International Journal of Health Studies2423-65948320220222 Inferior Frontal-Occipital Fasciculus (IFOF) is the Main Neural Pathway in Psychotic Symptoms Induced by Methamphetamine Abuse: A Tract-based Spatial Statistics Study 3539 10.22100/ijhs.v8i4.944 EN Javad Sheikhi Koohsar Center for Health-Related Social and Behavioral Sciences Research, Shahroud University of Medical Sciences, Shahroud, Iran. Salman Safdari Department of Radiology Technology, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Milad Bazghale Center for Health-Related Social and Behavioral Sciences Research, Shahroud University of Medical Sciences, Shahroud, Iran.. Sadegh Masjoodi Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.. Alireza Azizi Center for Health-Related Social and Behavioral Sciences Research, Shahroud University of Medical Sciences, Shahroud, Iran.. Hamid Kalalian Moghadam School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. Mohammad Niroumand Sarvandani Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. 20211125 20220111 20211226 Background: Chronic methamphetamine abuse can lead to white matter changes and increased levels of psychotic symptoms. This study aimed to investigate which neural pathway is most associated with the psychological symptoms of chronic Methamphetamine abuse. Methods: We recruited 42 chronic methamphetamine abuse subjects meeting DSM-5 criteria and 21 healthy controls. Psychotic signs were measured using the positive and negative syndrome scale (PANSS). We applied tract-based spatial statistics (TBSS) to investigate group differences in alteration DTI parameters and their association with psychotic symptoms. Results: Chronic methamphetamine abuse group had significantly lower FA and higher AD, RD, and MD in a wide range of white matter mainly IFOF, and subjects in the methamphetamine abuse group had significantly higher PANSS total scores when compared to the control group. Conclusions:  Chronic methamphetamine abuse shows subtle patterns of impaired white matter integrity of distinct cerebral nerve pathways, mainly IFOF relative to controls. The results are further suggested that neuronal tract-based pathology plays the main role in psychotic symptoms in methamphetamine abuse disorders. Keywords: Methamphetamine, psychotic symptoms, Tract-Based Spatial Statistics (TBSS), Inferior Frontal-Occipital Fasciculus (IFOF).