RESUMO
Oligodendrocytes continue to differentiate from their precursor cells even in adulthood, a process that can be modulated by neuronal activity and experience. Previous work has indicated that conditional ablation of oligodendrogenesis in adult mice leads to learning and memory deficits in a range of behavioral tasks. The current study replicated and re-evaluated evidence for a role of oligodendrogenesis in motor learning, using a complex running wheel task. Further, we found that ablating oligodendrogenesis alters brain microstructure (ex vivo MRI) and brain activity (in vivo EEG) independent of experience with the task. This suggests a role for adult oligodendrocyte formation in the maintenance of brain function and indicates that task-independent changes due to oligodendrogenesis ablation need to be considered when interpreting learning and memory deficits in this model.
Assuntos
Encéfalo , Oligodendroglia , Animais , Oligodendroglia/fisiologia , Oligodendroglia/patologia , Encéfalo/patologia , Camundongos , Masculino , Camundongos Transgênicos , Camundongos Endogâmicos C57BL , Atividade Motora/fisiologia , Imageamento por Ressonância Magnética , EletroencefalografiaRESUMO
Previous work has shown that motor skill learning stimulates and requires generation of myelinating oligodendrocytes (OLs) from their precursor cells (OLPs) in the brains of adult mice. In the present study we ask whether OL production is also required for non-motor learning and cognition, using T-maze and radial-arm-maze tasks that tax spatial working memory. We find that maze training stimulates OLP proliferation and OL production in the medial prefrontal cortex (mPFC), anterior corpus callosum (genu), dorsal thalamus and hippocampal formation of adult male mice; myelin sheath formation is also stimulated in the genu. Genetic blockade of OL differentiation and neo-myelination in Myrf conditional-knockout mice strongly impairs training-induced improvements in maze performance. We find a strong positive correlation between the performance of individual wild type mice and the scale of OLP proliferation and OL generation during training, but not with the number or intensity of c-Fos+ neurons in their mPFC, underscoring the important role played by OL lineage cells in cognitive processing.
Assuntos
Treino Cognitivo , Memória de Curto Prazo , Humanos , Camundongos , Animais , Masculino , Oligodendroglia , Camundongos Knockout , Cognição , Bainha de Mielina/fisiologiaRESUMO
Real-time functional MRI neurofeedback allows individuals to self-modulate their ongoing brain activity. This may be a useful tool in clinical disorders that are associated with altered brain activity patterns. Motor impairment after stroke has previously been associated with decreased laterality of motor cortex activity. Here we examined whether chronic stroke survivors were able to use real-time fMRI neurofeedback to increase laterality of motor cortex activity and assessed effects on motor performance and on brain structure and function. We carried out a randomized, double-blind, sham-controlled trial (ClinicalTrials.gov: NCT03775915) in which 24 chronic stroke survivors with mild to moderate upper limb impairment experienced three training days of either Real (n = 12) or Sham (n = 12) neurofeedback. Assessments of brain structure, brain function and measures of upper-limb function were carried out before and 1 week after neurofeedback training. Additionally, measures of upper-limb function were repeated 1 month after neurofeedback training. Primary outcome measures were (i) changes in lateralization of motor cortex activity during movements of the stroke-affected hand throughout neurofeedback training days; and (ii) changes in motor performance of the affected limb on the Jebsen Taylor Test (JTT). Stroke survivors were able to use Real neurofeedback to increase laterality of motor cortex activity within (P = 0.019), but not across, training days. There was no group effect on the primary behavioural outcome measure, which was average JTT performance across all subtasks (P = 0.116). Secondary analysis found improvements in the performance of the gross motor subtasks of the JTT in the Real neurofeedback group compared to Sham (P = 0.010). However, there were no improvements on the Action Research Arm Test or the Upper Extremity Fugl-Meyer score (both P > 0.5). Additionally, decreased white-matter asymmetry of the corticospinal tracts was detected 1 week after neurofeedback training (P = 0.008), indicating that the tracts become more similar with Real neurofeedback. Changes in the affected corticospinal tract were positively correlated with participants neurofeedback performance (P = 0.002). Therefore, here we demonstrate that chronic stroke survivors are able to use functional MRI neurofeedback to self-modulate motor cortex activity in comparison to a Sham control, and that training is associated with improvements in gross hand motor performance and with white matter structural changes.
Assuntos
Córtex Motor , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Recuperação de Função Fisiológica , Extremidade SuperiorRESUMO
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 carry out a pre-registered assessment of WM-behaviour relationships in 50 healthy individuals across multiple behavioural and anatomical domains, and complementing FA with myelin-sensitive quantitative MR modalities (MT, R1, R2∗). Surprisingly, we only find support for predicted relationships between FA and behaviour in one of three pre-registered tests. For one behavioural domain, where we failed to detect an FA-behaviour correlation, we instead find evidence for a correlation between behaviour and R1. This hints that multimodal approaches are able to identify a wider range of WM-behaviour relationships than focusing on FA alone. To test whether a common biological substrate such as myelin underlies WM-behaviour relationships, we then ran joint multimodal analyses, combining across all MRI parameters considered. No significant multimodal signatures were found and power analyses suggested that sample sizes of 40-200 may be required to detect such joint multimodal effects, depending on the task being considered. These results demonstrate that FA-behaviour relationships from the literature can be replicated, but may not be easily generalisable across domains. Instead, multimodal microstructural imaging may be best placed to detect a wider range of WM-behaviour relationships, as different MRI modalities provide distinct biological sensitivities. Our findings highlight a broad heterogeneity in WM's relationship with behaviour, suggesting that variable biological effects may be shaping their interaction.
Assuntos
Substância Branca , Anisotropia , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão , Humanos , Imageamento por Ressonância Magnética , Substância Branca/diagnóstico por imagemRESUMO
White matter (WM) plasticity supports skill learning and memory. Up- and downregulation of brain activity in animal models lead to WM alterations. But can bidirectional brain-activity manipulation change WM structure in the adult human brain? We employ fMRI neurofeedback to endogenously and directionally modulate activity in the sensorimotor cortices. Diffusion tensor imaging is acquired before and after two separate conditions, involving regulating sensorimotor activity either up or down using real or sham neurofeedback (n = 20 participants × 4 scans). We report rapid opposing changes in corpus callosum microstructure that depend on the direction of activity modulation. Our findings show that fMRI neurofeedback can be used to endogenously and directionally alter not only brain-activity patterns but also WM pathways connecting the targeted brain areas. The level of associated brain activity in connected areas is therefore a possible mediator of previously described learning-related changes in WM.
Assuntos
Imagem de Tensor de Difusão , Neurorretroalimentação , Córtex Sensório-Motor , Substância Branca , Adulto , Humanos , Masculino , Córtex Sensório-Motor/diagnóstico por imagem , Córtex Sensório-Motor/fisiopatologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologiaRESUMO
Neuroscience has seen substantial development in non-invasive methods available for investigating the living human brain. However, these tools are limited to coarse macroscopic measures of neural activity that aggregate the diverse responses of thousands of cells. To access neural activity at the cellular and circuit level, researchers instead rely on invasive recordings in animals. Recent advances in invasive methods now permit large-scale recording and circuit-level manipulations with exquisite spatio-temporal precision. Yet, there has been limited progress in relating these microcircuit measures to complex cognition and behaviour observed in humans. Contemporary neuroscience thus faces an explanatory gap between macroscopic descriptions of the human brain and microscopic descriptions in animal models. To close the explanatory gap, we propose adopting a cross-species approach. Despite dramatic differences in the size of mammalian brains, this approach is broadly justified by preserved homology. Here, we outline a three-armed approach for effective cross-species investigation that highlights the need to translate different measures of neural activity into a common space. We discuss how a cross-species approach has the potential to transform basic neuroscience while also benefiting neuropsychiatric drug development where clinical translation has, to date, seen minimal success. This article is part of the theme issue 'Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.
Assuntos
Encéfalo/fisiologia , Cognição/fisiologia , Neuroimagem Funcional , Neurônios/fisiologia , Animais , Humanos , Modelos Animais , NeurociênciasRESUMO
White matter (WM) plasticity during adulthood is a recently described phenomenon by which experience can shape brain structure. It has been observed in humans using diffusion tensor imaging (DTI) and myelination has been suggested as a possible mechanism. Here, we set out to identify molecular and cellular changes associated with WM plasticity measured by DTI. We combined DTI, immunohistochemistry and mRNA expression analysis and examined the effects of somatosensory experience in adult rats. First, we observed experience-induced DTI differences in WM and in grey matter structure. C-Fos mRNA expression, a marker of cortical activity, in the barrel cortex correlated with the MRI WM metrics, indicating that molecular correlates of cortical activity relate to macroscale measures of WM structure. Analysis of myelin-related genes revealed higher myelin basic protein (MBP) mRNA expression. Higher MBP protein expression was also found via immunohistochemistry in WM. Finally, unbiased RNA sequencing analysis identified 134 differentially expressed genes encoding proteins involved in functions related to cell proliferation and differentiation, regulation of myelination and neuronal activity modulation. In conclusion, macroscale measures of WM plasticity are supported by both molecular and cellular evidence and confirm that myelination is one of the underlying mechanisms.
Assuntos
Encéfalo , Bainha de Mielina , Plasticidade Neuronal/fisiologia , Percepção/fisiologia , Substância Branca , Animais , Imagem de Tensor de Difusão , Expressão Gênica , Masculino , Ratos , Ratos Long-EvansRESUMO
The white matter is a complex network of brain fibers connecting different information processing regions in the brain. In recent years, the investigation of white matter in humans and in animal models has greatly benefitted from the introduction of in vivo noninvasive magnetic resonance imaging (MRI) techniques. MRI allows for multiple in vivo time-point whole-brain acquisition in the same subject, thus it can be used longitudinally to monitor white matter brain change, intervention effects, as well as disease progression. However, MRI has low spatial resolution compared to gold standard cellular techniques and MRI measures are sensitive to a number of tissue properties resulting in a lack of specificity.The following chapter describes in simple technical terms to non-imaging experts some common MRI techniques that can be used to investigate white matter structure noninvasively, covering some of the advantages and pitfalls of each technique.
Assuntos
Imageamento por Ressonância Magnética/métodos , Substância Branca/diagnóstico por imagem , Progressão da Doença , Humanos , Processamento de Imagem Assistida por Computador/métodos , Substância Branca/patologiaRESUMO
The production of new myelin has been highlighted as an underappreciated mechanism of brain plasticity, but whether plastic decreases in myelin also happen in the adult brain has been largely unexplored. Recently, Sinclair et al. (Sinclair JS, Fischl MJ, Alexandrova O, Heß M, Grothe B, Leibold C, and Kopp-Scheinpflug C. J Neurosci 37: 8239-8255, 2017) have shown that auditory deprivation can lead to decrease in myelination and axon caliber even in healthy adulthood. These findings show that activity-regulated myelination is more complex than previously thought and expand our knowledge of how adult brain plasticity could operate on a cellular level.
Assuntos
Bainha de Mielina , Corpo Trapezoide , Axônios , Tronco Encefálico , Plasticidade NeuronalRESUMO
Working memory capacity is pivotal for a broad specter of cognitive tasks and develops throughout childhood. This must in part rely on development of neural connections and white matter microstructure maturation, but there is scarce knowledge of specific relations between this and different aspects of working memory. Diffusion tensor imaging (DTI) enables us to study development of brain white matter microstructure. In a longitudinal DTI study of 148 healthy children between 4 and 11 years scanned twice with an on average 1.6 years interval, we characterized change in fractional anisotropy (FA), mean (MD), radial (RD) and axial diffusivity (AD) in 10 major white matter tracts hypothesized to be of importance for working memory. The results showed relationships between change in several tracts and change in visuospatial working memory. Specifically, improvement in visuospatial working memory capacity was significantly associated with decreased MD, RD and AD in inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) in the right hemisphere, as well as forceps major (FMaj). No significant relationships were found between change in DTI metrics and change in verbal working memory capacity. These findings yield new knowledge about brain development and corresponding working memory improvements in childhood.
Assuntos
Encéfalo/crescimento & desenvolvimento , Memória de Curto Prazo , Memória Espacial , Percepção Visual , Substância Branca/crescimento & desenvolvimento , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Imagem de Tensor de Difusão , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/crescimento & desenvolvimento , Testes Neuropsicológicos , Psicologia da Criança , Caracteres Sexuais , Percepção Espacial , Substância Branca/diagnóstico por imagemRESUMO
The development of advanced noninvasive techniques to image the human brain has enabled the demonstration of structural plasticity during adulthood in response to motor learning. Understanding the basic mechanisms of structural plasticity in the context of motor learning is essential to improve motor rehabilitation in stroke patients. Here, we review and discuss the emerging evidence for motor-learning-related structural plasticity and the implications for stroke rehabilitation. In the clinical context, a few studies have started to assess the effects of rehabilitation on structural measures to understand recovery poststroke and additionally to predict intervention outcomes. Structural imaging will likely have a role in the future in providing measures that inform patient stratification for optimal outcomes.
Assuntos
Encéfalo/patologia , Aprendizagem/fisiologia , Atividade Motora/fisiologia , Plasticidade Neuronal/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologiaRESUMO
Neurofeedback training involves presenting an individual with a representation of their brain activity and instructing them to alter the activity using the feedback. One potential application of neurofeedback is for patients to alter neural activity to improve function. For example, there is evidence that greater laterality of movement-related activity is associated with better motor outcomes after stroke; so using neurofeedback to increase laterality may provide a novel route for improving outcomes. However, we must demonstrate that individuals can control relevant neurofeedback signals. Here, we performed two proof-of-concept studies, one in younger (median age: 26years) and one in older healthy volunteers (median age: 67.5years). The purpose was to determine if participants could manipulate laterality of activity between the motor cortices using real-time fMRI neurofeedback while performing simple hand movements. The younger cohort trained using their left and right hand, the older group trained using their left hand only. In both studies participants in a neurofeedback group were able to achieve more lateralized activity than those in a sham group (younger adults: F(1,23)=4.37, p<0.05; older adults: F(1,15)=9.08, p<0.01). Moreover, the younger cohort was able to maintain the lateralized activity for right hand movements once neurofeedback was removed. The older cohort did not maintain lateralized activity upon feedback removal, with the limitation being that they did not train with their right hand. The results provide evidence that neurofeedback can be used with executed movements to promote lateralized brain activity and thus is amenable for testing as a therapeutic intervention for patients following stroke.
Assuntos
Lateralidade Funcional , Atividade Motora/fisiologia , Córtex Motor/fisiologia , Neurorretroalimentação , Adulto , Idoso , Envelhecimento/fisiologia , Estudos de Coortes , Feminino , Mãos/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Estudo de Prova de Conceito , Adulto JovemRESUMO
Myelin is important for the normal development and healthy function of the nervous system. Recent developments in MRI acquisition and tissue modeling aim to provide a better characterization and more specific markers for myelin. This allows for specific monitoring of myelination longitudinally and noninvasively in the healthy brain as well as assessment of treatment and intervention efficacy. Here, we offer a nontechnical review of MRI techniques developed to specifically monitor myelin such as magnetization transfer (MT) and myelin water imaging (MWI). We further summarize recent studies that employ these methods to measure myelin in relation to development and aging, learning and experience, and neuropathology and psychiatric disorders. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 78: 136-151, 2018.
Assuntos
Imageamento por Ressonância Magnética/métodos , Bainha de Mielina , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , HumanosRESUMO
The study of brain plasticity has tended to focus on the synapse, where well-described activity-dependent mechanisms are known to play a key role in learning and memory. However, it is becoming increasingly clear that plasticity occurs beyond the synapse. This review focuses on the emerging concept of white matter plasticity. For example, there is growing evidence, both from animal studies and from human neuroimaging, that activity-dependent regulation of myelin may play a role in learning. This previously overlooked phenomenon may provide a complementary but powerful route through which experience shapes the brain.
Assuntos
Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Bainha de Mielina/fisiologia , Plasticidade Neuronal/fisiologia , Substância Branca/fisiologia , Animais , Humanos , Neuroimagem , Sinapses/fisiologiaRESUMO
Myelin sheaths in the vertebrate nervous system enable faster impulse propagation, while myelinating glia provide vital support to axons. Once considered a static insulator, converging evidence now suggests that myelin in the central nervous system can be dynamically regulated by neuronal activity and continues to participate in nervous system plasticity beyond development. While the link between experience and myelination gains increased recognition, it is still unclear what role such adaptive myelination plays in facilitating and shaping behaviour. Additionally, fundamental mechanisms and principles underlying myelin remodelling remain poorly understood. In this review, we will discuss new insights into the link between myelin plasticity and behaviour, as well as mechanistic aspects of myelin remodelling that may help to elucidate this intriguing process.
Assuntos
Encéfalo/fisiologia , Aprendizagem/fisiologia , Bainha de Mielina/fisiologia , Plasticidade Neuronal/fisiologia , Animais , Humanos , Substância Branca/fisiologiaRESUMO
The purpose of the present study was to detail the childhood developmental course of different white matter (WM) characteristics. In a longitudinal diffusion tensor imaging (DTI) study of 159 healthy children between 4 and 11years scanned twice, we used tract-based spatial statistics as well as delineation of 15 major WM tracts to characterize the regional pattern of change in fractional anisotropy (FA), mean (MD), radial (RD) and axial diffusivity (AD). We tested whether there were decelerations of change with increasing age globally and tract-wise, and also illustrated change along medial-to-lateral, posterior-to-anterior and inferior-to-superior gradients. We found a significant linear increase in global FA, and decrease in MD and RD over time. For mean AD, a weak decrease was observed. The developmental changes in specific WM tracts showed regional differences. Eight WM tracts showed non-linear development patterns for one or several DTI metrics, with a deceleration in change with age. Sex did not affect change in any DTI metric. Overall, greater rate of change was found in the left hemisphere. Spatially, there was a posterior-to-anterior gradient of change with greater change in frontal regions for all metrics. The current study provides a comprehensive characterization of the regional patters of change in WM microstructure across pre-adolescence childhood.
Assuntos
Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Substância Branca/anatomia & histologia , Substância Branca/crescimento & desenvolvimento , Criança , Pré-Escolar , Imagem de Tensor de Difusão , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , MasculinoRESUMO
Learning novel motor skills alters local inhibitory circuits within primary motor cortex (M1) (Floyer-Lea et al., 2006) and changes long-range functional connectivity (Albert et al., 2009). Whether such effects occur with long-term training is less well established. In addition, the relationship between learning-related changes in functional connectivity and local inhibition, and their modulation by practice, has not previously been tested. Here, we used resting-state functional magnetic resonance imaging (rs-fMRI) to assess functional connectivity and MR spectroscopy to quantify GABA in primary motor cortex (M1) before and after a 6 week regime of juggling practice. Participants practiced for either 30 min (high intensity group) or 15 min (low intensity group) per day. We hypothesized that different training regimes would be reflected in distinct changes in brain connectivity and local inhibition, and that correlations would be found between learning-induced changes in GABA and functional connectivity. Performance improved significantly with practice in both groups and we found no evidence for differences in performance outcomes between the low intensity and high intensity groups. Despite the absence of behavioral differences, we found distinct patterns of brain change in the two groups: the low intensity group showed increases in functional connectivity in the motor network and decreases in GABA, whereas the high intensity group showed decreases in functional connectivity and no significant change in GABA. Changes in functional connectivity correlated with performance outcome. Learning-related changes in functional connectivity correlated with changes in GABA. The results suggest that different training regimes are associated with distinct patterns of brain change, even when performance outcomes are comparable between practice schedules. Our results further indicate that learning-related changes in resting-state network strength in part reflect GABAergic plastic processes.
Assuntos
Aprendizagem/fisiologia , Córtex Motor/fisiologia , Destreza Motora/fisiologia , Inibição Neural/fisiologia , Plasticidade Neuronal/fisiologia , Ácido gama-Aminobutírico/metabolismo , Adaptação Fisiológica/fisiologia , Conectoma/métodos , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Rede Nervosa/fisiologia , Neurotransmissores/metabolismo , Adulto JovemRESUMO
The ability to predict learning performance from brain imaging data has implications for selecting individuals for training or rehabilitation interventions. Here, we used structural MRI to test whether baseline variations in gray matter (GM) volume correlated with subsequent performance after a long-term training of a complex whole-body task. 44 naïve participants were scanned before undertaking daily juggling practice for 6weeks, following either a high intensity or a low intensity training regime. To assess performance across the training period participants' practice sessions were filmed. Greater GM volume in medial occipito-parietal areas at baseline correlated with steeper learning slopes. We also tested whether practice time or performance outcomes modulated the degree of structural brain change detected between the baseline scan and additional scans performed immediately after training and following a further 4weeks without training. Participants with better performance had higher increases in GM volume during the period following training (i.e., between scans 2 and 3) in dorsal parietal cortex and M1. When contrasting brain changes between the practice intensity groups, we did not find any straightforward effects of practice time though practice modulated the relationship between performance and GM volume change in dorsolateral prefrontal cortex. These results suggest that practice time and performance modulate the degree of structural brain change evoked by long-term training regimes.
Assuntos
Encéfalo/citologia , Encéfalo/fisiologia , Substância Cinzenta/citologia , Substância Cinzenta/fisiologia , Aprendizagem/fisiologia , Destreza Motora/fisiologia , Córtex Pré-Frontal/fisiologia , Feminino , Humanos , Imageamento Tridimensional/métodos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Plasticidade Neuronal/fisiologia , Condicionamento Físico Humano/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
Abstract Spike timing-dependent plasticity (STDP) is an attractive candidate to mediate the synaptic changes that support circuit plasticity in sensory cortices during development. STDP is prevalent at excitatory synapses, but it is not known whether the underlying mechanisms are universal, or whether distinct mechanisms underpin STDP at different synapses. Here, we set out to compare and contrast STDP at vertical layer 4 and horizontal layer 2/3 inputs onto postsynaptic layer 2/3 neurons in the mouse barrel cortex. We find that both vertical and horizontal inputs show STDP, but that they display different time windows for induction of timing-dependent long-term depression (t-LTD). Moreover, whereas t-LTD at vertical inputs requires presynaptic NMDA receptors and is expressed presynaptically, using paired recordings we find that t-LTD at horizontal inputs requires postsynaptic NMDA receptors and is expressed postsynaptically. These results demonstrate that similar forms of plasticity on the same postsynaptic neuron can be mediated by distinct mechanisms, and suggest that these forms of plasticity may enable these two types of cortical synapses to support different functions.
RESUMO
Anatomically plausible networks of functionally inter-connected regions have been reliably demonstrated at rest, although the neurochemical basis of these 'resting state networks' is not well understood. In this study, we combined magnetic resonance spectroscopy (MRS) and resting state fMRI and demonstrated an inverse relationship between levels of the inhibitory neurotransmitter GABA within the primary motor cortex (M1) and the strength of functional connectivity across the resting motor network. This relationship was both neurochemically and anatomically specific. We then went on to show that anodal transcranial direct current stimulation (tDCS), an intervention previously shown to decrease GABA levels within M1, increased resting motor network connectivity. We therefore suggest that network-level functional connectivity within the motor system is related to the degree of inhibition in M1, a major node within the motor network, a finding in line with converging evidence from both simulation and empirical studies. DOI: http://dx.doi.org/10.7554/eLife.01465.001.