The relation between parietal GABA concentration and numerical skills

Several scientific, engineering, and medical advancements are based on breakthroughs made by people who excel in mathematics. Our current understanding of the underlying brain networks stems primarily from anatomical and functional investigations, but our knowledge of how neurotransmitters subserve numerical skills, the building block of mathematics, is scarce. Using 1H magnetic resonance spectroscopy (N = 54, 3T, semi-LASER sequence, TE = 32 ms, TR = 3.5 s), the study examined the relation between numerical skills and the brain's major inhibitory (GABA) and excitatory (glutamate) neurotransmitters. A negative association was found between the performance in a number sequences task and the resting concentration of GABA within the left intraparietal sulcus (IPS), a key region supporting numeracy. The relation between GABA in the IPS and number sequences was specific to (1) parietal but not frontal regions and to (2) GABA but not glutamate. It was additionally found that the resting functional connectivity of the left IPS and the left superior frontal gyrus was positively associated with number sequences performance. However, resting GABA concentration within the IPS explained number sequences performance above and beyond the resting frontoparietal connectivity measure. Our findings further motivate the study of inhibition mechanisms in the human brain and significantly contribute to our current understanding of numerical cognition's biological bases

Predicting learning and achievement using GABA and glutamate concentrations in human development

Previous research has highlighted the role of glutamate and gamma-aminobutyric acid (GABA) in learning and plasticity. What is currently unknown is how this knowledge translates to real-life complex cognitive abilities that emerge slowly and how the link between these neurotransmitters and human learning and plasticity is shaped by development. While some have suggested a generic role of glutamate and GABA in learning and plasticity, others have hypothesized that their involvement shapes sensitive periods during development. Here we used a cross-sectional longitudinal design with 255 individuals (spanning primary school to university) to show that glutamate and GABA in the intraparietal sulcus explain unique variance both in current and future mathematical achievement (approximately 1.5 years). Furthermore, our findings reveal a dynamic and dissociable role of GABA and glutamate in predicting learning, which is reversed during development, and therefore provide novel implications for models of learning and plasticity during childhood and adulthood

Hippocampal MRS and subfield volumetry at 7T detects dysfunction not specific to seizure focus

Ultra high-field 7T MRI offers sensitivity to localize hippocampal pathology in temporal lobe epilepsy (TLE), but has rarely been evaluated in patients with normal-appearing clinical MRI. We applied multimodal 7T MRI to assess if focal subfield atrophy and deviations in brain metabolites characterize epileptic hippocampi. Twelve pre-surgical TLE patients (7 MRI-negative) and age-matched healthy volunteers were scanned at 7T. Hippocampal subfields were manually segmented from 600μm isotropic resolution susceptibility-weighted images. Hippocampal metabolite spectra were acquired to determine absolute concentrations of glutamate, glutamine, myo-inositol, NAA, creatine and choline. We performed case-controls analyses, using permutation testing, to identify abnormalities in hippocampal imaging measures in individual patients, for evaluation against clinical evidence of seizure lateralisation and neuropsychological memory test scores. Volume analyses identified hippocampal subfield atrophy in 9/12 patients (75%), commonly affecting CA3. 7/8 patients had altered metabolite concentrations, most showing reduced glutamine levels (62.5%). However, neither volume nor metabolite deviations consistently lateralized the epileptogenic hippocampus. Rather, lower subiculum volumes and glutamine concentrations correlated with impaired verbal memory performance. Hippocampal subfield and metabolic abnormalities detected at 7T appear to reflect pathophysiological processes beyond epileptogenesis. Despite limited diagnostic contributions, these markers show promise to help elucidate mnemonic processing in TLE

The dynamics of cortical GABA in human motor learning

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 signalling by gamma‐aminobutyric acid (GABA) are thought to be crucial in inducing motor cortex plasticity. This study used magnetic resonance spectroscopy (MRS) to quantify the concentration of GABA in human motor cortex during a period of motor learning, as well as during a period of movement, and a period at rest. We report evidence for a reduction in the MRS‐measured concentration of GABA specific to learning. Further, the GABA concentration early in the learning task was strongly correlated with the magnitude of subsequent learning: higher GABA concentrations were associated with poorer learning. The results provide an initial insight into the neurochemical correlates of cortical plasticity associated with motor learning, specifically relevant in therapeutic efforts to induce cortical plasticity during stroke recovery. The ability to learn novel motor skills is 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 circuitry within the primary motor cortex (M1). This reorganisation has been hypothesised to be facilitated by a decrease in local inhibition via modulation of the neurotransmitter GABA, but this link has not been conclusively demonstrated in humans. Here, we used 7T MR Spectroscopy to investigate the dynamics of GABA concentrations in human M1 during the learning of an explicit, serial reaction time task. We observed a significant reduction in GABA concentration during motor learning that was not seen in an equivalent motor task lacking a learnable sequence, nor during a passive resting task of the same duration. No change in glutamate was observed in any group. Furthermore, M1 GABA measured early in task performance was strongly correlated with the degree of subsequent learning, such that greater inhibition was associated with poorer subsequent learning. This result suggests that higher levels of cortical inhibition may present a barrier that must be surmounted in order achieve an increase in M1 excitability, and hence encoding of a new motor skill. These results provide strong support for the mechanistic role of GABAergic inhibition in motor plasticity, raising questions regarding the link between population variability in motor learning and GABA metabolism in the brain

Repeated unilateral handgrip contractions alter functional connectivity and improve contralateral limb response times

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 approach to augment motor performance in the contralateral hand. In a within-participant, randomized, cross-over design, 15 right-handed adults had two magnetic resonance imaging (MRI) sessions, where functional-MRI and MR-Spectroscopic Imaging were acquired before and after repeated right-hand contractions at either 5% or 50% maximum voluntary contraction (MVC). Before and after scanning, response times (RTs) were determined in both hands. Nine minutes of 50% MVC contractions resulted in decreased handgrip force in the contracting hand, and decreased RTs and increased handgrip force in the contralateral hand. This improved motor performance in the contralateral hand was supported by significant neural changes: increased FC between SMA-SMA and increased FC between right M1 and right Orbitofrontal Cortex. At a neurochemical level, the degree of GABA decline in left M1, left and right SMA correlated with subsequent behavioural improvements in the left-hand. These results support the use of repeated handgrip contractions as a potential modality for improving motor performance in the contralateral hand

Representation of Multiple Body Parts in the Missing-Hand Territory of Congenital One-Handers.

Individuals born without one hand (congenital one-handers) provide a unique model for understanding the relationship between focal reorganization in the sensorimotor cortex and everyday behavior. We previously reported that the missing hand\u27s territory of one-handers becomes utilized by its cortical neighbor (residual arm representation), depending on residual arm usage in daily life to substitute for the missing hand\u27s function [1, 2]. However, the repertoire of compensatory behaviors may involve utilization of other body parts that do not cortically neighbor the hand territory. Accordingly, the pattern of brain reorganization may be more extensive [3]. Here we studied unconstrained compensatory strategies under ecological conditions in one-handers, as well as changes in activation, connectivity, and neurochemical profile in their missing hand\u27s cortical territory. We found that compensatory behaviors in one-handers involved multiple body parts (residual arm, lips, and feet). This diversified compensatory profile was associated with large-scale cortical reorganization, regardless of cortical proximity to the hand territory. Representations of those body parts used to substitute hand function all mapped onto the cortical territory of the missing hand, as evidenced by task-based and resting-state fMRI. The missing-hand territory also exhibited reduced GABA levels, suggesting a reduction in connectional selectivity to enable the expression of diverse cortical inputs. Because the same body parts used for compensatory purposes are those showing increased representation in the missing hand\u27s territory, we suggest that the typical hand territory may not necessarily represent the hand per se, but rather any other body part that shares the functionality of the missing hand [4]

Effect of age and the APOE gene on metabolite concentrations in the posterior cingulate cortex.

Proton magnetic resonance spectroscopy (1H-MRS) has provided valuable information about the neurochemical profile of Alzheimer's disease (AD). However, its clinical utility has been limited in part by the lack of consistent information on how metabolite concentrations vary in the normal aging brain and in carriers of apolipoprotein E (APOE) ε4, an established risk gene for AD. We quantified metabolites within an 8cm3 voxel within the posterior cingulate cortex (PCC)/precuneus in 30 younger (20-40 years) and 151 cognitively healthy older individuals (60-85 years). All 1H-MRS scans were performed at 3T using the short-echo SPECIAL sequence and analyzed with LCModel. The effect of APOE was assessed in a sub-set of 130 volunteers. Older participants had significantly higher myo-inositol and creatine, and significantly lower glutathione and glutamate than younger participants. There was no significant effect of APOE or an interaction between APOE and age on the metabolite profile. Our data suggest that creatine, a commonly used reference metabolite in 1H-MRS studies, does not remain stable across adulthood within this region and therefore may not be a suitable reference in studies involving a broad age-range. Increases in creatine and myo-inositol may reflect age-related glial proliferation; decreases in glutamate and glutathione suggest a decline in synaptic and antioxidant efficiency. Our findings inform longitudinal clinical studies by characterizing age-related metabolite changes in a non-clinical sample

Malleability of the cortical hand map following a finger nerve block

Electrophysiological studies in monkeys show that finger amputation triggers local remapping within the deprived primary somatosensory cortex (S1). Human neuroimaging research, however, shows persistent S1 representation of the missing hand's fingers, even decades after amputation. Here, we explore whether this apparent contradiction stems from underestimating the distributed peripheral and central representation of fingers in the hand map. Using pharmacological single-finger nerve block and 7-tesla neuroimaging, we first replicated previous accounts (electrophysiological and other) of local S1 remapping. Local blocking also triggered activity changes to nonblocked fingers across the entire hand area. Using methods exploiting interfinger representational overlap, however, we also show that the blocked finger representation remained persistent despite input loss. Computational modeling suggests that both local stability and global reorganization are driven by distributed processing underlying the topographic map, combined with homeostatic mechanisms. Our findings reveal complex interfinger representational features that play a key role in brain (re)organization, beyond (re)mapping

Malleability of the cortical hand map following a finger nerve block

Electrophysiological studies in monkeys show that finger amputation triggers local remapping within the deprived primary somatosensory cortex (S1). Human neuroimaging research, however, shows persistent S1 representation of the missing hand\u27s fingers, even decades after amputation. Here, we explore whether this apparent contradiction stems from underestimating the distributed peripheral and central representation of fingers in the hand map. Using pharmacological single-finger nerve block and 7-tesla neuroimaging, we first replicated previous accounts (electrophysiological and other) of local S1 remapping. Local blocking also triggered activity changes to nonblocked fingers across the entire hand area. Using methods exploiting interfinger representational overlap, however, we also show that the blocked finger representation remained persistent despite input loss. Computational modeling suggests that both local stability and global reorganization are driven by distributed processing underlying the topographic map, combined with homeostatic mechanisms. Our findings reveal complex interfinger representational features that play a key role in brain (re)organization, beyond (re)mapping

Fat-water separation by fast metabolite cycling magnetic resonance spectroscopic imaging at 3 T: A method to generate separate quantitative distribution maps of musculoskeletal lipid components

Purpose: To provide a rapid, noninvasive fat-water separation technique that allows producing quantitative maps of particular lipid components. Methods: The calf muscles in 5 healthy adolescents (age 12-16 years; body mass index = 20 ± 3 kg/m2 ) were scanned by two different fat fraction measurement methods. A density-weighted concentric-ring trajectory metabolite-cycling MRSI technique was implemented to collect data with a nominal resolution of 0.25 mL within 3 minutes and 16 seconds. For comparative purposes, the standard Dixon technique was performed. The two techniques were compared using structural similarity analysis. Additionally, the difference in the distribution of each lipid over the adolescent calf muscles was assessed based on the MRSI data. Results: The proposed MRSI technique provided individual fat fraction maps for eight musculoskeletal lipid components identified by LCModel analysis (IMC/L [CH3 ], EMCL [CH3 ], IMC/L [CH2 ]n , EMC/L [CH2 ]n , IMC/L [CH2 -CH], EMC/L [CH2 -CH], IMC/L [-CH=CH-], and EMC/L [-CH=CH-]) with mean structural similarity indices of 0.19, 0.04, 0.03, 0.50, 0.45, 0.04, 0.07, and 0.12, respectively, compared with the maps generated by the used Dixon method. Further analysis of voxels with zero structural similarity demonstrated an increased sensitivity of fat fraction lipid maps from the data acquired using this MRSI technique over the standard Dixon technique. The lipid spatial distribution over calf muscles was consistent with previously published findings in adults. Conclusion: This MRSI technique can be a useful tool when individual lipid fat fraction maps are desired within a clinically acceptable time and with a nominal spatial resolution of 0.25 mL