Charlotte J Stagg

University of Oxford | OX · Nuffield Department of Clinical Neurosciences

Background: Intermittent theta-burst stimulation (iTBS) is a transcranial magnetic stimulation (TMS) protocol which can temporarily modulate the corticospinal excitability. Conventionally, TBS is only applied using biphasic pulses due to hardware limitations. However, monophasic pulses are hypothesised to more selectively recruit cortical neurons t...

Transcranial ultrasonic stimulation (TUS), has been shown to evoke 'visual evoked potential (VEP)-like' potentials on EEG recordings, and also to modulate sensory evoked potentials. However, pulsed TUS is accompanied by an auditory confound, and it is possible that any observed effects were, in-part, evoked by this confound. Therefore, we used ramp...

Low-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive technique for focally modulating human brain function. The mechanisms and neurochemical substrates underlying TUS neuromodulation in humans and how these relate to excitation and inhibition are still poorly understood. In 24 healthy controls, we separately stimulate...

The recruitment of disabled participants for conducting usability evaluation of accessible information and communication technologies (ICT) is a challenge that current research faces. To overcome these challenges, researchers have been calling upon able-bodied participants to undergo disability simulations. However, this practice has been criticize...

Advances in functional magnetic resonance spectroscopy (fMRS) have enabled the quantification of activity-dependent changes in neurotransmitter concentrations in vivo. However, the physiological basis of the large changes in GABA and glutamate observed by fMRS (>10%) over short time scales of less than a minute remain unclear as such changes cannot...

Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as autism. GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigates whether application of anodal transcranial direct current stimulation (atDCS) can...

Background and objective Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that le...

Myelination has been increasingly implicated in the function and dysfunction of the adult human brain. Although it is known that axon myelination shapes axon physiology in animal models, it is unclear whether a similar principle applies in the living human brain, and at the level of whole axon bundles in white matter tracts. Here, we hypothesised t...

Background There is a paucity of reliable markers of disease activity and progression in ALS. Better biomarkers would also reduce clinical trial duration and cost by providing more sensitive measures of target engagement. Cortical hyperexcitability with transcranial magnetic stimulation, while promising, has not yet been clinically translatable. Mu...

Background Primary motor cortex hyperexcitability demonstrated in amyotrophic lateral sclerosis (ALS) is associated with wider network dysfunction. The precise topology and nature of these functional altera- tions remains unclear, including the extent of overlap between ALS and the pure upper-motor-neurone phenotype - primary lateral sclerosis (PLS...

Background and Objective Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that le...

Introduction Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive impairments, particularly with deficits in working memory. Prior research indicates that brain structure is affected in NF1, but it is unclear how these changes relate to aspects of cognition. Methods 29 adolescents aged 11-17 years were compared to age and...

Low-intensity transcranial electrical stimulation (tES), including alternating or direct current stimulation, applies weak electrical stimulation to modulate the activity of brain circuits. Integration of tES with concurrent functional MRI (fMRI) allows for the mapping of neural activity during neuromodulation, supporting causal studies of both bra...

Motor adaptation is crucial for performing accurate movements in a changing environment and relies on the cerebellum. Although cerebellar involvement has been well characterized, the neurochemical changes in the cerebellum underpinning human motor adaptation remain unknown. We used a novel Magnetic Resonance Spectroscopic Imaging (MRSI) technique t...

In N -methyl-D-aspartate receptor (NMDAR) antibody encephalitis, NMDAR-autoantibodies are hypothesised to cause prominent neuropsychiatric symptoms by internalizing NMDARs. However, supporting evidence comes chiefly from in vitro and rodent data with scant direct evidence from affected humans. Here, we used in vivo positron emission tomography (PET...

Skill learning is a fundamental adaptive process, but the mechanisms remain poorly understood. Some learning paradigms, particularly in the memory domain, are closely associated with gamma activity that is amplitude-modulated by the phase of underlying theta activity, but whether such nested activity patterns also underpin skill learning is unknown...

Many tasks require the skilled interaction of both hands, such as eating with knife and fork or keyboard typing. However, our understanding of the behavioural and neurophysiological mechanisms underpinning bimanual motor learning is still sparse. Here, we aimed to address this by first characterising learning-related changes of different levels of...

In humans, motor learning is underpinned by changes in sensorimotor network functional connectivity (FC). Unilateral contractions increase FC in the ipsilateral primary motor cortex (M1) and supplementary motor area (SMA); areas involved in motor planning and execution of the contralateral hand. Therefore, unilateral contractions are a promising ap...

Background: Neurofibromatosis 1 (NF1) is a single-gene neurodevelopmental disorder associated with cognitive and behavioural impairments, particularly with deficits in working memory. This study investigates the cerebral volumetric differences in adolescents with NF1 as compared to typically developing controls and how working memory task performan...

Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we car...

The development of assistive technologies and guidelines for their accessibility is impeded by the limited access to disabled participants. As a consequence, performing disability simulations on able bodied participants is a common practice in usability evaluation of assistive technologies. However, still little is known about how disability simula...

Transcranial direct current stimulation (tDCS) is an increasingly promising potential therapeutic intervention in the treatment of a range of psychiatric and neurological conditions. However, before its full potential can be utilized, more must be understood about its effects on the underlying brain tissue, both in regions local to the site of stim...

Interpreting cluttered scenes —a key skill for successfully interacting with our environment— relies on our ability to select relevant sensory signals while filtering out noise. Training is known to improve our ability to make these perceptual judgements by altering local processing in sensory brain areas. Yet, the brain-wide network mechanisms tha...

Background Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) & Attention Deficit Hyperactivity Disorder (ADHD). GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigat...

Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) & Attention Deficit Hyperactivity Disorder (ADHD). GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigates whether...

How we can optimise behavioural gains from training is a key neuroscientific question. The role of consolidation has often been overlooked but offers a substantial potential target for therapeutic approaches. Here, we discuss the mechanisms underpinning off-line skill acquisition, as reported in a recent study by Herszage and colleagues.

Stroke affects millions of people worldwide each year, and stroke survivors are often left with motor deficits. Current therapies to improve these functional deficits are limited, making it a priority to better understand the pathophysiology of stroke recovery and find novel adjuvant options. The excitation-inhibition balance undergoes significant...

Gamma activity (γ, >30 Hz) is universally demonstrated across brain regions and species. However, the physiological basis and functional role of γ sub-bands (slow-γ, mid-γ, fast-γ) have been predominantly studied in rodent hippocampus; γ activity in the human neocortex is much less well understood. Here we combined neuroimaging and non-invasive bra...

Magnetic Resonance Spectroscopy (MRS) allows for the non-invasive quantification of neurochemicals and has the potential to differentiate between the pathologically distinct diseases, multiple sclerosis (MS) and AQP4Ab-positive neuromyelitis optica spectrum disorder (AQP4Ab-NMOSD). In this study we characterised the metabolite profiles of brain les...

Understanding the role of neurotransmitters glutamate and GABA during normal and abnormal brain function and under external stimulation in humans are critical neuroscientific and clinical goals. The recent development of functional 1H-Magnetic resonance spectroscopy (fMRS) has allowed us to study neuro-transmitter activity in vivo for the first tim...

Proton (hydrogen 1 [¹H]) magnetic resonance spectroscopy (¹H-MRS) can be used to noninvasively quantify the regional levels of glutamate and gamma aminobutyric acid (GABA) within a given brain area. Since glutamate and GABA are two major neurotransmitters, ¹H-MRS is an important technique to understand the neurophysiological basis of noninvasive tr...

Background Low intensity transcranial electrical stimulation (tES), including alternating or direct current stimulation (tACS or tDCS), applies weak electrical stimulation to modulate brain circuits. Integration of tES with concurrent functional magnetic resonance imaging (fMRI) allows neuromodulation of brain regions while mapping network function...

Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we car...

Key points: Baclofen is a GABAB agonist prescribed as a treatment for spasticity in stroke, brain injury and multiple sclerosis patients, who are often undergoing concurrent motor rehabilitation. Decreasing GABAergic inhibition is a key feature of motor learning and so there is a possibility that GABA agonist drugs, such as baclofen, could impair...

Skill learning is a fundamental adaptive process, but the mechanisms remain poorly understood. Hippocampal learning is closely associated with gamma activity, which is amplitude-modulated by the phase of underlying theta activity. Whether such nested activity patterns also underpin skill acquisition in non-hippocampal tasks is unknown. Here we addr...

Background: Dual transcranial direct current stimulation (tDCS) to the bilateral primary motor cortices (M1s) has potential benefits in chronic stroke, but its effects in subacute stroke, when behavioural effects might be expected to be greater, have been relatively unexplored. Here, we examined the neurophysiological effects and the factors influ...

In real-world settings, learning is often characterised as intentional: learners are aware of the goal during the learning process, and the goal of learning is readily dissociable from the awareness of what is learned. Recent evidence has shown that reward and punishment (collectively referred to as valenced feedback) are important factors that inf...

Background The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be rest...

Background. Recovery of upper limb function post-stroke can be partly predicted by initial motor function, but the mechanisms underpinning these improvements have yet to be determined. Here, we sought to identify neural correlates of post-stroke recovery using longitudinal magnetoencephalography (MEG) assessments in subacute stroke survivors. Metho...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The human brain undergoes significant functional and structural changes in the first decades of life, as the foundations for human cognition are laid down. However, non-invasive imaging techniques to investigate brain function throughout neurodevelopment are limited due to growth in head-size with age and substantial head movement in young particip...

Besides its well established susceptibility to ageing, the hippocampus has also been shown to be affected by alcohol consumption. Proton spectroscopy (1H-MRS) of the hippocampus, particularly at high-field 7T MRI, may further our understanding of these associations. Here, we aimed to examine how hippocampal metabolites varied with age and alcohol c...

In real-world settings, learning is often characterised as intentional: learners are aware of the goal during the learning process. Recent evidence has shown that reward and punishment (collectively referred to as valenced feedback) are important factors that influence performance during learning. Presently, however, studies investigating the impac...

To investigate whether the observed anisotropic diffusion in cerebral cortex may reflect its columnar cytoarchitecture and myeloarchitecture, as a potential biomarker for disease‐related changes, we compared postmortem diffusion magnetic resonance imaging scans of nine multiple sclerosis brains with histology measures from the same regions. Histolo...

Reward and punishment shape behavior, but the mechanisms underlying their effect on skill learning are not well understood. Here, we tested whether the functional connectivity of premotor cortex (PMC), a region known to be critical for learning of sequencing skills, is altered after training when reward or punishment is given during training. Resti...

Translating noisy sensory signals to perceptual decisions is critical for successful interactions in complex environments. Learning is known to improve perceptual judgments by filtering external noise and task-irrelevant information. Yet, little is known about the brain mechanisms that mediate learning-dependent suppression. Here, we employ ultra-h...

Transcranial direct current stimulation provides researchers and clinicians with the ability to non-invasively modulate the firing rate of neurons. However, the focality and overall consequences of tDCS for neural systems is often unclear based on tDCS alone. When tDCS is paired with state-of-the-art neurophysiology, neuroimaging and spectroscopic...

Reward and punishment shape behavior, but the mechanisms underlying their effect on skill learning are not well understood. Here, we tested whether the functional connectivity of premotor cortex (PMC), a region known to be critical for learning of sequencing skills, is altered after training by reward or punishment given during training. Resting-st...

Key points: The ability to learn new motor skills is supported by plasticity in the structural and functional organisation of the primary motor cortex in the human brain. Changes inhibitory to signalling by GABA are thought to be crucial in inducing motor cortex plasticity. This study used magnetic resonance spectroscopy (MRS) to quantify the conc...

This is the first study to investigate functional brain activity in patients affected by autoimmune encephalitis with faciobrancial dystonic seizures (FBDS). Multimodal 3T MRI scans, including structural neuroimaging (T1-weighted, diffusion weighted) and functional neuroimaging (scene-encoding task known to activate hippocampal regions), were perfo...

Background Damage to the primary visual cortex (V1) due to stroke often results in permanent loss of sight affecting one side of the visual field (homonymous hemianopia). Some rehabilitation approaches have shown improvement in visual performance in the blind region, but require a significant time investment. Methods Seven patients with cortical d...

Figure S1. In each patient the upper row shows the activation (red‐yellow) to visual stimulation in the sighted hemifield prior to training. Figure S2. As in Figure 6, the upper row shows the activation (red‐yellow) to visual stimulation in the sighted hemifield prior to training.

Background: Pregnancy-induced analgesia is known to occur in association with the very high levels of estradiol and progesterone circulating during pregnancy. In women with natural ovulatory menstrual cycles, more modest rises in these hormones occur on a monthly basis. We therefore hypothesized that the high estradiol high progesterone state indic...

Learning a novel motor skill is dependent both on regional changes within the primary motor cortex (M1) contralateral to the active hand and also on modulation between and within anatomically distant but functionally connected brain regions. Interregional changes are particularly important in functional recovery after stroke, when critical plastic...

Although neuroimaging techniques have provided vital insights into the anatomical regions involved in motor learning, the underlying changes in temporal dynamics are not well understood. Using magnetoencephalography and Hidden Markov Modelling to model the dynamics of neural oscillations on data-adaptive time-scales, we detected specific changes in...

The ability to learn novel motor skills is both a central part of our daily lives and can provide a model for rehabilitation after a stroke. However, there are still fundamental gaps in our understanding of the physiological mechanisms that underpin human motor plasticity. The acquisition of new motor skills is dependent on changes in local circuit...

Purpose of Review An increase in oscillatory activity in the γ-frequency band (approximately 50–100 Hz) has long been noted during human movement. However, its functional role has been difficult to elucidate. The advent of novel techniques, particularly transcranial alternating current stimulation (tACS), has dramatically increased our ability to s...

Magnetic resonance spectroscopic imaging (MRSI) is a promising technique in both experimental and clinical settings. However, to date, MRSI has been hampered by prohibitively long acquisition times and artifacts caused by subject motion and hardware-related frequency drift. In the present study, we demonstrate that density weighted concentric ring...

Stroke is a leading cause of long-term disability, with around three-quarters of stroke survivors experiencing motor problems. Intensive physiotherapy is currently the most effective treatment for post-stroke motor deficits, but much recent research has been targeted at increasing the effects of the intervention by pairing it with a wide variety of...

Objectives Beta and gamma oscillations are the dominant oscillatory activity in the human motor cortex (M1). However, their physiological basis and precise functional significance remain poorly understood. To this end, we employed Transcranial Magnetic Stimulation (TMS) to examine the physiological basis and behavioural relevance of driving beta an...

There is increasing interest in how the phase of local oscillatory activity within a brain area determines the long-range functional connectivity of that area. For example, increasing convergent evidence from a range of methodologies suggests that beta (20 Hz) oscillations may play a vital role in the function of the motor system [1-5]. The "commun...

Supplementary material

Understanding both the organization of the human cortex and its relation to the performance of distinct functions is fundamental in neuroscience. The primary sensory cortices display topographic organization, whereby receptive fields follow a characteristic pattern, from tonotopy to retinotopy to somatotopy [1]. GABAergic signaling is vital to the...

Supplementary figures