**3. MR Spectroscopy (MRS) studies**

MRS techniques are used to distinguish between patients with active neurodegenerative process. N-acetyl groups, bearing phospholipids, choline, creatine (Cr), phosphocreatine, lipid and lactate levels can be measured by proton MRS. N-acetyl aspartate (NAA) is a marker of neuronal integrity and lower NAA/Cr ratio is associated with neuronal loss or damage. Choline reflects the integrity of cell membranes and increased levels of choline or choline/Cr ratio indicate increased cell destruction, the destruction of myelin, gliosis or inflammation. Creatine is sometimes used as a standard for relatively fixed elements of cellular energy metabolism in the brain. Creatine signals reflect glial and neuronal cell density. Myo-inositol plays a role in neuronal homeostasis [58].

It has been determined that NAA, creatine and myo-inositol concentration decrease signifi‐ cantly in children with autism spectrum disorders between the ages of three and four [59]. In several studies, it has been shown that NAA concentrations significantly decreased in the amygdaloid-hippocampal region, cerebellum and Brodmann's [41-42] areas (primary auditory area) in children and adults with autism [60, 61]. These findings can be associated with neuronal loss or functional immaturity in these regions, which play an important role in cognitive and emotional processes [60].

Levitt and colleagues [62], in a study involving autistic children, showed that choline and creatine levels increased in the head of the right caudate nucleus, while choline levels de‐ creased in the left inferior anterior cingulate cortex. In the same study, decreased levels of creatine were found in the left body portion of the nucleus caudatus and right occipital cortex. These findings were associated with changes in membrane metabolism and energy metabo‐ lism in these regions. In a different study, NAA and glutamate/glutamine (Glx) levels were found to be significantly decreased on the grey matter which involves many cerebral lobes in a common area. at children with autism. These findings have been associated with neuronal integrity and dysfunction, which spreads over a wide area at glutamatergic neurons in autistic children [63]. In some MRS studies, no significant changes have been found in metabolite levels in white matter [63, 64].

Vasconcelos et al. [65] reported that myo-inositol and choline levels were increased in the anterior cingulate cortex and left striatum, in contrast with previous studies that reported no significant changes in NAA levels.

When evaluated, these molecular indicators, amendments and increased white and grey matter volume have been believed to reflect changes in a) the number and size of neurons and glia; b) in the development of axons, dendrites and synapses; c) axodendritic pruning; d) programmed cell death; e) the occurrence of the cortical column; f) changes in myelination [66].
