Personalized brain stimulation of memory networks

Available online 13 September 2022Background: The finding that transcranial magnetic stimulation (TMS) can enhance memory performance via stimulation of parietal sites within the Cortical-Hippocampal Network counts as one of the most exciting findings in this field in the past decade. However, the first independent effort aiming to fully replicate this finding found no discernible influence of TMS on memory performance. Objective: We examined whether this might relate to interindividual spatial variation in brain connectivity architecture, and the capacity of personalisation methodologies to overcome the noise inherent across independent scanners and cohorts. Methods: We implemented recently detailed personalisation methodology to retrospectively compute individual-specific parietal targets and then examined relation to TMS outcomes. Results: Closer proximity between actual and novel fMRI-personalized targets associated with greater improvement in memory performance. Conclusion: These findings demonstrate the potential importance of aligning brain stimulation targets according to individual-specific differences in brain connectivity, and extend upon recent findings in prefrontal cortex.Robin F.H. Cash, Joshua Hendrikse, Kavisha B Fernando, Sarah Thompson, Chao Suo, Alex Fornito, Murat Yücel, Nigel C. Rogasch, Andrew Zalesky, James P. Coxo

The correspondence between EMG and EEG measures of changes in cortical excitability following transcranial magnetic stimulation

First published: 18 February 2021Key points: TMS is commonly used to study excitatory/inhibitory neurotransmission in cortical circuits. Changes in cortical excitability following TMS are typically measured from hand (using EMG; limited to motor cortex) or scalp (using EEG), however it is unclear whether these two measures represent the same activity when assessing motor cortex. We found that TMS-EMG and TMS-EEG measures of motor cortex excitability are differentially impacted by sensory confounds at different time points masking any actual relationship between them in the time domain. In the frequency domain, local high-frequency oscillations in EEG recordings were minimally confounded by sensory artefacts and demonstrated strong correlations with EMG measures of cortical excitability across time, regardless of TMS intensity or waveform. Therefore, despite the effects of sensory artefacts, the two measures of motor cortex excitability share a response component, suggesting that they index a similar cortical activity and perhaps the same neuronal population.AbstractTranscranial magnetic stimulation (TMS) is a powerful tool to investigate cortical circuits. Changes in cortical excitability following TMS are typically assessed by measuring changes in either conditioned motor-evoked potentials (MEPs) following paired-pulse TMS over motor cortex or evoked potentials measured with electroencephalography following single-pulse TMS (TEPs). However, it is unclear whether these two measures of cortical excitability index the same cortical response. Twenty-four healthy participants received local and interhemispheric paired-pulse TMS over motor cortex with eight inter-pulse intervals, sub- and suprathreshold conditioning intensities, and two different pulse waveforms, while MEPs were recorded from a hand muscle. TEPs were also recorded in response to single-pulse TMS using the conditioning pulse alone. The relationships between TEPs and conditioned-MEPs were evaluated using metrics sensitive to both their magnitude at each timepoint and their overall shape across time. The impacts of undesired sensory potentials resulting from TMS pulse and muscle contractions were also assessed on both measures. Both conditioned-MEPs and TEPs were sensitive to re-afferent somatosensory activity following motor-evoked responses, but over different post-stimulus timepoints. Moreover, the amplitude of low-frequency oscillations in TEPs was strongly correlated with the sensory potentials, whereas early and local high-frequency responses showed minimal relationships. Accordingly, conditioned-MEPs did not correlate with TEPs in the time domain but showed high shape similarity with the amplitude of high-frequency oscillations in TEPs. Therefore, despite the effects of sensory confounds, the TEP and MEP measures share a response component, suggesting that they index a similar cortical response and perhaps the same neuronal populations. This article is protected by copyright. All rights reserved.Mana Biabani, Alex Fornito, James P. Coxon, Ben D. Fulcher, Nigel C. Rogasc

Visuomotor task acquisition is reduced by priming paired associative stimulation in older adults

Transcranial magnetic stimulation may represent an effective means for improving motor function in the elderly. The aim of this study was therefore to investigate the effects of paired associative stimulation (PAS; a plasticity-inducing transcranial magnetic stimulation paradigm) on acquisition of a novel visuomotor task in young and older adults. Fourteen young (20.4 ± 0.6 years) and 13 older (69.0 ± 1.6 years) adults participated in 3 experimental sessions during which training was preceded (primed) by PAS. Within each session, the interstimulus interval used for PAS was set at either the N20 latency plus 5 ms (PASLTP), the N20 latency minus 10 ms (PASLTD), or a constant 100 ms (PASControl). After training, the level of motor skill was not different between PAS conditions in young subjects (all p-values > 0.2), but was reduced by both PASLTP (p = 0.02) and PASLTD (p = 0.0001) in older subjects. Consequently, priming PAS was detrimental to skill acquisition in older adults, possibly suggesting a need for interventions that are optimized for use in elderly populations.George M. Opie, Brodie J. Hand, James P. Coxon, Michael C. Ridding, Ulf Ziemann, John G. Semmle

Regular aerobic exercise is positively associated with hippocampal structure and function in young and middle-aged adults

First published: 27 December 2021Regular exercise has numerous benefits for brain health, including the structure and function of the hippocampus. The hippocampus plays a critical role in memory function, and is altered in a number of psychiatric disorders associated with memory impairments (e.g., depression and schizophrenia), as well as healthy aging. While many studies have focused on how regular exercise may improve hippocampal integrity in older individuals, less is known about these effects in young to middle-aged adults. Therefore, we assessed the associations of regular exercise and cardiorespiratory fitness with hippocampal structure and function in these age groups. We recruited 40 healthy young to middle-aged adults, comprised of two groups (n = 20) who self-reported either high or low levels of exercise, according to World Health Organization guidelines. We assessed cardiorespiratory fitness using a graded exercise test (VO₂max) and hippocampal structure via manual tracing of T1-weighted magnetic resonance images. We also assessed hippocampal function using magnetic resonance spectroscopy to derive estimates of N-acetyl-aspartate concentration and hippocampal-dependent associative memory and pattern separation tasks. We observed evidence of increased N-acetyl-aspartate concentration and associative memory performance in individuals engaging in high levels of exercise. However, no differences in hippocampal volume or pattern separation capacity were observed between groups. Cardiorespiratory fitness was positively associated with left and right hippocampal volume and N-acetyl-aspartate concentration. However, no associations were observed between cardiorespiratory fitness and associative memory or pattern separation. Therefore, we provide evidence that higher levels of exercise and cardiorespiratory fitness are associated with improved hippocampal structure and function. Exercise may provide a low-risk, effective method of improving hippocampal integrity in an early-to-mid-life stage.Joshua Hendrikse, Yann Chye, Sarah Thompson, Nigel C. Rogasch, Chao Suo, James P. Coxon, Murat Yüce

Multi-day rTMS exerts site-specific effects on functional connectivity but does not influence associative memory performance

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique with the capacity to modulate brain network connectivity and cognitive function. Recent studies have demonstrated long-lasting improvements in associative memory and resting-state connectivity following multi-day repetitive TMS (rTMS) to individualised parietal-hippocampal networks. We aimed to assess the reproducibility and network- and cognitive-specificity of these effects following multi-day rTMS. Participants received four days of 20 Hz rTMS to a subject-specific region of left lateral parietal cortex exhibiting peak functional connectivity to the left hippocampus. In a separate week, the same stimulation protocol was applied to a subject-specific region of pre-supplementary motor area (pre-SMA) exhibiting peak functional connectivity to the left putamen. We assessed changes to associative memory before and after each week of stimulation (N = 39), and changes to resting-state functional connectivity before and after stimulation in week one (N = 36). We found no evidence of long-lasting enhancement of associative memory or increased parieto-hippocampal connectivity following multi-day rTMS to the parietal cortex, nor increased pre-SMA-putamen connectivity following multi-day rTMS to pre-SMA. Instead, we observed some evidence of site-specific modulations of functional connectivity lasting ~24 h, with reduced connectivity within targeted networks and increased connectivity across distinct non-targeted networks. Our findings suggest a complex interplay between multi-day rTMS and network connectivity. Further work is required to develop reliable rTMS paradigms for driving changes in functional connectivity between cortical and subcortical regions.Joshua Hendrikse, James P. Coxon, Sarah Thompson, Chao Suo, Alex Fornito, Murat Yücel and Nigel C. Rogasc

GABA concentration in sensorimotor cortex following high-intensity exercise and relationship to lactate levels

First published online 21 November 2017KEY POINTS:Magnetic resonance spectroscopy was conducted before and after high-intensity interval exercise. Sensorimotor cortex GABA concentration increased by 20%. The increase was positively correlated with the increase in blood lactate. There was no change in dorsolateral prefrontal cortex. There were no changes in the glutamate-glutamine-glutathione peak. ABSTRACT: High-intensity exercise increases the concentration of circulating lactate. Cortical uptake of blood borne lactate increases during and after exercise; however, the potential relationship with changes in the concentration of neurometabolites remains unclear. Although changes in neurometabolite concentration have previously been demonstrated in primary visual cortex after exercise, it remains unknown whether these changes extend to regions such as the sensorimotor cortex (SM) or executive regions such as the dorsolateral prefrontal cortex (DLPFC). In the present study, we explored the acute after-effects of high-intensity interval training (HIIT) on the concentration of gamma-Aminobutyric acid (GABA) and the combined glutamate-glutamine-glutathione (Glx) spectral peak in the SM and DLPFC, as well as the relationship with blood lactate levels. Following HIIT, there was a robust increase in GABA concentration in the SM, as evident across the majority of participants. This change was not observed in the DLPFC. Furthermore, the increase in SM GABA was positively correlated with an increase in blood lactate. There were no changes in Glx concentration in either region. The observed increase in SM GABA concentration implies functional relevance, whereas the correlation with lactate levels may relate to the metabolic fate of exercise-derived lactate that crosses the blood-brain barrier.James P. Coxon, Robin F.H. Cash, Joshua J. Hendrikse, Nigel C. Rogasch, Ellen Stavrinos, Chao Suo and Murat Yüce

A Bayesian analysis of the association between Leukotriene A4 Hydrolase genotype and survival in tuberculous meningitis

Contains fulltext : 230370.pdf (publisher's version ) (Open Access

Signatures of magnetic separatrices at the borders of a crater flux transfer event connected to an active x-line

In this paper, we present Magnetospheric Multiscale (MMS) observations of a flux transfer event (FTE) characterized by a clear signature in the magnetic field magnitude, which shows maximum at the center flanked by two depressions, detected during a period of stable southward interplanetary magnetic field. This class of FTEs are called “crater‐FTEs” and have been suggested to be connected with active reconnection X line. The MMS burst mode data allow the identification of intense fluctuations in the components of the electric field and electron velocity parallel to the magnetic field at the borders of the FTE, which are interpreted as signatures of the magnetic separatrices. In particular, the strong and persistent fluctuations of the parallel electron velocity at the borders of this crater‐FTE reported for the first time in this paper, sustain the field‐aligned current part of the Hall current system along the separatrix layer, and confirm that this FTE is connected with an active reconnection X line. Our observations suggest a stratification of particles inside the reconnection layer, where electrons are flowing toward the X line along the separatrix, are flowing away from the X line along the reconnected field lines adjacent to the separatrices, and more internally ions and electrons are flowing away from the X line with comparable velocities, forming the reconnection jets. This stratification of the reconnection layer forming the FTE, together with the reconnection jet at the trailing edge of the FTE, suggests clearly that this FTE is formed by the single X line generation mechanism