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GABA γ-Aminobutyric acid (H3N+CH2CH2CH2COO−)  is the major inhibitory neurotransmitter in the brain. It is synthesized from the Glutamte in the GABAergic neurons.When it synapses, it binds with GABA receptors GABAA, GABAB in the post-synaptic membrane and causes the ionic channels to open and permits charged particles to move in and out of the neurons. As a result, the polarity of the post-synaptic membrane will increase which in turn decreases the likelihood that the neuron firing and consequent action. Disturbance of GABAergic process has been linked to many neurological and psychiatric disorders.For example ,in epilepsy ., Cortical plasticity, depression and motor disorder. Thus,GABA measurement and its exact quantification has been the target of scientific research. As a result there are many studies that have tried to establish GABA's role in shaping individual behaviour both in healthy and diseased cases. GABA concentration in the brain is relativity low 1 to 2 mM-Concentration, e.g.(mmol/kgww). Taking a direct sample from blood and CSF (lumber puncture) are the conventional methods of measuring GABA that are also considered to be indirect ways of measuring GABA level in the brain, i.e. they cannot reflect the exact regional concentration of GABA in the cortex. Alternatively, MRS spectroscopy can provide a direct regional measurement of metabolites non-invasively and in vivo. It also permits temporal assessments of disease progress and drug effectivness throughout the treatment course.

=GABA Spectroscopy= Despite of the low concentration of GABA for a given volume in the brain and its scattered peaks in the nMR spectrum, as a result of j-coupling phenomenon, there are a few possible approaches for extracting the GABA peaks using H MR spectroscopy; Spectral editing methods(j-difference editing), Two-Dimentional MRI spectroscopy and Ultr-High field spectroscopy GABA has three peaks in the nMR spectrum that correspond to the three methylene groups (CH2) in γ-Aminobutyric acid (H3N+CH2CH2CH2COO−). These peaks are overshadowed by stronger signals corresponding to highly concentrated metabolites, see the graph at this section. At 2.00 ppm there is NAA (Acetyle Aspartate), at 2.3 ppm is the Glx, (glutamine+glutamate), and at 3 ppm  Cr (creatine). Interpretation of nMR requires at least understanding of two physical phenomena, 'chemical shift' and 'scalar coupling'. The shape and strength of the electron clouds within certain molecules determine the position of that molecule across the x-axis in the NMR spectrum; this phenomena is knowen as a chemical shift. Hydrogen nuclei within one molecule may split into multiple peaks due to the nature of interaction between neighboring hydrogens. This is called Spin-spin coupling, which occurs when hydrogen is influenced not only by the main magnetic field but also by their coupled hydrogen nuclei; this link is mediated by bounding electrons It should be noted that Scalar coupling causes the GABA signal to be weak and broad Since GABA is overlapping with other abundant metabolites, it would be desirable to reduce this overlap and retain GABA signal. However, there are few methods that are being used now to measure the GABA concentration across individuals and/or between different cortical regions.

Editing method
It was firstly proposed by Rothman et al. when they tried to establish the relationship between anti-seizure drugs and GABA concentration. Simply, it is a subtraction method ( j-difference methods) where two interleaved MRS pulse sequence are acquired, one with frequency-selective pulse and the other without. The difference between the two data set will reveal few signals including the GABA itself. The first data set is acquired with a frequency-selective pulse that is applied directly at 1.9 ppm, this is known to be the edit pulse, which has an indirect effect on the coupled hydrogen neuclei at 3 ppm due to the j-coupling between hydrogen nuclei in GABA molecule. However, other signal in 3 ppm remain unaffected by this edit pulse, simply because they are not coupled to the 1.9 ppm signal. If this edited spectrum is subtracted from the non-frequency selected spectroscopy, the remaining data would contain only those signal that are affected by the edited pulse. Many GABA spectroscopy techniques have emerged, but the more importantly and widely use is the MEGA-PRESS.

MEGA-PRESS Spectroscopy
MEGA-PRESS (MEshcher–GArwood Point RESolved Spectroscopy) is based on the j-difference techniques and it is a common technique among GABA spectroscopy methods because it is easily incorporated into the two most common spectroscopy pulse sequences PRSS and STEAM. The simplest version, would be adding two 180 RF pulse symmetrically around the the PRESS 180 refocusing pulses (note that they have an identical flip angle). The first one is set to the water signal and the second one to the 1.9ppm group. It is thought to be insensitive to RF inhomogeneity and it has robust water suppression ability without any consequences on the phase coherence of the coupled GABA signal.However, water peak can be acquired as part of the PRESS for quantification purposes. The edited MEGA-PRESS spectroscopy usually shows the following signals: all signal at 1.9 ppm because they are directly affected by the 180 frequency-selected pulses, the GABA signal at 3 ppm which is indirectly affected (hence, refocused) by thier coupled hydrogen at 1.9 ppm, the (Glx) peaks at 3.75 ppm because they are coupled to the Glx resonances at approximately 2.1 ppm, and J-coupled macromolecular (MM) peaks.

2D-dimensional MRS (J-resolved)
While the 1D conventional MRI spectroscopy shows only the chemical shift between hydrogen nuclei including these overlapped ones, 2-D spectroscopy reveals both the chemical shift information in one axis and j-coupling data in the second axis. This can be achieved by acquiring additional data set which is different in echo time. Thus, such techniques are time consuming and produce a huge amount of data that needs further processing and computarisation.However,2-D resolved spectroscopy is a powerful technique fro examining the whole j-coupled protons in just one session.

High field methods
Ultra-high magnetic field ,e.g. 7 Tela, are being utilized increasingly in research, as a result many studies on the field of NMR spectroscopy has been conducted invivo.Although there are many inherent technical factors that make it difficult to achieve a clear cut, high quality spectroscopy; for instance, the exaggerated susceptibility effect and RF inhomogeneity make the spectrosopy technique very sensitive to artifacts. However, adjacent and overlapping peaks are potentially a separate line in the resultant spectra compared to lower magnetic fields.Special technical consideration and fine tuning are required to quantify the metabolite of interest. In addition to the high signal spectrum that can be aquired by high magnetic fields,there is another unique advantage, which is the possibility of applying narrower frequency-selective pulse that affect the GABA signal at1.9 ppm exclusively. Consequently, coincide j-coupling like the one in macromolecules can be minimise.

='Application of GABA MRI spectroscopy'=

GABA spectroscopy has been utilized to directly detect the variation of GABA concentration associated with performing behavioral tasks, psychological diseases or as a result of pharmacological intervention.It is hoped that this technique will also open a new window to physiologically understand the inhibition process during normal brain function as well as during neurological conditions.

plasticity and behavioral performance
It has been shown that the presence of GABA during the critical time after brain injury is essential for cortical reorganization. In this study, they used MRI spectroscopy to track the GABA fluctuation during a reversible (induced) ischemic nerve block experiment. Rapid reduction of GABA was observed in the MRI spectrum, which at least indicative to the fact that even the very early GABA changes are detectable by MRI spectroscopy. Individuals variation in performing a behavioral task are speculated to be mainly related to the concentration of GABA in certain cortical region; here are few examples, using orientation discrimination task, motor learning task,

Because MR spectroscopy can be repeatedly applied noninvasively, researcher can monitor the metabolites of interest during and after the experiment conditions/intervention.

GABA variation across other measures: Time ,Gender.
GABA spectroscopy has been utilized to assess the concentration of GABA in healthy subjects during the daytime between 7am and 7pm. According to the study there was no major variation. It was also utilized to assess the relationship between GABA level and gender. GABA was found to fluctuate during the menstrual cycle in healthy women. it can be seen from the above examples that MRI spectroscopy is a robust tool, not only for examining the underlying factor of causing of neuropsychological disorder but also to investigate the physiological basis of inhibition in normal brain function.

Epilepsy
GABAergic disturbance has been hypothesised as a contributor to seizure activity.Low GABA level may lead to uncontrolled excitatory synaptic activity. Based on this, most of anti-epileptic medications have an effect in increasing the GABAergic activity. Serial MRI spectroscopy experiments and CSF based tests can be performed to monitor the GABA concentration under different kinds of treatment, including the surgical one. For example, a rapid increase of GABA has been documented immediately in epileptic patients few hours after they have received Vigabatrin and Topiramate (anti-elliptic drugs). In general, MRI spectroscopy can help clinicians to closely observe the effect of seizure medications, so they can improve their management to control seizure disorder.