基于rs-fNIRS同步尿动力学监测的OAB患者前额叶内部功能连接研究

Functional connectivity within prefrontal cortex in patients with overactive bladder based on rs-fNIRS measurement synchronous urodynamic monitoring

目的检测膀胱过度活动症(OAB)患者前额叶皮层(PFC)内部功能连接(FC)的异常情况,探讨OAB的中枢发病机制。方法2020年8—12月采用前瞻性研究方法对OAB患者(OAB组)和同期健康受试者(HC组)进行研究。OAB组纳入标准:符合国际尿控协会(ICS)OAB诊断标准,症状持续时间≥3个月;排除标准:有其他引起下尿路症状的明确原因(如反复泌尿系感染、膀胱结石、膀胱肿瘤、外科手术史、前列腺增生、神经系统疾病等),尿潴留(残余尿量>150 ml),妊娠或哺乳期,各系统重大疾病(如肿瘤、心脏病、呼吸系统疾病等),存在认知障碍不能配合者。HC组纳入标准:无下尿路症状,记录3 d排尿日记(每次排尿量200~400 ml),24 h排尿量1500~3000 ml,24 h排尿次数<8次,夜尿次数≤1次,无漏尿;排除标准:有神经系统及泌尿系统相关疾病,全身各系统重大疾病(如心脏病、肿瘤、糖尿病及呼吸系统疾病),口服药物或尿路感染引起的膀胱功能障碍,妊娠期或月经期。对所有受试者进行前额静息态近红外光谱脑功能成像(rs-fNIRS)扫描同步尿动力学监测,分别在膀胱空虚状态和强烈尿意/尿动力学检查提示逼尿肌过度活动(DO)时进行两次rs-fNIRS扫描。计算22个通道时间序列之间的Pearson相关系数(r值)做为脑功能连接(FC)值,得到每例受试者的22×22 FC矩阵。比较HC组膀胱空虚与强烈尿意时的FC值差异,以及HC组与OAB组FC值的差异。结果本研究OAB组纳入7例患者,男1例,女6例;平均年龄(47.6±16.0)岁;均为右利手;受教育年限(11.9±3.2)年;3 d排尿日记中24 h排尿次数11(9~21)次,次均排尿量(172.6±83.4)ml,24h尿失禁次数1(0~5.3)次,24 h尿急次数7(4~20)次,残余尿量<10 ml;OABSS 10(8~12)分;尿动力检查中初感尿意膀胱容量(127.7±52.4)ml,最大膀胱测压容量(192.0±93.8)ml,储尿期最大逼尿肌压力32(17~95)cmH2O(1 cmH2O=0.098 kPa);第2次扫描时尿急程度评分(8.1±0.7)分。HC组纳入13例健康人,男3例,女10例;平均年龄(49.9±9.2)岁;均为右利手;受教育年限(10.4±3.4)年;3 d排尿日记中24 h排尿次数6(5~7)次,次均排尿量(373.5±41.7)ml,24 h尿失禁次数0次,24 h尿急次数0次,残余尿量<10 ml;OABSS 0分;尿动力检查初感尿意膀胱容量(209.9±44.1)ml,最大膀胱测压容量(432.6±76.5)ml,储尿期最大逼尿肌压力5(2~13)cmH2O;第2次扫描时尿急程度评分(7.9±0.9)分。两组的年龄、性别、教育年限、利手、第2次扫描时尿急程度评分比较差异均无统计学意义(P>0.05)。OAB组的OABSS、3 d排尿日记参数(排尿次数/24h、尿失禁次数/24h、尿急次数/24h)和储尿期最大逼尿肌压力均显著大于HC组,差异有统计学意义(P<0.01)。OAB组的次均排尿量、初感尿意膀胱容量和最大膀胱测压容量均显著小于HC组,差异有统计学意义(P<0.01)。在膀胱充盈至强烈尿意过程中,HC组尿动力学监测显示逼尿肌压力平稳,未出现DO,OAB组6例出现DO。与膀胱空虚状态相比,HC组强烈尿意时PFC内部的FC显著增强的范围涉及5个Brodmann脑区(BA)和13条边,分别为BA9[左侧背外侧前额叶(DLPFC)和右侧DLPFC]、BA10(左侧额极和右侧额极)、BA44(左侧布洛卡区岛盖部)、BA45(左侧三角部)、BA46(左侧DLPFC:);FC显著减弱的区域涉及3个BA和2条边,分别为BA9(左侧DLPFC)、BA10(左侧额极和右侧额极)、BA46(右侧DLPFC)。膀胱空虚状态下,OAB组和HC组间PFC内部的FC差异无统计学意义(P>0.05)。强烈尿意状态下,OAB组PFC内部的FC矩阵有显著异常(P<0.05)。与HC组相比,OAB组PFC内部的FC显著增强的范围涉及4个BA和4条边,分别为BA9(右侧DLPFC和左侧DLPFC)、BA10(右侧额极)、BA45(左侧三角部)、BA46(右侧DLPFC);FC显著减弱的区域涉及3个BA和4条边,分别为BA9(右侧DLPFC和左侧DLPFC)、BA10(左侧额极)和BA46(左侧DLPFC)。结论OAB患者的PFC内部的FC与健康人群相比有显著异常,这可能引起PFC内部功能"协同失调",导致额叶功能障碍,累及感觉整合、动机驱动、情绪控制以及决策是否排尿等方面,从而导致尿控功能障碍,表现为尿急、尿频甚至急迫性尿失禁等OAB的典型临床症状。

Objective To detect the abnormalities within the functional connectivity(FC)of the prefrontal cortex(PFC)in patients with overactive bladder(OAB)and to explore its central pathogenesis.Methods Seven OAB patients(OAB group,6 females,mean age 47.6±16.0 years)and 13 healthy controls[HC](HC group,10 females,mean age 49.9±9.2 years)were prospectively enrolled from August to December 2020.All subjects underwent rs-fNIRS scanning synchronized with urodynamic monitoring,and two rs-fNIRS scans were performed when the bladder was empty and when the desire to void was strong/urodynamic monitoring indicated detrusor hyperactivity(DO).The Pearson's correlation coefficients(r value,i.e.,FC value)between time series of the 22 channels were calculated,and a 22×22 FC matrix for each subject was obtained.A paired-sample t-test(P<0.05,FDR corrected)was used to compare the difference in FC values between the HC group and the OAB group when the bladder was empty and the desire to void was strong.A two-sample t-test(P<0.05,FDR corrected)was used to compare the group differences in FC values between OAB and HC groups.Results In this study,7 patients were included in the OAB group,including 1 male and 6 female.The mean age was(47.6±16.0)years old.In HC group,13 healthy subjects were included,including 3 males and 10 females.The mean age was(49.9±9.2)years.There was no significant difference in baseline data between the two groups,including age,sex composition,years of education,handedness and urgency score at the second scan(P>0.05).Residual urine volume in both groups was less than 10 ml.The OABSS score,3-day urine diary parameters(frequency of urination/24 h,frequency of urinary incontinence/24 h,frequency of urgency/24 h)and maximum detrusor pressure during urine storage in OAB group were significantly higher than those in HC group,with statistical significance(P<0.01).The average urination volume/time,bladder capacity at first sensation and maximum bladder capacity in OAB group were significantly lower than those in HC group,and the differences were statistically significant(P<0.01).In the process of bladder filling to strong desire to void,the detrusor pressure in HC group was stable without DO,and 6 cases in OAB group had DO.Compared to empty bladder state,healthy subjects with strong desire to void showed significantly increased FC within PFC in 5 Brodmann area(BA9,BA10,BA44,BA45,BA46)and 13 edges,such as the BA9(left dorsolateral prefrontal cortex[DLPFC]:ch 4,5,7 and right DLPFC:ch 3),BA10(left frontopolar area:ch 12,21 and right frontopolar area:ch 10,18),BA44(left pars opercularis Broca's area:ch 15),BA45(left pars triangularis:ch 22),BA46(left DLPFC:ch 6,14);significantly decreased FC in 3 brain regions(BA9,BA10 and BA46)and 2 edges,such as the BA9(left DLPFC:ch 7),BA10(left frontopolar area:ch21 and right frontopolar area:ch 17),BA46(right DLPFC:ch 9).There was no significant difference in FC within PFC between OAB and HC groups with empty bladder.However,during the strong desire to void state,the FC within PFC in OAB patients was significantly abnormal when compared with HC.OAB patients showed significantly increased FC within PFC in 4 brain regions(BA9,BA10,BA45 and BA46)and 4 edges,such as the BA9(right DLPFC:ch 1 and left DLPFC:ch 7),BA10(right frontopolar area:ch 17),BA45(left pars triangularis:ch 22),BA46(right DLPFC:ch 9,16);significantly decreased FC in 3 brain regions(BA9,BA10 and BA46)and 4 edges,such as the BA9(right DLPFC:ch 3 and left DLPFC:ch 4),BA10(left frontopolar area:ch 12,21),BA46(left DLPFC:ch 14)Conclusion Compared with HC group,the PFC in OAB group showed significant abnormalities,which may lead to"dyssynergia"of PFC internal functions,result in frontal lobe dysfunction,involving sensory integration,motivation drive,emotional control and decision whether to urinate or not,etc.,leading to urinary control dysfunction,which manifested as typical clinical symptoms of OAB.Our findings contribute to the understanding of the central pathogenesis of OAB and may provide a theoretical basis for the emergence of targeted brain therapy in the future.