Long-term Potentiation-like Plasticity Research Articles

Age-related differences in long-term potentiation-like plasticity and short-latency afferent inhibition and their association with cognitive function

BackgroundThe neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.AimsTo reveal the differences in long-term potentiation (LTP)-like plasticity...

Effects of a periodic intermittent theta burst stimulation in Alzheimer’s disease

BackgroundPrevious studies have demonstrated that excitatory repetitive transcranial magnetic stimulation (rTMS) can improve the cognitive function of patients with Alzheimer’s disease (AD). Intermittent theta burst stimulation (iTBS) is a novel...

A comparative transcranial magnetic stimulation study: Assessing cortical excitability and plasticity in Alzheimer's disease, dementia with Lewy bodies and Frontotemporal dementia.

Here, we aimed to investigate the roles of long-term potentiation-like (LTP-like) plasticity using intermittent theta burst (iTBS) protocol and resting motor threshold (rMT) in the differential diagnosis of Alzheimer's disease (AD), diffuse dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We enrolled 21 subjects with AD, 28 subjects with DLB, 14 subjects with FTD, and 33 elderly subjects with normal cognitive functions into the study. We recorded rMT and percentage amplitude change of motor evoked potentials (MEPs) after the iTBS protocol in each group. In patients with AD and DLB, the percentage amplitude change of MEPs, and rMTs were significantly lower than in healthy subjects. However, no significant difference was observed in individuals with FTD. Our findings showed that transcranial magnetic stimulation measures, particularly rMTs and LTP-like plasticity, may be potential biomarkers to distinguish between different dementia subtypes. Impaired motor cortical excitability and synaptic plasticity were more prominent in AD and DLB than in FTD. This aligns with the evidence that cortical motor networks are usually spared in FTDs in early-to-middle stages.

Preventive exercise and physical rehabilitation promote long-term potentiation-like plasticity expression in patients with multiple sclerosis.

Loss of long-term potentiation (LTP) expression has been associated with a worse disease course in relapsing-remitting multiple sclerosis (RR-MS) and represents a pathophysiological hallmark of progressive multiple sclerosis (PMS). Exercise and physical rehabilitation are the most prominent therapeutic approaches to promote synaptic plasticity. We aimed to explore whether physical exercise is able to improve the expression of LTP-like plasticity in patients with multiple sclerosis (MS). In 46 newly diagnosed RR-MS patients, we explored the impact of preventive exercise on LTP-like plasticity as assessed by intermittent theta-burst stimulation. Patients were divided into sedentary or active, based on physical activity performed during the 6 months prior to diagnosis. Furthermore, in 18 patients with PMS, we evaluated the impact of an 8-week inpatient neurorehabilitation program on clinical scores and LTP-like plasticity explored using paired associative stimulation (PAS). Synaptic plasticity expression was compared in patients and healthy subjects. Reduced LTP expression was found in RR-MS patients compared with controls. Exercising RR-MS patients showed a greater amount of LTP expression compared with sedentary patients. In PMS patients, LTP expression was reduced compared with controls and increased after 8 weeks of rehabilitation. In this group of patients, LTP magnitude at baseline predicted the improvement in hand dexterity. Both preventive exercise and physical rehabilitation may enhance the expression of LTP-like synaptic plasticity in MS, with potential beneficial effects on disability accumulation.

After-effects of repetitive transcranial magnetic stimulation with parameter dependence on long-term potentiation-like plasticity and object recognition memory in rats.

To investigate the after-effects of 25-Hz repetitive transcranial magnetic stimulation (rTMS) at 60, 100, and 120% resting motor threshold (rMT) on long-term potentiation (LTP) in the rat hippocampus, to clarify the intensity dependence of rTMS, and to determine whether it simultaneously affects learning and memory ability. Five rats were randomly selected from 70 male Wistar rats, and evoked rMT potentials were recorded in response to magnetic stimulation. The remaining 65 rats were randomly assigned to five groups (n = 13), including sham rTMS, 1 Hz 100% rMT, and 25 Hz rTMS groups with 3 subgroups of 60% rMT, 100% rMT, and 120% rMT. Five rats in each group were anesthetized and induced by a priming TMS-test design for population spike (PS) response of the perforant path-dentate gyrus in the hippocampus; the remaining eight rats in each group were evaluated for object recognition memory in the novel object recognition (NOR) task after the different rTMS protocols. Forty-five percent (approximately 1.03 T) of the magnetic stimulator output was confirmed as rMT in the biceps femoris muscle. The PS ratio was ranked as follows: 25 Hz 100% rMT (267.78 ± 25.71%) > sham rTMS (182 ± 9.4%) >1 Hz 100% rMT (102.69 ± 6.64%) > 25 Hz 120% rMT (98 ± 11.3%) > 25 Hz 60% rMT (36 ± 8.5%). Significant differences were observed between the groups, except for the difference between the 25 Hz 120% rMT and the 1 Hz 100% rMT groups (p = 0.446). LTP was successfully induced over the 60-min recording period only in the sham rTMS and 25 Hz 100% rMT groups. Moreover, these two groups spent more time exploring a novel object than a familiar object during the NOR task (p < 0.001), suggesting long-term recognition memory retention. In the between-group analysis of the discrimination index, the following ranking was observed: 25 Hz 100% rMT (0.812 ± 0.158) > sham rTMS (0.653 ± 0.111) > 25 Hz 120% rMT (0.583 ± 0.216) >1 Hz 100% rMT (0.581 ± 0.145) > 25 Hz 60% rMT (0.532 ± 0.220). The after-effect of 25-Hz rTMS was dependent on stimulus intensity and provided an inverted (V-shaped) bidirectional modulation on hippocampal plasticity that involved two forms of metaplasticity. Furthermore, the effects on the recognition memory ability were positively correlated with those on LTP induction in the hippocampus in vivo.

Cortical paired associative stimulation shows impaired plasticity of inhibition networks as a function of chronic alcohol use.

Response inhibition - or the ability to withhold a suboptimal response - relies on the efficacy of fronto-striatal networks, and is impaired in neuropsychiatric disorders including addiction. Cortical paired associative stimulation (cPAS) is a form of transcranial magnetic stimulation (TMS) which can strengthen neuronal connections via spike-timing-dependent plasticity mechanisms. Here, we used cPAS targeting the fronto-striatal inhibitory network to modulate performance on a response inhibition measure in chronic alcohol use. Fifty-five participants (20 patients with a formal alcohol use disorder (AUD) diagnosis (26-74 years, 6[30%] females) and 20 matched healthy controls (HCs) (27-73 years, 6[30%] females) within a larger sample of 35 HCs (23-84 years, 11[31.4%] females) underwent two randomized sessions of cPAS 1-week apart: right inferior frontal cortex stimulation preceding right presupplementary motor area stimulation by either 4 ms (excitation condition) or 100 ms (control condition), and were subsequently administered the Stop Signal Task (SST) in both sessions. HCs showed decreased stop signal reaction time in the excitation condition (t(19) = -3.01, p = 0.007, [CIs]:-35.6 to -6.42); this facilitatory effect was not observed for AUD (F(1,31) = 9.57, p = 0.004, CIs: -68.64 to -14.11). Individually, rates of SST improvement were substantially higher for healthy (72%) relative to AUD (13.6%) groups (OR: 2.33, p = 0.006, CIs:-3.34 to -0.55). In line with previous findings, cPAS improved response inhibition in healthy adults by strengthening the fronto-striatal network through putative long-term potentiation-like plasticity mechanisms. Furthermore, we identified a possible marker of impaired cortical excitability, and, thus, diminished capacity for cPAS-induced neuroplasticity in AUD with direct implications to a disorder-relevant cognitive process.

Long-term potentiation-like plasticity is retained during relapse in patients with Multiple Sclerosis

ObjectiveTo investigate the degree of synaptic plasticity in Multiple Sclerosis (MS) patients during acute relapses compared to stable MS patients and healthy controls (HCs) and to analyze its functional relevance. MethodsFacilitatory quadripulse stimulation (QPS) was applied to the primary motor cortex in 18 acute relapsing and 18 stable MS patients, as well as 18 HCs. The degree of synaptic plasticity was measured by the change in motor evoked potential amplitude following QPS. Symptom recovery was assessed three months after relapse. ResultsSynaptic plasticity was induced in all groups. The degree of induced plasticity did not differ between acute relapsing patients, HCs, and stable MS patients. Plasticity was significantly higher in relapsing patients with motor disability compared to relapsing patients without motor disability. In most patients (n = 9, 50%) symptoms had at least partially recovered three months after the relapse, impeding meaningful analysis of the functional relevance of baseline synaptic plasticity. ConclusionsQPS-induced synaptic plasticity is retained during acute MS relapses. Subgroup analyses suggest that stabilizing metaplastic mechanisms may be more important to prevent motor disability but its functional relevance needs to be verified in larger, longitudinal studies. SignificanceNew insights into synaptic plasticity during MS relapses are provided.

Baseline long-term potentiation-like cortical plasticity is associated with longitudinal cortical thinning in healthy adults and in adults with bipolar disorder type II.

The precise neurobiological processes underlying cerebral cortical thinning in aging and psychiatric illnesses remain undetermined, yet aging- and synaptic dysfunction-related loss of synapses are potentially important mechanisms. We used long-term potentiation-like plasticity of the visual evoked potential as an index of synaptic function in the cortex and hypothesized that plasticity at baseline would be negatively associated with future cortical thinning in healthy adults and in adults with bipolar disorder type II. Thirty-two healthy adults and 15 adults with bipolar disorder type II underwent electroencephalography-based measurement of visual evoked potential plasticity and 3T magnetic resonance imaging of the brain at baseline and a follow-up brain scan on average 2.3 years later. The relationships between visual evoked potential plasticity at baseline and longitudinal cortical thickness changes were examined using Freesurfer and the Permutation Analysis of Linear Models tool. The analyses showed a negative association between the plasticity of the N1 visual evoked potential amplitude at baseline and thinning rate in the medial and lateral parietal and medial occipital cortices in healthy adults and in the right medial occipital cortex in the total sample of healthy adults and adults with bipolar disorder type II, indicating greater thinning over time in subjects with less N1 plasticity (pFWER < .05). Although preliminary, the results indicate an association between visual evoked potential plasticity and the future rate of cortical thinning in healthy adults and in bipolar disorder type II, supporting the hypothesis that cortical thinning might be related to synaptic dysfunction.

Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer's disease-like pathology.

Intracerebroventricularly (icv) injected streptozotocin (STZ) is a widely used model for sporadic Alzheimer's disease (sAD)-like pathology, marked by oxidative stress-mediated pathological progression. Intermittent theta burst stimulation (iTBS) is a noninvasive technique for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for several neurological diseases, including AD. The present study aims to investigate the effect of the iTBS protocol on the animal model of STZ-induced sAD-like pathology in the context of antioxidant, anti-inflammatory, and anti-amyloidogenic effects in the cortex, striatum, hippocampus, and cerebellum. Male Wistar rats were divided into four experimental groups: control (icv normal saline solution), STZ (icv STZ-3 mg/kg), STZ + iTBS (STZ rats subjected to iTBS protocol), and STZ + Placebo (STZ animals subjected to placebo iTBS noise artifact). Biochemical assays and immunofluorescence microscopy were used to evaluate functional and structural changes. The icv STZ administration induces oxidative stress and attenuates antioxidative capacity in all examined brain regions. iTBS treatment significantly reduced oxidative and nitrosative stress parameters. Also, iTBS decreased Aβ-1-42 and APP levels. The iTBS enhances antioxidative capacity reported as elevated activity of its enzymatic and non-enzymatic components. In addition, iTBS elevated BDNF expression and attenuated STZ-induced astrogliosis confirmed by decreased GFAP+/VIM+/C3+ cell reactivity in the hippocampus. Our results provide experimental evidence for the beneficial effects of the applied iTBS protocol in attenuating oxidative stress, increasing antioxidant capacity and decreasing reactive astrogliosis in STZ-administrated rats.

Hippocampal-prefrontal long-term potentiation-like plasticity with transcranial direct current stimulation in rats

Transcranial direct current stimulation (tDCS) has been explored as a new treatment method for improving cognitive and motor functions. However, the neuronal mechanisms of tDCS in modulating brain functions, especially cognitive and memory functions, are not well understood. In the present study, we assessed whether tDCS could promote neuronal plasticity between the hippocampus and prefrontal cortex in rats. This is important because the hippocampus-prefrontal pathway is a key pathway in cognitive and memory functions and is involved in various psychiatric and neurodegenerative disorders. Specifically, the effect of anodal or cathodal tDCS on the medial prefrontal cortex was investigated in rats by measuring the medial prefrontal cortex response to electrical stimulation applied to the CA1 region of the hippocampus. Following anodal tDCS, the evoked prefrontal response was potentiated compared to that in the pre-tDCS condition. However, the evoked prefrontal response did not show any significant changes following cathodal tDCS. Furthermore, the plastic change of the prefrontal response following anodal tDCS was only induced when hippocampal stimulation was continuously applied during tDCS. Anodal tDCS without hippocampal activation showed little or no changes. These results indicate that combining anodal tDCS of the prefrontal cortex with hippocampal activation induces long-term potentiation (LTP)-like plasticity in the hippocampus-prefrontal pathway. This LTP-like plasticity can facilitate smooth information transmission between the hippocampus and the prefrontal cortex and may lead to improvements in cognitive and memory function.

Decreased Frontal Gamma Activity in Alzheimer Disease Patients.

ObjectiveIn Alzheimer disease (AD) animal models, synaptic dysfunction has recently been linked to a disorder of high‐frequency neuronal activity. In patients, a clear relation between AD and oscillatory activity remains elusive. Here, we attempt to shed light on this relation by using a novel approach combining transcranial magnetic stimulation and electroencephalography (TMS‐EEG) to probe oscillatory activity in specific hubs of the frontoparietal network in a sample of 60 mild‐to‐moderate AD patients.MethodsSixty mild‐to‐moderate AD patients and 21 age‐matched healthy volunteers (HVs) underwent 3 TMS‐EEG sessions to assess cortical oscillations over the left dorsolateral prefrontal cortex, the precuneus, and the left posterior parietal cortex. To investigate the relations between oscillatory activity, cortical plasticity, and cognitive decline, AD patients underwent a TMS‐based neurophysiological characterization and a cognitive evaluation at baseline. The latter was repeated after 24 weeks to monitor clinical evolution.ResultsAD patients showed a significant reduction of frontal gamma activity as compared to age‐matched HVs. In addition, AD patients with a more prominent decrease of frontal gamma activity showed a stronger impairment of long‐term potentiation–like plasticity and a more pronounced cognitive decline at subsequent follow‐up evaluation at 24 weeks.InterpretationOur data provide novel evidence that frontal lobe gamma activity is dampened in AD patients. The current results point to the TMS‐EEG approach as a promising technique to measure individual frontal gamma activity in patients with AD. This index could represent a useful biomarker to predict disease progression and to evaluate response to novel pharmacological therapies. ANN NEUROL 2022;92:464–475

Intermittent theta burst stimulation ameliorates cognitive impairment and hippocampal gliosis in the Streptozotocin-induced model of Alzheimer's disease

Intracerebroventricularly (icv) injected streptozotocin (STZ) model of Alzheimer's disease (AD) is used to explore the effect of intermittent theta burst stimulation (iTBS) on astrocyte and microglia reactivity in selectively vulnerable brain regions and answer the question whether these changes are in the context of cognitive capacity. The iTBS is a non-invasive approach for stimulating neuronal and glial activity with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for different neurological diseases, including AD. Male Wistar rats were assigned to five groups: 1. Control subjected to icv saline solution, 2. STZ subjected to icv-STZ (bilaterally, 3 mg/kg), 3. STZ+iTBS subjected to iTBS therapy after icv-STZ, 4. STZ+iTBS placebo subjected to noise artifact after icv-STZ and 5. Control+iTBS subjected to iTBS therapy after icv- saline solution. The RotaRod result showed that STZ did not alter motor function in rats. Eight arm radial maze test results showed that iTBS significantly improved cognitive impairment induced by STZ intoxication. Reactive gliosis in the hippocampus and periventricular area, manifested through elevated levels of Iba1+ and GFAP+/VIM+ following icv-STZ, was ameliorated after iTBS treatment. Our research identifies iTBS as an effective therapeutic candidate against STZ-induced neurotoxicity and AD-like changes. The beneficial effects of iTBS on cognitive dysfunction might be due to targeting microglia and astrocytes, as they exert a protective role in neurodegenerative and neuroinflammatory diseases. The results could provoke translation into clinical practice as an early/add-on non-invasive therapeutic intervention for cognitive impairment in AD.

Abnormal synaptic plasticity and impaired cognition in schizophrenia.

Schizophrenia (SCZ) is a severe mental illness that affects several brain domains with relation to cognition and behaviour. SCZ symptoms are typically classified into three categories, namely, positive, negative, and cognitive. The etiology of SCZ is thought to be multifactorial and poorly understood. Accumulating evidence has indicated abnormal synaptic plasticity and cognitive impairments in SCZ. Synaptic plasticity is thought to be induced at appropriate synapses during memory formation and has a critical role in the cognitive symptoms of SCZ. Many factors, including synaptic structure changes, aberrant expression of plasticity-related genes, and abnormal synaptic transmission, may influence synaptic plasticity and play vital roles in SCZ. In this article, we briefly summarize the morphology of the synapse, the neurobiology of synaptic plasticity, and the role of synaptic plasticity, and review potential mechanisms underlying abnormal synaptic plasticity in SCZ. These abnormalities involve dendritic spines, postsynaptic density, and long-term potentiation-like plasticity. We also focus on cognitive dysfunction, which reflects impaired connectivity in SCZ. Additionally, the potential targets for the treatment of SCZ are discussed in this article. Therefore, understanding abnormal synaptic plasticity and impaired cognition in SCZ has an essential role in drug therapy.

Transcranial direct current stimulation induces long-term potentiation-like plasticity in the human visual cortex

Transcranial direct current stimulation (tDCS) is increasingly used as a form of noninvasive brain stimulation to treat psychiatric disorders; however, its mechanism of action remains unclear. Prolonged visual stimulation (PVS) can enhance evoked EEG potentials (visually evoked potentials, VEPs) and has been proposed as a tool to examine long-term potentiation (LTP) in humans. The objective of the current study was to induce and analyze VEP plasticity and examine whether tDCS could either modulate or mimic plasticity changes induced by PVS. Thirty-eight healthy participants received tDCS, PVS, either treatment combined or neither treatment, with stimulation sessions being separated by one week. One session consisted of a baseline VEP measurement, one stimulation block, and six test VEP measurements. For PVS, a checkerboard reversal pattern was presented, and for tDCS, a constant current of 1 mA was applied via each bioccipital anodal target electrode for 10 min (Fig. S1). Both stimulation types decreased amplitudes of C1 compared to no stimulation (F = 10.1; p = 0.002) and led to a significantly smaller increase (PVS) or even decrease (tDCS) in N1 compared to no stimulation (F = 4.7; p = 0.034). While all stimulation types increased P1 amplitudes, the linear mixed effects model did not detect a significant difference between active stimulation and no stimulation. Combined stimulation induced sustained plastic modulation of C1 and N1 but with a smaller effect size than what would be expected for an additive effect. The results demonstrate that tDCS can directly induce LTP-like plasticity in the human cortex and suggest a mechanism of action of tDCS relying on the restoration of dysregulated synaptic plasticity in psychiatric disorders such as depression and schizophrenia.

Induction of long-term potentiation-like plasticity in the primary motor cortex with repeated anodal transcranial direct current stimulation – Better effects with intensified protocols?

BackgroundA single session of anodal tDCS induces LTP-like plasticity which lasts for about 1 h, while repetition of stimulation within a time interval of 30 min results in late-phase effects lasting for at least 24 h with standard stimulation protocols. ObjectiveIn this pilot study, we explored if the after-effects of a recently developed intensified single session stimulation protocol are relevantly prolonged in the motor cortex by repetition of this intervention. Methods16 healthy right-handed subjects participated in this study. The effects of an intensified (3 mA-20min) and a standard anodal tDCS protocol (1 mA-15min) with short (20 min) and long (3 h) repetition intervals were compared with the effects of respective single session tDCS protocols (3 mA-20min, 1 mA-15min, and Sham). Cortical excitability alterations were monitored by single-pulse TMS-elicited MEPs. ResultsCompared to sham, both single session tDCS protocols (1 mA-15min, and 3 mA-20min) resulted in cortical excitability enhancements lasting for about 30 min after stimulation. The short repetition interval (20 min) resulted in a prolongation of after-effects for the standard protocol, which lasted for more than 24 h after stimulation. For the intensified protocol, the prolongation of after-effects was limited to 120 min after stimulation. The long repetition interval (3 h) resulted in no excitability-enhancing after-effects for the intensified, and only minor excitability enhancement within the first 30 min after the intervention for the standard protocol. ConclusionThese results suggest a non-linearity of late-phase LTP-like plasticity induction, which was dependent not only on the interval of intervention repetition, but also on other protocol characteristics, including intensity, and duration of tDCS. Further studies in larger samples are needed to confirm these results.

Sleep orchestrates indices of local plasticity and global network stability in the human cortex.

Animals and humans spend on average one third of their lives in sleep, but its functions remain to be specified. Distinct lines of research propose that sleep promotes local strengthening of information-bearing synapses (plasticity) and global downscaling of synaptic strength (stability) in neural networks-prerequisites for adaptive behavior in a changing environment. However, the potential orchestration of these processes, particularly in humans, needs to be further characterized. Here, we use electrophysiological, behavioral, and molecular indices to noninvasively study cortical plasticity and network stability in humans. We observe indices of local strengthening of prior induced long-term potentiation-like plasticity (paired associative stimulation induced change in motor-evoked potential) and global network stabilization (homeostatic regulation of wake EEG theta activity) after brief periods of nonrapid eye movement sleep compared with wakefulness. The interplay of local sleep slow oscillations and spindle activity, previously related to synaptic refinements during sleep, is identified as a potential mechanism. Our findings are consistent with the notion that sleep-specific brain activity patterns reduce the plasticity-stability dilemma by orchestrating local plasticity and global stability of neural assemblies in the human cortex. Future studies are needed to further decipher the neural mechanisms underlying our indirect observations.

Nicotine modulates human brain plasticity via calcium-dependent mechanisms.

Nicotine (NIC) modulates cognition and memory function by targeting the nicotinic ACh receptor and releasing different transmitter systems postsynaptically. With both NIC-generated mechanisms, calcium influx and calcium permeability can be regulated, which is a key requirement for the induction of long-term potentiation, comprising the physiological basis of learning and memory function. We attempt to unmask the underlying mechanism of nicotinic effects on anodal transcranial direct current stimulation (tDCS)-induced long-term potentiation-like plasticity based on the hypothesis of calcium-dependency. Abolished tDCS-induced neuroplasticity as a result of NIC administration is reversed by calcium channel blockade with flunarizine in a dose-dependent manner. The results of the present study suggest that there is a dose determination of NIC/NIC agonists in therapeutical settings when treating cognitive dysfunction, which partially explains the heterogeneous results on cognition observed in subjects in different experimental settings. Nicotine (NIC) modulates neuroplasticity and improves cognitive performance in animals and humans mainly by increased calcium permeability and modulation of diverse transmitter systems. NIC administration impairs calcium-dependent plasticity induced by non-invasive brain stimulation with transcranial direct current stimulation (tDCS) in non-smoking participants probably as a result of intracellular calcium overflow. To test this hypothesis, we analysed the effect of calcium channel blockade with flunarizine (FLU) on anodal tDCS-induced cortical excitability changes in healthy non-smokers under NIC. We applied anodal tDCS combined with NIC patch and FLU at three different doses (2.5, 5 and 10mg) or with placebo medication. NIC abolished anodal tDCS-induced neuroplasticity. Under medium dosage (but not under low and high dosage) of FLU combined with NIC, plasticity was re-established. For FLU alone, the lowest dosage weakened long-term potentiation (LTP)-like plasticity, whereas the highest dosage again abolished tDCS-induced plasticity. The medium dosage turned LTP-like plasticity in long-term depression-like plasticity. The results of the present study suggest a key role of calcium influx and calcium levels in nicotinic effects on LTP-like plasticity in humans. This knowledge might be relevant for the development of new therapeutic strategies in cognitive dysfunction.

Poststimulation time interval-dependent effects of motor cortex anodal tDCS on reaction-time task performance.

Anodal transcranial direct current stimulation (tDCS) induces long-term potentiation-like plasticity, which is associated with long-lasting effects on different cognitive, emotional, and motor performances. Specifically, tDCS applied over the motor cortex is considered to improve reaction time in simple and complex tasks. The timing of tDCS relative to task performance could determine the efficacy of tDCS to modulate performance. The aim of this study was to compare the effects of a single session of anodal tDCS (1.5 mA, for 15 min) applied over the left primary motor cortex (M1) versus sham stimulation on performance of a go/no-go simple reaction-time task carried out at three different time points after tDCS-namely, 0, 30, or 60 min after stimulation. Performance zero min after anodal tDCS was improved during the whole course of the task. Performance 30 min after anodal tDCS was improved only in the last block of the reaction-time task. Performance 60 min after anodal tDCS was not significantly different throughout the entire task. These findings suggest that the motor cortex excitability changes induced by tDCS can improve motor responses, and these effects critically depend on the time interval between stimulation and task performance.

25. The LRRK2-R1441C mutation disrupts long-term potentiation-like plasticity in Parkinson’s disease patients

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) account for up to 13% of dominant familial Parkinson’s disease (PD) cases. The clinical and pathological features of LRRK2-PD are often indistinguishable from idiopathic PD (iPD). Recent evidence pointed out that LRRK2 acts directly at the secretory and endocytic molecular machinery. Importantly, in southern Italy the R1441C mutation is the most frequent mutation reported so far. Based on the LRRK2-role on synaptic transmission, we aimed to investigate in vivo excitability and plasticity of the motor cortex by means of transcranial magnetic stimulation (TMS). Paired pulse TMS was used to investigate cortical excitability by using short intracortical inhibition and facilitation and short afferent inhibition paradigm. Intermittent theta burst stimulation (iTBS) was used to test long-term potentiation-like cortical plasticity (LTP). Eight LRRK2-PD patients harboring the R1441C mutation and 11 iPD were tested on the more affected side in ON l-dopa therapy. We observed the lack of LTP-like motor cortex plasticity in R1441C-LRRK2 patients compared to healthy-subjects and with a similar profile observed for iPD patients. Motor cortex excitability profile did not exhibit any difference among the three groups. R1441C mutation disrupts motor cortex LTP-like plasticity in Parkinson’s disease patients.

P271 The LRRK2-R1441C mutation disrupts long-term potentiation-like plasticity in Parkinson’s disease patients

Background Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) account for up to 13% of dominant familial Parkinson’s disease (PD) cases. The clinical and pathological features of LRRK2-PD are often indistinguishable from idiopathic PD (iPD). Recent evidence pointed out that LRRK2 acts directly at the secretory and endocytic molecular machinery. Importantly, in southern Italy the R1441C mutation is the most frequent mutation reported so far. Objective Based on the LRRK2-role on synaptic transmission, we aimed to investigate in vivo excitability and plasticity of the motor cortex by means of transcranial magnetic stimulation (TMS). Methods Paired pulse TMS was used to investigate cortical excitability by using short intracortical inhibition and facilitation and short afferent inhibition paradigm. Intermittent theta burst stimulation (iTBS) was used to test long-term potentiation-like cortical plasticity (LTP). Eight LRRK2-PD patients harboring the R1441C mutation and 11 iPD were tested on the more affected side in ON l-dopa therapy. Results We observed the lack of LTP-like motor cortex plasticity in R1441C-LRRK2 patients compared to healthy-subjects and with a similar profile observed for iPD patients. Motor cortex excitability profile did not exhibit any difference among the three groups. Conclusions R1441C mutation disrupts motor cortex LTP-like plasticity in Parkinson’s disease patients.