Microstructural and neurochemical plasticity mechanisms interact to enhance human perceptual decision-making.

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.

Neurochemical and functional interactions for improved perceptual decisions through training.

Learning and experience are known to improve our ability to make perceptual decisions. Yet, our understanding of the brain mechanisms that support improved perceptual decisions through training remains limited. Here, we test the neurochemical and functional interactions that support learning for perceptual decisions in the context of an orientation identification task. Using magnetic resonance spectroscopy (MRS), we measure neurotransmitters (i.e., glutamate, GABA) that are known to be involved in visual processing and learning in sensory [early visual cortex (EV)] and decision-related [dorsolateral prefrontal cortex (DLPFC)] brain regions. Using resting-state functional magnetic resonance imaging (rs-fMRI), we test for functional interactions between these regions that relate to decision processes. We demonstrate that training improves perceptual judgments (i.e., orientation identification), as indicated by faster rates of evidence accumulation after training. These learning-dependent changes in decision processes relate to lower EV glutamate levels and EV-DLPFC connectivity, suggesting that glutamatergic excitation and functional interactions between visual and dorsolateral prefrontal cortex facilitate perceptual decisions. Further, anodal transcranial direct current stimulation (tDCS) in EV impairs learning, suggesting a direct link between visual cortex excitation and perceptual decisions. Our findings advance our understanding of the role of learning in perceptual decision making, suggesting that glutamatergic excitation for efficient sensory processing and functional interactions between sensory and decision-related regions support improved perceptual decisions.NEW & NOTEWORTHY Combining multimodal brain imaging [magnetic resonance spectroscopy (MRS), functional connectivity] with interventions [transcranial direct current stimulation (tDCS)], we demonstrate that glutamatergic excitation and functional interactions between sensory (visual) and decision-related (dorsolateral prefrontal cortex) areas support our ability to optimize perceptual decisions through training.

Functional Interactions between Sensory and Memory Networks for Adaptive Behavior.

The brain's capacity to adapt to sensory inputs is key for processing sensory information efficiently and interacting in new environments. Following repeated exposure to the same sensory input, brain activity in sensory areas is known to decrease as inputs become familiar, a process known as adaptation. Yet, the brain-wide mechanisms that mediate adaptive processing remain largely unknown. Here, we combine multimodal brain imaging (functional magnetic resonance imaging [fMRI], magnetic resonance spectroscopy) with behavioral measures of orientation-specific adaptation (i.e., tilt aftereffect) to investigate the functional and neurochemical mechanisms that support adaptive processing. Our results reveal two functional brain networks: 1) a sensory-adaptation network including occipital and dorsolateral prefrontal cortex regions that show decreased fMRI responses for repeated stimuli and 2) a perceptual-memory network including regions in the parietal memory network (PMN) and dorsomedial prefrontal cortex that relate to perceptual bias (i.e., tilt aftereffect). We demonstrate that adaptation relates to increased occipito-parietal connectivity, while decreased connectivity between sensory-adaptation and perceptual-memory networks relates to GABAergic inhibition in the PMN. Thus, our findings provide evidence that suppressive interactions between sensory-adaptation (i.e., occipito-parietal) and perceptual-memory (i.e., PMN) networks support adaptive processing and behavior, proposing a key role of memory systems in efficient sensory processing.

Cultural differences in visual perceptual learning.

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.

GABA and glutamate deficits from frontotemporal lobar degeneration are associated with disinhibition.

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.

Where functional MRI stops, metabolism starts.

Combining techniques that track blood oxygenation and biochemicals during neuronal activity reveals how the brain computes perceived and unperceived stimuli.

Learning to optimize perceptual decisions through suppressive interactions in the human brain.

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-high field magnetic resonance spectroscopy of GABA to test whether suppressive processing in decision-related and visual areas facilitates perceptual judgments during training. We demonstrate that parietal GABA relates to suppression of task-irrelevant information, while learning-dependent changes in visual GABA relate to enhanced performance in target detection and feature discrimination tasks. Combining GABA measurements with functional brain connectivity demonstrates that training on a target detection task involves local connectivity and disinhibition of visual cortex, while training on a feature discrimination task involves inter-cortical interactions that relate to suppressive visual processing. Our findings provide evidence that learning optimizes perceptual decisions through suppressive interactions in decision-related networks.

GABA, not BOLD, reveals dissociable learning-dependent plasticity mechanisms in the human brain.

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.

Beta-band frequency peaks inside the subthalamic nucleus as a biomarker for motor improvement after deep brain stimulation in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) remains an empirical, yet highly effective, surgical treatment for advanced Parkinson's disease (PD). DBS outcome depends on accurate stimulation of the STN sensorimotor area which is a trial-and-error procedure taking place during and after surgery. Pathologically enhanced beta-band (13-35 Hz) oscillatory activity across the cortico-basal ganglia pathways is a prominent neurophysiological phenomenon associated with PD. We hypothesized that weighing together beta-band frequency peaks from simultaneous microelectrode recordings in "off-state" PD patients could map the individual neuroanatomical variability and serve as a biomarker for the location of the STN sensorimotor neurons. We validated our hypothesis with 9 and 11 patients that, respectively, responded well and poorly to bilateral DBS, after at least two years of follow up. We categorized "good" and "poor" DBS responders based on their clinical assessment alongside a > 40% and <30% change, respectively, in "off" unified PD rating scale motor scores. Good (poor) DBS responders had, in average, 1 mm (3.5 mm) vertical distance between the maximum beta-peak weighted across the parallel microelectrodes and the center of the stimulation area. The distances were statistically different in the two groups ( p = 0.0025 ). Our biomarker could provide personalized intra- and postoperative support in stimulating the STN sensorimotor area associated with optimal long-term clinical benefits.