitatory responses, questioning its translation into a useful therapy for patients with brain injury. Objective. To investigate whether repeated PAS in both ârespondersâ and ânonrespondersâ could enhance cortical excitability in pharyngeal MI more robustly. Methods. Based on their responses after single PAS, healthy participants were stratified into 2 groups of ârespondersâ and ânonrespondersâ and underwent 2 periods (60 minutes inter-PAS interval) of active and sham PAS in a randomized order. Neurophysiological measurements with single TMS pulses from pharyngeal motor representation were collected up to 90 minutes after the second PAS period. Results. Repeated PAS increased cortical excitability up to 95% at 60 minutes following the second PAS in both the ârespondersâ and ânonresponders.â Moreover, cortical excitability in the ânonrespondersâ was significantly different after repeated PAS compared with single and sham application (P = .02; z = â2.2). Conclusions. Double dose PAS switched ânonrespondersâ to âresponders.â These results are important for PAS application to dysphagic stroke patients who do not initially respond to a single application
Distributed cortical structural properties contribute to motor cortical excitability and inhibition
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.[Abstract]: IntroducciĂłn:The link between the local structure of the primary motor cortex and motor function has been well documented. However, motor function relies on a network of interconnected brain regions and the link between the structural properties characterizing these distributed brain networks and motor function remains poorly understood. Here, we examined whether distributed patterns of brain structure, extending beyond the primary motor cortex can help classify two forms of motor function: corticospinal excitability and intracortical inhibition. To this effect, we recorded high-resolution structural magnetic resonance imaging scans in 25 healthy volunteers. To measure corticospinal excitability and inhibition in the same volunteers we recorded motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS) and short-interval intracortical inhibition (SICI) in a separate session. Support vector machine (SVM) pattern classification was used to identify distributed multivoxel gray matter areas, which distinguished subjects who had lower and higher MEPs and SICIs. We found that MEP and SICI classification could be predicted based on a widely distributed, largely nonoverlapping pattern of voxels in the frontal, parietal, temporal, occipital and cerebellar regions. Thus, structural properties distributed over the brain beyond the primary motor cortex relate to motor function
Resting state morphology predicts the effect of theta burst stimulation in false belief reasoning:ventrolateral prefrontal cortex in false belief reasoning
When required to represent a perspective that conflicts with one's own, functional magnetic resonance imaging (fMRI) suggests that the right ventrolateral prefrontal cortex (rvlPFC) supports the inhibition of that conflicting self-perspective. The present task dissociated inhibition of self-perspective from other executive control processes by contrasting belief reasoning-a cognitive state where the presence of conflicting perspectives was manipulated-with a conative desire state wherein no systematic conflict existed. Linear modeling was used to examine the effect of continuous theta burst stimulation (cTBS) to rvlPFC on participants' reaction times in belief and desire reasoning. It was anticipated that cTBS applied to rvlPFC would affect belief but not desire reasoning, by modulating activity in the Ventral Attention System (VAS). We further anticipated that this effect would be mediated by functional connectivity within this network, which was identified using resting state fMRI and an unbiased model-free approach. Simple reaction-time analysis failed to detect an effect of cTBS. However, by additionally modeling individual measures from within the stimulated network, the hypothesized effect of cTBS to belief (but, importantly, not desire) reasoning was demonstrated. Structural morphology within the stimulated region, rvlPFC, and right temporoparietal junction were demonstrated to underlie this effect. These data provide evidence that inconsistencies found with cTBS can be mediated by the composition of the functional network that is being stimulated. We suggest that the common claim that this network constitutes the VAS explains the effect of cTBS to this network on false belief reasoning. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc
Resting state morphology predicts the effect of theta burst stimulation in false belief reasoning
When required to represent a perspective that conflicts with one's own, functional magnetic resonance imaging (fMRI) suggests that the right ventrolateral prefrontal cortex (rvlPFC) supports the inhibition of that conflicting self-perspective. The present task dissociated inhibition of self-perspective from other executive control processes by contrasting belief reasoning-a cognitive state where the presence of conflicting perspectives was manipulated-with a conative desire state wherein no systematic conflict existed. Linear modeling was used to examine the effect of continuous theta burst stimulation (cTBS) to rvlPFC on participants' reaction times in belief and desire reasoning. It was anticipated that cTBS applied to rvlPFC would affect belief but not desire reasoning, by modulating activity in the Ventral Attention System (VAS). We further anticipated that this effect would be mediated by functional connectivity within this network, which was identified using resting state fMRI and an unbiased model-free approach. Simple reaction-time analysis failed to detect an effect of cTBS. However, by additionally modeling individual measures from within the stimulated network, the hypothesized effect of cTBS to belief (but, importantly, not desire) reasoning was demonstrated. Structural morphology within the stimulated region, rvlPFC, and right temporoparietal junction were demonstrated to underlie this effect. These data provide evidence that inconsistencies found with cTBS can be mediated by the composition of the functional network that is being stimulated. We suggest that the common claim that this network constitutes the VAS explains the effect of cTBS to this network on false belief reasoning. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.</p
Cortical thickness in primary sensorimotor cortex influences the effectiveness of paired associative stimulation
Non-invasive brain stimulation protocols in general and paired associative stimulation (PAS) in particular seem to alter corticospinal excitability and thereby to influence behaviour with a high degree of inter-subject variability. The cause of this variability is multidimensional and to some extent still unknown. Here, we tested the hypothesis that individual variations in cortical thickness can explain some of the variability of PAS-induced excitability changes. Ten minutes of a facilitatory PAS protocol (PASLTP) rapidly increased corticospinal excitability in the majority of the subjects (14/19 subjects) while others showed no such effect (5/19 subjects). A whole brain correlation analysis based on high resolution T1-weighted images revealed a significant positive relationship of PASLTP-induced excitability changes with cortical thickness of the underlying left sensorimotor cortex (SM1) only. Cortical thickness alone, among other potential influencing factors, explained about half of the PASLTP variance, indicating that subjects with a strong after-effect were those with thicker gray matter in this region. Based on these findings, we provide novel evidence that local brain structure influences the individual amount of functional plasticity induced by PASLTP. While the underlying neurophysiological and/or anatomical reasons for this effect still remain elusive at this point, we conclude that cortical thickness should be considered as an important and until now not recognized modulating factor in studies employing non-invasive brain stimulation techniques
Paired associative transcranial magnetic stimulation to primary motor cortex and inferior parietal lobule : a functional MRI study
Les mĂ©thodes non-invasives de neuro-imagerie et de neurostimulation peuvent ĂȘtre
combinées pour mieux comprendre les connexions dans le cerveau. Pour la premiÚre fois,
une Ă©tude combine de façon sĂ©quentielle lâIRM fonctionnelle (fMRI) et un protocole de TMS
associative pairée cortico-corticale (TMS-PAScc) sur le cortex moteur primaire (M1) et sur
le lobule pariĂ©tal infĂ©rieur (LPI) dans lâhĂ©misphĂšre gauche. La TMS module-t-elle le couplage
neurovasculaire et permet-elle de renforcer une connexion fonctionnelle qui soit
dĂ©tectable Ă la fMRI Ă lâĂ©tat de repos (RS-fMRI)? 10 sujets droitiers et en santĂ© font une
session de TMS-PAScc LPI-M1 de courte durĂ©e (180 paires dâimpulsions, frĂ©quence de
stimulation Ă 0.02 Hz). Les mĂȘmes sujets font 2 sessions de la RS-fMRI, avant et aprĂšs le
protocole PAScc. Les résultats montrent que la corrélation du signal BOLD entre les régions
LPI-M1 avant et aprÚs la PAScc ne change pas de façon significative (avant-PAS=0.10±0.07
et aprĂšs-PAS=0.09±0.07, p=0.64), tout comme lâamplitude des potentiels Ă©voquĂ©s moteurs
(PEM) des impulsions pairées LPI-M1 ne change pas de façon significative du début de la
PAScc à 25 minutes aprÚs la PAScc (PASdébut=0.71±0.46mV, PASpost25min=0.72±0.89mV,
p=0.338). Toutefois, les PEM des impulsions pairées LPI-M1 sont réduites par rapport aux
PEM des impulsions simples M1, avant la PAScc et aprÚs la PAScc (PEM simples_pré et
PASdébut, réduction de 0.32mV, p=0.05; PEM simples_post et PASpost25min, réduction de
0.39mV p=0.008), illustrant la prĂ©sence dâun lien fonctionnel de nature inhibitrice entre LPI
et M1. Toutefois, lâamplitude de cette inhibition nâest pas modulĂ©e de façon significative
par la TMS-PAScc (ratio mesures pairées/mesures simples préPAS=0.9 et ratio postPAS=0.6,
p=0.257). Dans lâensemble, la TMS-PAScc ne montre pas dâeffet soutenu sur la connectivitĂ©
cérébrale telle que mesurée par la RS-fMRI et la TMS et ce, bien que le LPI montre un lien
inhibiteur sur M1 de façon aigue. Plusieurs hypothÚses peuvent expliquer cette absence
dâeffet soutenu, notamment, il est possible que lâaltĂ©ration de la connectivitĂ© ne soit visible
que lorsque le rĂ©seau LPI-M1 est activement sollicitĂ©, comme durant lâexĂ©cution dâune
tĂąche motrice. Il est aussi possible que le nombre de pairages soit insuffisant pour induire
des changements mesurables, mais que la connectivité fonctionnelle suite à des sessions
répétées de protocole PAScc pourrait modifier le couplage neurovasculaire et la plasticité
cérébrale.Abstract : Noninvasive neuroimagery and neurostimulation methods can be combined to
further the understanding of the human brain connections. For the first time, resting state
functional MRI (RS-fMRI) and paired associative cortico-cortical TMS (TMS-PAScc) of the
motor cortex (M1) and the cortex of the inferior parietal lobule (LPI) of the left hemisphere
are combined in a serial manner. Is TMS able to modify the neurovascular coupling as to
facilitate LPI-M1 functional connectivity and change the fMRI BOLD signal? 10 right-handed
and healthy subjects did a LPI-M1 TMS-PAScc session of short duration (180 paired pulses
at 0.02 Hz, 15 min total). The same subjects underwent 2 fMRI sessions, before and after
TMS-PAScc LPI-M1. Results show that the BOLD signal correlation between LPI-M1 does not
change significantly before and after PAS (prePAS=0.10±0.07 et postPAS=0.09±0.07,
p=0.64). TMS measures of motor evoked potentials (PEM) were taken before and after PAS
LPI-M1. The paired pulse PEM measures did not change significantly from the start of PAScc
to 25 minutes postPAS (PASstart=0.71 ± 0.46 mV, PASpost25min=0.72±0.89 mV, p=0.338).
Paired PEM measures are statistically reduced from PAS PEM single measures, before and
afterPAS (sPEM_pre et PASstart, significant 0.32mV reduction, p=0.05; PEMs_post et
PASpost25min, 0.39mV reduction, p=0.008). PAScc did not show any significant
neuroplasticity effect after 20 minutes because paired pulses did not change before and
after PAScc. The PEM reduction of paired pulses is most likely related to the inhibiting effect
of the conditioning stimulus of LPI on the test stimulus of M1 at 8ms. This inhibition is an
effect limited to the measure itself and does not increase significantly with time
(pairedpulse/singlepulsemeasures prePASratio=0.9 and postPASratio=0.6, p=0.257). TMSPAScc
did not show a sustained effect on cerebral connectivity as measured by RS-fMRI
although stimulation of LPI showed an acute inhibiting effect on M1 during paired
measures. LPI-M1 TMS-PAScc did not show sustained connectivity and it could be because
no task was involved in our study to actively solicit both cerebral regions during PAS. It is
also possible that the number of paired stimulation was not enough to bring a change of
connectivity and that PAS needs to be repeated on different days to eventually have a
sustainable effect
Pharmaco-TMS-EEG as a new tool to characterize human cortical excitability and connectivity
Excitation and inhibition in human cortex can be measured by transcranial magnetic stimulation (TMS) combined with electromyography (EMG) and
electroencephalography (EEG) by way of specific markers of TMS-evoked muscle and brain responses. It has been shown that this capacity can be strongly
enhanced by combining TMS-EMG/EEG with central nervous system (CNS)
active drugs. Early studies have systematically investigated the role of a wide variety of CNS active drugs on motor evoked potentials (MEPs) and this
knowledge is now partially applied to clinical settings. However, pharmacological alteration of TMS evoked EEG potentials (TEPs), which can provide direct information on cortical excitability and connectivity, has not been systematically
elucidated yet. Here, we complement previous findings by using pharmaco-TMSEEG/EMG approaches to explore the physiological signatures of TEPs. In Experiment 1, we studied the effects of the experimental compound S44819, a selective α5-GABAAR antagonist, on TEPs and MEPs in 18 healthy young adults
in a phase I study. In experiment 2, we investigated the role of three anti-epileptic
drugs (carbamazepine, brivaracetam and tiagabine) on TEPs and MEPs in 15
healthy male adults. 100 mg S44819 enhanced cortical excitability, as denoted
by reduction of the amplitude of the N45 TEP component, as well as decrease of
the motor threshold; carbamazepine decreased the amplitude of the P25 and P180 TEP components and increased motor threshold; brivaracetam decreased
the N100 TEP amplitude and increased MEP threshold; tiagabine had no effect
on TEPs and/or MEPs. Results of experiment 1 demonstrated for the first time effects of S44819 in the human cortex, that are relevant as S44819 showed potential to improve plasticity and learning in animal models of cerebral stroke.
These findings led to further development of S44819 in a clinical phase II study
to test its efficacy in enhancing recovery of function in stroke patients. Results of experiment 2 confirmed and extended previous findings that the P25 TEP
component reflects axonal excitability of the corticospinal system, the N100 potential in the non-stimulated hemisphere propagated activity mediated by
inhibition of presynaptic neurotransmitter release, and the P180 late activity
dependent on voltage-gated sodium channels (VGSCs). We believe that these updated pharmacological characterization of TEPs will prove useful for the understanding of normal and dysfunctional cortical excitability and inhibition of
the human brain
L'impact du vieillissement neuroanatomique sur les ondes lentes du sommeil
Les ondes lentes (OL) sur lâĂ©lectroencĂ©phalogramme caractĂ©risent le sommeil dit lent. Leur production dĂ©pend de la synchronisation de lâactivitĂ© neuronale dans un large rĂ©seau nĂ©ocortical. Les OL prĂ©sentent dâimportants changements au cours du vieillissement, et ce, dĂšs le milieu de lâĂąge adulte. Lâobjectif de ce mĂ©moire est dâĂ©valuer la contribution de lâamincissement cortical dans les modifications des caractĂ©ristiques des OL durant lâĂąge adulte. Notre Ă©tude montre que la densitĂ© (nb/min) et lâamplitude (”V) des OL est liĂ©e Ă lâĂ©paisseur de plusieurs rĂ©gions du cortex chez des sujets jeunes et ĂągĂ©s. Toutefois, la pente des OL (”V/s) nâa pas semblĂ© en relation avec la neuroanatomie. Des analyses de mĂ©diation montrent que la diminution de la densitĂ© des OL chez les personnes ĂągĂ©s sâexplique par lâamincissement de gyri frontaux et temporaux, alors que les effets de lâĂąge sur lâamplitude des OL sâexpliquent par lâamincissement dâun ensemble plus grand de rĂ©gions corticales.Sleep slow waves (SW) on the electroencephalogram (EEG) reflect synchronous alternance between depolarization and hyperpolarisation states in many cortical neurons. As soon as in the middle-years of life (around 45-50 years old), sleep SW change considerably. In this masterâs thesis, we investigated the role of cortical thinning in normal age-related changes in characteristics of sleep SW. Our results show that SW amplitude (”V) and density(nb/min) are linked to cortical thickness in many cerebral regions in young and older subjects. However, SW slope did not present significant associations with cortical thickness. Mediation analysis showed that specific thinning in right middle frontal and middle temporal gyri explained age-related changes in SW density, whereas thinning in a large-scale network of regions explained age-related changes in SW amplitude. As a whole, our results shows that thinning in cortical regions involved in SW generation and propagation are associated with age-related changes in sleep SW