Induction Of Cortical Plasticity Research Articles

Alpha Oscillatory Activity Causally Linked to Working Memory Retention: Insights From Online Phase-Locking Closed-Loop Transcranial Alternating Current Stimulation

Responses to plasticity-inducing brain stimulation protocols are highly variable. However, no data are available concerning the variability of responses to quadripulse stimulation (QPS).We assessed the QPS parameters of motor cortical plasticity induction in a systematic manner, and later investigated the variability of QPS using optimal parameters.First, two different interburst intervals (IBI) with the same total number of pulses were compared. Next we investigated three different IBIs with a different total number of pulses but with same duration of intervention. We also compared the after-effects of monophasic and biphasic QPS. Finally, variability of QPS was tested in 35 healthy subjects. Twenty motor evoked potentials (MEPs) were measured every 5–10 min for up to one hour after intervention.QPS at an IBI of 5 s produced MEPs changes that are dependent on the interstimulus interval of the four magnetic pulses, consistent with previous reports. Unexpectedly, QPS at an IBI of 2.5 s did not induce any plasticity, even with the same total number of pulses, that is, 1440. QPS at an IBI of 7.5 s produced a variable response but was likely to be comparable to conventional QPS. Biphasic QPS had shorter lasting after-effects compared with monophasic QPS. Finally, the after-effects of QPS were relatively consistent across subjects: more than 80% of subjects responded as expected in the excitatory QPS at an IBI of 5 s.The IBI, total duration of the procedure and pulse waveform strongly affected the magnitude or duration of the plasticity induced by QPS. In this cohort, 80% of subjects responded to excitatory QPS as expected.

Direct comparison of efficacy of the motor cortical plasticity induction and the interindividual variability between TBS and QPS

BackgroundTheta burst stimulation (TBS) and quadripulse stimulation (QPS) are known to induce synaptic plasticity in humans. There have been no head-to-head comparisons of the efficacy and variability between TBS and QPS. ObjectiveTo compare the efficacy and interindividual variability between the original TBS and QPS protocols. We hypothesized that QPS would be more effective and less variable than TBS. MethodsForty-six healthy subjects participated in this study. Thirty subjects participated in the main comparison experiment, and the other sixteen subjects participated in the experiment to obtain natural variation in motor-evoked potentials. The facilitatory effects were compared between intermittent TBS (iTBS) and QPS5, and the inhibitory effects were compared between continuous TBS (cTBS) and QPS50. The motor-evoked potential amplitudes elicited by transcranial magnetic stimulation over the primary motor cortex were measured before the intervention and every 5 min after the intervention for 1 h. To investigate the interindividual variability, the responder/nonresponder/opposite-responder rates were also analyzed. ResultsThe facilitatory effects of QPS5 were greater than those of iTBS, and the inhibitory effects of QPS50 were much stronger than those of cTBS. The responder rate of QPS was significantly higher than that of TBS. QPS had a smaller number of opposite responders than TBS. ConclusionQPS is more effective and stable for synaptic plasticity induction than TBS.

Impaired motor cortical plasticity associated with cannabis use disorder in young adults.

Maladaptive cortical plasticity has been described in individuals with heroin and methamphetamine addiction and may mediate other substance abuse disorders. It is unknown whether cannabis dependence in humans alters the capacity for induction of cortical plasticity. The aim of this study was to non-invasively investigate cortical plasticity with transcranial magnetic stimulation in young adults who meet DSM-5 criteria for cannabis use disorder (CUD). Thirty men (ages 20- 30) who used cannabis daily over the previous 6 months (15 diagnosed of CUD) and 15 demographically matched non-users were enrolled in this study. All participants underwent two sessions of theta burst stimulation (TBS) in which either continuous TBS (cTBS; 600 pulses, 80% active motor threshold) or intermittent TBS (iTBS; 2-s train of cTBS repeated every 10 s for a total of 190 s, 600 pulses) was applied over the primary motor cortex. The effects of these protocols were assessed by analysing the contralateral motor evoked potentials (MEPs). The relationships between cortical plasticity and problematic cannabis use, degree of dependence, and nicotine addiction were also investigated. Significant MEP inhibition after cTBS was observed in both cannabis users without CUD and non-users, while this inhibition was not seen in cannabis users with CUD. Strikingly, less motor cortical plasticity was observed in subjects with severe problematic cannabis use. No significant differences between users and non-users were found in the iTBS-induced cortical plasticity measures. Our study provides the first evidence of maladaptive cortical plasticity associated with cannabis use disorder and problematic cannabis use in humans.

Modified ischaemic nerve block of the forearm: use for the induction of cortical plasticity in distal hand muscles.

Ischaemic nerve block (INB) of the forearm rapidly reduces somatosensory input to a part of the body, which leads to the functional reorganization of the temporarily deafferented primary motor cortex (M1). We applied a novel modified INB (mINB) to the forearm, maintaining mean blood pressure, to assess cortical plasticity in the primary somatosensory cortex (S1) and the M1 regions associated with small hand muscles. S1 excitability was measured by median nerve somatosensory-evoked potentials (SEPs), while M1 excitability was evaluated by motor-evoked potentials (MEPS), using transcranial magnetic stimulation. The finding that S1 excitability increased and M1 excitability decreased after the mINB was removed reflects the differential short-term cortical plasticity of the S1 and M1 regions. These opposite effects observed for the S1 and M1 regions following the mINB may indicate a possible intra-hemispheric interaction between the S1 and M1 regions. Ischaemic nerve block (INB) causes short-term sensory deprivation, leading to functional reorganization in the deafferented motor cortex (M1). We used a modified INB (mINB) to evaluate cortical plasticity in the somatosensory cortex (S1) and M1 region associated with small hand muscles, because INB strongly inhibits muscles distal to the tourniquet. Thirty-three healthy adults participated in different combinations of four experiments. A pneumatic tourniquet was placed just below the right elbow and inflated to induce a mINB. We recorded the median nerve somatosensory- and motor-evoked potentials (SEPs and MEPs) before, during and after mINB placement and assessed spinal cord excitability using F-wave measurements. SEPs at Erb's point (N9) were abolished during the mINB; those at cortical N20 were suppressed. After removing the mINB, N20 amplitudes increased significantly, while those at N9 did not fully recover. P14 amplitudes after tourniquet deflation immediately recovered to baseline levels. M1-MEP amplitudes decreased during the mINB, and Erb-MEPs were suppressed. After the mINB was removed, M1-MEPs remained suppressed, while Erb-MEPs fully recovered. F-waves were not affected by the intervention. Therefore, sensory, but not motor, nerve function was affected by the mINB. S1 excitability was enhanced after the mINB was removed, indicating that S1 and M1 excitability were modulated in opposing directions after deflation. These after-effects may reflect isolated effects or interactions between the S1 and M1 regions. Our findings may facilitate improved understanding of the sensorimotor modulations that occur distal to the tourniquet due to temporal deafferentation and lead to development of novel neuromodulation protocols.

Involvement of different neuronal components in the induction of cortical plasticity with associative stimulation

BackgroundPaired associative stimulation (PAS), with stimulus interval of 21.5 or 25 ms, using transcranial magnetic stimulation in the posterior-anterior (PA) current direction, produces a long-term-potentiation-like effect. Stimulation with PA directed current generates both early and late indirect (I)-waves while that in anterior-posterior (AP) current predominantly elicits late I-waves. Short interval intracortical inhibition (SICI) inhibits late I-waves but not early I-waves. ObjectiveTo investigate how cortical inhibition modulates the effects of PAS. MethodsPAS at stimulus interval of 21.5 ms conditioned by SICI (SICI-PAS) was compared to PAS alone with both PA and AP directed currents. ResultsPAS with both current directions increased cortical excitability. SICI-PAS increased cortical excitability in the PA but not the AP current direction. ConclusionsBoth early and late I-waves circuits can mediate cortical PAS plasticity under different conditions. Plasticity induction with the late but not the early I-wave circuits is blocked by SICI.

Age‐related changes in late I‐waves influence motor cortex plasticity induction in older adults

The response to neuroplasticity interventions using transcranial magnetic stimulation (TMS) is reduced in older adults, which may be due, in part, to age-related alterations in interneuronal (I-wave) circuitry. The current study investigated age-related changes in interneuronal characteristics and whether they influence motor cortical plasticity in older adults. While I-wave recruitment was unaffected by age, there was a shift in the temporal characteristics of the late, but not the early I-waves. Using I-wave periodicity repetitive TMS (iTMS), we showed that these differences in I-wave characteristics influence the induction of cortical plasticity in older adults. Previous research shows that neuroplasticity assessed using transcranial magnetic stimulation (TMS) is reduced in older adults. While this deficit is often assumed to represent altered synaptic modification processes, age-related changes in the interneuronal circuits activated by TMS may also contribute. Here we assessed age-related differences in the characteristics of the corticospinal indirect (I) waves and how they influence plasticity induction in primary motor cortex. Twenty young (23.7±3.4years) and 19 older adults (70.6±6.0years) participated in these studies. I-wave recruitment was assessed by changing the direction of the current used to activate the motor cortex, whereas short-interval intracortical facilitation (SICF) was recorded to assess facilitatory I-wave interactions. In a separate study, I-wave periodicity TMS (iTMS) was used to examine the effect of I-wave latency on motor cortex plasticity. Data from the motor-evoked potential (MEP) onset latency produced using different coil orientations suggested that there were no age-related differences in preferential I-wave recruitment (P=0.6). However, older adults demonstrated significant reductions in MEP facilitation at all 3 SICF peaks (all P values<0.05) and a delayed latency of the second and third SICF peaks (all P values<0.05). Using I-wave intervals that were optimal for young and older adults, these changes in the late I-waves were shown to influence the plasticity response in older adults after iTMS. These findings suggest that temporal characteristics are delayed for the late I-waves in older adults, and that optimising TMS interventions based on I-wave characteristics may improve the plasticity response in older adults.

Induction of cortical plasticity reveals the mechanism of the phantom limb pain and develops novel treatment

Induction of cortical plasticity reveals the mechanism of the phantom limb pain and develops novel treatment

Neurochemical changes underpinning the development of adjunct therapies in recovery after stroke: A role for GABA?

Stroke is a leading cause of long-term disability, with around three-quarters of stroke survivors experiencing motor problems. Intensive physiotherapy is currently the most effective treatment for post-stroke motor deficits, but much recent research has been targeted at increasing the effects of the intervention by pairing it with a wide variety of adjunct therapies, all of which aim to increase cortical plasticity, and thereby hope to maximize functional outcome. Here, we review the literature describing neurochemical changes underlying plasticity induction following stroke. We discuss methods of assessing neurochemicals in humans, and how these measurements change post-stroke. Motor learning in healthy individuals has been suggested as a model for stroke plasticity, and we discuss the support for this model, and what evidence it provides for neurochemical changes. One converging hypothesis from animal, healthy and stroke studies is the importance of the regulation of the inhibitory neurotransmitter GABA for the induction of cortical plasticity. We discuss the evidence supporting this hypothesis, before finally summarizing the literature surrounding the use of adjunct therapies such as non-invasive brain stimulation and SSRIs in post-stroke motor recovery, both of which have been show to influence the GABAergic system.

The effect of type of afferent feedback timed with motor imagery on the induction of cortical plasticity

A peripherally generated afferent volley that arrives at the peak negative (PN) phase during the movement related cortical potential (MRCP) induces significant plasticity at the cortical level in healthy individuals and chronic stroke patients. Transferring this type of associative brain-computer interface (BCI) intervention into the clinical setting requires that the proprioceptive input is comparable to the techniques implemented during the rehabilitation process. These consist mainly of functional electrical stimulation (FES) and passive movement induced by an actuated orthosis. In this study, we compared these two interventions (BCIFES and BCIpassive) where the afferent input was timed to arrive at the motor cortex during the PN of the MRCP.Twelve healthy participants attended two experimental sessions. They were asked to perform 30 dorsiflexion movements timed to a cue while continuous electroencephalographic (EEG) data were collected from FP1, Fz, FC1, FC2, C3, Cz, C4, CP1, CP2, and Pz, according to the standard international 10-20 system. MRCPs were extracted and the PN time calculated. Next, participants were asked to imagine the same movement 30 times while either FES (frequency: 20Hz, intensity: 8–35mAmp) or a passive ankle movement (amplitude and velocity matched to a normal gait cycle) was applied such that the first afferent inflow would coincide with the PN of the MRCP. The change in the output of the primary motor cortex (M1) was quantified by applying single transcranial magnetic stimuli to the area of M1 controlling the tibialis anterior (TA) muscle and measuring the motor evoked potential (MEP). Spinal changes were assessed pre and post by eliciting the TA stretch reflex.Both BCIFES and BCIpassive led to significant increases in the excitability of the cortical projections to TA (F(2,22)=4.44, p=0.024) without any concomitant changes at the spinal level. These effects were still present 30min after the cessation of both interventions. There was no significant main effect of intervention, F(1,11)=0.38, p=0.550, indicating that the changes in MEP occurred independently of the type of afferent inflow.An afferent volley generated from a passive movement or an electrical stimulus arrives at the somatosensory cortex at similar times. It is thus likely that the similar effects observed here are strictly due to the tight coupling in time between the afferent inflow and the PN of the MRCP. This provides further support to the associative nature of the proposed BCI system.

Artificial induction of cortical plasticity by high frequency cortical stimulation permits to increase resection of brain tumors located in Eloquent areas

Artificial induction of cortical plasticity by high frequency cortical stimulation permits to increase resection of brain tumors located in Eloquent areas

The effects of repetitive transcranial magnetic stimulation in an animal model of tinnitus.

Tinnitus (phantom auditory perception associated with hearing loss) can seriously affect wellbeing. Its neural substrate is unknown however it has been linked with abnormal activity in auditory pathways. Though no cure currently exists, repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce tinnitus in some patients, possibly via induction of cortical plasticity involving brain derived neurotrophic factor (BDNF). We examined whether low intensity rTMS (LI-rTMS) alleviates signs of tinnitus in a guinea pig model and whether this involves changes in BDNF expression and hyperactivity in inferior colliculus. Acoustic trauma was used to evoke hearing loss, central hyperactivity and tinnitus. When animals developed tinnitus, treatment commenced (10 sessions of 10 minutes 1 Hz LI-rTMS or sham over auditory cortex over 14 days). After treatment ceased animals were tested for tinnitus, underwent single-neuron recordings in inferior colliculus to assess hyperactivity and samples from cortex and inferior colliculus were taken for BDNF ELISA. Analysis revealed a significant reduction of tinnitus after LI-rTMS compared to sham, without a statistical significant effect on BDNF levels or hyperactivity. This suggests that LI-rTMS alleviates behavioural signs of tinnitus by a mechanism independent of inferior colliculus hyperactivity and BDNF levels and opens novel therapeutic avenues for tinnitus treatment.

Variability in Response to Quadripulse Stimulation of the Motor Cortex.

Responses to plasticity-inducing brain stimulation protocols are highly variable. However, no data are available concerning the variability of responses to quadripulse stimulation (QPS). We assessed the QPS parameters of motor cortical plasticity induction in a systematic manner, and later investigated the variability of QPS using optimal parameters. First, two different interburst intervals (IBI) with the same total number of pulses were compared. Next we investigated three different IBIs with a different total number of pulses but with same duration of intervention. We also compared the after-effects of monophasic and biphasic QPS. Finally, variability of QPS was tested in 35 healthy subjects. Twenty motor evoked potentials (MEPs) were measured every 5-10 min for up to one hour after intervention. QPS at an IBI of 5 s produced MEPs changes that are dependent on the interstimulus interval of the four magnetic pulses, consistent with previous reports. Unexpectedly, QPS at an IBI of 2.5 s did not induce any plasticity, even with the same total number of pulses, that is, 1440. QPS at an IBI of 7.5 s produced a variable response but was likely to be comparable to conventional QPS. Biphasic QPS had shorter lasting after-effects compared with monophasic QPS. Finally, the after-effects of QPS were relatively consistent across subjects: more than 80% of subjects responded as expected in the excitatory QPS at an IBI of 5 s. The IBI, total duration of the procedure and pulse waveform strongly affected the magnitude or duration of the plasticity induced by QPS. In this cohort, 80% of subjects responded to excitatory QPS as expected.

Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease.

We introduced a new experimental paradigm to test the hypothesis that pairing subthalamic nucleus deep-brain stimulation (STN-DBS) with motor cortical transcranial magnetic stimulation (M1-TMS) at specific times can induce cortical plasticity in patients with Parkinson's disease (PD). We found that repeated pairing of STN-DBS with TMS at short (∼ 3 ms) and medium (∼ 23 ms) intervals increased cortical excitability that lasted for up to 45 min, whereas the control condition (fixed latency of 167 ms) had no effects on cortical excitability. This is the first demonstration of associative plasticity in the STN-M1 circuits in PD patients using this novel technique. The potential therapeutic effects of combining DBS and noninvasive cortical stimulation should be investigated further.

Induction of cortical plasticity for reciprocal muscles by paired associative stimulation.

BackgroundPaired associative stimulation (PAS) is widely used to induce plasticity in the human motor cortex. Although reciprocal inhibition of antagonist muscles plays a fundamental role in human movements, change in cortical circuits for reciprocal muscles by PAS is unknown.MethodsWe investigated change in cortical plasticity for reciprocal muscles during PAS. PAS consisted of 200 pairs of peripheral electric stimulation of the right median nerve at the wrist at a frequency of 0.25 Hz followed by transcranial magnetic stimulation of the left M1 at the midpoint between the center of gravities of the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles. Measures of motor cortical excitability included resting motor threshold (RMT), GABAA-mediated short-interval intracortical inhibition (SICI), and GABAB-mediated long-interval intracortical inhibition (LICI).ResultsMotor evoked potential amplitude-conditioned LICI for the FCR muscle was significantly decreased after PAS (P = 0.020), whereas that for the ECR muscle was significantly increased (P = 0.033). Changes in RMT and SICI for the FCR and ECR muscles were not significantly different before and after PAS. Corticospinal excitability for both reciprocal muscles was increased during PAS, but GABAB-mediated cortical inhibitory functions for the agonist and antagonist muscles were reciprocally altered after PAS.ConclusionThese results implied that the cortical excitability for reciprocal muscles including GABAB-ergic inhibitory systems within human M1 could be differently altered by PAS.

Wakefulness delta waves increase after cortical plasticity induction

ObjectiveDelta waves (DW) are present both during sleep and in wakefulness. In the first case, DW are considered effectors of synaptic plasticity, while in wakefulness, when they appear in the case of brain lesions, their functional meaning is not unanimously recognized. To throw light on the latter, we aimed to investigate the impact on DW exerted by the cortical plasticity-inducing protocol of intermittent theta burst stimulation (iTBS). MethodsTwenty healthy subjects underwent iTBS (11 real iTBS and nine sham iTBS) on the left primary motor cortex with the aim of inducing long-term potentiation (LTP)-like phenomena. Five-minute resting open-eye 32-channel EEG, right opponens pollicis motor-evoked potentials (MEPs), and alertness behavioral scales were collected before and up to 30min after the iTBS. Power spectral density (PSD), interhemispheric coherence between homologous sensorimotor regions, and intrahemispheric coherence were calculated for the frequency bands ranging from delta to beta. ResultsReal iTBS induced a significant increase of both MEP amplitude and DW PSD lasting up to 30min after stimulation, while sham iTBS did not. The DW increase was evident over frontal areas ipsilateral and close to the stimulated cortex (electrode F3). Neither real nor sham iTBS induced significant modifications in the PSD of theta, alpha, and beta bands and in the interhemispheric coherence. Behavioral visuo-analogic scales score did not demonstrate changes in alertness after stimulations. No correlations were found between MEP amplitude and PSD changes in the delta band. ConclusionsOur data showed that LTP induction in the motor cortex during wakefulness, by means of iTBS, is accompanied by a large and enduring increase of DW over the ipsilateral frontal cortex. SignificanceThe present results are strongly in favor of a prominent role of DW in the neural plasticity processes taking place during the awake state.

P679: Wakefulness delta waves increase after cortical plasticity induction

P679: Wakefulness delta waves increase after cortical plasticity induction

Electrical stimulation during skill training with a therapeutic glove enhances the induction of cortical plasticity and has a positive effect on motor memory

To examine whether afferent stimulation of hand muscles has a facilitating effect on motor performance, learning and cortical excitability, healthy subjects were trained on the grooved pegboard test (GTP) while wearing a mesh glove (MG) with incorporated electrical stimulation. Three study groups (n=12) were compared in a between subjects design, the bare handed (BH), gloved (MG) and gloved with electrical stimulation (MGS) groups. Motor performance was assessed by the GPT completion time across 4 training blocks, and further one block was retested 7 days later to determine the off-line effects. On-line learning was obtained by normalizing the completion time values to the first training block, and off-line learning was obtained by normalizing the retest values to the last training block. Cortical excitability was assessed via single and paired-pulse transcranial magnetic stimulation (TMS) at pre-training, post-training and 30min post-training. Motor evoked potential recruitment curve, short-latency intracortical inhibition and intracortical facilitation were estimated from the TMS assessments. Motor performance across all 4 training blocks was poor in the MG and MGS groups, while on-line learning was not affected by wearing the glove or by afferent stimulation. However, off-line learning, tested 7 days after training, was improved in the MGS group compared to the MG group. In addition, post-training corticospinal excitability was increased in the MGS group. It can be concluded that afferent stimulation improves off-line learning and thus has a positive effect on motor memory, likely due to LTP-like cortical plasticity in the consolidation phase.

20. Wakefulness delta waves increase after cortical plasticity induction

Delta waves (Dw) during sleep are considered effectors of synaptic plasticity. During wakefulness Dw appear when brain lesions occur, but their functional meaning is not unanimously recognized. We aimed at testing whether Dw change after inducing cortical plasticity by intermittent theta burst stimulation (iTBS). Thirteen healthy subjects underwent iTBS on left primary motor cortex to induce long term potentiation (LTP) like phenomena. Five-minutes resting opened-eyes 32-channels EEG, right opponens pollicis motor evoked potentials (MEP) and alertness behavioural scales were collected before and up to 30 min after iTBS. Power spectral density (PSD) from delta to beta frequency bands of bilateral sensorimotor areas was calculated. iTBS induced a significant increase of both MEP amplitude and bilateral Dw (+87.5%) lasting up to 30 min after stimulation. No changes on behavioural scales were found. Our data showed that motor LTP induction during wakefulness, by means of iTBS, is accompanied by a large and enduring increase of Dw over sensorimotor areas. Present results evidenced that Dw own a prominent role in neural plasticity processes in the awake state.

P 93. Induction of cortical plasticity by transcranial biphasic quadro-pulse stimulation

Long-term potentiation (LTP) and long-term depression (LTD) are forms of cortical plasticity and are considered to be synaptic processes underlying learning and memory. Transcranial magnetic stimulation (TMS) with monophasic quadro-pulses (QPS) demonstrated to be effective to induce LTD-and LTP-like plasticity in human motor cortex (M1). Here, we aimed to study whether biphasic QPS at different inter-stimulus-and inter-burst-intervals induces plastic changes in human M1. We investigated healthy volunteers ( n = 10 per protocol) with quadro-pulse stimulation (QPS) consisting of repeated bursts of four biphasic TMS pulses (duration: 160 μs) separated by inter-stimulus intervals of 1.5 ms and 50 ms and inter-burst intervals of 200 ms, 1 s and 5 s resulting in 6 different protocols (QPS 1.5−200 , QPS 1.5−1 , QPS 1.5−5 , QPS 50−200 , QPS 50−1 , QPS 50−5 ; 1440 total stimulus counts per protocol). TMS was applied by a custom-made magnetic stimulator (IMETUM, Munich). Resting motor threshold (rMT), and motor evoked potential (MEP) amplitudes with stimulus intensities to target amplitudes of 1mv and 0.4 mV (SI 1mV and SI 0.4mV ) were measured before (Pre) QPS directly after (Post1), after 15 min (Post2), after 30 min (Post3) and after 60 min (Post4). We found a significant increase of MEPs after QPS 1.5−5 at SI 0.4mV and a significant decrease after QPS 50−200 , QPS 50−5 and QPS 1.5−200 at SI 1 mV . QPS 1.5−1 and QPS 50−1 had no significant effect on MEPs, respectively. Significant changes in rMT, referring to a model of intrinsic plasticity, were observed for QPS 50−200 but not for QPS 50−5 . Biphasic QPS demonstrated to induce intensity and frequency dependent LTP-or LTD-like effects displayed by an increase or decrease in MEP amplitudes. This form of stimulation might offer new opportunities in investigations of cortical plasticity in humans.

P 15. Delta waves increase after cortical plasticity induction during wakefulness

Objective Delta waves are the most prominent electroencephalographic (EEG) feature of non-rapid eye movement sleep with cortical origin. Several human studies suggested they are sensor of synaptic weight and possible effectors of sleep-dependent synaptic plasticity. During wakefulness delta waves are almost absent in physiological conditions, but they come out when a subcortical brain lesion occurs. For these reasons delta waves during wakefulness are considered as a lesional sign but no definitive data about its functional significance were provided. Our aim was to verify whether delta waves can be a sign of plastic cortical modifications. Materials and methods 11 young healthy subjects (28 ± 3) were enrolled in the study. Intermittent theta burst stimulation (iTBS) was administered on left primary motor cortex to induce enduring cortical motor plasticity. High density scalp EEG (32 channels) was recorded all along the experiment. PSD for standard frequency bands (delta 1–3.5 Hz, theta 4–7.5 Hz, alpha 8–12 Hz, beta 13–22 Hz) was calculated in each longitudinal bipolar derivation. 5-min resting opened-eyes EEG was analyzed pre-iTBS (T0) and immediately after iTBS (T1), after 15 (T2) and 30 (T3) min. MEP amplitude and visual analogic scales about sleepiness, alertness, and the Stanford Sleepiness Scale were analyzed at the same time-points to explore motor plasticity induction and alertness status. Results iTBS induced a 9%-increase of MEP amplitude which remained stable until 30 min after stimulation (T1vsT0 p = 0.005; T2vsT1 p = 0.560; T3vsT2 p = 0.158). A selective increase (+87.5%) in delta band PSD was evident at T1 vs T0, remaining stable all along the experiment (T1vsT0 p = 0.019, T2vsT1 p = 0.724, T3vsT2 p = 1). Significant changes were bilaterally present only in fronto-central derivations ( p Discussion Our experiment firstly demonstrated a large and enduring increase in EEG delta activity in cortical areas undergoing plasticity induction during wakefulness. Present results may open new scenarios in interpreting scalp EEG slow waves after brain lesions not only as sign of lesion but also as sign of neuronal plastic rearrangement not with a negative value.