Functional connectivity alterations in migraineurs with Alice in Wonderland syndrome

Neurol Sci. 2023 Jan;44(1):305-317. doi: 10.1007/s10072-022-06404-1. Epub 2022 Sep 17.


Background and purpose: Alice in Wonderland syndrome (AIWS) is a neurological disorder characterized by erroneous perception of the body schema or surrounding space. Migraine is the primary cause of AIWS in adults. The pathophysiology of AIWS is largely unknown, especially regarding functional abnormalities. In this study, we compared resting-state functional connectivity (FC) of migraine patients experiencing AIWS, migraine patients with typical aura (MA) and healthy controls (HCs).

Methods: Twelve AIWS, 12 MA, and 24 HCs were enrolled and underwent 3 T MRI scanning. Independent component analysis was used to identify RSNs thought to be relevant for AIWS: visual, salience, basal ganglia, default mode, and executive control networks. Dual regression technique was used to detect between-group differences in RSNs. Finally, AIWS-specific FC alterations were correlated with clinical measures.

Results: With respect to HCs, AIWS and MA patients both showed significantly lower (p < 0.05, FDR corrected) FC in lateral and medial visual networks and higher FC in salience and default mode networks. AIWS patients alone showed higher FC in basal ganglia and executive control networks than HCs. When directly compared, AIWS patients showed lower FC in visual networks and higher FC in all other investigated RSNs than MA patients. Lastly, AIWS-specific FC alterations in the executive control network positively correlated with migraine frequency.

Conclusions: AIWS and MA patients showed similar FC alterations in several RSNs, although to a different extent, suggesting common pathophysiological underpinnings. However, AIWS patients showed additional FC alterations, likely due to the complexity of AIWS symptoms involving high-order associative cortical areas.

Keywords: Alice in Wonderland syndrome (AIWS); Functional connectivity (FC); Migraine with aura (MA); Resting-state functional MRI.

MeSH terms

  • Alice in Wonderland Syndrome* / diagnostic imaging
  • Alice in Wonderland Syndrome* / etiology
  • Cerebral Cortex
  • Humans
  • Magnetic Resonance Imaging
  • Migraine Disorders* / diagnosis