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Grigoras, I. F.

Publications and source records attributed to Grigoras, I. F..

3 recordsLinked to original sources

Longitudinal neurochemical profiling after experimental stroke using edited MR spectroscopy

Background: Alterations in excitatory and inhibitory neurotransmission contribute to stroke pathology and recovery, yet longitudinal assessment of these changes in vivo remains limited. We investigated the feasibility of longitudinal edited proton magnetic resonance spectroscopy (1H-MRS) to quantify {gamma}-aminobutyric acid (GABA) and glutamate following experimental focal cerebral ischaemia. Methods: Male rats underwent endothelin-1-induced striatal ischaemia or sham surgery. Longitudinal edited 1H-MRS was performed at baseline and 2-, 7- and 30-days post-stroke at 7-tesla with a MEGA-sLASER sequence. A voxel was positioned within the ipsilesional motor cortex adjacent to the lesion. Behavioural outcomes (grip strength, adhesive removal and CatWalk gait analysis) were assessed alongside spectroscopy, and immunohistochemistry for Iba1, GFAP and ICAM-1 was performed at 30 days. Results: Stroke induced a transient reduction in GABA+/tCr within the ipsilesional motor cortex, with significantly lower concentrations than sham animals at 7 days (p<0.05), returning to baseline by 30 days. Glutamate/tCr and GABA/glutamate ratio were unchanged throughout the study. Behavioural deficits were mild, with significant effects on motor outcomes such as grip strength, gait swing speed and paw placement, while sensory areas of the brain seemed largely unaffected. Histological analysis revealed no persistent differences in cortical Iba1, GFAP or ICAM-1 immunoreactivity at 30 days. Conclusions: Longitudinal 1H-MRS is a feasible approach for monitoring dynamic changes in inhibitory neurochemistry following experimental stroke. The transient reduction in peri-lesional GABA, despite minimal behavioural impairment and an absence of persistent cortical inflammation, supports the use of edited spectroscopy as a translational tool to investigate neurochemical mechanisms underlying network dynamics in post-stroke recovery.

neuroscience↗

Baclofen, a GABAB receptor agonist, impairs motor learning in healthy people and changes inhibitory dynamics in motor areas

Inhibition mediated by {gamma}-aminobutyric acid (GABA) is implicated in motor plasticity and learning, with [GABA] in the motor cortex decreasing during motor learning. However, the causal relationship between [GABA] and learning has yet to be determined. Here, we conducted a within-subject, double-blind, placebo-controlled, crossover study to investigate the effect of increased GABAergic inhibition via GABAB-receptor agonist baclofen on motor learning and Magnetic Resonance Spectroscopic Imaging (MRSI) metrics. Increasing GABA-mediated inhibition with baclofen did not change response times, but significantly impaired motor sequence learning. In parallel, we demonstrated a blunting of the expected decrease in [GABA] during motor learning. These results highlight a causal role for GABAergic inhibition in motor learning and may have clinical implications: baclofen is commonly used to treat post brain-injury spasticity, but may impair motor learning during rehabilitation.

neuroscience↗

Ultrasound system for precise neuromodulation of human deep brain circuits

Transcranial ultrasound stimulation (TUS) has emerged as a promising technique for non-invasive neuromodulation, but current systems lack the precision to target deep brain structures effectively. Here, we introduce an advanced TUS system that achieves unprecedented precision in deep brain neuromodulation. The system features a 256-element, helmet-shaped transducer array operating at 555 kHz, coupled with a stereotactic positioning system, individualised treatment planning, and real-time monitoring using functional MRI. In a series of experiments, we demonstrate the systems ability to selectively modulate the activity of the lateral geniculate nucleus (LGN) and its functionally connected regions in the visual cortex. Participants exhibited significantly increased visual cortex activity during concurrent TUS and visual stimulation, with high reproducibility across individuals. Moreover, a theta-burst TUS protocol induced robust neuromodulatory effects, with decreased visual cortex activity observed for at least 40 minutes post-stimulation. These neuromodulatory effects were specific to the targeted LGN, as confirmed by control experiments. Our findings highlight the potential of this advanced TUS system to non-invasively modulate deep brain circuits with high precision and specificity, offering new avenues for studying brain function and developing targeted therapies for neurological and psychiatric disorders. The unprecedented spatial resolution and prolonged neuromodulatory effects demonstrate the transformative potential of this technology for both research and clinical applications, paving the way for a new era of non-invasive deep brain neuromodulation.

neuroscience↗