The Multimodal Imaging Study Of The Fear Memory Neural Circuits

Fear memory is a normal physiological function and plays important roles in protecting human beings and animals from harmful stimuli.However,the failure of fear memory extinction would lead to some mental disorders,such as post-traumatic stress disorder(PTSD)and anxiety disorder.At present,the research on the neural circuits of fear memory has become a hot and important topic.Pavlovian fear conditioning is regarded as the classic paradigm to study the fear memory.Using this model paradigm,researchers have conducted a large number of studies on the neural mechanisms of fear memory by using electrophysiological,neurophysiological,molecular biology and brain imaging methods.These studies found several key brain regions and neural circuits involved in fear memory.However,most of the previous results have been obtained from research on the fear memory of rodents,which can not apply to the human brain studies properly.With the continuous development of imaging techniques and image processing analysis methods,it is possible to study the human brain fear memory circuits in vivo.In this study,we recruited a comparatively large sample of normal subjects,and acquired high resolution multimodal brain imaging data using 3.0T MRI scanner,including the resting-state functional magnetic resonance imaging(rs-fMRI),T1 weighted three-dimensional images and magnetic resonance diffusion tensor imaging(DTI)data.Using the methods of computational three-dimensional reconstruction,visualization,mathematical modeling,correlation analysis,fiber bundle tracking and reconstruction and image post-processing technology,we explored the important brain regions and fiber pathways involved in the fear memory.The present study mainly clarifies two issues:(1)The brain regions involved in the fear memory.(2)The neural circuits of the fear memory in human brain.In part one,high-quality rs-fMRI and 3D T1 structure data of 95 healthy right-handed college students(50 females and 45 males),which were selected and screened by the strict inclusion and exclusion criteria,were used for conducting the functional connectivity analysis.The aim of this study was to find out the brain areas involved in the fear memory.DPARSF were used to perform the functional connection analysis,while SPM8 and REST were used for statistical analysis.Our study got two main findings.First,the brain activation area involved in the fear memory included the amygdala,medial prefrontal cortex(mPFC),cingulate cortex,temporal lobe,insular lobe,parahippocampus,hippocampus,and thalamus.Second,comparing the functional connectivity results between female and male,we found that the precuneus and cuneus were more activated in females than in males,while males had greater activation in the temporal lobe,parahippocampus,inferior frontal gyrus and precentral gyrus.High-quality DTI and 3D T1 structure MRI data of 95 healthy right-handed college students(50 females and 45 males),which were strictly selected and screened were used in part two.According to the results of functional connectivity in part one,and the findings from the previous animal experimental study,we chose the amygdala as the seed,and the included areas were the ventromedial prefrontal cortex(vmPFC)and the hippocampus.Using FreeSurfer,BrainSuite and MRtrix,we carried out the probabilistic tractography and three-dimensional reconstruction of the fiber pathways to investigate the neural circuit involved in the fear memory.Our study demonstrated that there are two main neural pathways:one neural circuit was passing through the fornix and connecting the amygdala,vmPFC and hippocampus;the other one was passing through the cingulum and connecting the amygdala,vmPFC and hippocampus.In one word,our study revealed that:(1)The amygdala,cingulate cortex,medial prefrontal cortex,insular lobe,hippocampus,parahippocampus,temporal lobe and thalamus served as key areas involved in fear memory.(2)There should be a gender difference in activation strength in the involved brain areas of fear memory.(3)There were two mainly neural circuits in fear memory:the amygdala-hippocampus-fornix-vmPFC pathway and the amygdala-hippocampus-cingulum-vmPFC pathway.Thus,the present study could not only be helpful for exploring the neural mechanism of fear memory,but also provide new sights in the anatomical basis of some disorders of fear memory.