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Pasanta, D.

Publications and source records attributed to Pasanta, D..

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Examining excitation-inhibition modulation during social processing using functional Magnetic Resonance Spectroscopy

An imbalance of brain excitation-inhibition has been implicated in social communication function across neurodevelopmental and psychiatric conditions. Recent advances in functional magnetic resonance spectroscopy (fMRS) allow non-invasive measurement of dynamic changes in excitation-inhibition neurometabolites (glutamate and GABA), revealing potential links with cognitive processes. This study used functional MRS (fMRS) to investigate whether socially-laden stimuli modulate excitatory or inhibitory neurometabolites, and whether modulation relates to social function. Forty neurotypical adults (18-40 years; 20 male) underwent 3T MRI, with fMRS data acquired using a J-difference edited MRS sequence. GABA+macromolecules (GABA+) and glutamate+glutamine (Glx) were quantified in a right social brain region (superior temporal/temporoparietal junction [STG/TPJ]) and a control region (occipital cortex). Participants viewed a fixation cross (traditional resting state MRS; 5 min), silent video clips of social interaction, and a flashing checkerboard as control stimulus (5 min each; counterbalanced). The Social Responsiveness Scale (SRS-2) assessed social function. Block analysis showed no significant differences between resting and functional (social or checkerboard) GABA+ or Glx levels (ps<.05), although Bayesian analyses showed evidence for decreased STG/TPJ GABA+ and increased occipital cortex Glx for checkerboard compared to rest. Higher SRS-2 scores were associated with higher resting STG/TPJ Glx but not GABA+, and functional metabolite levels were not associated with SRS-2 scores (ps>.1). Sliding time- window analyses showed significantly reduced Glx in social brain during social stimulation. Despite sound data collection and analysis techniques, shifts in Glx and GABA+ following social stimuli were minimal. Future research could utilise more challenging social stimuli and examine alternate social brain regions.

neuroscience↗

Decoupling of GABA and Glutamine-Glutamate Dynamics and their role in tactile perception: An fMRS Study

Tactile processing is fundamental for our daily lives. In particular, adaptation, the mechanism by which neural (and behavioural) responses change due to repeated stimulation, is key in adjusting our responses to the environment and is often affected in neurodevelopmental conditions such as autism and ADHD. While GABA and glutamate--the main inhibitory and excitatory neurotransmitters-- are known to be fundamental for encoding sensory input, we know little regarding the dynamic responses of the GABA and glutamatergic systems during tactile processing. Here, we examine how GABA and glutamine+glutamate (Glx) in vivo dynamics change during repetitive tactile stimulation and how these changes relate to tactile perception in a healthy population, using functional magnetic resonance spectroscopy (fMRS). Our study showed that repetitive tactile stimulation induced a decoupling between GABA and Glx during the first stimulation blocks as suggested by a negative correlation between GABA and Glx, which changed from a positive correlation at baseline. Subsequently, a multivariate time series analysis showed a predictive temporal relationship between Glx and GABA, showing that changes in these metabolites are temporally linked with an estimated lag of 6 seconds informing on a complex metabolite response function. The absence of gross metabolite change suggests that Glx and GABA adjust in relation to each other in response to repeated tactile stimulation. Furthermore, individual differences in the changed GABA and Glx levels correlated with perceptual measures of touch. Together, our study highlights the complex relationship between GABA and glutamate in tactile processing and demonstrates that experience-dependence plasticity induces a decoupling between these key metabolites. Further study into their dynamic interplay may be key to understanding adaptation as meso-levels in the brain and how these mechanisms differ in neurodevelopmental and neurological conditions.

neuroscience↗

The developmental trajectory of 1H-MRS brain metabolites from childhood to adulthood.

Human brain development is ongoing throughout childhood, with for example myelination of nerve fibres and refinement of synaptic connections continuing until early adulthood. 1H-Magnetic Resonance Spectroscopy (1H-MRS) can be used to quantify the concentrations of endogenous metabolites (e.g., glutamate and {gamma}-aminobutyric acid (GABA)) in the human brain in vivo and so can provide valuable, tractable insight into the biochemical processes that support postnatal neurodevelopment. This can feasibly provide new insight into and aid management of neurodevelopmental disorders by providing chemical markers of atypical development. This study aims to characterize the normative developmental trajectory of various brain metabolites, as measured by 1H-MRS from a midline posterior parietal voxel. We find significant non-linear trajectories for GABA+, Glx, tNAA and tCr concentrations. Glx and GABA+ concentrations steeply decrease across childhood. tNAA concentrations are relatively stable in childhood but gradually decrease from early adulthood, while tCr concentrations increase from childhood to early adulthood. tCho was the only metabolite to have a strictly linear association with age. Trajectories likely reflect fundamental neurodevelopmental processes (including local circuit refinement) which occur from childhood to early adulthood and can be associated with cognitive development; we find GABA+ concentrations significantly positively correlate with recognition memory scores across post-natal development.

neuroscience↗

GABA and Glutamate response to social processing; a functional MRS study

Several studies have suggested that atypical social processing in multiple psychiatric conditions (e.g., autism) is associated with differences in excitation and inhibition, through changes in the levels of glutamate and GABA levels. While associations between baseline metabolite levels and behaviours can be insightful, assessing the neurometabolic response of GABA and Glutamate during social processing may inform altered neurochemical function in more depth. Thus far, there have been no attempts to determine whether changes in metabolite levels are detectable using functional magnetic resonance spectroscopy (fMRS) during social processing in a control population. We performed MEGA-PRESS edited fMRS to measure the dynamic response of GABA and glutamate in the superior temporal sulcus (STS) and visual cortex (V1) while viewing social stimuli, using a design that allows for analysis in both block and event-related approaches. Sliding window analyses were used to investigate GABA and glutamate dynamics at higher temporal resolution. A small decrease in GABA levels was observed during social stimulus presentation in V1, but no change was observed in STS. Conversely, non-social stimulus elicited changes in both GABA and glutamate levels in both regions. We discuss the feasibility of using fMRS analysis approaches to assess changes in metabolite response during social processing.

neuroscience↗

Functional MRS studies of GABA and Glutamate/Glx: a systematic review and meta-analysis

Functional magnetic resonance spectroscopy (fMRS) can be used to investigate neurometabolic responses to external stimuli in-vivo, but findings are inconsistent. We performed a systematic review and meta-analysis on fMRS studies of the primary neurotransmitters Glutamate (Glu), Glx (Glutamate + Glutamine), and GABA. Data were extracted, grouped by metabolite, stimulus domain, and brain region, and analysed by determining standardized effect sizes. The quality of individual studies was rated. When results were analysed by metabolite type small to moderate effect sizes of 0.29-0.47 (p < 0.05) were observed for changes in Glu and Glx regardless of stimulus domain and brain region, but no significant effects were observed for GABA. Further analysis suggests that Glu, Glx and GABA responses differ by stimulus domain or task and vary depending on the time course of stimulation and data acquisition. Here, we establish effect sizes and directionality of GABA, Glu and Glx response in fMRS. This work highlights the importance of standardised reporting and minimal best practice for fMRS research.

neuroscience↗