| Objective:Mild traumatic brain injury(mTBI),the most common type of TBI,often results in changes in brain structure and/or function,and may even show multiple persistent cognitive impairments lasting three months or longer after the trauma,such as attention deficit,fatigue,impulsivity,irritability,learning and memory problems,and communication and social difficulties.Currently,objective criteria to measure mTBI and its persistent cognitive dysfunction are insufficient in forensic medical identification,which cannot be used as the basis of diagnosis.In this study,we investigated various specific biomarkers of mTBI patients in the chronic stage,including imaging morphological measurement,neuropsychological scales,and electroencephalography(EEG)indicators,to provide objective elec trophy siological evidence of persistent cognitive impairment in the chronic stage of mTBI patients,and to explore the compensatory mechanism of cognitive function.Methods:According to different types of mTBI,this study is divided into two sections:intracranial hemorrhage and brain injury,and specific biomarkers in the chronic stage are studied respectively.The first section recruited 24 healthy control(HC)volunteers and 38 patients with non-parenchymal injury,and the patients included 19 patients with epidural hematoma(EDH)and 19 patients with subdural hematoma(SDH).Imaging data of patients were collected in the acute and chronic stages,and the ventriculocranial ratio and cortical thickness were measured.In addition,neuropsychological tests and EEG were performed only in the chronic stage.Neuropsychological tests were used to study different aspects of cognitive function.In the Go/NoGo task,subjects were asked to press a button for the Go stimulus and not for the NoGo stimulus,while behavioral data were recorded and EEG was collected.Then,the neural dynamics of the subjects were studied by event-related potential(ERP),event-related oscillation(ERO)and functional connectivity.The patients were further divided into four subgroups based on the neuropsychological scale results to evaluate the ability of these EEG indicators to detect different rehabilitation outcomes in patients with epidural/subdural hematoma and to explore possible compensatory mechanisms.The second section recruited 26 healthy control volunteers and 24 patients with parenchymal injury,and the patients included 12 patients with unilateral frontal lobe injury(UFLI)and 12 patients with bilateral frontal lobe injury(BFLI).Imaging data of patients were collected in the acute and chronic stages,and lesion volume was measured.As in section one,neuropsychological tests and EEG were performed only in the chronic stage.Neuropsychological tests were used to study different aspects of cognitive function.In the Go/NoGo task,subjects were asked to press a button for the Go stimulus and not for the NoGo stimulus,while behavioral data were recorded and EEG was collected.Then,the neural dynamics of the subjects were studied by ERP,ERO,and functional connectivity.According to the time course of the cognitive control function,EEG indicators were correlated with bottom-up perceptual processing,top-down anticipatory preparation,conflict monitoring and response decision processes,to investigate which subprocess of cognitive control was impaired in patients with unilateral/bilateral frontal lobe injury and whether the corresponding compensation mechanism existed.Results:The results of the mTBI-intracranial hemorrhage study showed as follows:(1)For the imaging morphological measurements,the ventriculocranial ratio of both EDH and SDH groups was enlarged and restored to normal level in the chronic stage compared with the acute stage,but there was no significant structural difference between EDH and SDH in the chronic stage.(2)For neuropsychological tests,compared with the HC group,the scores of EDH and SDH groups were all lower,but there was no difference between EDH and SDH.(3)For behavioral results,compared with the HC group,EDH and SDH groups showed longer response time,lower accuracy rate and higher error rate,while EDH and SDH groups showed very similar behavior performances.(4)For ERP,the mean amplitude of Go-P3 in the SDH group was lower than that in the HC group,and there was no difference between the EDH group and the other two groups,but there was a trend of a gradual decrease in HC,EDH and SDH groups.The mean amplitude of NoGo-P3 and P3d in EDH and SDH groups was lower than that in the HC group,but there was no statistical difference between EDH and SDH groups.(5)For ERO,the total and induced power of theta band induced by NoGo stimuli in EDH and SDH groups were lower than those in the HC group,and in the EDH group,only the induced power of the injured hemisphere was lower than that of HC group,while in SDH group,the induced power of the injured hemisphere and the uninjured hemisphere was lower than that of HC group.(6)For functional connectivity,compared with the HC group,EDH and SDH groups showed weakened intra-hemispheric functional connectivity in theta and alpha bands,while enhanced inter-hemispheric functional connectivity in theta and alpha bands(except T3-T4),and the CP3-CP4 connectivity in the alpha band in SDH group was stronger than that in EDH group.(7)In combination with EEG and neuropsychological tests,poor prognosis patients had more impaired intrahemispheric connectivity between different regions,and increased inter-hemispheric connectivity in the central parietal region or frontal region.The results of the brain injury-frontal lobe contusion study showed as follows:(1)For the imaging morphological measurements,the lesion volume of the BFLI group was larger than that of the UFLI group in the acute stage,while there was no significant structural difference between UFLI and BFLI group in the chronic stage.(2)For neuropsychological tests,compared with HC group,the scores of UFLI and BFLI groups were all lower,but there was no difference between UFLI and BFLI;(3)For behavioral results,compared with HC group,UFLI and BFLI groups showed longer response time,lower accuracy rate and higher error rate,while UFLI and BFLI showed very similar behavior performances.(4)For perceptual processing,compared with the HC group,the total and induced power of the parietal region and alpha functional connectivity between posterior brain regions was weakened only in the BFLI group.(5)For anticipatory preparation,compared with the HC group,the total and induced power of the sensorimotor region in the UFLI and BFLI groups were decreased,while the functional connectivity of the dorsal frontoparietal network was decreased in the BFLI group and increased in the UFLI group.(6)For conflict monitoring,compared with the HC group,only the BFLI group showed a longer N2d latency and weakened functional connectivity between the midfrontal and dorsal frontal/parietal regions.(7)For response decision,compared with the HC group,the P3 amplitude and the total and induced power of the frontal region in the UFLI and BFLI groups were decreased,while the functional connectivity between the dorsal and ventral frontoparietal network was decreased in the BFLI group and enhanced in the UFLI group.Conclusion:(1)Imaging techniques can be used to diagnose and describe mTBI in the acute stage,but their application in the chronic stage is limited.(2)The scores of neuropsychological scales and the performances of the Go/NoGo task can be used to distinguish the HC group from several types of mTBI patients,confirming the existence of different aspects of cognitive impairment,but cannot distinguish the degree of cognitive impairment in different types of mTBI patients.(3)EEG analysis in time domain,frequency domain and spatial domain can distinguish several types of mTBI patients from healthy subjects.Especially,non-parenchymal injury and parenchymal injury studies reflect the integrity and strength of functional connectivity from different perspectives,which can be used as objective indicators to evaluate the severity and rehabilitation outcome of mTBI.(4)The inter-hemispheric connectivity of the central parietal region and the inter-hemispheric connectivity of the frontal region in patients with non-parenchymal injury may be the compensatory mechanism for the defective response execution and inhibition after mTBI,respectively.(5)Bilateral frontal lobe injury patients can recover bottom-up perceptual processing through compensatory connectivity in the posterior brain network,but the subsequent three top-down cognitive control processes are decompensated.Only unilateral frontal lobe injury patients have compensatory connectivity within the dorsal frontoparietal network on the uninjured hemisphere and between the dorsal and ventral frontoparietal network can restore top-down anticipatory preparation and response decision functions,except that perceptual processing and conflict monitoring were not impaired. |
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