**5. Functional MRI (fMRI) studies**

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

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

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

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‐

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,

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

adjacent to the amygdala), which are components of the mentalization network [30].

relationship between autism and serotonergic/dopaminergic systems.

tabolism and consequently reflects damage in brain functions [75].

thalamic and hippocampal regions [81].

the context of autism [82].

autism [72].

38 Autism Spectrum Disorder - Recent Advances

According to the SPECT and PET methods, the fMRI method has superior spatial and temporal resolution, is not an invasive procedure and does not involve ionizing radiation [67].

Autistic individuals have corrupted cognitive processing, both in a self-referential and otherreferential context. Lombardo et al. recently conducted an fMRI study focusing on when autistic disorder adults made reflective "mentalizing" (reflective mentalizing) or physical judgments about themselves or the Queen of England. In another recent study, healthy individuals were compared to autistic patients for self-other reference tasking. The results revealed that autistic patients responded more to other mentalization as opposed to selfreferential mentalization at the middle cingulate cortex, while these two operations respond equally at the ventromedial prefrontal cortex [84]. This finding is consistent with earlier study results that reported decreased activity in the middle cingulate cortex while high-functioning autism making their decisions the social condition [85]. These atypical responses only occur in areas that primarily process self-knowledge and do not affect the area that primarily responds to other-referential information. The neural self-other distinction at the ventromedial prefrontal cortex is closely associated with the degree of social impairment in autism in early childhood. It has been shown that individuals whose ventromedial prefrontal cortex can make the obvious distinction between self- and other mentalizing have had the least social disruption during early childhood, while individuals whose ventromedial prefrontal cortex makes little/ any distinction between self- and other mentalizing are more likely to have experienced maximum social disruption during early childhood. These findings are important in terms of showing the atypical organization of neural circuits, primarily in self-information encoding, in the context of autism [84].

Brain regions such as the medial prefrontal cortex, rostral anterior cingulate, posterior cingulate and the precuneus have high metabolic activity during resting states. Internally managed processes (self-trial thought and higher-level social and emotional processes) continuously activate the medial cortical network, which includes the medial prefrontal cortex, rostral anterior cingulate, posterior cingulate and precuneus. This metabolic activity is suppressed during tasks that require cognitive effort. The suppression during activity, which is observed as "deactivations" using the fMRI method, is indicative of interrupted mental activity during rest. Kennedy et al. [86] showed that this deactivation does not appear in autistic individuals. These findings have been associated with the absence or abnormal mental processes in autism. The absence of this deactivation in autism has shown abnormalities in internally managed process and these findings have been suggested to be associated with social and emotional deficits regarding autism.

Individuals with autistic disorders and Asperger's syndrome experience abnormalities in the perception of faces. It has been shown that healthy individuals have increased activation in the fusiform gyrus during face processing and increased activation in the inferior temporal gyrus during processing object activation, while individuals with autistic disorders or Asperger's syndrome have less activation in the right fusiform gyrus and more activation during face discrimination (this is not the case for objects). The autism group tends to use more of the inferior temporal gyrus during face processing when compared to controls. This finding shows that they process faces like objects [87]. The basic zone associated with face processing in healthy individuals is the lateral fusiform gyrus (called as "fusiform face area"). It has been reported to decrease activation in the fusiform gyrus and other areas associated with process‐ ing face detection such as the inferior occipital gyrus, superior temporal gyrus and amygdala in individuals with autism during face detection tasks. It has also been reported that autistic individuals use different neuronal systems for seeing faces and have individual-specific, scattered activation patterns when compared to normal individuals [88].

In a fMRI study with high-function autistic adults, detected decreased activation in the fusiform gyrus during the identification of the person who has been seen before, in contrast to previous studies. Social dysfunction in autism has been associated with common abnor‐ malities observed in the social brain network. The severity of impairment in social functioning is associated with a reduction in the connections between fusiform face area and amygdala and also increment in the connections between fusiform face area and right inferior frontal cortex.. This result indicates neuronal abnormalities in the limbic system to be associated with a prevalence of poor social impairment in autism [89].

Neuronal activation fields associated with working memory have been studied using fMRI methods. Luna et al. [90] reported lower activation in the dorsolateral prefrontal cortex and posterior cingulate regions during spatial working memory. Koshino et al. [91] showed that autistic individuals had lower activation in the inferior left prefrontal area (verbal processing and working memory-related) and right posterior temporal area (associated with theory of mind) during a working memory task that used photographic facial stimuli. The same study noted activation in the different division of the fusiform area in autistic individuals. It has also been shown that fusiform activation is in the lower and lateral division and also displaced from the typical region activated during face detection, compared to the region activated during object detection in an autistic group. These findings support the notion that face processing in autism analyse face characteristics as an object in terms of humanitarian significance. Abnormal fusiform activation showing a lower-level link with the frontal area is associated with the presence of the neuronal communication network, which has reduced synchronization [91].

A study conducted by Müller et al. [92] determined activation on opposite sides of the primary sensorimotor (the most powerful) cortex, premotor and/or supplementary motor areas during a simple finger movement task completed by healthy individuals in contrast, autistic groups showed no significant activation. [92]. Autistic individuals showed activation in regions that are not associated with these tasks, e.g., the superior parietal lobe and posterior neuronal precuneus.

Over time, neural outputs decrease in response to recurrent stimuli. This adaptation is believed to be associated with plasticity and learning. In the case of autism, it has been shown that there is no neural adaptation in the amygdala in response to neutral facial stimuli. In the case of autism, abnormal sustained amygdala stimulation in response to social stimuli is believed to be associated with social disruption, as observed in [89] (activation levels in the amygdala never reach the maximum level in healthy individuals).

The mirror neuron system (the pars opercularis in the inferior frontal gyrus) is active during observation, imitation and understanding the actions of others. Therefore, it is considered to provide a neuronal mechanism for a complete understanding of the purpose and actions of others. When on the move, along with the limbic system, it is thought to mediate an under‐ standing of emotions or facilitating sympathy with someone else's feelings. Thus, the feelings of others are perceived as real and not simply at a cognitive level, but understood at an emotional level (empathy). It has been shown that there is no activation of mirror neurons on the pars opercularis during the observation or imitation of emotional expression in children with autism. Activation in this region is inversely proportional to the severity of the symptoms shown. Early functional defects that emerge in the mirror neuron system have been suggested as the primary cause of social and emotional deficits in autistic disorders [93].

In FMRI studies with autistic individuals, a significant reduction has been revealed in the timing of the activation or synchronization between cortical areas associated with memory functioning, language, problem solving and social cognition. These findings support the hypothesis referred to as "insufficient functional connectivity" (underconnectivity) within and between neocortical systems [93].
