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ObjectiveStimulus-selective response modulation (SRM) of sensory evoked potentials represents a well-established non-invasive index of long-term potentiation-like (LTP-like) synaptic plasticity in the human sensory cortices. Although our understanding of the mechanisms underlying stimulus-SRM has increased over the past two decades, it remains unclear how this form of LTP-like synaptic plasticity is related to other basic learning mechanisms, such as perceptual learning. The aim of the current study was twofold; firstly, we aimed to corroborate former stimulus-SRM studies, demonstrating modulation of visual evoked potential (VEP) components following high-frequency visual stimulation. Secondly, we aimed to investigate the association between the magnitudes of LTP-like plasticity and visual perceptual learning (VPL).Methods42 healthy adults participated in the study. EEG data was recorded during a standard high-frequency stimulus-SRM paradigm. Amplitude values were measured from the peaks of visual components C1, P1, and N1. Embedded in the same experimental session, the VPL task required the participants to discriminate between a masked checkerboard pattern and a visual “noise” stimulus before, during and after the stimulus-SRM probes.ResultsWe demonstrated significant amplitude modulations of VEPs components C1 and N1 from baseline to both post-stimulation probes. In the VPL task, we observed a significant change in the average threshold levels from the first to the second round. No significant association between the magnitudes of LTP-like plasticity and performance on the VPL task was evident.ConclusionTo the extent of our knowledge, this study is the first to examine the relationship between the visual stimulus-RM phenomenon and VPL in humans. In accordance with previous studies, we demonstrated robust amplitude modulations of the C1 and N1 components of the VEP waveform. However, we did not observe any significant correlations between modulation magnitude of VEP components and VPL task performance, suggesting that these phenomena rely on separate learning mechanisms implemented by different neural mechanisms.

BackgroundBackground: In Parkinson's disease (PD) long-term motor outcomes of subthalamic nucleus deep brain stimulation (STN-DBS) are well documented, while comprehensive reports on non-motor outcomes are fewer and less consistent. Objective Objective: To report motor and non-motor symptoms after 5-years of STN-DBS. Methods Methods:We performed an open 5-year extension study of a randomized trial that compared intraoperative verification versus mapping of STN using microelectrode recordings. Changes from preoperative to 5-years of STN-DBS were evaluated for motor and non-motor symptoms (MDS-UPDRS I-IV), sleep disturbances (PDSS), autonomic symptoms (Scopa-Aut), quality of life (PDQ-39) and cognition through a neuropsychological test battery. We evaluated whether any differences between the two randomization groups were still present, and assessed preoperative predictors of physical dependence after 5 years of treatment using logistic regression. ResultsResults: We found lasting improvement of off-medication motor symptoms (total MDS-UPDRS III, bradykinetic-rigid symptoms and tremor), on-medication tremor, motor fluctuations, and sleep disturbances, but reduced performance across all cognitive domains, except verbal memory. Reduction of verbal fluency and executive function was most pronounced the first year and may thus be more directly related to the surgery than worsening in other domains. The group mapped with multiple microelectrode recordings had more improvement of bradykinetic-rigid symptoms and of PDQ-39 bodily discomfort sub-score, but also more reduction in word fluency. Older age was the most important factor associated with physical dependence after 5 years. Conclusion Conclusion:STN-DBS offers good long-term effects, including improved sleep, despite disease progression. STN-DBS surgery may negatively impact verbal fluency and executive function. Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for Parkinson's disease (PD) with motor fluctuations or tremor not responsive to levodopa. While shortterm effects have been well documented both on motor symptoms, 1-7 and non-motor symptoms (NMS), [8][9][10][11][12] studies on long-term effects of STN-DBS (≥5 years) have mainly reported effects on motor symptoms. A sustained effect has been shown on bradykinesia, rigidity and tremor, but less so on axial symptoms like gait freezing, postural instability and dysarthria that worsen gradually in parallel with advancing disease. [13][14][15][16][17][18] Studies reporting long-term effects on sleep and dysautonomia are lacking, and reports on the long-term impact on cognitive functions are few and show conflicting results. 19 Many long-term studies are small and some have relatively high drop-out rates (in the range 37-82%), causing methodological challenges. [20][21][22] Drop-outs from such studies occur more frequently

Long-term potentiation (LTP) is one of the most extensively studied forms of neuroplasticity and is considered the strongest candidate mechanism for memory and learning. The use of event-related potentials and sensory stimulation paradigms has allowed for the translation from animal studies to non-invasive studies of LTP-like synaptic plasticity in humans. Accumulating evidence suggests that synaptic plasticity as measured by stimulus-specific response modulation is reduced in neuropsychiatric disorders such as major depressive disorder (MDD), bipolar disorders and schizophrenia, suggesting that impaired synaptic plasticity plays a part in the underlying pathophysiology of these disorders. This is in line with the neuroplasticity hypothesis of depression, which postulate that deficits in neuroplasticity might be a common pathway underlying depressive disorders. The current study aims to replicate and confirm earlier reports that visual stimulus-specific response modulation is a viable probe into LTP-like synaptic plasticity in a large sample of healthy adults (n = 111). Further, this study explores whether impairments in LTP-like synaptic plasticity is associated with self-reported subclinical depressive symptoms and stress in a healthy population. Consistent with prior research, the current study replicated and confirmed reports demonstrating significant modulation of visual evoked potentials (VEP) following visual high-frequency stimulation. Current results further indicate that reduced LTP-like synaptic plasticity is associated with higher levels of self-reported symptoms of depression and perceived stress. This indicate that LTP-like plasticity is sensitive to sub-clinical levels of psychological distress, and might represent a vulnerability marker for the development of depressive symptoms.

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