Modelling thalamocortical circuitry shows that visually induced LTP changes laminar connectivity in human visual cortex

Sumner, Rachael L.; Spriggs, Meg J.; Shaw, Alexander D

doi:10.1371/journal.pcbi.1008414

Cited by 7 publications

(15 citation statements)

References 66 publications

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“…Drugs hypothesised to increase cortical excitability, such as 3-h post ketamine infusion and acutely following a dose of d-cycloserine, have a facilitatory effect on visual LTP 36 , 37 . However, there is evidence that increases in inhibitory activity occur in tandem with excitatory changes at different cellular layers of the visual cortex following LTP induction with a visual tetanus 38 . It is possible that previous contrasting findings are a result of different mechanisms being captured by different methods of understanding excitatory and inhibitory activity (e.g.…”

Section: Discussionmentioning

confidence: 99%

Acute exercise as a modifier of neocortical plasticity and aperiodic activity in the visual cortex

Cadwallader,

Steiniger,

Cooper

et al. 2023

Sci Rep

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Long-term potentiation (LTP) is a form of neuroplasticity commonly implicated in mechanistic models of learning and memory. Acute exercise can boost LTP in the motor cortex, and is associated with a shift in excitation/inhibition (E:I) balance, but whether this extends to other regions such as the visual cortex is unknown. We investigated the effect of a preceding bout of exercise on LTP induction and the E:I balance in the visual cortex using electroencephalography (EEG). Young adults (N = 20, mean age = 24.20) engaged in 20 min of high-intensity interval training (HIIT) exercise and rest across two counterbalanced sessions. LTP was induced using a high frequency presentation of a visual stimulus; a “visual tetanus”. Established EEG markers of visual LTP, the N1b and P2 component of the visual evoked potential, and an EEG-derived measure of the E:I balance, the aperiodic exponent, were measured before and after the visual tetanus. As expected, there was a potentiation of the N1b following the visual tetanus, with specificity to the tetanised stimulus, and a non-specific potentiation of the P2. These effects were not sensitive to a preceding bout of exercise. However, the E:I balance showed a late shift towards inhibition following the visual tetanus. A preceding bout of exercise resulted in specificity of this E:I balance shift to the tetanised stimulus, that was not seen following rest. This novel finding suggests a possible exercise-induced tuning of the visual cortex to stimulus details following LTP induction.

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Section: Discussionmentioning

confidence: 99%

Acute exercise as a modifier of neocortical plasticity and aperiodic activity in the visual cortex

Cadwallader,

Steiniger,

Cooper

et al. 2023

Sci Rep

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“…A biologically grounded model of thalamo-cortical circuitry [ 34 ] has previously been used to build a neural mass model of human brain networks related to visual processing, such that the production of signal at the scalp is plausibly explained by alterations to the connectivity between and within cell populations in the thalamus and layers 2–6 of the visual cortex, as well as receptor time constants (open time and decay rate) of neurotransmitters [ 35 ]. Application of this thalamo-cortical model (TCM) to EEG LTP data without a drug condition has previously demonstrated modulation of connections consistent with in vivo LTP research, including increased excitatory connectivity between the thalamus and layer 4 neurons in the visual cortex, as well as from layer 4 to layers 2/3 [ 36 ], but has not yet been applied to microdoses of LSD.…”

Section: Introductionmentioning

confidence: 94%

Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial

Murphy,

Godfrey,

Shaw

et al. 2024

BMC Neurosci

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Background Microdosing psychedelics is a phenomenon with claimed cognitive benefits that are relatively untested clinically. Pre-clinically, psychedelics have demonstrated enhancing effects on neuroplasticity, which cannot be measured directly in humans, but may be indexed by non-invasive electroencephalography (EEG) paradigms. This study used a visual long-term potentiation (LTP) EEG paradigm to test the effects of microdosed lysergic acid diethylamide (LSD) on neural plasticity, both acutely while on the drug and cumulatively after microdosing every third day for six weeks. Healthy adult males (n = 80) completed the visual LTP paradigm at baseline, 2.5 h following a dose of 10 µg of LSD or inactive placebo, and 6 weeks later after taking 14 repeated microdoses. Visually induced LTP was used as indirect index of neural plasticity. Surface level event-related potential (ERPs) based analyses are presented alongside dynamic causal modelling of the source localised data using a generative thalamocortical model (TCM) of visual cortex to elucidate underlying synaptic circuitry. Results Event-related potential (ERP) analyses of N1b and P2 components did not show evidence of changes in visually induced LTP by LSD either acutely or after 6 weeks of regular dosing. However modelling the complete timecourse of the ERP with the TCM demonstrated changes in laminar connectivity in primary visual cortex. This primarily included changes to self-gain and inhibitory input parameters acutely. Layer 2/3 to layer 5 excitatory connectivity was also different between LSD and placebo groups. After regular dosing only excitatory input from layer 2/3 into layer 5 and inhibitory input into layer 4 were different between groups. Conclusions Without modulation of the ERPs it is difficult to relate the findings to other studies visually inducing LTP. It also indicates the classic peak analysis may not be sensitive enough to demonstrate evidence for changes in LTP plasticity in humans at such low doses. The TCM provides a more sensitive approach to assessing changes to plasticity as differences in plasticity mediated laminar connectivity were found between the LSD and placebo groups. Trial registration: ANZCTR registration number ACTRN12621000436875; Registered 16/04/2021 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381476.

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“…In the current study, the finding of enhanced P2 potentiation on day 21 may plausibly represent a mechanism of greater excitation or reduced inhibition underlying preserved cyclicity of LTP increases in the perimenstrual-like phase. Previous studies have shown that generative, neurobiologically informed models of cortical activation during EEG can be used to disentangle these possibilities after administration of drugs [57][58][59][60] and in disorder [61,62], as they have demonstrated sensitivity to the change in visual cortex microcircuitry that underlie LTP [35] and change over the menstrual cycle [63].…”

Section: The Effect Of Preserved Cyclicitymentioning

confidence: 99%

“…AMPA, NMDA, GABA-A, GABA-B, M and H channels are also parameterised. This model has previously demonstrated sensitivity to (invasively demonstrated [37, 38]) changes to the visual cortex evoked by LTP [35].…”

Section: Introductionmentioning

confidence: 99%

Changes in Visual Long-Term Potentiation Show Preserved Cyclicity in Human Females Taking Combined Oral Contraceptives

Stone¹,

Alshakhouri²,

Shaw³

et al. 2023

Neuroendocrinology

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Introduction: The combined oral contraceptive pill (COC) is often employed to address physical and neurological symptoms in menstrual cycle-related disorders by suppressing shifts in endogenous gonadal hormone fluctuations. Symptom persistence, especially in the lead up to the hormone free interval (HFI) suggests an underlying neurobiological mechanism of preserved cycling. Our study utilised a non-invasive method of visually inducing long-term potentiation (LTP) to index changes in neural plasticity in the absence of hormonal fluctuations.   Methods:  Visually induced LTP was recorded using electroencephalography in 24 healthy female COC users across three sessions; day 3 and 21 during active hormone pills, and day 24 during the HFI. The Daily Record of the Severity of Problems (DRSP) questionnaire tracked premenstrual symptoms. Dynamic causal modelling (DCM) was used to elucidate the neural connectivity and receptor activity changes associated with LTP across different days of COC.   Results: Visually induced LTP was greater on day 21 than day 3 (p=0.011) and was localised to the P2 visually evoked potential. There was no effect of the HFI (day 24) on LTP. DCM of differences between day 3 and 21 showed changes to inhibitory interneuronal gating of LTP in cortical layer VI. The DRSP only showed a significant increase in symptoms in the HFI, meaning the LTP result appeared more sensitive to cyclicity. Conclusions: This study provides objective evidence of preserved cyclicity in COC users through enhanced LTP on day 21 compared to day 3 of a 28-day COC regimen, indicating that relatively higher excitation in the brain despite peripheral gonadal suppression may underlie and exacerbate menstrual cycle-related disorders.

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Modelling thalamocortical circuitry shows that visually induced LTP changes laminar connectivity in human visual cortex

Cited by 7 publications

References 66 publications

Acute exercise as a modifier of neocortical plasticity and aperiodic activity in the visual cortex

Acute exercise as a modifier of neocortical plasticity and aperiodic activity in the visual cortex

Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial

Changes in Visual Long-Term Potentiation Show Preserved Cyclicity in Human Females Taking Combined Oral Contraceptives

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