Biology subjects

Sumner, R. L.

Publications and source records attributed to Sumner, R. L..

4 recordsLinked to original sources

bioRxiv2025

Females with epilepsy show abnormal changes to perimenstrual sensory induced long-term potentiation

IntroductionCatamenial epilepsy refers to a cyclical exacerbation of seizure frequency and/or severity linked to stages of the menstrual cycle. To investigate the contribution of underlying excitatory and inhibitory mechanisms of this exacerbation we induced and measured long-term potentiation (LTP). Oestradiol modulates primarily NMDA receptor driven excitation and would enhance visual LTP. Allopregnanolone modulates GABA receptor mediated inhibition and would suppress visual LTP. MethodA control cohort (n = 25) and a cohort with epilepsy (n = 20) were recruited. Participants took part in a visual LTP task while EEG was recorded. Three study visits were timed to capture the mid-follicular (days +5 to +8), mid-luteal (days -9 to -5) phases, as well as the hormone withdrawal in the perimenstrual phase (days -3 to +2). Blood samples confirmed session timing. Generative computational modelling of thalamocortical changes in the EEG was paired with standard evoked potential analysis. Result17 (age 26 {+/-} 9.40) participants with epilepsy, and a control cohort of 25 (age 30 {+/-} 7.06) without epilepsy completed the study. The P2 visually evoked potential (a positive-going component of the visual event related potential waveform) was significantly more enhanced by LTP induction in the mid-follicular phase than the mid-luteal or perimenstrual phases in the control cohort (F(2, 144) =11.54, p = 0.004 corrected). In contrast, in the epilepsy cohort the P2 was significantly more potentiated in the perimenstrual phase than the mid-follicular or mid-luteal phases (F(2,108) = 12.21, p = 0.005 corrected). The effect of cycle on visual LTP was robust, with only 3/17 participants with epilepsy showing highest P2 modulation in the mid-follicular phase (which is the pattern the healthy cohort showed). The computational modelling showed that in epilepsy, the perimenstrual phase was associated with a decrease in superficial pyramidal grain control as well as decreased LTP driven modulation of feed-forward superficial connections to layer 5 and layer 6 to thalamus. DiscussionOur finding of enhanced visual LTP in the luteal phase and perimenstrual phase of females with epilepsy indicates a breakthrough of glutamatergic excitation. Given the relationship between oestrogen and n-methyl-D-aspartate (NMDA) receptor dependent LTP this is plausibly NMDA receptor driven. Several thalamocortical model parameter changes observed warrant further investigation in studies stratifying participants by catamenial epilepsy type. Overall, while research into allopregnanolone and its inhibitory effects dominate perimenstrual catamenial epilepsy research, this study justifies consideration of the role of seizure exacerbating oestradiol.

neuroscience↗

bioRxiv2020

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

Neuroplasticity is essential to learning and memory in the brain; it has therefore also been implicated in numerous neurological and psychiatric disorders, making measuring the state of neuroplasticity of foremost importance to clinical neuroscience. Long-term potentiation (LTP) is a key mechanism of neuroplasticity and has been studied extensively, and invasively in non-human animals. Translation to human application largely relies on the validation of non-invasive measures of LTP. The current study provides validation for the use of a thalamocortical computational model of visual cortex for investigating and replicating interlaminar connectivity changes using non-invasive EEG recording of humans, and a commonly used visual sensory LTP paradigm. The model demonstrated remarkable accuracy recapitulating post-tetanus changes including increased excitatory connectivity from thalamus to layer IV and from layer IV to II/III. The findings also further validate visual sensory induced LTP and evoked potential modulation for measuring of the state of LTP in cortex.

neuroscience↗

bioRxiv2017

Peak gamma frequency and cortical laminar processing are modified across the healthy menstrual cycle

Fluctuations in gonadal hormones over the course of the menstrual cycle are known to cause functional brain changes and are thought to modulate changes in the balance of cortical excitation and inhibition. Animal research has shown this occurs primarily via the major metabolite of progesterone, allopregnanolone, and its action as a positive allosteric modulator of the GABAA receptor. Our study used EEG to record gamma oscillations induced in the visual cortex using stationary and moving gratings. Recordings took place during twenty females' mid-luteal phase when progesterone and oestradiol are highest, and early follicular phase when progesterone and oestradiol are lowest. Significantly higher (~5 Hz) gamma frequency was recorded during the luteal compared to the follicular phase for both stimuli types. Using dynamic causal modelling these changes were linked to stronger self-inhibition of superficial pyramidal cells in the luteal compared to the follicular phase. In addition the connection from inhibitory interneurons to deep pyramidal cells was found to be stronger in the follicular compared to the luteal phase. These findings show that complex functional changes in synaptic microcircuitry occur across the menstrual cycle and that menstrual cycle phase should be taken into consideration when including female participants in research into gamma-band oscillations.

neuroscience↗

bioRxiv2017

Indexing sensory plasticity: Evidence for distinct Predictive Coding and Hebbian Learning mechanisms in the cerebral cortex

HighlightsO_LIERP and DCM study of two sensory plasticity paradigms: roving MMN and visual LTP\nC_LIO_LIFirst demonstration of multiple learning mechanisms under different task demands\nC_LIO_LIEvidence for both Predictive Coding and Hebbian learning mechanisms\nC_LIO_LIThe BDNF Val66Met polymorphism modulates ERPs for both paradigms\nC_LIO_LIHowever, the polymorphism only modulates MMN network connectivity\nC_LI\n\nThe Roving Mismatch Negativity (MMN), and Visual LTP paradigms are widely used as independent measures of sensory plasticity. However, the paradigms are built upon fundamentally different (and seemingly opposing) models of perceptual learning; namely, Predictive Coding (MMN) and Hebbian plasticity (LTP). The aims of the current study were to 1) compare the generative mechanisms of the MMN and visual LTP, therefore assessing whether Predictive Coding and Hebbian mechanisms co-occur in the brain, and 2) assess whether the paradigms identify similar group differences in plasticity. Forty participants were split into two groups based on the BDNF Val66Met polymorphism and were presented with both paradigms. Consistent with Predictive Coding and Hebbian predictions, Dynamic Causal Modelling revealed that the generation of the MMN modulates forward and backward connections in the underlying network, while visual LTP only modulates forward connections. Genetic differences were identified in the ERPs for both paradigms, but were only apparent in backward connections of the MMN network. These results suggest that both Predictive Coding and Hebbian mechanisms are utilized by the brain under different task demands. Additionally, both tasks provide unique insight into plasticity mechanisms, which has important implications for future studies of aberrant plasticity in clinical populations.

neuroscience↗