Background Visual mental imagery, the ability to volitionally form perceptual representations without corresponding external stimuli, allows reliving of past events, solving problems and imagining the future. The absence of visual mental imagery, called aphantasia, has recently been recognized to occur in about 1% of the general population but the cause is uncertain. By studying rare cases of acquired aphantasia we can identify regions that when injured cause loss of visual mental imagery.

Methods We analyzed aphantasia lesions, identified from case reports by systematic review, and previously studied control lesions causing other neuropsychiatric symptoms (n=887). The network of brain regions connected to each lesion location was computed using resting-state functional connectivity from healthy subjects (n=1000). First, we tested the connectivity of aphantasia lesions and controls to the fusiform imagery node, a region in the ventral visual pathway which is active during visual mental imagery tasks. Then, we performed a data-driven analysis assessing whole brain lesion connectivity that was sensitive (100% overlap) and specific (family-wise error p<0.05) for aphantasia. Finally, we compared our aphantasia lesion network to activations previously associated with visual mental imagery tasks.

Results We identified 12 cases of lesion-induced aphantasia which occurred in multiple different brain regions. However, 100% of these lesion locations were functionally connected to a region in the left fusiform gyrus, recently termed the fusiform imagery node. Connectivity to this region was both sensitive (100% overlap) and specific (family-wise error p<0.05) for aphantasia. The aphantasia lesion network aligned with functional connections previously associated with visual mental imagery tasks.

Conclusions and Relevance Lesions causing aphantasia are located in many different brain regions but are all functionally connected to a specific location in the left fusiform gyrus. These findings support the hypothesis that the fusiform imagery node is a key brain region involved in visual mental imagery and offers clinical insight into which locations of brain injury are likely to cause aphantasia.

MDF reported receiving grants from the NIH, Neuronetics, the Kaye Family Research Endowment, the Ellison/Baszucki Family Foundation, and the Manley Family outside the submitted work; holding intellectual property on the use of brain connectivity imaging to analyze lesions and guide brain stimulation; and consulting for Magnus Medical, Soterix, Abbott, Boston Scientific, and Tal Medical. No other disclosures were reported.

JK reports receiving support from the German Academic Exchange Service Biomedical Education Program. IK received support from NIH NINDS L30 NS134024. CWH reports receiving support from the Canadian Clinician Investigator Program. MDF reported receiving grants from the NIH (R01MH113929, R21MH126271, R56AG069086, R21NS123813, R01NS127892, R01MH130666, UM1NS132358) Neuronetics, the Kaye Family Research Endowment, the Ellison/Baszucki Family Foundation, and the Manley Family outside the submitted work.

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To compute functional connectivity, we used a publicly available resting-state functional connectome: https://doi.org/10.7910/DVN/ILXIKS. Lesion and fMRI locations used in this analysis are all publicly available on PubMed and related databases. Statistical neuroimaging analyses were performed in Matlab, version R2024b (Mathworks Inc) and using FSL (version 6.0.7.16). Brain images were created using FSLeyes (version 1.13.0).

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