scholarly journals Critical Period Plasticity as a Framework for Psychedelic-Assisted Psychotherapy

2021 ◽  
Vol 15 ◽  
Author(s):  
Lauren Lepow ◽  
Hirofumi Morishita ◽  
Rachel Yehuda
Keyword(s):  
Visual System ◽  
Critical Period ◽  
Randomized Clinical Trials ◽  
Ocular Dominance ◽  
Biological Psychiatry ◽  
Brain State ◽  
Critical Periods ◽  
Post Traumatic Stress ◽  
Environmental Input ◽  
Causal Pathways

As psychedelic compounds gain traction in psychiatry, there is a need to consider the active mechanism to explain the effect observed in randomized clinical trials. Traditionally, biological psychiatry has asked how compounds affect the causal pathways of illness to reduce symptoms and therefore focus on analysis of the pharmacologic properties. In psychedelic-assisted psychotherapy (PAP), there is debate about whether ingestion of the psychedelic alone is thought to be responsible for the clinical outcome. A question arises how the medication and psychotherapeutic intervention together might lead to neurobiological changes that underlie recovery from illness such as post-traumatic stress disorder (PTSD). This paper offers a framework for investigating the neurobiological basis of PAP by extrapolating from models used to explain how a pharmacologic intervention might create an optimal brain state during which environmental input has enduring effects. Specifically, there are developmental “critical” periods (CP) with exquisite sensitivity to environmental input; the biological characteristics are largely unknown. We discuss a hypothesis that psychedelics may remove the brakes on adult neuroplasticity, inducing a state similar to that of neurodevelopment. In the visual system, progress has been made both in identifying the biological conditions which distinguishes the CP and in manipulating the active ingredients with the idea that we might pharmacologically reopen a critical period in adulthood. We highlight ocular dominance plasticity (ODP) in the visual system as a model for characterizing CP in limbic systems relevant to psychiatry. A CP framework may help to integrate the neuroscientific inquiry with the influence of the environment both in development and in PAP.

Critical periods for functional and anatomical compensation in lateral suprasylvian visual area following removal of visual cortex in cats

1984 ◽  
Vol 52 (5) ◽  
pp. 941-960 ◽  
Author(s):  
L. Tong ◽  
R. E. Kalil ◽  
P. D. Spear
Keyword(s):  
Visual Cortex ◽  
Critical Period ◽  
Ocular Dominance ◽  
Direction Selectivity ◽  
Visual Area ◽  
Critical Periods ◽  
Cortex Lesion ◽  
Thalamic Projections ◽  
Adult Cats ◽  
Visual Cortical

Previous experiments have found that neurons in the cat's lateral suprasylvian (LS) visual area of cortex show functional compensation following removal of visual cortical areas 17, 18, and 19 on the day of birth. Correspondingly, an enhanced retino-thalamic pathway to LS cortex develops in these cats. The present experiments investigated the critical periods for these changes. Unilateral lesions of areas 17, 18, and 19 were made in cats ranging in age from 1 day postnatal to 26 wk. When the cats were adult, single-cell recordings were made from LS cortex ipsilateral to the lesion. In addition, transneuronal autoradiographic methods were used to trace the retino-thalamic projections to LS cortex in many of the same animals. Following lesions in 18- and 26-wk-old cats, there is a marked reduction in direction-selective LS cortex cells and an increase in cells that respond best to stationary flashing stimuli. These results are similar to those following visual cortex lesions in adult cats. In contrast, the percentages of cells with these properties are normal following lesions made from 1 day to 12 wk of age. Thus the critical period for development of direction selectivity and greater responses to moving than to stationary flashing stimuli in LS cortex following a visual cortex lesion ends between 12 and 18 wk of age. Following lesions in 26-wk-old cats, there is a decrease in the percentage of cells that respond to the ipsilateral eye, which is similar to results following visual cortex lesions in adult cats. However, ocular dominance is normal following lesions made from 1 day to 18 wk of age. Thus the critical period for development of responses to the ipsilateral eye following a lesion ends between 18 and 26 wk of age. Following visual cortex lesions in 2-, 4-, or 8-wk-old cats, about 30% of the LS cortex cells display orientation selectivity to elongated slits of light. In contrast, few or no cells display this property in normal adult cats, cats with lesions made on the day of birth, or cats with lesions made at 12 wk of age or later. Thus an anomalous property develops for many LS cells, and the critical period for this property begins later (between 1 day and 2 wk) and ends earlier (between 8 and 12 wk) than those for other properties.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Critical periods in amblyopia

2018 ◽  
Vol 35 ◽  
Author(s):  
TAKAO K. HENSCH ◽  
ELIZABETH M. QUINLAN
Keyword(s):  
Visual Cortex ◽  
Critical Period ◽  
Molecular Mechanisms ◽  
Ocular Dominance ◽  
Molecular Genetic ◽  
Monocular Deprivation ◽  
Critical Periods ◽  
Developmental Constraints ◽  
Early Postnatal Development ◽  
Visual Cortical

AbstractThe shift in ocular dominance (OD) of binocular neurons induced by monocular deprivation is the canonical model of synaptic plasticity confined to a postnatal critical period. Developmental constraints on this plasticity not only lend stability to the mature visual cortical circuitry but also impede the ability to recover from amblyopia beyond an early window. Advances with mouse models utilizing the power of molecular, genetic, and imaging tools are beginning to unravel the circuit, cellular, and molecular mechanisms controlling the onset and closure of the critical periods of plasticity in the primary visual cortex (V1). Emerging evidence suggests that mechanisms enabling plasticity in juveniles are not simply lost with age but rather that plasticity is actively constrained by the developmental up-regulation of molecular ‘brakes’. Lifting these brakes enhances plasticity in the adult visual cortex, and can be harnessed to promote recovery from amblyopia. The reactivation of plasticity by experimental manipulations has revised the idea that robust OD plasticity is limited to early postnatal development. Here, we discuss recent insights into the neurobiology of the initiation and termination of critical periods and how our increasingly mechanistic understanding of these processes can be leveraged toward improved clinical treatment of adult amblyopia.

scholarly journals Progressive maturation of silent synapses governs the duration of a critical period

2015 ◽  
Vol 112 (24) ◽  
pp. E3131-E3140 ◽  
Author(s):  
Xiaojie Huang ◽  
Sophia K. Stodieck ◽  
Bianka Goetze ◽  
Lei Cui ◽  
Man Ho Wong ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Critical Period ◽  
Neural Circuit ◽  
Ocular Dominance ◽  
Critical Periods ◽  
Ocular Dominance Plasticity ◽  
Silent Synapses ◽  
Synapse Maturation ◽  
Silent Synapse ◽  
Visual Cortical

During critical periods, all cortical neural circuits are refined to optimize their functional properties. The prevailing notion is that the balance between excitation and inhibition determines the onset and closure of critical periods. In contrast, we show that maturation of silent glutamatergic synapses onto principal neurons was sufficient to govern the duration of the critical period for ocular dominance plasticity in the visual cortex of mice. Specifically, postsynaptic density protein-95 (PSD-95) was absolutely required for experience-dependent maturation of silent synapses, and its absence before the onset of critical periods resulted in lifelong juvenile ocular dominance plasticity. Loss of PSD-95 in the visual cortex after the closure of the critical period reinstated silent synapses, resulting in reopening of juvenile-like ocular dominance plasticity. Additionally, silent synapse-based ocular dominance plasticity was largely independent of the inhibitory tone, whose developmental maturation was independent of PSD-95. Moreover, glutamatergic synaptic transmission onto parvalbumin-positive interneurons was unaltered in PSD-95 KO mice. These findings reveal not only that PSD-95–dependent silent synapse maturation in visual cortical principal neurons terminates the critical period for ocular dominance plasticity but also indicate that, in general, once silent synapses are consolidated in any neural circuit, initial experience-dependent functional optimization and critical periods end.

scholarly journals Multiple Roles for Nogo Receptor 1 in Visual System Plasticity

2016 ◽  
Vol 22 (6) ◽  
pp. 653-666 ◽  
Author(s):  
Céleste-Élise Stephany ◽  
Michael G. Frantz ◽  
Aaron W. McGee
Keyword(s):  
Visual Acuity ◽  
Visual System ◽  
Critical Period ◽  
Ocular Dominance ◽  
Mouse Genetics ◽  
Multiple Roles ◽  
Neural Function ◽  
Visual Plasticity ◽  
Species Specific ◽  
Abnormal Visual

During the developmental critical period for visual plasticity, discordant vision alters the responsiveness of neurons in visual cortex. The subsequent closure of the critical period not only consolidates neural function but also limits recovery of acuity from preceding abnormal visual experience. Despite species-specific differences in circuitry of the visual system, these characteristics are conserved. The nogo-66 receptor 1 ( ngr1) is one of only a small number of genes identified thus far that is essential to closing the critical period. Mice lacking a functional ngr1 gene retain developmental visual plasticity as adults and their visual acuity spontaneously improves after prolonged visual deprivation. Experiments employing conditional mouse genetics have revealed that ngr1 restricts plasticity within distinct circuits for ocular dominance and visual acuity. However, the mechanisms by which NgR1 limits plasticity have not been elucidated, in part because the subcellular localization and signal transduction of the protein are only partially understood. Here we explore potential mechanisms for NgR1 function in relation to manipulations that reactivate visual plasticity in adults and propose lines of investigation to address relevant gaps in knowledge.

scholarly journals Temporal patterns of fluoxetine-induced plasticity in the mouse visual cortex

2018 ◽  
Author(s):  
Anna Steinzeig ◽  
Cecilia Cannarozzo ◽  
Eero Castren
Keyword(s):  
Visual Cortex ◽  
Critical Period ◽  
Ocular Dominance ◽  
Temporal Patterns ◽  
Monocular Deprivation ◽  
Adult Brain ◽  
Postnatal Life ◽  
Critical Periods ◽  
Mouse Visual Cortex

Heightened neuronal plasticity expressed during early postnatal life has been thought to permanently decline once critical periods have ended. For example, monocular deprivation is able to shift ocular dominance in the mouse visual cortex during the first months of life, but this effect is lost later in life. However, various treatments such as the antidepressant fluoxetine can reactivate a critical period-like plasticity in the adult brain. When monocular deprivation is supplemented with chronic fluoxetine administration, a major shift in ocular dominance is produced after the critical period has ended. In the current study, we characterized the temporal patterns of fluoxetine-induced plasticity in the adult mouse visual cortex, using in vivo optical imaging. We found that artificially-induced plasticity in ocular dominance extended beyond the duration of the naturally occurring critical period, and continued as long as fluoxetine was administered. However, this fluoxetine-induced plasticity period ended as soon as the drug was not given. Taken together, our data highlights how a combination of pharmacological treatment and environmental change could be used to improve strategies in antidepressant therapy in humans.

scholarly journals Modification of Peak Plasticity Induced by Brief Dark Exposure

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Alexander J. Lingley ◽  
Donald E. Mitchell ◽  
Nathan A. Crowder ◽  
Kevin R. Duffy
Keyword(s):  
Visual System ◽  
Neural Plasticity ◽  
Critical Period ◽  
Ocular Dominance ◽  
Monocular Deprivation ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Soma Size ◽  
Slow Progress ◽  
Dark Exposure ◽  
Central Visual System

The capacity for neural plasticity in the mammalian central visual system adheres to a temporal profile in which plasticity peaks early in postnatal development and then declines to reach enduring negligible levels. Early studies to delineate the critical period in cats employed a fixed duration of monocular deprivation to measure the extent of ocular dominance changes induced at different ages. The largest deprivation effects were observed at about 4 weeks postnatal, with a steady decline in plasticity thereafter so that by about 16 weeks only small changes were measured. The capacity for plasticity is regulated by a changing landscape of molecules in the visual system across the lifespan. Studies in rodents and cats have demonstrated that the critical period can be altered by environmental or pharmacological manipulations that enhance plasticity at ages when it would normally be low. Immersion in complete darkness for long durations (dark rearing) has long been known to alter plasticity capacity by modifying plasticity-related molecules and slowing progress of the critical period. In this study, we investigated the possibility that brief darkness (dark exposure) imposed just prior to the critical period peak can enhance the level of plasticity beyond that observed naturally. We examined the level of plasticity by measuring two sensitive markers of monocular deprivation, namely, soma size of neurons and neurofilament labeling within the dorsal lateral geniculate nucleus. Significantly larger modification of soma size, but not neurofilament labeling, was observed at the critical period peak when dark exposure preceded monocular deprivation. This indicated that the natural plasticity ceiling is modifiable and also that brief darkness does not simply slow progress of the critical period. As an antecedent to traditional amblyopia treatment, darkness may increase treatment efficacy even at ages when plasticity is at its highest.

scholarly journals An Emulation of Randomized Trials of Administrating Antipsychotics in PTSD Patients for Outcomes of Suicide-Related Events

2021 ◽  
Vol 11 (3) ◽  
pp. 178
Author(s):  
Noah R. Delapaz ◽  
William K. Hor ◽  
Michael Gilbert ◽  
Andrew D. La ◽  
Feiran Liang ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Previous History ◽  
Current Treatment ◽  
Careful Consideration ◽  
P Value ◽  
Post Traumatic Stress ◽  
Increased Risk ◽  
History Of ◽  
Almost All

Post-traumatic stress disorder (PTSD) is a prevalent mental disorder marked by psychological and behavioral changes. Currently, there is no consensus of preferred antipsychotics to be used for the treatment of PTSD. We aim to discover whether certain antipsychotics have decreased suicide risk in the PTSD population, as these patients may be at higher risk. A total of 38,807 patients were identified with a diagnosis of PTSD through the ICD9 or ICD10 codes from January 2004 to October 2019. An emulation of randomized clinical trials was conducted to compare the outcomes of suicide-related events (SREs) among PTSD patients who ever used one of eight individual antipsychotics after the diagnosis of PTSD. Exclusion criteria included patients with a history of SREs and a previous history of antipsychotic use within one year before enrollment. Eligible individuals were assigned to a treatment group according to the antipsychotic initiated and followed until stopping current treatment, switching to another same class of drugs, death, or loss to follow up. The primary outcome was to identify the frequency of SREs associated with each antipsychotic. SREs were defined as ideation, attempts, and death by suicide. Pooled logistic regression methods with the Firth option were conducted to compare two drugs for their outcomes using SAS version 9.4 (SAS Institute, Cary, NC, USA). The results were adjusted for baseline characteristics and post-baseline, time-varying confounders. A total of 5294 patients were eligible for enrollment with an average follow up of 7.86 months. A total of 157 SREs were recorded throughout this study. Lurasidone showed a statistically significant decrease in SREs when compared head to head to almost all the other antipsychotics: aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (p < 0.0001 and false discovery rate-adjusted p value < 0.0004). In addition, olanzapine was associated with higher SREs than quetiapine and risperidone, and ziprasidone was associated with higher SREs than risperidone. The results of this study suggest that certain antipsychotics may put individuals within the PTSD population at an increased risk of SREs, and that careful consideration may need to be taken when prescribed.

scholarly journals Demand Response Coupled with Dynamic Thermal Rating for Increased Transformer Reserve and Lifetime

Energies ◽  
2021 ◽  
Vol 14 (5) ◽  
pp. 1378
Author(s):  
Ildar Daminov ◽  
Rémy Rigo-Mariani ◽  
Raphael Caire ◽  
Anton Prokhorov ◽  
Marie-Cécile Alvarez-Hérault
Keyword(s):  
Ambient Temperature ◽  
Demand Response ◽  
Thermal Model ◽  
Critical Period ◽  
Optimization Problem ◽  
Integrated Management ◽  
Critical Periods ◽  
Network Access ◽  
Maximal Amplitude ◽  
Demand Response Program

(1) Background: This paper proposes a strategy coupling Demand Response Program with Dynamic Thermal Rating to ensure a transformer reserve for the load connection. This solution is an alternative to expensive grid reinforcements. (2) Methods: The proposed methodology firstly considers the N-1 mode under strict assumptions on load and ambient temperature and then identifies critical periods of the year when transformer constraints are violated. For each critical period, the integrated management/sizing problem is solved in YALMIP to find the minimal Demand Response needed to ensure a load connection. However, due to the nonlinear thermal model of transformers, the optimization problem becomes intractable at long periods. To overcome this problem, a validated piece-wise linearization is applied here. (3) Results: It is possible to increase reserve margins significantly compared to conventional approaches. These high reserve margins could be achieved for relatively small Demand Response volumes. For instance, a reserve margin of 75% (of transformer nominal rating) can be ensured if only 1% of the annual energy is curtailed. Moreover, the maximal amplitude of Demand Response (in kW) should be activated only 2–3 h during a year. (4) Conclusions: Improvements for combining Demand Response with Dynamic Thermal Rating are suggested. Results could be used to develop consumer connection agreements with variable network access.

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