Visual Cortical Plasticity Research Articles

Activation of p38 MAPK hinders the reactivation of visual cortical plasticity in adult amblyopic mice

ObjectiveTo investigate the impact of p38 mitogen-activated protein kinase (MAPK) signaling on reactivating visual cortical plasticity in adult amblyopic mice. Materials and methodsReverse suture (RS), environment enrichment (EE), and combined with left intracerebroventricular injection of p38 MAPK inhibitor (SB203580, SB) or p38 MAPK agonist (dehydrocorydaline hydrochloride, DHC) were utilized to treat adult amblyopic mice with monocular deprivation (MD). The visual water task, visual cliff test, and Flash visual-evoked potential were used to measure the visual function. Then, Golgi staining and transmission electron microscopy were used to assess the reactivation of structural plasticity in adult amblyopic mice. Western blot and immunohistochemistry detected the expression of ATF2, PSD-95, p38 MAPK, and phospho-p38 MAPK in the left visual cortex. ResultsNo statistically significant difference was observed in the visual function in each pre-intervention group. Compared to pre-intervention, the visual acuity of deprived eyes was improved significantly, the impairment of visual depth perception was alleviated, and the P wave amplitude and C/I ratio were increased in the EE + RS, the EE + RS + SB, and the EE + RS + DMSO groups, but no significant difference was detected in the EE + RS + DHC group. Compared to EE + RS + DHC group, the density of dendritic spines was significantly higher, the synaptic density of the left visual cortex increased significantly, the length of the active synaptic zone increased, and the thickness of post-synaptic density (PSD) thickened in the left visual cortex of EE + RS, EE + RS + SB, and EE + RS + DMSO groups. And that, the protein expression of p-p38 MAPK increased while that of PSD-95 and ATF2 decreased significantly in the left visual cortex of the EE + RS + DHC group mice. ConclusionRS and EE intervention improved the visual function and synaptic plasticity of the visual cortex in adult amblyopic mice. However, activating p38 MAPK hinders the recovery of visual function by upregulating the phosphorylation of p38 MAPK and decreasing the ATF2 protein expression.

Stability of steady-state visual evoked potential contrast response functions.

Repetitive sensory stimulation has been shown to induce neuroplasticity in sensory cortical circuits, at least under certain conditions. We measured the plasticity-inducing effect of repetitive contrast-reversal-sweep steady-state visual-evoked potential (ssVEP) stimuli, hoping to employ the ssVEP's high signal-to-noise electrophysiological readout in the study of human visual cortical neuroplasticity. Steady-state VEP contrast-sweep responses were measured daily for 4 days (four 20-trial blocks per day, 20 participants). No significant neuroplastic changes in response amplitude were observed either across blocks or across days. Furthermore, response amplitudes were stable within-participant, with measured across-block and across-day coefficients of variation (CV = SD/mean) of 15-20 ± 2% and 22-25 ± 2%, respectively. Steady-state VEP response phase was also highly stable, suggesting that temporal processing delays in the visual system vary by at most 2-3 ms across blocks and days. While we fail to replicate visual stimulation-dependent cortical plasticity, we show that contrast-sweep steady-state VEPs provide a stable human neurophysiological measure well suited for repeated-measures longitudinal studies.

Regulatory role of the p38 MAPK/ATF2 signaling pathway in visual function and visual cortical plasticity in mice with monocular deprivation

BackgroundThis study aimed to examine the role of the p38 mitogen-activated protein kinase (MAPK)/ activating transcription factor 2 (ATF2) signaling in visual function impairment and visual cortical plasticity in mice with monocular deprivation (MD). MethodsVisual behavioral tests, including visual water task, visual cliff test, and flash visual evoked potential, were performed on each group. We studied the density of dendritic spines and the synaptic ultrastructure by Golgi staining and transmission electron microscope. We performed Western blot and immunohistochemistry and detected the expression of ATF2, PSD-95, p38 MAPK, and phosphor-p38 MAPK in the left visual cortex. ResultsIn the MD + SB group, the visual acuity in deprived eyes substantially improved, the impairment of visual depth perception was alleviated, and the P wave amplitude and C/I ratio increased. The density of dendritic spines and the numerical density of synapses increased significantly, the width of the synaptic cleft decreased significantly, and the length of the active synaptic zone and the thickness of post-synaptic density (PSD) increased substantially. The protein expression of phosphor-p38 MAPK decreased, whereas that of PSD-95 and ATF2 increased significantly. ConclusionsInhibiting the phosphorylation of p38 MAPK and negative feedback upregulated ATF2 expression, alleviated damage to visual function, and protected against synaptic plasticity in mice with MD.

Durable recovery from amblyopia with donepezil

An elevated threshold for neuroplasticity limits visual gains with treatment of residual amblyopia in older children and adults. Acetylcholinesterase inhibitors (AChEI) can enable visual neuroplasticity and promote recovery from amblyopia in adult mice. Motivated by these promising findings, we sought to determine whether donepezil, a commercially available AChEI, can enable recovery in older children and adults with residual amblyopia. In this open-label pilot efficacy study, 16 participants (mean age 16 years; range 9–37 years) with residual anisometropic and/or strabismic amblyopia were treated with daily oral donepezil for 12 weeks. Donepezil dosage was started at 2.5 or 5.0 mg based on age and increased by 2.5 mg if the amblyopic eye visual acuity did not improve by 1 line from the visit 4 weeks prior for a maximum dosage of 7.5 or 10 mg. Participants < 18 years of age further patched the dominant eye. The primary outcome was visual acuity in the amblyopic eye at 22 weeks, 10 weeks after treatment was discontinued. Mean amblyopic eye visual acuity improved 1.2 lines (range 0.0–3.0), and 4/16 (25%) improved by ≥ 2 lines after 12 weeks of treatment. Gains were maintained 10 weeks after cessation of donepezil and were similar for children and adults. Adverse events were mild and self-limited. Residual amblyopia improves in older children and adults treated with donepezil, supporting the concept that the critical window of visual cortical plasticity can be pharmacologically manipulated to treat amblyopia. Placebo-controlled studies are needed.

Visual Cortical Plasticity: Molecular Mechanisms as Revealed by Induction Paradigms in Rodents

Assessing the molecular mechanism of synaptic plasticity in the cortex is vital for identifying potential targets in conditions marked by defective plasticity. In plasticity research, the visual cortex represents a target model for intense investigation, partly due to the availability of different in vivo plasticity-induction protocols. Here, we review two major protocols: ocular-dominance (OD) and cross-modal (CM) plasticity in rodents, highlighting the molecular signaling pathways involved. Each plasticity paradigm has also revealed the contribution of different populations of inhibitory and excitatory neurons at different time points. Since defective synaptic plasticity is common to various neurodevelopmental disorders, the potentially disrupted molecular and circuit alterations are discussed. Finally, new plasticity paradigms are presented, based on recent evidence. Stimulus-selective response potentiation (SRP) is one of the paradigms addressed. These options may provide answers to unsolved neurodevelopmental questions and offer tools to repair plasticity defects.

Antioxidants Prevent the Effects of Physical Exercise on Visual Cortical Plasticity

Physical activity has been recently shown to enhance adult visual cortical plasticity, both in human subjects and animal models. While physical activity activates mitochondrial oxidative metabolism leading to a transient production of reactive oxygen species, it remains unknown whether this process is involved in the plasticizing effects elicited at the visual cortical level. Here, we investigated whether counteracting oxidative stress through a dietary intervention with antioxidants (vitamins E and C) interferes with the impact of physical exercise on visual cortex plasticity in adult rats. Antioxidant supplementation beyond the closure of the critical period blocked ocular dominance plasticity in response to eye deprivation induced by physical activity in adult rats. Antioxidants exerted their action through a mithormetic effect that involved dampening of oxidative stress and insulin-like growth factor 1 (IGF-1) signaling in the brain.

Plasticity of visual evoked potentials in patients with neurofibromatosis type 1

ObjectiveThe inability to properly process visual information has been frequently associated with neurofibromatosis type 1 (NF1). Based on animal studies, the cause of cognitive disabilities in NF1 is hypothesized to arise from decreased synaptic plasticity. Visual cortical plasticity in humans can be investigated by studying visual evoked potentials (VEPs) in response to visual stimulation. MethodsVEP plasticity was assessed by measuring the increase of the peak amplitudes C1, P1, and N1 induced by 10-min modulation of checkerboard reversals in 22 adult NF1 patients and 30 controls. VEP signals were recorded pre-modulation, during modulation, and at 2, 7, 12, 17, 22, 27 min post-modulation. ResultsThe P1 amplitude increased significantly comparing post-modulation to pre-modulation in the control group. This potentiation was not observed in the NF1 group. ConclusionsVisual cortical plasticity could be measured using VEPs in response to visual stimulation in the control group. Individuals with NF1 may have reduced visual cortical plasticity, as indicated by their non-potentiated response to VEP induction. These findings should be interpreted with caution due to high inter-subject variability. SignificanceThe present study contributes to an improved assessment of the feasibility for using neurophysiological outcome measures in intervention studies of cognitive deficits among patients with NF1.

Mutual interaction between visual homeostatic plasticity and sleep in adult humans.

Sleep and plasticity are highly interrelated, as sleep slow oscillations and sleep spindles are associated with consolidation of Hebbian-based processes. However, in adult humans, visual cortical plasticity is mainly sustained by homeostatic mechanisms, for which the role of sleep is still largely unknown. Here, we demonstrate that non-REM sleep stabilizes homeostatic plasticity of ocular dominance induced in adult humans by short-term monocular deprivation: the counterintuitive and otherwise transient boost of the deprived eye was preserved at the morning awakening (>6 hr after deprivation). Subjects exhibiting a stronger boost of the deprived eye after sleep had increased sleep spindle density in frontopolar electrodes, suggesting the involvement of distributed processes. Crucially, the individual susceptibility to visual homeostatic plasticity soon after deprivation correlated with the changes in sleep slow oscillations and spindle power in occipital sites, consistent with a modulation in early occipital visual cortex.

Limited Pairings of Electrical Micro-stimulation of the Ventral Tegmental Area and a Visual Stimulus Enhance Visual Cortical Responses.

Previous studies demonstrated that pairing a visual stimulus and electrical micro-stimulation of the ventral tegmental area (VTA-EM) for multiple days is sufficient to induce visual cortical plasticity and changes perception. However, a brief epoch of VTA-EM-stimulus pairing within a single day has been shown to result in a behavioral preference for the paired stimulus. Here, we investigated whether a brief single-day session of VTA-EM-stimulus pairings is sufficient to induce changes in visual cortical responses. We examined macaque posterior inferior temporal (PIT) cortex because previous studies demonstrated response changes after VTA-EM stimulus pairing in that area. Multi-unit recordings in PIT were interleaved with VTA-EM-stimulus pairing epochs. During the short VTA-EM-stimulus pairing epochs (60 pairings), one image (fractal) was paired with VTA-EM (STIM) whereas another, unpaired fractal was presented as control. Two other fractals (dummies) were presented only during the recordings. The difference in response between the STIM and control fractals already increased after the first VTA-EM-stimulus pairing epoch, reflecting a relative increase of the response to the STIM fractal. However, the response to the STIM fractal did not increase further with more VTA-EM-stimulus pairing epochs. The relative increase in firing rate for the paired fractal was present early in the response, in line with a local/ bottom-up origin. These effects were absent when comparing the responses to the dummies pre- and post-VTA-EM. This study shows that pairing a visual image and VTA-EM in a brief single-day session is sufficient to increase the response for the paired image in macaque PIT.

Invited Session III: Reawakening plasticity in visual cortex: Lifting brakes on visual cortical plasticity

Enduring amblyopia after early imbalanced binocular input is a classic example of critical period biology across species. Recovery of visual acuity is typically poor in adulthood due to both the extensive loss of connections and declining neuroplasticity in primary sensory areas. The discovery that rewiring is actively limited in adulthood rather than passively lost with age inspires novel therapeutic approaches to lift such brakes on plasticity. Notably, these mechanisms converge on pivotal inhibitory circuits in primary visual cortex. This talk will overview insights from rodent models of acuity recovery which may augment that of humans endowed with higher visual areas exhibiting prolonged plasticity.

Plasticity in visual cortex is disrupted in a mouse model of tauopathy

Alzheimer’s disease and other dementias are thought to underlie a progressive impairment of neural plasticity. Previous work in mouse models of Alzheimer’s disease shows pronounced changes in artificially-induced plasticity in hippocampus, perirhinal and prefrontal cortex. However, it is not known how degeneration disrupts intrinsic forms of brain plasticity. Here we characterised the impact of tauopathy on a simple form of intrinsic plasticity in the visual system, which allowed us to track plasticity at both long (days) and short (minutes) timescales. We studied rTg4510 transgenic mice at early stages of tauopathy (5 months) and a more advanced stage (8 months). We recorded local field potentials in the primary visual cortex while animals were repeatedly exposed to a stimulus over 9 days. We found that both short- and long-term visual plasticity were already disrupted at early stages of tauopathy, and further reduced in older animals, such that it was abolished in mice expressing mutant tau. Additionally, visually evoked behaviours were disrupted in both younger and older mice expressing mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy. This simple measure of plasticity may help understand how tauopathy disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease.

The gut microbiota of environmentally enriched mice regulates visual cortical plasticity.

Exposing animals to an enriched environment (EE) has dramatic effects on brain structure, function, and plasticity. The poorly known "EE-derived signals'' mediating the EE effects are thought to be generated within the central nervous system. Here, we shift the focus to the body periphery, revealing that gut microbiota signals are crucial for EE-driven plasticity. Developmental analysis reveals striking differences in intestinal bacteria composition between EE and standard rearing (ST) mice, as well as enhanced levels of short-chain fatty acids (SCFA) in EE mice. Depleting the microbiota of EE mice with antibiotics strongly decreases SCFA and prevents activation of adult ocular dominance plasticity, spine dynamics, and microglia rearrangement. SCFA treatment in ST mice mimics EE induction of ocular dominance plasticity and microglial remodeling. Remarkably, transferring the microbiota of EE mice to ST recipients activates adult ocular dominance plasticity. Thus, experience-dependent changes in gut microbiota regulate brain plasticity.

Inhibition of Cdk5 in PV Neurons Reactivates Experience-Dependent Plasticity in Adult Visual Cortex.

Cyclin-dependent kinase 5 (Cdk5) has been shown to play a critical role in brain development, learning, memory and neural processing in general. Cdk5 is widely distributed in many neuron types in the central nervous system, while its cell-specific role is largely unknown. Our previous study showed that Cdk5 inhibition restored ocular dominance (OD) plasticity in adulthood. In this study, we specifically knocked down Cdk5 in different types of neurons in the visual cortex and examined OD plasticity by optical imaging of intrinsic signals. Downregulation of Cdk5 in parvalbumin-expressing (PV) inhibitory neurons, but not other neurons, reactivated adult mouse visual cortical plasticity. Cdk5 knockdown in PV neurons reduced the evoked firing rate, which was accompanied by an increment in the threshold current for the generation of a single action potential (AP) and hyperpolarization of the resting membrane potential. Moreover, chemogenetic activation of PV neurons in the visual cortex can attenuate the restoration of OD plasticity by Cdk5 inhibition. Taken together, our results suggest that Cdk5 in PV interneurons may play a role in modulating the excitation and inhibition balance to control the plasticity of the visual cortex.

Stimulation of the ventral tegmental area induces visual cortical plasticity at the neuronal level.

fMRI studies have shown that pairing a task-irrelevant visual feature with electrical micro-stimulation of the ventral tegmental area (VTA-EM) is sufficient to increase the sensory cortical representation of the paired feature and to improve perceptual performance. However, since fMRI provides an indirect measure of neural activity, the neural response changes underlying the fMRI activations are unknown. Here, we pair a task-irrelevant grating orientation with VTA-EM while attention is directed to a difficult orthogonal task. We examine the changes in neural response properties in macaques by recording spiking activity in the posterior inferior temporal cortex, the locus of fMRI-defined plasticity in previous studies. We observe a relative increase in mean spike rate and preference for the VTA-EM paired orientation compared to an unpaired orientation, which is unrelated to attention. These results demonstrate that VTA-EM-stimulus pairing is sufficient to induce sensory cortical plasticity at the spiking level in nonhuman primates.

Pharmacological and optical activation of TrkB in Parvalbumin interneurons regulate intrinsic states to orchestrate cortical plasticity

Elevated states of brain plasticity typical for critical periods of early postnatal life can be reinstated in the adult brain through interventions, such as antidepressant treatment and environmental enrichment, and induced plasticity may be critical for the antidepressant action. Parvalbumin-positive (PV) interneurons regulate the closure of developmental critical periods and can alternate between high and low plasticity states in response to experience in adulthood. We now show that PV plasticity states and cortical networks are regulated through the activation of TrkB neurotrophin receptors. Visual cortical plasticity induced by fluoxetine, a widely prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant, was lost in mice with reduced expression of TrkB in PV interneurons. Conversely, optogenetic gain-of-function studies revealed that activation of an optically activatable TrkB (optoTrkB) specifically in PV interneurons switches adult cortical networks into a state of elevated plasticity within minutes by decreasing the intrinsic excitability of PV interneurons, recapitulating the effects of fluoxetine. TrkB activation shifted cortical networks towards a low PV configuration, promoting oscillatory synchrony, increased excitatory-inhibitory balance, and ocular dominance plasticity. OptoTrkB activation promotes the phosphorylation of Kv3.1 channels and reduces the expression of Kv3.2 mRNA providing a mechanism for the lower excitability. In addition, decreased expression and puncta of Synaptotagmin2 (Syt2), a presynaptic marker of PV interneurons involved in Ca2+-dependent neurotransmitter release, suggests lower inputs onto pyramidal neurons suppressing feed-forward inhibition. Together, the results provide mechanistic insights into how TrkB activation in PV interneurons orchestrates the activity of cortical networks and mediating antidepressant responses in the adult brain.

The spatiotemporal organization of experience dictates hippocampal involvement in primary visual cortical plasticity

The hippocampus and neocortex are theorized to be crucial partners in the formation of long-term memories. Here, we assess hippocampal involvement in two related forms of experience-dependent plasticity in the primary visual cortex (V1) of mice. Like control animals, those with hippocampal lesions exhibit potentiation of visually evoked potentials after passive daily exposure to a phase-reversing oriented grating stimulus, which is accompanied by long-term habituation of a reflexive behavioral response. Thus, low-level recognition memory is formed independently of the hippocampus. However, response potentiation resulting from daily exposure to a fixed sequence of four oriented gratings is severely impaired in mice with hippocampal damage. A feature of sequence plasticity in V1 of controls, which is absent in lesioned mice, is the generation of predictive responses to an anticipated stimulus element when it is withheld or delayed. Thus, the hippocampus is involved in encoding temporally structured experience, even within the primary sensory cortex.

Bariatric surgery restores visual cortical plasticity in nondiabetic subjects with obesity.

Obesity leads to changes in synaptic plasticity. We aimed at investigating the impact of bariatric surgery (RYGB) on visual neural plasticity (NP) and its relationship with the main gut peptides, leptin, and brain-derived neurotrophic factor (BDNF). NP was assessed testing binocular rivalry before and after 2 h of monocular deprivation (index of visual brain plasticity) in 15 subjects with obesity (age 42.3 ± 9.8 years; BMI 46.1 ± 4.9 kg/m2) before and after RYGB. Gut peptides, leptin, and BDNF were obtained at baseline and 6 months after surgery in 13 subjects. A significant reduction in BMI (p < 0.001 vs. baseline) and a significant increase of disposition index (DI, p = 0.02 vs baseline) were observed after RYGB. Total and active GLP-1 release in response to glucose ingestion significantly increased after RYGB, while no changes occurred in VIP, GIP, and BDNF levels. Fasting leptin concentration was lower after RYGB (p = 0.001 vs. baseline). Following RYGB, NP was progressively restored (p < 0.002). NP was correlated with DI and fasting glucose at baseline (r = 0.75, p = 0.01; r = -0.7, p = 0.02; respectively), but not with BMI. A positive correlation between post-pre-RYGB changes in AUCactive GLP-1 and NP was observed (r = 0.70, p < 0.01). Leptin was inversely correlated with NP 6 months after surgery (r = -0.63, p = 0.02). No correlation was observed between GIP, VIP, BDNF, and NP. Visual plasticity is altered in subjects with obesity, and it can be restored after RYGB. The improvement may be mediated by amelioration of insulin sensitivity, increased GLP-1 levels, and reduced leptin levels.

Evidence for Reduced Long-Term Potentiation-Like Visual Cortical Plasticity in Schizophrenia and Bipolar Disorder.

Several lines of research suggest that impairments in long-term potentiation (LTP)-like synaptic plasticity might be a key pathophysiological mechanism in schizophrenia (SZ) and bipolar disorder type I (BDI) and II (BDII). Using modulations of visually evoked potentials (VEP) of the electroencephalogram, impaired LTP-like visual cortical plasticity has been implicated in patients with BDII, while there has been conflicting evidence in SZ, a lack of research in BDI, and mixed results regarding associations with symptom severity, mood states, and medication. We measured the VEP of patients with SZ spectrum disorders (n = 31), BDI (n = 34), BDII (n = 33), and other BD spectrum disorders (n = 2), and age-matched healthy control (HC) participants (n = 200) before and after prolonged visual stimulation. Compared to HCs, modulation of VEP component N1b, but not C1 or P1, was impaired both in patients within the SZ spectrum (χ 2 = 35.1, P = 3.1 × 10−9) and BD spectrum (χ 2 = 7.0, P = 8.2 × 10−3), including BDI (χ 2 = 6.4, P = .012), but not BDII (χ 2 = 2.2, P = .14). N1b modulation was also more severely impaired in SZ spectrum than BD spectrum patients (χ 2 = 14.2, P = 1.7 × 10−4). N1b modulation was not significantly associated with Positive and Negative Syndrome Scale (PANSS) negative or positive symptoms scores, number of psychotic episodes, Montgomery and Åsberg Depression Rating Scale (MADRS) scores, or Young Mania Rating Scale (YMRS) scores after multiple comparison correction, although a nominal association was observed between N1b modulation and PANSS negative symptoms scores among SZ spectrum patients. These results suggest that LTP-like plasticity is impaired in SZ and BD. Adding to previous genetic, pharmacological, and electrophysiological evidence, these results implicate aberrant synaptic plasticity as a mechanism underlying SZ and BD.

Impairment of visual cortical plasticity by amyloid-beta species

IntroductionA variety of transgenic and knock-in mice that express mutant alleles of Amyloid precursor protein (APP) have been used to model the effects of amyloid-beta (Aβ) on circuit function in Alzheimer's disease (AD); however phenotypes described in these mice may be affected by expression of mutant APP or proteolytic cleavage products independent of Aβ. In addition, the effects of mutant APP expression are attributed to elevated expression of the amyloidogenic, 42-amino acid-long species of Aβ (Aβ42) associated with amyloid plaque accumulation in AD, though elevated concentrations of Aβ40, an Aβ species produced with normal synaptic activity, may also affect neural function. MethodsTo explore the effects of elevated expression of Aβ on synaptic function in vivo, we assessed visual system plasticity in transgenic mice that express and secrete Aβ throughout the brain in the absence of APP overexpression. Transgenic mice that express either Aβ40 or Aβ42 were assayed for their ability to appropriately demonstrate ocular dominance plasticity following monocular deprivation. ResultsUsing two complementary approaches to measure the plastic response to monocular deprivation, we find that male and female mice that express either 40- or 42-amino acid–long Aβ species demonstrate a plasticity defect comparable to that elicited in transgenic mice that express mutant alleles of APP and Presenilin 1 (APP/PS1 mice). ConclusionsThese data support the hypothesis that mutant APP-driven plasticity impairment in mouse models of AD is mediated by production and accumulation of Aβ. Moreover, these findings suggest that soluble species of Aβ are capable of modulating synaptic plasticity, likely independent of any aggregation. These findings may have implications for the role of soluble species of Aβ in both development and disease settings.

Visual cortical plasticity and the risk for psychosis: An interim analysis of the North American Prodrome Longitudinal Study

BackgroundAdolescence/early adulthood coincides with accelerated pruning of cortical synapses and the onset of schizophrenia. Cortical gray matter reduction and dysconnectivity in schizophrenia are hypothesized to result from impaired synaptic plasticity mechanisms, including long-term potentiation (LTP), since deficient LTP may result in too many weak synapses that are then subject to over-pruning. Deficient plasticity has already been observed in schizophrenia. Here, we assessed whether such deficits are present in the psychosis risk syndrome (PRS), particularly those who subsequently convert to full psychosis. MethodsAn interim analysis was performed on a sub-sample from the NAPLS-3 study, including 46 healthy controls (HC) and 246 PRS participants. All participants performed an LTP-like visual cortical plasticity paradigm involving assessment of visual evoked potentials (VEPs) elicited by vertical and horizontal line gratings before and after high frequency (“tetanizing”) visual stimulation with one of the gratings to induce “input-specific” neuroplasticity (i.e., VEP changes specific to the tetanized stimulus). Non-parametric, cluster-based permutation testing was used to identify electrodes and timepoints that demonstrated input-specific plasticity effects. ResultsInput-specific pre-post VEP changes (i.e., increased negative voltage) were found in a single spatio-temporal cluster covering multiple occipital electrodes in a 126–223 ms time window. This plasticity effect was deficient in PRS individuals who subsequently converted to psychosis, relative to PRS non-converters and HC. ConclusionsInput-specific LTP-like visual plasticity can be measured from VEPs in adolescents and young adults. Interim analyses suggest that deficient visual cortical plasticity is evident in those PRS individuals at greatest risk for transition to psychosis.