Study On The Neuroimaging Mechanism And Rehabilitation Of Post-Stroke Aphasia

BackgroundPost-stroke aphasia(PSA)is one of the most common cognitive dysfunctions in stroke,mainly characterized by difficulties in production,word finding,repetition,denomination,or comprehension of language.PSA is the primary cause of communication disorders,bringing serious troubles to patients’ life,work and social interaction.At present,there is no unified conclusion on the neural mechanism of PSA.Previous studies on the neural mechanisms of aphasia have mostly used task-state functional magnetic resonance imaging,but most patients with moderate to severe aphasia have difficulty in cooperating to complete task-state functional MRI scans.In addition,task-state fMRI only shows neural activity under specific task conditions and does not reflect changes in neural activity in the patient’s whole brain.Resting-state functional magnetic resonance imaging(rs-fMRI)can explore neural activity in the whole brain without any task stimulation and is a good tool to resolve the neural mechanisms of post-stroke aphasia.The use of rs-fMRI to explore changes in neural activity in subacute post-stroke aphasia provides a reference for the analysis of the neural mechanisms of post-stroke aphasia.Some patients with PSA can recover spontaneously,and based on the longitudinal changes of brain function before and after spontaneous recovery,it can provide a research window for exploring the rehabilitation mechanism of PSA,and also provide a method for verifying the neural mechanism of PSA.Based on the mutual validation of cross-sectional neural mechanism and longitudinal rehabilitation mechanism study,it can more reliably depict the neural mechanism of aphasia,and also provide a target for targeted neuromodulation therapy based on neural mechanism of PSA.Speech and language therapy(SLT)has been shown to be an important rehabilitation tool for aphasia,but its efficacy is still limited,and the rehabilitation effect on speech comprehension is even worse.Recent studies have found that non-invasive brain stimulation(NIBS)plus SLT can enhance the response to SLT in patients with aphasia.Transcranial magnetic stimulation and transcranial direct current stimulation are NIBS techniques commonly used in aphasic rehabilitation,which have a reasonable effect on the rehabilitation of speech expression ability,but are basically ineffective in improving speech comprehension.Therefore,based on reliable neuromodulation targets,it is of great significance to explore new neuromodulation methods that are effective for both speech comprehension and expression.Neuronal oscillations in language-related cortical regions are regarded as essential for efficient speech processing and comprehension.Transcranial alternating current stimulation(tACS)has been shown to modulate neuronal oscillation and improve speech processing in healthy subjects,and has achieved remarkable efficacy for brain disorders.However,it remains unclear whether tACS can improve language function in aphasia by regulating neural oscillations in language-related brain areas.ObjectiveIn this study,rs-fMRI imaging was used to explore the neural mechanism of PSA and reveal potential intervention targets.Longitudinal imaging data of aphasic patients with spontaneous recovery were used to verify the changes in neural activity of the target brain area and verify the reliability of the target.The specific target was used as the stimulation point of tACS to explore the efficacy of tACS in the rehabilitation of PSA.The specific contents are as follows:(1)This study aims to investigate abnormal local and connectional level within language network in subacute PSA to provide a basis for subsequent identification of targets.(2)Resting-state fMRI data were used to explore brain functional differences in post-stroke aphasia of before and after spontaneous recovery to further verify the effectiveness of the targets.(3)Based on the targets of Study 1 and Study 2,the clinical efficacy of tACS was confirmed by exploring the improvement of speech comprehension and expression ability by tACS intervention.Methods(1)This study included thirty-five aphasic patients and thirty-five healthy controls(HCs)matched in gender,age and educational years with aphasic patients in this study.All participants received MRI scan session and neuropsychological evaluation.The significantly abnormal regions in local activity between PSA and HCs were identified and then were selected as seeds to calculate functional connectivity.For the amplitude of low frequency fluctuations(ALFF)maps and connectivity maps,we conducted voxel-wise group comparisons using independent two-sample t test within language mask between HCs and PSA.The mean value(ALFF,functional connectivity)of significantly different regions was extracted.Further,exploratory Spearman correlation analyses were conducted between the functional variables(ALFF,functional connectivity)and language performance.(2)Rs-fMRI scans and language functions were assessed in 21 patients with PSA before and after improving language functions.Longitudinal image analysis was conducted to explore the alterations of neural activity in the two time points of PSA.The mean value of ALFF was extracted at baseline and follow-up time point.Then,Spearman correlation analyses were performed between the ALFF at baseline and language performance at follow-up time point,as well as between the two time points improvements of ALFF and language performance.(3)The abnormal brain regions were used as targets for aphasic rehabilitation to explore the efficacy of tACS combined with SLT in 25 chronic aphasia after stroke.Results(1)Compared with healthy controls,subacute PSA presented decreased ALFF in left inferior frontal gyrus(IFG)(0.94 ± 0.16 vs.1.22 ± 0.29,p < 0.001)and decreased resting-state functional connectivity(rs FC)in left IFG with bilateral frontal gyrus(SMA)(0.19 ± 0.20 vs.0.41 ± 0.16,p < 0.001)and right superior temporal gyrus(STG)(0.14 ±0.19 vs.0.34 ± 0.16,p < 0.001).(2)Compared with baseline,aphasic patients with follow-up presented increased ALFF in SMA(1.49 ± 0.31 vs.1.20 ± 0.23,p < 0.001).There was also no significant correlation between the two time points improvements of ALFF values and language performance.(3)Repeated measures ANOVA revealed significant group(sham vs.active)× time(pre-vs.post-treatment)interaction effects on Aphasia Quotient(AQ)(F = 15.56,p =0.001 Bonferroni corrected)and auditory verbal comprehension(F = 24.15,p < 0.001 Bonferroni corrected).Post hoc tests revealed that active tACS combined with SLT improved overall language performance,auditory verbal comprehension,spontaneous speech,repetition,and naming compared to baseline,while only AQ and naming were improved in the sham tACS plus SLT group.The improvement ratios(relative to baseline)of AQ and auditory verbal comprehension were also significantly greater in the active tACS plus SLT group than the sham tACS plus SLT group(AQ ratio: z =-2.85,p = 0.004;auditory verbal comprehension: z =-3.12,p = 0.002).Conclusion(1)The local activity and connectivity within language network of subacute PSA were reduced.The decreased IFG-SMA functional connectivity may be the neural mechanism of subacute PSA.(2)Improvement in local function of SMA may be the neural mechanism for spontaneous rehabilitation of aphasia after stroke.(3)The combination of tACS stimulation of SMA with SLT treatment significantly improves language comprehension in chronic aphasic patients.