Keywords: Neurotransmission, Neuro, pharmacological MRI, functional MRS

Motivation: An integrated imaging approach using functional magnetic resonance imaging (fMRI) and functional proton magnetic resonance spectroscopy (fMRS) can increase our understanding of the functional response to antidepressant medication like es-ketamine.

Goal(s): We aimed to assess the dose- and time-dependent effects of the antidepressant es-ketamine on the functional brain response. 

Approach: We used an interleaved fMRI and fMRS experiment to assess whole-brain changes in BOLD signal and neurometabolite changes in the anterior cingulate cortex.

Results: Es-ketamine increased glutamate levels and the BOLD signal, and decreased aspartate and glucose levels in the first 10-15 minutes following administration, with specific dose-dependent effects.

Impact: Our results show both dose- and time-dependent neurometabolic and hemodynamic responses to es-ketamine. Understanding the contribution of these two determinants of the functional response might advance our understanding of the effects of antidepressant medication on the human brain.

Keywords: Neurotransmission, Brain

Motivation: The assessment of GABA and Glx levels within the brain with MEscher-Garwood Point RESolved Spectroscopy (MEGA-PRESS) has an important role in the diagnosis and treatment of neuropsychiatric disorders.

Goal(s): We evaluate the daily fluctuations of GABA levels within the parietal lobe (PL) and anterior cingulate gyrus (ACC) regions.

Approach: The GABA+, GABA+/Cr , Glx/Cr ,Glx were measured at six different time points throughout the day using MEGA-PRESS.

Results: Significant variations in GABA+/Cr levels within the PL region, with the lowest point occurring at 9:00 and the highest peak occurring at 21:00 . The melatonin levels were positively correlated with GABA+/Cr within the ACC region.

Impact: GABA changes in localized brain regions are strongly associated with many psychiatric disorders. The outcomes of this study could be used to guide the diagnosis and treatment of neuropsychiatric disorders.

Keywords: Neurotransmission, Brain, 7T, MRS, Laminar fMRI, Brain Function

Motivation: To gain insights into the neurochemical underpinnings of brain function by investigating the association between the cortical depth-dependent BOLD signal and neurometabolite concentrations in the PCC.

Goal(s): Examine the relationship between neurometabolites and laminar-fMRI metrics in the PCC to uncover layer-specific functional relationships

Approach: Laminar fMRI and MRS at 7T and assessment of correlations between cortical depth-dependent fMRI-metrics and neurometabolites

Results: Glutamate positively correlated with the fMRI ECM-metric in the intermediate layers of the PCC, suggesting increased long-range neural excitability. Conversely, lactate concentration negatively correlated with the fMRI ALFF-metric in superficial layers of the PCC, indicating potential layer-specific metabolic and functional differences

Impact: This study exposes the intricate relationship between regional neurometabolite concentrations and laminar fMRI metrics in the posterior cingulate cortex (PCC) that contribute to our understanding of brain activity and functional connectivity at rest

Keywords: Neurotransmission, Spectroscopy

Motivation: Examining the impact of the excitatory-inhibitory balance on cognitive function in healthy individuals holds great significance in research.

Goal(s): Exploring the excitatory-inhibitory balance at the neurotransmitter level and studying the relationship between excitatory-inhibitory balance and cognitive functions.

Approach: The study involved the collection of glutamate and γ-aminobutyric acid using magnetic resonance spectroscopy in 268 healthy participants, alongside the assessment of cognitive function in the subjects.

Results: In the anterior cingulate cortex, we observed a positive correlation between glutamate and γ-aminobutyric acid levels. Additionally, we found that a higher ratio of excitatory balance was associated with improved working memory performance at this specific location.

Impact: This study enhances our understanding of the excitatory-inhibitory balance at the neurotransmitter level and identifies a correlation between the level of excitatory inhibition and cognitive function. These findings provide valuable insights into the impact of excitatory inhibition on cognitive function.

Keywords: Neurotransmission, Metabolism, Spectroscopy, Brain, Animal

Motivation:  Electroconvulsive shock (ECS) therapy is an established treatment for drug-resistant depression. However, the status of neurometabolic activity during ECS-induced seizure is not clear. 

Goal(s): This study was carried out to measure neurometabolic activity during ECS-induced Seizure. 

Approach: ¹H-[¹³C]-NMR spectroscopy was used in conjunction with intravenous [1,6-¹³C₂]glucose or [2-¹³C]acetate infusion to measure neuronal and astroglial metabolic activity, respectively. 

Results: The neurometabolic activity was increased while astroglial activity remained unchanged during ECS-induced seizure. Moreover, the anaerobic glucose consumption was highly increased, suggesting the dominance of glycolysis during the seizure state.

Impact: The assessment of metabolic activity of Glutamatergic, GABA’ergic neurons, and astrocytes during ECS-induced seizures, provides valuable information about glucose consumption during enhanced energy demand, and the interplay of different cell types in the brain.  

Keywords: Neurotransmission, Spectroscopy, Functional MRS

Motivation: Changes in GABA and Glutamate associated with positive/negative BOLD activation in the visual cortex due to central and peripheral stimulation of the visual field are measured with functional MRS.  

Goal(s): How does stimulation of the central visual field affects concentrations of excitatory and inhibitory neurotransmitters and could these changes be consistent with negative and positive BOLD activation? 

Approach: An fMRS paradigm was applied on four volunteers to measure average changes in GABA and Glu due to alternating periods of central and peripheral visual stimulation, using a non-edited semi-LASER sequence.

Results: GABA decreased on average with peripheral stimulation while Glutamate showed an inconsistent trend. 

Impact: Indirect effects of negative and positive BOLD activation can be explored with functional MRS by measuring changes of GABA (inhibitory) and Glutamate (excitatory) neurotransmitters in the visual cortex resulting from central and peripheral stimulation of the visual field.

Keywords: Neurotransmission, Spectroscopy, Hurst Exponent, Excitatory-Inhibitory Balance, Brain Criticality

Motivation: Animal and computational studies have been used as a basis to assume a link between excitatory-inhibitory (E/I) ratio and Hurst exponent (H) in the human brain; however, it has yet to be sufficiently demonstrated in healthy human subjects.

Goal(s): We seek to test the E/I-Hurst link in the visual cortex during rest and movie-watching.

Approach: Multi-echo functional MRI, sLASER, and MEGAPRESS sequences are used in 17 healthy human adults (ages 21-53 years; 13 female, 4 male) with MRS voxel ROI in visual cortex.

Results: E/I and Hurst are not significantly correlated in either the MRS voxel ROI or visual network.

Impact: Hurst exponent (H) is assumed to correlated with excitatory-inhibitory (E/I) ratio without sufficient human evidence. Given the role of E/I imbalance in neuropsychiatric illness and the technical difficulty to measure it, understanding if H acts as its proxy is critical.

Keywords: Neurotransmission, Spectroscopy

Motivation: Many types of visual stimuli were reported effective for visual perception. However, it’s uncertain whether certain types of visual stimuli illicit larger responses.

Goal(s): We aim to measure the metabolic changes in response to different types of visual stimuli to observe which types of visual stimuli can excite larger and more consistent responses.

Approach: We designed three different types of stimuli sessions ( non-sense images, houses, and faces)  for visual stimulation and observed the metabolic changes in the fMRS data at 5T.

Results: Preliminary experiments show that compared to non-sense images and “no interesting” houses, faces stimulate larger responses with dynamic increase.

Impact: An fMRS study is implemented to measure the dynamic changes in response to different types of visual stimuli. Preliminary experiments indicate that faces stimulate larger responses.

Keywords: Neurotransmission, Spectroscopy, BOLD, Brain, Magnetic Resonance, Neural activation, Temperature, Thermometry, Visual cortex, Visual stimulation

Motivation: It is unclear if magnetic resonance spectral response to neural activation offers insight into brain temperature variation. 

Goal(s): To measure visual cortex temperature during visual stimulation.

Approach: During single and continuous stimulation, spectra were collected from the activated visual cortex region (n = 4). Frequency shifts of the N-acetyl aspartate, creatine and choline peaks from the water peak were calibrated to measure temperature using pre-determined regression equations for each peak. Spectral responses to neural activation were estimated as percentage changes in their height, width and area. 

Results: Continuous neural activation was associated with significant decrease in visual cortex temperature.

Impact: Continuous neural activation of the visual cortex increases cerebral blood flow to the activated region, which helps dissipate heat from visual cortex tissues as observed in the consistent temperature reduction. The observed spectral changes indicate clear response to neural activation.

Keywords: Neurotransmission, Deuterium, Neurometabolism, brain, Neuroscience, Spectroscopy

Motivation: Lower sensitivity of ¹³C NMR spectroscopy requires longer acquisition time while quantifying brain metabolites. An alternative technique is essential to aid faster detection.

Goal(s): To evaluate the kinetics of ²H labeling brain metabolites from [6,6’-²H₂]glucose using ²H NMR spectroscopy.

Approach: The cortical extracts of rats infused with [6,6’-²H₂]glucose were analyzed using ²H NMR spectroscopy. 

Results: The signals of deuterated Glc_C6, Glu_C4, Lac_C3, GABA_C2and Gln_C4 are seen in the  ²H NMR spectrum of cortical extract obtained after 90 min of [6,6’-²H₂]glucose infusion. The resonances of Asp_C2, Glu_C2, and Glu_C3 are absent suggesting complete loss/dilution of ²H from the TCA cycle intermediates beyond α-ketoglutarate.

Impact: Judicious use of ²H NMR together with suitable deuterated substrates may an alternative for neurometabolic analysis in neurological disorders.

Keywords: Neurotransmission, Metabolism, Spectroscopy, Brain, Animal

Motivation: Recently FDA has approved S-ketamine for the treatment of drug-resistant depression. However, the impact of long-term use of ketamine on mood, cognition, and neurotransmitter pathways is not clear.

Goal(s): To assess the impacts of chronic ketamine administration on mood, cognition, and neurometabolism in the mice model. 

Approach: ¹H-[¹³C]-NMR spectroscopy in conjunction with an intravenous [1,6-¹³C₂]glucose infusion was used for neurometabolic measurements.

Results: Ketamine administered mice showed hyperactivity, reduced cognition, and depression-like phenotypes. Moreover, chronic ketamine exposure increased the metabolic activity of glutamatergic and GABAergic neurons in the cerebral cortex.

Impact: Ketamine, a rapid-acting antidepressant, has been abused as a party drug historically. This study was performed to uncover the adverse effects of chronic ketamine administration and will be useful in designing better treatment approaches for depression.

Keywords: Neurotransmission, Metabolism, Glutamate, GABA, Isoflurane, Urethane

Motivation: Anesthetics are routinely used in surgery, and neurometabolic analysis in different neurological conditions but their impact on brain energy metabolism is not well understood.

Goal(s): To evaluate the impact of anesthetics on excitatory and inhibitory neurotransmission in the brain.

Approach: Infuse [1,6-¹³C₂]glucose in mice maintained under isoflurane (1.5%) or urethane (1.5 g/kg), and monitor ¹³C labeling of brain metabolites by ¹H-[¹³C]-NMR spectroscopy.

Results: The glutamatergic and GABAergic neurometabolic activity was suppressed in isoflurane as well as in urethane anesthetized mice. The inhibitory and excitatory neurotransmission increase or decrease together with the brain activity.

Impact: These findings will have implications for the interpretation of function signals in the brain.

Keywords: Neurotransmission, Neuroscience

Motivation: The functional role of Inhibitory tone in the motor cortex is not completely understood. Previous work has been limited by the coarse spatial resolution in single-voxel spectroscopy.

Goal(s): We applied a novel high spatial resolution MR spectroscopic imaging technique to test the relationship between inhibitory tone and motor network (MN) connectivity.

Approach: We performed voxel-wise analysis of neurochemical data to correlate measures of inhibitory and excitatory tone with age as a confounder, MN and default mode network (DMN).

Results: In the motor hand areas, we demonstrated a reciprocal correlation of inhibitory tone with MN and DMN connectivity. Inhibitory tone could “switch” node connectivity.

Impact: The connectivity of key motor network nodes could be influenced by their inhibitory tone and the excitation–inhibition difference. This finding advances the understanding of motor network function and could be a target for modulation in clinical settings.

Keywords: Neurotransmission, Brain, Migraine,GABA

Motivation: To investigate the variation of GABA concentrations in the anterior cingulate cortex and posterior cingulate cortex of migraine patients without aura during a migraine attack and the interictal stage.

Goal(s): To elucidate the role of GABA in the migraine pathophysiology.

Approach: We prospectively enrolled 12 migraineurs and 16 healthy controls and acquired MEGA-PRESS on a 3T MR from voxels located in the ACC and the PCC.

Results: Among migraineurs,  a significant increase in GABA+ in the PCC during  a migraine attack versus the interictal stage(P=0.0023).  Measurements in ACC and PCC showed a statistically significant elevation of GABA+ in migraineurs than healthy controls(P=0.0017, P=0.0031).

Impact: We speculate that increased GABA levels may reflect a compensating mechanism to reduce a hyperexcitatory state and a protective role for GABA in suppressing headaches. We will probe into the mechanism of GABAergic Drugs for the treatment of migraine.

Keywords: Head & Neck/ENT, Metabolism, coffee, MEGA-PRESS, GABA, MRS, sleepiness

Motivation: The effects of acute caffeine intake on brain metabolite levels remain largely unknown.

Goal(s): Illustrate the sensitivity of MRS to fluctuations in brain metabolites, investigate the difference among different caffeine consumption habit groups and to explore the association between metabolite changes and sleepiness.

Approach: MRS was performed at three time point after the participants consumed coffee.

Results: GABA+, GPC/GPC + PCH, Ins, Glu, and Glx levels were significantly altered after caffeine consumption. The levels of Glu, GPC, Cr + PCr, Glx, and Ins were significantly influenced by caffeine consumption habits. GABA+ levels in TH voxels significantly correlate with subjective sleepiness.

Impact: This study should prove valuable in the study of the sensitivity of MRS to fluctuations in brain metabolites, the brain metabolites alteration differences among different coffee consumption habits, and MRS studies of GABA.

Keywords: Neurotransmission, Spectroscopy, GABA, Glx

Motivation: Reproducibility is critical in longitudinal studies to monitor subtle alterations of GABA and Glx concentration in neurodegenerative disorders.

Goal(s): To evaluate the reproducibility of GABA and Glx measurements of the midbrain and basal ganglia regions in healthy subjects.

Approach: The MEGA-PRESS sequence was scanned twice with a two-week gap for each subject to obtain the GABA and Glx level in the left basal ganglia and bilateral midbrain. The reproducibility was evaluated.

Results: We observed good agreement between two scans for the GABA and Glx quantification based on the Bland-Altman analysis.

Impact: The reproducibility analysis of GABA and Glx measurements in the basal ganglia and midbrain regions are needed for the follow-up studies. The preliminary results informed that applying ¹H-MRS to investigate the progression of GABA and Glx levels is applicable.