Table 4.

Functional imaging studies—methods, main findings and clinical interpretations.

Study	Method and Procedure	Data Analysis	Presentation of the Main Findings	Clinical Interpretations
SPECT
Kojima (2005)	SPECT Tested at two time points: at baseline (T1) and after weight recovery (T2).	(HMPAO)	AN (T1) vs. HC: Decreased rCBF in AN in the bilateral frontal lobes, including the ACC, PCC, bilateral precentral gyri, right insula, and right lingual gyrus. A positive correlation between the rCBF and BMI in the occipital lobe was found. AN (T2) vs. HC: Significant increases in the right parietal lobe and the left superior frontal gyrus. Decreases in the left superior temporal gyrus, left putamen, right IFG, right amygdala, and right cerebellum.	Hypoperfusion in the ACC and the parietal lobe may be associated not only with low body weight but also with abnormal brain functions relative to clinical features of AN.
Takano (2001)	SPECT Tested at one time point.	I-123-MIBG SPM approach	AN vs. HC: Hypoperfusion in the mPFC and ACC. Hyperperfusion in the thalamus and amygdala-hippocampus complex.	Hypoperfusion of the ACC may reflect depressive symptoms, while hyperactivity of the thalamus may be associated with chronic and refractory AN.
Matsumoto(2006)	SPECT Tested at two time points: at baseline (T1) and before discharge (T2).	123I-IMP	AN-T1 vs. AN-T2: Significant increase in rCBF in right dlPFC and medial parietal cortex including the precuneus and in the PCC. At the same lower threshold (p < 0.002) rCBF in the ACC and mPFC increased to an almost significant level. Significant decrease of rCBF in the right putamen.	Changes in rCBF may be associated with the improvement of interoceptive awareness following treatment.
Komatsu (2010)	SPECT Tested at two time points: at baseline (T1) and after 3 months (T2).	123I-IMP SPM approach	AN-T1 vs. AN-T2: Significant increased rCBF in bilateral parietal lobes and right PCC. No regions of decreased rCBF. A positive correlation between BMI and rCBF in right thalamus, right parietal lobe and right cerebellum.	PCC activation after weight gain might reflect affective changes for eating motivation during the recovery process of early-onset AN.
fMRI
Gaudio (2015)	fMRI + MRI Tested at one time point.	whole brain ICA analysis	AN vs. HC: Eight networks were identified. Statistically significant reduced connectivity between the Executive control network (ECN) and the ACC. The decrease in functional connectivity in the ACC was positively correlated with BMI and negatively correlated with drive for thinness, perfectionism and harm avoidance scores. No significant differences in GM volumes.	The decreased functional connectivity between the ECN and the ACC could explain the cognitive inflexibility in relation to body image.
Boehm (2014)	fMRI Tested at one time point.	ICA network based analysis	AN vs. HC: The networks of interest were the Fronto parietal network (FPN), DMN, Salience network (SN), visual and sensory-motor network. Increased functional connectivity between the angular gyrus and the FPN and between the anterior insula and the DMN. Positive correlations for both networks (DMN, FPN) with self-report measures in healthy controls. Functional connectivity in the anterior insula was positively associated with interoceptive difficulties in HC.	Increased functional connectivity within the FPN might be related to excessive cognitive control. The increased functional connectivity of insula with the DMN may mirror difficulties to disengage from thoughts about food and body appearance when not engaged in a task.
Amianto (2013)	fMRI, MRI Tested at one time point.	ICA network based analysis	AN vs. HC: Within the cerebellar intrinsic connectivity network, a greater connectivity was found with insulae, temporal poles, vermis and paravermis and a lesser connectivity with parietal lobe. Additionally, GM volume reduction in cerebellar hemispheres, cingulate cortex, precuneus and OFC.	The vermian hyper-connection could be linked to some psychopathological core features, such as “drive for thinness” which express the dissatisfaction with body weight. The cerebellar-parietal network dysfunction could be related to the disturbances in the body image perception. A stronger connection between cerebellum and temporal lobes may be related to greater emotional activation elicited by social behaviors in subjects with AN.
Gaudio (2018)	fMRI, MRI Tested at one time point.	Graph analysis whole brain and network based	AN vs. HC: Decreased connectivity in the sub-network including the left and right rostral ACC, left paracentral lobule, left cerebellum, left posterior insula, left medial orbito-frontal gyrus and right superior occipital gyrus. No significant differences in GM, WM, and CSF volumes.	The altered sub-network functional connectivity may sustain an altered self-body imge through an impaired integration of somatosensory, visual and interoceptive signals.
Geisler (2015)	fMRI Tested at one time point.	Graph analysis whole brain	AN vs. HC: Decreased functional connectivity in the thalamo-insular subnetwork. Longer average routes between nodes and more nodes with a similar connectedness link together. Additionally, altered global network architecture.	The altered network global topology indicates wide-scale disturbance in information flow across brain networks. The local thalamo-insular network disruption may explain the impaired integration of visuospatial and homeostatic signals.
Ehrlich (2015)	fMRI Tested at one time point.	Network based statistics	AN vs. HC: Reduced functional connectivity in the thalamo-insular network (in particular in a subnetwork consisting of the thalamus, amygdala, basal ganglia, fusiform gyrus and posterior insula).	The decreased functional connectivity in the thalamo-insular network may explain the striking discrepancy between patient’s actual and perceived internal body state.