**4. PET and SPECT studies**

and motor integration such as bimanual motor coordination, visual attention scrolling and procedural memory processes. In autism, especially in the posterior region of the corpus callosum, a volume decline was noted in [55]. These findings are associated with interhemi‐

It has been shown that the caudate nucleus volume is increased in autism. This increase may be associated with observed repetitive and ritualistic behaviour in adolescents and adults with

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

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

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

spheric weakness in autism [20].

36 Autism Spectrum Disorder - Recent Advances

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

plays a role in neuronal homeostasis [58].

cognitive and emotional processes [60].

in white matter [63, 64].

**2.8. Caudate nucleus**

autism [56, 57].

In the context of autism, functional neuroimaging studies were performed at rest or during various activities. Injected or inhaled radiopharmaceuticals were applied in positron emission tomography (PET) methods. Dissolved radioactive isotopes emit positrons that are detected by the PET camera. Some PET methods measure blood flow, while others measure cerebral metabolic rate [67].

In PET studies performed with autistic children at rest it has been determined that a decrease in blood flow occurred in the temporal lobes. Functional dysfunction in the temporal lobe was concentrated within the auditory associative cortex and superior temporal sulcus. Functional impairment in the auditory cortex of autistic children may explain initial diagnoses of going deaf and experiencing serious deterioration in communication. It has been suggested that functional deterioration in the superior temporal sulcus might explain emotional and cognitive components of autistic symptoms indirectly, due to these being closely linked with the frontoparietal and limbic regions of the multimodal association [68].

A PET scan study conducted with autistic adults found a wide increase in glucose utilization in the brain at rest [69]. Despite these findings, different results during the performance of different tasks have also been found. Haznedar et al. [70] reported a decrease in glucose metabolism in the anterior and posterior cingulate gyrus during a verbal learning test for autism and Asperger's syndrome [70]. Similarly, in a different PET study, it a decrease in relative glucose metabolism was determined for frontal lobe medial/cingulate areas during verbal memory operations. The same study showed an increase in relative glucose metabolism for the occipital and parietal regions [71].

Neuronal activation areas associated with auditory cortical processing was also examined using the PET method. In a study by Boddaert et al. [72], activation in the superior temporal gyrus was observed while listening to the complex speech-like sounds of adults with autism, which was similar to the control group [72]. However, while this activation was observed for the right superior temporal gyrus in the autistic group, the opposite pattern was observed in the control group. It has been shown that although there is less activation at the left temporal areas, there is pronounced activation patterns at the right middle frontal gyrus among autistic individuals [73]. In a different study involving children with autism, lower activation patterns in the left superior temporal gyrus (in fields related with auditory) have been identified when listening to speech-like sounds, similar to what was found for adults. According to these findings, it is suggested that abnormalities in auditory cortical processing are associated with defects in language skills and that they result in a poor response to the voice among those with autism [72].

A PET scan study with high functioning autistic adults which practiced during instruction the tasks of theory of mind identified decreased activity in the medial prefrontal cortex, bilateral superior temporal sulcus and basal temporal area (right temporal tip and left fusiform gyrus adjacent to the amygdala), which are components of the mentalization network [30].

In several PET studies, the association between neurotransmitter systems and autism has been investigated. In a PET study with autistic children, Nakamura et al. [74] showed a reduction in the binding capacity of serotonin transporter protein throughout the entire brain. In autistic individuals, decreased serotonin transporter protein binding capacity in the anterior and posterior cingulate cortex has been associated with deterioration in social cognition, similar to decreased serotonin transporter protein binding capacity in the thalamus being associated with recurrent and obsessive behaviours. It has also been reported that dopamine transporter protein (the dopamine transporter = DAT) binding correlates in the opposite direction with serotonin transporter binding protein in the orbitofrontal cortex. These findings support the relationship between autism and serotonergic/dopaminergic systems.

The single-photon emission tomography (SPECT) method provides information on regional cerebral blood flow and provides a cerebral blood flow map according to the regional cerebral glucose metabolism of the brain. A decrease in regional cerebral blood flow reflects hypome‐ tabolism and consequently reflects damage in brain functions [75].

In accordance with several PET studies, reduced regional blood flow in the temporal cortex [76, 77, 78], frontal cortex [76], parietal cortex [77], occipital cortex, thalamus, basal ganglia [79] and cerebellar hemisphere [80] has been observed in SPECT studies with autistic children and adults. In a study of children and adolescents with high-functioning autism, evidence has been provided that the presence of abnormal neuronal network lateralization. In this study, it has been found lower blood flow at the right angular region than left angular region and also lower blood flow at left pericallosal, thalamic and hippocampal regions than right pericallosal, thalamic and hippocampal regions [81].

A decrease in regional cerebral blood flow in the bilateral insula, superior temporal gyrus and left prefrontal cortex has been reported by Ohnishi et al. in a SPECT study with autistic children. Autistic symptoms are associated with perfusion patterns at the limbic system and the medial prefrontal cortex. In this SPECT study by Ohnishi et al., support is provided for impairments in communication and social interaction that is thought to be related to the theory of mind deficits associated with perfusion changes in the medial prefrontal cortex and anterior cingulate gyrus, as well as the obsessive desire for sameness, which is associated with the right medial temporal lobe. Regional blood flow patterns are important in terms of indicating the possible location of abnormalities in brain function that underlie abnormal behaviour within the context of autism [82].

A SPECT study that investigated the relationship between neurotransmitter systems and autism showed a reduction of serotonin transporter protein binding capacity in the medial frontal cortex in accordance with PET studies in this area; however, DAT binding capacity did not differ in autistic individuals [83].
