| Objective:The aim of this study was to investigate the effect of venlafaxine on the language functional reorganization in patients with subcortical aphasia.From the perspective of functional neuroimaging,to determine whether venlafaxine can adjust the cortical language functional rehabilitation after stroke and improve the prognosis of subcortical aphasia,and to provide a theoretical basis for the clinical drug treatment of patients with subcortical aphasia.Materials and methods:All the patients we recruited were diagnosed as acute cerebral infarction with aphasia in General Hospital of Guangzhou Military Command from January 2016 to January 2018.According to the inclusion criteria and exclusion criteria,a total of 32 patients with subcortical aphasia were enrolled and randomly divided into venlafaxine group and placebo group(16 in each group).This was a randomized,placebo-controlled,single-blind,longitudinal trial.All patients underwent assessments of language functional behavior and examines of functional magnetic resonance imaging(fMRI)on 3±2 days(T1 session),30±7 days(T2 session)and 90±7 days(T3 session)after onset.Venlafaxine group and placebo group were given venlafaxine capsule or placebo capsule respectively within one day after completing the assessment on T1 session,until 4 weeks after onset.Language functional behavioral assessments included the Chinese version of Western Aphasia Battery(WAB),spontaneous language frequency test(SLFT)and picture naming test(PNT).Examines of fMRI included task-state fMRI and resting-state fMRI.The procession of fMRI data were performed on the platform of Matlab R201 3b with the DPARSF software package and the SPM8 software package.One-sample t-test was used in the in-group analysis(p<0.05,corrected by FDR,ke>10),while two-samples t-test was used in the inter-group analysis(p<0.001,uncorrected,ke>10).Activation maps were presented by xjview software and superimposed on the standard three-dimensional brain membrane,with acquiring the region of interest(ROI),the most active MNI coordinates,activation voxels and maximum activation intensity.General quantitative data were expressed as mean ±standard deviation,Levenne's homogeneity of variance test and normal distribution test were used firstly,and two-samples t-test was used for quantitative data which satisfied Levenne's homogeneity of variance test and normal distribution,and the rates of two group were compared by Fisher exact probabilities.The repeated measurement data was analyzed by repeated measures analysis of variance.Comparisons inter-group were performed by using a two-samples t-test,and pair-samples t-test was used to compare pairs of time points.All the above analyses used SPSS23.0 software package,P<0.05(two-tailed)was considered statistically significant.And the bivariate correlation option in this software package was used to analyze the correlation between the improvement of Aphasia Quotient and the change of activation of task-state fMRI.Results:1.There was no significant difference between the venlafaxine group and placebo group in demographics,cerebrovascular risk factors,and HAMA,HAMD,MMSE in T1 session(p>0.05).Repeated-measures analysis of variance found that the comparison inter-groups,comparison of time points,and interaction between groups and time points were statistically significant(p<0.05).Venlafaxine group had no significant difference in AQ(78.16±7.93 vs 78.60±6.38.p=0.856),SLFT scores(5.31±1.99 vs 5.75±1.81,p=0.520)and PNT scores(39.19±5.19 vs 38.31±5.23,p=0.638)in T1 session compared with placebo group.However,the venlafaxine group had higher scores in both T2 session(AQ:88.24±6.15 vs 83.51 ±5.37,p=0.028;SLFT scores:9.31±1.54 vs 8.13±1.50,p=0.035;PNT scores:46.38±4.95 vs 43.56±4.63,p=0.042)and T3 session(AQ:94.23±4.38 vs 88.55±3.95,p=0.000;SLFT scores:12.69±1.49 vs 10.81 ±1.33,p=0.000;PNT scores:52.25±2.60 vs 48.31 ±3.96,p<0.002)than the placebo group,and the difference was statistically significant.The AQ,SLFT scores,and PNT scores in the venlafaxine group and placebo group showed improvement over time(p<0.05).2.The activated areas of' Venlafaxine group and placebo group in T1 session mainly included inferior frontal gyrus,bilateral inferior occipital gyrus and bilateral fusiform gyrus.The activated areas of venlafaxine group in T2 session included bilateral inferior frontal gyrus,bilateral lentiform nucleus,left middle frontal gyrus,and left parahippocampa gyrus,while the activated areas of placebo group in T2 session were bilateral inferior frontal gyrus,bilateral inferior occipital gyrus,bilateral fusiform gyrus,left superior temporal gyrus and left cingulate gyrus.The activated areas of venlafaxine group in T3 session included bilateral inferior frontal gyrus,bilateral inferior occipital gyrus,bilateral fusiform gyrus,left superior temporal gyrus,left cingulate gyrus and left cerebellum,while activated areas of placebo group in T3 session were similar to T2 session but bilateral parahippocampa gyrus and left insula.3.There were no significant changes in activation between the venlafaxine group and placebo group in T1 session.Compared with the placebo group,the venlafaxine group in T2 session showed the hyperactivated areas in bilateral posterior part of inferior frontal gyrus(Broca's area)and left medial frontal gyrus,while the hypoactivated areas in bilateral inferior occipital gyrus,bilateral fusiform gyrus and right precuneus.A comparison of the activation in the venlafaxine group and placebo group in the T3 session showed the hyperactivated areas in bilateral posterior part of inferior frontal gyrus(Broca's area),left superior temporal gyrus,right middle temporal gyrus and cingulate gyrus.4.In the venlafaxine group,when the left or the right Broca's area as the ROI,there was a positive correlation between the increase of activation intensity and the improvement of AQ from T1 session to T2 session and from T2 session to T3 session.In the placebo group,there was a similar correlation to venlafaxine group when the left Broca's area as the ROI or the right Broca's area as the ROI from TI session to T2 session.However,there was a positive correlation between the decrease of activation intensity and the improvement of AQ from T2 session to T3 session when the right Broca's area as the ROI.5.When the left Broca's area as the seed point,the functional connectivity(FC)of the venlafaxine group or the placebo group from T1 session to T3 session were gradually increasing,especially in the right middle and inferior frontal gyrus.When the right Broca's area as the seed point,the FC of the venlafaxine group were also increasing and right posterior part of temporal cortices particularly,while the FC of placebo group showed that the default network FC gradually increased.When the left or right Wernicke's area as the seed point,the FC of the venlafaxine group and the placebo group showed a gradual increase in left Broca's area and the contralateral Wernicke's area.6.Comparison between placebo group and venlafaxine group showed increasing FC in bilateral middle frontal gyrus,and decreasing FC in corpus callosum when the left Broca's area as the seed point in T2 session;but increasing FC in left inferior frontal gyrus,and decreasing FC in left basal ganglia and corpus callosum when the right Broca's area as the seed point in T2 session.Compared with placebo group,venlafaxine group showed increasing FC in left interior temporal gyrus,left middle frontal gyrus,right inferior frontal gyrus and right superior tfrontal gyrus,and decreasing FC in corpus callosum when the left Broca's area as the seed point in T3 session;but showed increasing FC in left middle and inferior frontal gyrus,and decreasing FC in left lentiform nucleus and corpus callosum when the right Broca's area as the seed point in T3 session.Conclusion:1.Patients with subcortical aphasia usually undergo a natural language function recovery,and the early usage of venlafaxine can significantly promote the procession of language recovery,especially in the abilities of spontaneous language and picture naming.2.In subacute early stage,the recovery of language function in patients with subcortical aphasia is accompanied by increased activation of the left Broca's area,and there are a positive correlation between them.In subacute late stage,the recovery of language function is positively correlated with the activation of the bilateral Broca's area.In the subacute stage of cerebral infarction,venlafaxine has an effect which promote the increase of functional activation in the left Broca's area and prolong the maintenance of functional activation in the right Broca's area.3.The recovery of language function in patients with subcortical aphasia is mainly related to the enhancement of functional connectivity in the bilateral Broca's area and the bilateral Wernicke's area,whereas venlafaxine can enhance the functional connectivity in the bilateral language area.4.Venlafaxine promotes the recovery of language function in patients with subcortical aphasia,accompanied by decrease of the functional connectivity between Broca's area and bilateral corpus callosum,which may be related to the weakening of the corpus callosum inhibition effect. |
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