Visual spatial attention influences plasticity in the human motor cortex

Event Abstract Back to Event Spatial Attention Influences Plasticity Induction in the Motor Cortex Marc Kamke1*, Alexander Ryan2, Martin Sale1, Megan Campbell1, Stephan Riek3, Timothy Carroll3 and Jason Mattingley4 1 The University of Queensland, Queensland Brain Institute, Australia 2 The University of Queensland, The School of Psychology, Australia 3 The University of Queensland, School of Human Movement Studies, Australia 4 The University of Queensland , Queensland Brain Institute and School of Psychology, Australia It is widely accepted that alterations in the strength of communication between neurons, or 'Hebbian' (synaptic) plasticity, plays a major role in the capacity of the adult brain to adapt. Such plasticity is critical for responding to changes in sensory input, learning new skills and behaviours, and recovering from injury to the nervous system. Numerous physiological influences on synaptic plasticity have now been identified, but little is known about how plasticity is affected by cognitive processes. Here, we investigated the influence of visual spatial attention on plasticity induced by external stimulation of the motor cortex. Transcranial magnetic stimulation (TMS) and a paired associative stimulation (PAS) procedure were used to alter functional responses in the thumb area of the primary motor cortex. In different experiments PAS was used to induce either an increase or a decrease in cortical excitability, as indexed by the amplitude of motor-evoked potentials. These PAS-induced effects reflect, respectively, long-term potentiation (LTP)-like and long-term depression (LTD)-like synaptic plasticity. During the induction of plasticity, participants focused their attention on one of two visual stimulus streams located adjacent to each hand. When participants attended to visual stimuli located near the left thumb, which was targeted by the plasticity procedure, LTP-like increases in excitability were enhanced relative to when they attended instead to stimuli located near the right thumb. In contrast, LTD-like decreases in excitability were reduced when attention was directed toward the visual stimuli located near the left, relative to the right, thumb. These findings suggest that voluntary attention can exert an important influence on the functional organisation of the human cortex by both enhancing LTP-like plasticity and suppressing LTD-like effects. Keywords: Attention, Motor Cortex, Transcranial Magnetic Stimulation, plasticity, spatial attention, Paired associative stimulation Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Attention Citation: Kamke M, Ryan A, Sale M, Campbell M, Riek S, Carroll T and Mattingley J (2015). Spatial Attention Influences Plasticity Induction in the Motor Cortex. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00258 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Dr. Marc Kamke, The University of Queensland, Queensland Brain Institute, Brisbane, Australia, m.kamke@uq.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Marc Kamke Alexander Ryan Martin Sale Megan Campbell Stephan Riek Timothy Carroll Jason Mattingley Google Marc Kamke Alexander Ryan Martin Sale Megan Campbell Stephan Riek Timothy Carroll Jason Mattingley Google Scholar Marc Kamke Alexander Ryan Martin Sale Megan Campbell Stephan Riek Timothy Carroll Jason Mattingley PubMed Marc Kamke Alexander Ryan Martin Sale Megan Campbell Stephan Riek Timothy Carroll Jason Mattingley Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Current models of motor cortical plasticity, developed in studies on experimental animals, emphasize the importance of the conjoint activity of somatosensory afferents and intrinsic motor cortical circuits. The hypothesis that an enduring change in excitability in the cortical output circuitry can be induced in the human motor cortex by a paired-stimulation protocol was tested. Low-frequency median nerve stimulation was paired with transcranial magnetic stimulation (TMS) over the optimal cranial site for stimulating the abductor pollicis brevis muscle (APB). This protocol induced an increase in the amplitudes of the motor evoked potentials (MEPs) in the resting APB as well as a prolongation of the silent period measured in the precontracted APB following TMS; amplitudes of MEPs measured in voluntary contraction remained unchanged. Experiments testing the excitability of spinal motoneurons using F-wave studies and electrical stimulation of the brainstem suggested that the site of the plastic changes was within the motor cortex. The increases in resting amplitudes and silent period duration were conditionally dependent on the timing between the afferent and the magnetic stimulation in that they were present when events elicited by afferent and magnetic stimulation were synchronous at the level of the motor cortex. Plasticity induced by paired stimulation evolved rapidly (within 30 min), was persistent (minimum duration 30-60 min) yet reversible, and was topographically specific. This combination of features and the similarity to properties of induced enduring changes in synaptic efficacy, as elucidated in animal studies, leads us to propose that the induced plasticity may represent a signature of associative long-term potentiation of cortical synapses or closely related neuronal mechanisms in the human cortex.

Dopamine (DA) is involved in learning and memory formation, which are thought to depend on synaptic modifications like long-term potentiation (LTP) and long-term depression (LTD). Despite huge efforts to unravel the dopaminergic impact on these functions, the respective knowledge is still far from being complete. This might especially be due to the neuromodulatory impact of DA on cortical function, i.e. DA might affect cortical excitability and plasticity differently, dependent on DA dosage, DA sub-receptors, and the focality of plasticity induced, amongst others. The aim of the present thesis, which contains three studies, was to explore the impact of DA on cortical plasticity in healthy humans into larger detail. Specifically, we sought to determine if the multiple modes of action of DA on neuroplasticity depend on sub-receptor specificity, concentration level and type of plasticity. In all experiments the primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential (MEP) amplitudes via transcranial magnetic stimulation (TMS). Focal plasticity was induced non-invasively by paired associative stimulation (PAS), while non-focal plasticity was generated by transcranial direct current stimulation (tDCS). In the first study we explored the impact of D1 receptor activity on plasticity. Here, shifting the balance of DA activation in direction of D1 by D2 block abolished non-focal plasticity and focal inhibition. Further enhancing D1 activity by adding L-dopa under D2 block reestablished all kinds of plasticity. In concordance with animal experiments, the results favor an important impact of D1 receptor activity on neuroplasticity in humans. In the second study, in order to reveal if DA receptor activation exerts a non-linear dosedependent effect on cortical plasticity, we explored the impact of different dosages of Ldopa on tDCS-induced plasticity. In accordance, the results show a nonlinear dosageeffect relation of dopamine receptor activation on plasticity, resulting in a U -shaped dose-response curve for anodal tDCS and in an inverted U -shaped dose-response curve for cathodal tDCS. The results are pinpointing to the importance of a specific dosage of dopamine optimally suited to improve plasticity. In the third study, we combined different doses of the D2/D3 dopamine agonist ropinirole (RP) with focal and non-focal plasticity induction in order to determine if the nonlinear effect of DA on plasticity depends on sub-receptor specificity and the kind of plasticity induced. D2-like receptor activation produced an inverted U -shaped dose response curve on plasticity for facilitatory tDCS and PAS and for inhibitory tDCS. However, no dose-dependent response effect of D2-like receptor activation was evident for iPAS. The results of this study support the assumption that modulation of D2-like receptors exerts a dosedependent non-linear effect on neuroplasticity in the human motor cortex, which differs for the type of plasticity induced. In summary, our results demonstrate that the dopaminergic influence on cortical plasticity (a) is specific for DA sub-receptors, and (b) is dosage-dependent. They furthermore demonstrate that (c) the effect differs for the specific kind of plasticity induced, and (d) suggest that the focusing effect and the stabilizing effect of DA on plasticity depends on the interaction of dopaminergic subreceptors. These results might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results of former studies.

We investigated whether the pulsed high frequency electromagnetic field (EMF) emitted by a mobile phone has short term effects on the human motor cortex. We measured motor evoked potentials (MEPs) elicited by single pulse transcranial magnetic stimulation (TMS), before and after mobile phone exposure (active and sham) in 10 normal volunteers. Three sites were stimulated (motor cortex (CTX), brainstem (BST) and spinal nerve (Sp)). The short interval intracortical inhibition (SICI) of the motor cortex reflecting GABAergic interneuronal function was also studied by paired pulse TMS method. MEPs to single pulse TMS were also recorded in two patients with multiple sclerosis showing temperature dependent neurological symptoms (hot bath effect). Neither MEPs to single pulse TMS nor the SICI was affected by 30 min of EMF exposure from mobile phones or sham exposure. In two MS patients, mobile phone exposure had no effect on any parameters of MEPs even though conduction block occurred at the corticospinal tracts after taking a bath. As far as available methods are concerned, we did not detect any short-term effects of 30 min mobile phone exposure on the human motor cortical output neurons or interneurons even though we can not exclude the possibility that we failed to detect some mild effects due to a small sample size in the present study. This is the first study of MEPs after electromagnetic exposure from a mobile phone in neurological patients.

The human motor cortex contains a dynamic and distributed network of motor representations. Formation, maintenance, and modification of these representations is an activity-driven process. Repeated stimulation of one representation results in increased motor output from this representation, a process referred to as "within-representation plasticity." We showed previously that within-representation plasticity of the upper arm representation occurs when repetitive transcranial magnetic stimulation (rTMS) is delivered to that representation during transient ischemic nerve block (INB) of the contralateral hand. INB reduces inhibition in the motor cortex and thus lowers the threshold for stimulation-induced plasticity. Here we studied the effects of rTMS delivered to nearby body part representations on the motor output from the upper arm representation. Six healthy subjects underwent INB-alone (control), or INB plus 30 min of focal 0.1 Hz rTMS of either the face, hand, arm, leg, or overlap arm/hand representations in motor cortex. INB-alone and rTMS of the leg representation resulted in only a short-lasting (< 20 min) increase in motor output from the arm representation, as measured by motor evoked potentials in the biceps. rTMS of arm and arm/hand representations induced a prolonged (> 60 min) within-representation increase. In contrast, rTMS of face or hand representations canceled the short-lasting increase and even led to a long-lasting decrease of motor output from the arm representation. Therefore, rTMS of the experimentally disinhibited motor cortex induces within-representation increase, and across-representation decrease of motor cortical output. This bidirectional plasticity might be used for purposeful modulation of human cortical function.

Recent studies have proposed therapeutic potential for repetitive transcranial magnetic stimulation (rTMS) in swallowing rehabilitation, yet its outcomes vary across individuals and studies. Such variability may be related to the brain state before stimulation. Metaplasticity is a higher order plasticity which regulates cortical response to plasticity changes. Studies have shown that preconditioning of the hand motor cortex could increase cortical capacity for neuroplastic change and enhance rTMS outcomes. We investigated, for the first time, the directional metaplastic properties in human pharyngeal motor cortex using preconditioned rTMS. We found that preconditioned rTMS with specific time intervals between preconditioning and conditioning rTMS had stronger stimulation effects in both swallowing neurophysiology and behaviour than that without preconditioning. Our results provide evidence for enhanced directional metaplasticity in pharyngeal motor cortex and new insights into its clinical application for dysphagia. Despite growing evidence that repetitive transcranial magnetic stimulation (rTMS) can be used as a treatment for dysphagia, its efficacy varies across individuals. Such variability may relate to the pre-stimulation state of neuronal activation. Previous studies found that preconditioning the hand motor cortex before rTMS could enhance stimulation outcomes through metaplasticity. No studies have investigated such mechanisms in human pharyngeal motor cortex. Therefore, we investigated the preconditioning effects of rTMS on swallowing neurophysiology and behaviour. Healthy adults were recruited for swallowing neurophysiological (n=14) and behavioural (n=14) experiments. They were first given eight different preconditioned (1 and 5Hz) rTMS interventions with varying inter-rTMS intervals. Motor evoked potentials (MEPs) were measured before and for 60min post-rTMS. Based on the changes in pharyngeal MEPs, the optimal preconditioned 1Hz and 5Hz rTMS protocols were then applied as interventions while assessing swallowing performance using a reaction time task. We found that 5Hz rTMS preconditioned with 1Hz rTMS with 30min inter-rTMS interval induced the greatest increase on pharyngeal cortical excitability (F1,13 =21.244; P<0.001). By comparison, 1Hz rTMS preconditioned with 5Hz rTMS with 90min inter-rTMS interval was most optimal for suppressing pharyngeal motor cortex (F1,13 =13.547; P=0.003). Behaviourally, swallowing accuracy was improved after preconditioned 5Hz rTMS (F1,13 =10.109, P=0.007) and reduced after preconditioned 1Hz rTMS (F1,13 =14.108, P=0.009) compared to sham. Thus, two optimal protocols for inducing functional metaplasticity in human pharyngeal motor cortex have been identified. These protocols appear superior to conventional rTMS and may be relevant to future clinical application in neurogenic dysphagia.

Introduction A single nucleotide polymorphism (SNP) of brain-derived neurotrophic factor ( BDNF ) gene has been shown to influence neurological function. Transcranial magnetic stimulation (TMS) studies have suggested that the BDNF SNP producing a valine to methionine substitution can modulate plasticity in human motor cortex.12 This study aimed to determine if the SNP influences the outcome of two excitatory forms of neurostimulation applied to the swallowing motor system. Methods Healthy subjects (n=22, 6 males, mean age 59) with predetermined BDNF SNP status (Val/Val or non-Val/Val), underwent bi-hemispheric single pulse TMS measurements of pharyngeal EMG responses recorded from a swallowed intra luminal catheter to assess corticobulbar excitability. Following baseline assessment with TMS, subjects received either pharyngeal electrical stimulation (PES) at 5 Hz, 75% of sensory threshold, for 10 minutes (n=16, 9 Val/Val and 7 non-Val/Val) or 250 pulses of 5 Hz repetitive TMS (rTMS) over the dominant pharyngeal motor cortex (n=22, 15 Val/Val and 7 non-Val/Val). Repeated measurements of the cortical excitability were assessed with TMS up to 60 minutes following the two interventions. Pharyngeal motor cortical excitability for the 2 BDNF SNP genotypes was compared using 2-way ANOVA. Results PES significantly increased the amplitude of pharyngeal motor evoked potentials (MEPs) in the Val/Val group compared to the non-Val/Val group with a strong Genotype*Time interaction ( F 8112 =2.4, p=0.018) (see Abstract 21). By contrast, there was a significant reduction in latencies of the non-Val/Val group after 5 Hz rTMS (Genotype∗Time interaction, F 3,60 =4.9, p=0.04). There was no significant difference in MEP latencies between groups following PES. Conclusion SNPs of the BDNF gene predicts the degree of plasticity in the human swallowing motor system to differing forms of neurostimulation. Our results suggest that therapeutic response to swallowing interventions in pathology such as dysphagic stroke may be guided by BDNF genotype profiling.

The human motor cortex has a tendency to resonant activity at about 20 Hz so stimulation should more readily entrain neuronal populations at this frequency. We investigated whether and how different interneuronal circuits contribute to such resonance by using transcranial magnetic stimulation (TMS) during transcranial alternating current stimulation (tACS) at motor (20 Hz) and a nonmotor resonance frequency (7 Hz). We tested different TMS interneuronal protocols and triggered TMS pulses at different tACS phases. The effect of cholinergic short-latency afferent inhibition (SAI) was abolished by 20 Hz tACS, linking cortical beta activity to sensorimotor integration. However, this effect occurred regardless of the tACS phase. In contrast, 20 Hz tACS selectively modulated MEP size according to the phase of tACS during single pulse, GABAAergic short-interval intracortical inhibition (SICI) and glutamatergic intracortical facilitation (ICF). For SICI this phase effect was more marked during 20 Hz stimulation. Phase modulation of SICI also depended on whether or not spontaneous beta activity occurred at ~20 Hz, supporting an interaction effect between tACS and underlying circuit resonances. The present study provides in vivo evidence linking cortical beta activity to sensorimotor integration, and for beta oscillations in motor cortex being promoted by resonance in GABAAergic interneuronal circuits.

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.

BackgroundTranscranial direct current stimulation (tDCS) is capable of eliciting changes in cortical neuroplasticity. Increasing duration or repetition of tDCS during the after-effects of a first stimulation has been hypothesized to enhance efficacy. Computational models suggest sequential stimulation patterns with changing polarities to further enhance effects. Lasting tDCS effects on neural plasticity are of great importance for clinical applications.ObjectiveThe study systematically examined the influence of different tDCS paradigms on long term potentiation (LTP)-like plasticity in humans, focusing on stimulation duration, repetition frequency and sequential combinations of changing polarities as the underlying characteristics.MethodsAmplitude changes of motor evoked potentials (MEP) were measured in response to paired associative stimulation (PAS) 6 h after application of different tDCS protocols. In total, 36 healthy participants completed the study, randomised into three groups with different stimulation protocols (N = 12 each).ResultstDCS was able to display lasting modulatory effects on the inducibility of LTP-like plasticity in the human motor cortex 6 h after stimulation. TDCS with the anode on primary motor cortex significantly increased MEP amplitudes following PAS induction. Further analyses highlighted single stimulation block duration to be of higher importance than repetitive protocols for efficacy of effects.ConclusionstDCS is capable of inducing lasting changes in the brain’s capability to interact with future stimuli. Especially, effects on the inducibility of LTP-like plasticity might only be detectable with specific tests such as PAS and might otherwise be overlooked. Refined tDCS protocols should focus on higher current and duration of single stimulations instead of implementing complex repetitive schedules.

Introduction. Paired associative stimulation (PAS) is an established technique to investigate synaptic plasticity in the human motor cortex (M1). Classically, to induce long-term depression- (LTD-) or long-term potentiation-like effects in the human M1, studies have used low frequency and long duration trains of PAS. In the present study, we explored an LTD-like effect using very short duration and low frequency of PAS10 ms protocols in human M1. Methods. Six protocols of low frequency PAS10 ms (ranging from 0.2 Hz to 1 Hz) were investigated with very short durations of 1 and 2 minutes stimulation. Six healthy volunteers were included in each protocol. We obtained motor-evoked potentials from right abductor pollicis brevis muscle before and after applying PAS10 ms up to 30 minutes. After we found PAS10 ms protocol which induced an LTD-like effect, we tested that protocol on additional 5 subjects. Results. One-way repeated-measures ANOVA showed that only the group of 1-minute stimulation of 0.25 Hz induced an LTD-like effect. When adding the additional subjects, the effect remained and lasted for 30 minutes. Conclusion. Low frequency and very short duration of PAS10 ms potentially induced an LTD-like effect in human M1. With further verification, this method might be useful for research relating to synaptic plasticity by reducing the duration of study and minimizing subject discomfort.

Oscillatory brain activity coordinates the response of cortical neurons to synaptic inputs in a phase-dependent manner. Larger motor-evoked responses are obtained in a hand muscle when transcranial magnetic stimulation (TMS) is synchronized to the phase of the sensorimotor μ-rhythm. In this study we further showed that TMS applied at the negative vs. positive peak of the μ-rhythm is associated with higher absolute amplitude of the evoked EEG potential at 100ms after stimulation. This demonstrates that cortical responses are sensitive to excitability fluctuation with brain oscillations Our results indicate that brain state-dependent stimulation is a new useful technique for the investigation of stimulus-related cortical dynamics. Oscillatory brain activity coordinates the response of cortical neurons to synaptic inputs in a phase-dependent manner. Transcranial magnetic stimulation (TMS) of the human primary motor cortex elicits larger motor-evoked potentials (MEPs) when applied at the negative vs. positive peak of the sensorimotor μ-rhythm recorded with EEG, demonstrating that this phase represents a state of higher excitability of the cortico-spinal system. Here, we investigated the influence of the phase of the μ-rhythm on cortical responses to TMS as measured by EEG. We tested different stimulation intensities above and below resting motor threshold (RMT), and a realistic sham TMS condition. TMS at 110% RMT applied at the negative vs. positive peak of the μ-rhythm was associated with higher absolute amplitudes of TMS-evoked potentials at 70ms (P70) and 100ms (N100). Enhancement of the N100 was confirmed with negative peak-triggered 90% RMT TMS, while phase of the μ-rhythm did not influence evoked responses elicited by sham TMS. These findings extend the idea that TMS applied at the negative vs. positive peak of the endogenous μ-oscillation recruits a larger portion of neurons as a function of stimulation intensity. This further corroborates that brain oscillations determine fluctuations in cortical excitability and establishes phase-triggered EEG-TMS as a sensitive tool to investigate the effects of brain oscillations on stimulus-related cortical dynamics.

The environment often engages multiple sensory channels simultaneously. When events or objects stimulate more than one sensory organ, they are more likely to be detected and more efficiently processed than events stimulating just one sensory modality (e.g. Stein & Stanford, 2008). Such crossmodal enhancement requires that the sensory inputs arising from one event are correctly assigned to that object (termed the ‘correspondence problem’; Ernst & Bulthoff, 2004). Multisensory research has demonstrated that features that are shared by all sensory systems, such as space, time or meaning are used for crossmodal binding (for recent reviews see Driver & Noesselt, 2008; Stein & Stanford, 2008). For example, in a cocktail party setting, matching of the temporal dynamics of lip movements and of speech sound allows us to assign the correct message to each speaker. Furthermore, this ability of crossmodal binding assists in orienting spatial attention to a particular conversation partner while ignoring other sources of distracting sensory information, such as other peoples’ conversations. The binding of synchronous auditory and visual (speech) signals seems to happen automatically and pre-attentively (see Driver, 1996; Bertelson et al., 2000; Vroomen et al., 2001a). The voluntary orienting of spatial attention to one particular speaker or, more generally, to an event is an example of endogenous attention allocation. By contrast, stimulus-driven orienting of spatial attention, elicited by the saliency of the stimulus, has been termed exogenous attention. Due to their relatively high salience, such pre-attentively detected, congruent cross-modal stimuli may function as exogenous attentional cues (Spence & Driver, 2000; Stekelenburg et al., 2004; Senkowski et al., 2008). In this issue, Fairhall & Macaluso (2009) provide evidence for the operation of both mechanisms: (i) pre-attentively crossmodal matching and (ii) enhancement of crossmodal interaction by endogenous attention. The authors presented the lips of two speaking faces, one in the left and one in the right visual hemifield. The centrally presented auditory stream was matched with the lip movements of one speaker only. In such a situation people generally perceive the auditory speech signal as originating from the location of the matching lips. This phenomenon is well known as the ‘ventriloquist effect’. Critically, Fairhall and Macaluso also asked participants to perform a visual detection task in one hemifield only. This task served to systematically manipulate the focus of visual spatial attention. The auditory stream did not have any significance to the participants and thus could be ignored. This paradigm allowed the authors to compare brain responses as assessed with functional magnetic resonance imaging (fMRI) to multisensory, matching audio-visual speech sequences that occurred either at the location of visual spatial attention (‘congruent condition’) or on the opposite side (‘incongruent condition’) while keeping physical stimulation constant. The authors report that visual attention enhances activity in brain regions well accepted as multisensory integration areas (Driver & Noesselt, 2008), such as the superior temporal sulcus (STS) and the superior colliculus (SC), only when the auditory track matched the attended lip movements. Similar effects were observed in several visual brain regions, including the primary visual cortex. These results suggest that the processing of congruent cross-modal stimuli within the locus of endogenous visual spatial attention is enhanced. Furthermore, the data of Fairhall & Macaluso are compatible with the view that binding of audio-visual speech can occur pre-attentively. When audio-visual matching speech was presented on the opposite side of the locus of visual-spatial attention (incongruent condition), participants performed worse in the visual detection task than when matching stimuli were presented on the same side as the focus of participant’s endogenous visual spatial attention (congruent condition). These behavioural results, together with findings from earlier studies (Spence & Driver, 2000; Vroomen et al., 2001b), suggest that the audio-visual binding process that elicited a ventriloquist illusion towards the opposite side of the visual attention focus took place outside the locus of endogenous attention and resulted in an exogenously attentional shift towards the task irrelevant side, which in turn interfered with the visual detection task. In summary, the results described by Fairhall and Macaluso suggest that endogenous (visual) spatial attention amplifies the processing of congruent cross-modal input that is likely integrated and detected pre-attentively. Fairhall and Macaluso did not attempt to link the enhanced activity in multisensory and early visual cortical regions to behavioural data such as, for example, improved speech comprehension. The question of whether activity changes in multisensory regions due to endogenous spatial attention are accompanied by altered multisensory performance (Alsius et al., 2005) remains to be investigated in future work. Moreover, other top-down influences on multisensory integration such as plausibility and meaning (Kitagawa & Spence, 2005; Hein et al., 2007) will need to be investigated in more detail to extend our understanding of the conditions when and which multisensory binding processes are subject to voluntary modulation. European Journal of Neuroscience, Vol. 29, pp. 1245–1246, 2009 doi:10.1111/j.1460-9568.2009.06715.x

T124. Effect of subthreshold paired associative stimulation during voluntary contraction on different forms of motor learning

Animal studies have shown that cerebellar projections influence both excitatory and inhibitory neurones in the motor cortex but this connectivity has yet to be demonstrated in human subjects. In human subjects, magnetic or electrical stimulation of the cerebellum 5-7 ms before transcranial magnetic stimulation (TMS) of the motor cortex decreases the TMS-induced motor-evoked potential (MEP), indicating a cerebellar inhibition of the motor cortex (CBI). TMS also reveals inhibitory and excitatory circuits of the motor cortex, including a short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). This study used magnetic cerebellar stimulation to investigate connections between the cerebellum and these cortical circuits. Three experiments were performed on 11 subjects. The first experiment showed that with increasing test stimulus intensities, LICI, CBI and ICF decreased, while SICI increased. The second experiment showed that the presence of CBI reduced SICI and increased ICF. The third experiment showed that the interaction between CBI and LICI reduced CBI. Collectively, these findings suggest that cerebellar stimulation results in changes to both inhibitory and excitatory neurones in the human motor cortex.