Search

Acknowledgements: We would like to thank the MR physics and radiographer teams at the Cambridge Wolfson Brain Imaging Centre, and Lilia Kukovska for their support and help with data collection. We would also like to thank Martina Callaghan, Nickolas Weiskopf, and the Wellcome Centre for Human Neuroimaging for providing the MPM sequences, and Guy Williams and Steve Sawiak for their expert assistance in MR-sequence testing. We would like to thank Thora Karadottir, Sonja Hofer, Jasper Poort, and Martina Callaghan for helpful comments and suggestions., Experience and training are known to boost our skills and mold the brain's organization and function. Yet, structural plasticity and functional neurotransmission are typically studied at different scales (large-scale networks, local circuits), limiting our understanding of the adaptive interactions that support learning of complex cognitive skills in the adult brain. Here, we employ multimodal brain imaging to investigate the link between microstructural (myelination) and neurochemical (GABAergic) plasticity for decision-making. We test (in males, due to potential confounding menstrual cycle effects on GABA measurements in females) for changes in MRI-measured myelin, GABA, and functional connectivity before versus after training on a perceptual decision task that involves identifying targets in clutter. We demonstrate that training alters subcortical (pulvinar, hippocampus) myelination and its functional connectivity to visual cortex and relates to decreased visual cortex GABAergic inhibition. Modeling interactions between MRI measures of myelin, GABA, and functional connectivity indicates that pulvinar myelin plasticity interacts-through thalamocortical connectivity-with GABAergic inhibition in visual cortex to support learning. Our findings propose a dynamic interplay of adaptive microstructural and neurochemical plasticity in subcortico-cortical circuits that supports learning for optimized decision-making in the adult human brain., This work was supported by grants to ZK from the Wellcome Trust [grant number 205067/Z/16/Z, 221633/Z/20/Z], the Biotechnology and Biological Sciences Research Council [grant numbers H012508, BB/P021255/1].

Cultural differences in visual perceptual learning (VPL) could be attributed to differences in the way that people from individualistic and collectivistic cultures preferentially attend to local objects (analytic) or global contexts (holistic). Indeed, individuals from different cultural backgrounds can adopt distinct processing styles and learn to differentially construct meaning from the environment. Therefore, the present work investigates if cross-cultural differences in VPL can vary as a function of holistic processing. A shape discrimination task was used to investigate whether the individualistic versus collectivistic backgrounds of individuals affected the detection of global shapes embedded in cluttered backgrounds. Seventy-seven participants-including Asian (collectivistic background) and European (individualistic background) students-were trained to discriminate between radial and concentric patterns. Singelis's self-construal scale was also used to assess whether differences in learning could be attributed to independent or interdependent self-construal. Results showed that collectivists had faster learning rates and better accuracy performance than individualists following training-thereby reflecting their tendency to attend holistically when learning to extract global forms. Further, we observed a negative association between independent self-construal-which has previously been linked to analytic processing-with performance. This study provides insight into how socio-cultural backgrounds affect VPL.

Behavioural disinhibition is a common feature of the syndromes associated with frontotemporal lobar degeneration (FTLD). It is associated with high morbidity and lacks proven symptomatic treatments. A potential therapeutic strategy is to correct the neurotransmitter deficits associated with FTLD, thereby improving behaviour. Reductions in the neurotransmitters glutamate and GABA correlate with impulsive behaviour in several neuropsychiatric diseases and there is post-mortem evidence of their deficit in FTLD. Here, we tested the hypothesis that prefrontal glutamate and GABA levels are reduced by FTLD in vivo, and that their deficit is associated with impaired response inhibition. Thirty-three participants with a syndrome associated with FTLD (15 patients with behavioural variant frontotemporal dementia and 18 with progressive supranuclear palsy, including both Richardson's syndrome and progressive supranuclear palsy-frontal subtypes) and 20 healthy control subjects were included. Participants undertook ultra-high field (7 T) magnetic resonance spectroscopy and a stop-signal task of response inhibition. We measured glutamate and GABA levels using semi-LASER magnetic resonance spectroscopy in the right inferior frontal gyrus, because of its strong association with response inhibition, and in the primary visual cortex, as a control region. The stop-signal reaction time was calculated using an ex-Gaussian Bayesian model. Participants with frontotemporal dementia and progressive supranuclear palsy had impaired response inhibition, with longer stop-signal reaction times compared with controls. GABA concentration was reduced in patients versus controls in the right inferior frontal gyrus, but not the occipital lobe. There was no group-wise difference in partial volume corrected glutamate concentration between patients and controls. Both GABA and glutamate concentrations in the inferior frontal gyrus correlated inversely with stop-signal reaction time, indicating greater impulsivity in proportion to the loss of each neurotransmitter. We conclude that the glutamatergic and GABAergic deficits in the frontal lobe are potential targets for symptomatic drug treatment of frontotemporal dementia and progressive supranuclear palsy.

Identifying targets in cluttered scenes is critical for our interactions in complex environments. Our visual system is challenged to both detect elusive targets that we may want to avoid or chase and discriminate between targets that are highly similar. These tasks require our visual system to become an expert at detecting distinctive features that help us differentiate between indistinguishable targets. As the human brain is trained on this type of visual tasks, we observe changes in its function that correspond to improved performance. We use functional brain imaging, to measure learning-dependent modulations of brain activation and investigate the processes that mediate functional brain plasticity. I propose that dissociable brain mechanisms are engaged when detecting targets in clutter vs. discriminating between highly similar targets: for the former, background clutter needs to be suppressed for the target to be recognised, whereas for the latter, neurons are tuned to respond to fine differences. Although GABAergic inhibition is known to suppress redundant neuronal populations and tune neuronal representations, its role in visual learning remains largely unexplored. Here, I propose that GABAergic inhibition plays an important role in visual plasticity through training on these tasks. The purpose of my PhD is to investigate the inhibitory mechanisms that mediate visual perceptual learning; in particular, learning to detect patterns in visual clutter and discriminate between highly similar patterns. I show that BOLD signals as measured by functional Magnetic Resonance Imaging (fMRI) do not differentiate between the two proposed mechanisms. In contrast, Magnetic Resonance Spectroscopy (MRS) provides strong evidence for the distinct involvement of GABAergic inhibition in visual plasticity. Further, my findings show GABA changes during the time-course of learning providing evidence for a distinct role of GABA in learning-dependent plasticity across different brain regions involved in visual learning. Finally, I test the causal link between inhibitory contributions and visual plasticity using a brain stimulation intervention that perturbs the excitation-inhibition balance in the visual cortex and facilitates learning.

Experience and training have been shown to facilitate our ability to extract and discriminate meaningful patterns from cluttered environments. Yet, the human brain mechanisms that mediate our ability to learn by suppressing noisy and irrelevant signals remain largely unknown. To test the role of suppression in perceptual learning, we combine fMRI with MR Spectroscopy measurements of GABA, as fMRI alone does not allow us to discern inhibitory vs. excitatory mechanisms. Our results demonstrate that task-dependent GABAergic inhibition relates to functional brain plasticity and behavioral improvement. Specifically, GABAergic inhibition in the occipito-temporal cortex relates to dissociable learning mechanisms: decreased GABA for noise filtering, while increased GABA for feature template retuning. Perturbing cortical excitability during training with tDCs alters performance in a task-specific manner, providing evidence for a direct link between suppression and behavioral improvement. Our findings propose dissociable GABAergic mechanisms that optimize our ability to make perceptual decisions through training., eLife digest When searching for a friend in the crowd or telling identical twins apart, your visual system must solve a complex puzzle. It must ignore all irrelevant information (e.g., unfamiliar faces in the crowd) and focus on key features (e.g., your friend’s familiar face) that will allow you to make a decision. We become better at solving complex visual discriminations with practice. But exactly how the brain achieves this improved performance is unclear. To answer this question, Frangou et al. trained healthy volunteers on two such visual tasks. The first (target detection task) involved locating a target (e.g. circular shape made of dots among randomly distributed dots in the background), a task similar to identifying a friend in the crowd. The second (feature discrimination task) involved assigning highly alike shapes in two different categories, similar to telling apart identical twins. To solve this problem, volunteers had to identify distinct features that allowed them to distinguish these shapes. During training on this task, they updated and refined the representation of these distinct features in their brain. This enabled them to make finer discriminations and assign each image correctly to one of the two categories. While the volunteers trained on the tasks, Frangou et al. measured levels of a chemical called GABA in brain areas that process visual information. GABA is the brain's main inhibitory molecule and controls the activity of neurons. As the volunteers learned the two tasks, their brains showed opposite changes in GABA levels. In the first, target detection task, individuals did better if their GABA decreased during training. In the second, feature discrimination task, they achieved more if their GABA increased during training. To confirm these findings, Frangou et al. used a second technique to activate or suppress processing in visual areas of the brain. Activating visual areas enhanced performance on the target detection task. Suppressing them enhanced performance on the fine discrimination task. These changes are thus consistent with those seen in GABA levels. As well as revealing how we learn to make decisions based on the information from our eyes, these findings suggest that adjusting brain activity could help patients regain skills lost as a result of eye-related or neurological conditions. Understanding the role of GABA in brain plasticity is also relevant to conditions like autism and psychosis, which have been shown to relate to changes in brain inhibition.