低频重复经颅磁刺激辅助运动前区治疗强迫症的疗效分析

目的探讨低频重复经颅磁刺激(low-frequency repetitive transcranial magnetic stimulation, LF-rTMS作用于辅助运动前区(pre-supplementary motor area, pre-SMA)对强迫症(obsessive-compulsive disorder,OCD)患者的疗效。方法按照随机数字表法将100例强迫症患者分为pre-SMA组(33例)、背外侧前额叶(dorsolateral prefrontal cortex,DLPFC)组(32例)和对照组(35例),在原药物治疗基础上,pre-SMA组和DLPFC组分别于相应脑区给予1 Hz rTMS治疗,对照组给予假性刺激,分别在治疗前、治疗后第4周末和第12周末用耶鲁-布朗强迫量表(Yale-Brown obsessive compulsive scale,Y-BOCS)评估患者强迫症状。结果重复测量方差分析显示,Y-BOCS评分时间主效应、时间与组别交互作用有统计学意义(P0.01)。治疗前比较3组总强迫评分差异无统计学意义(P0.05);治疗4周末,DLPFC组强迫评分低于pre-SMA组、对照组(P0.05);治疗12周末,pre-SMA组和DLPFC组强迫评分低于对照组(P0.05)。pre-SMA组、DLPFC组、对照组强迫评分减分率(35.77%±10.51%vs. 54.18%±10.09%vs. 18.85%±6.52%)差异有统计学意义(F=110.38, P0.01)。结论 LF-rTMS刺激preSMA对改善强迫症患者症状具有临床意义。     

重症肌无力患者30例视觉工作记忆损害

目的 探讨重症肌无力(myasthenia gravis,MG)患者的视觉工作记忆损害情况.方法 采用自行修订的视觉工作记忆检查软件(以Smith的检测方法为基础)对30例MG患者及28名健康对照进行视觉物体及视觉空间工作记忆检查.结果 在视觉物体工作记忆检查中,MG患者组与对照组成绩(MG组正确率73.4%±9.7%,对照组正确率72.7%±8.5%)差异无统计学意义.在视觉空间工作记忆检查中,MG组正确率(76.6%±16.5%)低于对照组(86.6%±7.5%),两者差异有统计学意义(Z=-2.204,P=0.028).结论 MG患者可能存在视觉空间工作记忆损害,而视觉物体工作记忆相对保留.

Abstract：

Objective To investigate the situation of visual memory impairment in patients with myasthenia gravis (MG).Methods Thirty MG patients and 28 normal control subjects were tested with a battery of computerized tests (modified Smith working memory software), which was designed to assess visual-spatial and visual-object working memory.Results There was no significant difference in the accuracy rate of visual-object working memory test between the MG group and normal controls (MG group 73.4% ±9.7%, normal controls 72.7% ±8.5%).The accuracy rate of the visual-spatial working memory test in the MG group (76.6% ± 16.5%) was significantly lower than that in the normal controls (86.6% ±7.5%, Z = -2.204, P = 0.028).Conclusion The visual-spatial working memory is probably impaired while the visual-object working memory is relatively spared in MG patients.     

帕金森病患者工作记忆障碍研究

目的　探讨帕金森病 (PD)患者工作记忆状况。方法　仿制并修订了Smith工作记忆检查软件 ,对 6 6例PD患者及 6 0名对照者进行工作记忆检查。结果　早期PD患者视觉空间工作记忆正确率较对照组低 (分别为 82 8%± 12 1%,90 9%± 6 7%) ,差异有显著意义 (t=3 0 76 ,P <0 0 1) ,视觉物体形状工作记忆正确率与对照组相近 (6 9 2 %± 10 9%,72 7%± 8 1%) ,差异无显著意义 (t=1 389,P >0 0 5 ) ;中期PD患者视觉空间与物体形状工作记忆正确率 (分别为 6 9 6 %± 15 6 %,6 3 11%±5 4 %) ,均较对照组低 ,差异有极显著意义 (t=6 399、t=3 377,P <0 0 0 0 1、P <0 0 1) ;中期PD患者视觉空间与物体形状工作记忆正确率均较早期PD患者低 ,差异有显著意义 (t=2 6 14、t =2 140 ,P <0 0 5 ) ;早期PD患者视觉颜色工作记忆正确率与对照组相近 (6 5 1%± 11 4 %,6 9 9%± 10 1%) ,差异无显著意义 (t=1 6 81,P >0 0 5 )。相关性分析发现 ,Hoehn Yahr分级与工作记忆正确率呈负相关。　结论PD患者早期即有视觉空间工作记忆损伤 ,而视觉物体形状工作记忆及颜色工作记忆正常 ,随着疾病进展至中期 ,PD患者视觉空间与物体形状工作记忆均受损伤 ,且程度较早期加重。     

前额叶损伤患者情绪记忆的改变

目的 探讨前额叶损伤患者情绪记忆的损害情况,验证前额叶参与情绪记忆神经机制的假说.方法 建立情绪记忆的神经心理学测验方法,测试年龄、教育程度相匹配的40名健康人和40例前额叶损伤患者的情绪记忆情况.结果 与健康对照组[正性(11.68±2.18)分和负性(12.93±1.33)分]相比,前额叶损伤组[正性(8.20±2.02)分和负性(8.68±1.14)分]情绪效价图片再认成绩差异有统计学意义(t=7.41、-2.75,P＜0.05),而中性的情绪效价图片再认成绩差异无统计学意义.左、右侧前额叶损伤组的正性[(8.90±2.01)分、(7.50±1.79)分]和负性[(7.30±1.10)分、(9.05±1.00)分]情绪效价图片再认成绩差异均有统计学意义(Z=-2.15、-2.07,P＜0.05).结论 前额叶损伤患者的情绪记忆存在损害,且左、右侧前额叶损伤患者的正性与负性效价记忆相对存在不同差别的损害,表明其可能有不同的神经机制.

Abstract：

Objective To investigate the emotional memory impairment in patients with lesions located in prefrontal cortex(PFC), and to test the hypothesis that prefrontal cortex is involved in the emotional memory network. Methods The 40 patients with lesions in PFC and forty age-education-level matched healthy adults were given emotional memory tasks using positive, neutral and negative valence images. Results Compared with the healthy adults(positively(11.68 ± 2. 18)and negatively(12. 93 ±1.33)), the patients had significant loss in positively(8. 20 ± 2.02)and negatively(8. 68 ± 1.14)valence image memorizing(t = 7.41, - 2. 75, both P ＜ 0. 05). There was no insignificant impairment in neutral stimuli. Performance difference between left PFC and right PFC in positively(8. 90 ±2. 01 vs 7.50 ± 1.79)and negatively(7.30 ± 1.10 vs 9. 05 ± 1. 00)valence image recognition was significant(Z = -2. 15,-2. 07,both P ＜ 0. 05). Conclusion The results suggest that emotional memory is impaired in the patients with lesions in PFC. The impairment difference between left PFC and right PFC indicates that they may have different neuromechanisms.     

轻度认知功能障碍患者的执行功能和工作记忆研究

目的 了解轻度认知功能障碍(MO)患者的执行功能和工作记忆是否损害及工作记忆损害特点,探讨执行功能对MCI患者的日常生活活动能力(ADL)的影响.方法 运用神经心理学测试的方法对30例MCI患者进行执行功能、工作记忆及其他认知功能检查,同时进行ADL评定,另外选择30名健康老人作为对照组.结果 MCI组的执行功能和工作记忆成绩(分)显著低于对照组,其中数字颜色连线干扰(130.8±58.2)、数字颜色连线B(210.2±81.8)、词汇流畅性测试(8.9±5.4)、视觉客体工作记忆(0.73±0.12)和数字广度(3.4±0.9),除视觉空间工作记忆外,与对照组比较(52.0±13.5、121.0±33.4、16.4±5.4、0.85±9.18、4.2±1.1)差异均有统计学意义(t=7.108、5.159、-4.879、-4.351、-2.544,均P<0.01或P<0.05).用多元逐步回归方法分析执行功能对ADL的影响,结果 客体工作记忆、空间工作记忆和词汇流畅性与ADL的影响相关,而客体工作记忆与ADL的影响有显著相关性(β=-0.720,t=-3.571,P=0.001).结论 MCI患者具有明显的执行功能障碍和工作记忆损害,工作记忆与MCI患者的ADL有良好相关性,而且视觉客体工作记忆与MCI患者的ADL测查具有显著相关性,因此MCI患者的执行功能障碍可能是导致其ADL下降和客体工作记忆损害的主要因素.     

轻度认知障碍患者视空间工作记忆的变化

目的 探索轻度认知障碍(MCI)患者视空间工作记忆的广度和准确度的变化.方法 根据临床记忆检查和Blessed-Roth生活评定结果诊断的MCI患者20例和与之匹配的正常对照20例进行扫视记忆和重现数字位置的试验.结果 MCI组扫视记忆的正确率比对照组下降,差异有统计学意义(P<0.05).扫视的平均速度与对照组的差异无统计学意义(P>0.05).两组能正确记忆位置的数字个数差异无统计学意义(P>0.05),为达到最好的记忆效果,MCI组需要数字呈现的时间比对照组长,差异有统计学意义(P<0.05).结论 MCI患者视觉空间工作记忆的中央执行系统运转正常,视空间模板的存贮空间保留,视空间工作记忆的广度正常,而视空间初步加工系统中两种次级记忆的准确性下降,导致视空间工作记忆的准确度下降.     

认知矫正治疗前后慢性精神分裂症患者功能磁共振成像的对照研究

目的 探讨认知矫正治疗对精神分裂症患者工作记忆相关脑区活动的影响.方法 对10例病情稳定的慢性精神分裂症患者进行为期6个月的认知矫正治疗,分别于治疗前后进行韦克斯勒记忆量表(WMS)测查及功能磁共振成像(fMRI)测量.结果 (1)WMS测查:治疗后再认[(8.11±4.34)分]和再生[(10.22±3.35)分]以及Benton错误[(3.75±2.92)分]均较治疗前[分别为(5.78±2.95)分、(8.56±3.21)分和(8.00±6.28)分]改善,均P＜0.05.(2)fMRI:治疗前后的反应时和正确率比较,差异无统计学意义(P＞0.05).治疗后在高负荷条件下,背侧前额叶皮质(DLPFC)区域(Brodmann46区)的激活范围(x,y,z=-51,36,15;k=40,t=7.21)小于治疗前的激活范围(x,y,z=-48,24,24,k=154,t=12.72),治疗前后DLPFC区域激活(x,y,z=-24,36,18,k=12,t=3.75)的差异有统计学意义(P＜0.005);在低负荷条件下,治疗前后DLPFC区域激活的差异无统计学意义(P＞0.05).结论 认知矫正治疗能改善精神分裂症患者工作记忆相关脑区的活动.     

磁共振导航定位高频重复经颅磁刺激治疗抑郁发作的初步研究

目的探讨重复经颅磁刺激(repetitive transcranial magnetic stimulation, r TMS)治疗中应用磁共振导航定位与"标准5 cm法"定位的位置差异。方法对12例抑郁发作患者分别采用磁共振导航定位和5 cm定位法定位背外侧前额叶(dorsolateral prefrontal cortex, DLPFC),比较两者位置的差异,并使用汉密尔顿抑郁量表(Hamilton depression rating scale, HAMD)观察抗抑郁治疗效果。结果磁共振引导下定位与传统定位的DLPFC相距平均(17.42±9.62)mm,该距离具有统计学意义(t=6.00, P0.01)。共有9例患者接受超过5次r TMS治疗(最少6次,最多25次),r TMS治疗前后的HAMD分别为(24.56±4.50)分与(7.78±4.71)分,差异具有统计学意义(t=-11.20,P0.01),其中有4例患者达到临床痊愈。结论磁共振导航定位与标准5 cm方法定位的位置存在明显差异,在r TMS抗抑郁治疗研究中采用磁共振引导定位,能够更精准定位DLPFC区域。     

右侧额叶低频重复经颅磁刺激治疗抑郁症的meta分析

目的系统评价右侧额叶低频重复经颅磁刺激(repetitive transcranial magnetic stimulation,r TMS)治疗抑郁症的疗效。方法检索Pub Med、Web of Science、CBM、CNKI、VIP数据库中有关低频r TMS刺激右侧额叶背外侧皮质(dorsolateral prefrontal cortex,DLPFC)治疗抑郁症的临床随机对照研究(randomized controlled trials,RCT)。采用Rev Man 5.2软件,根据对照组刺激方法的不同,分别以无效刺激及高频r TMS为对照,对治疗应答率进行meta分析。结果纳入以无效刺激为对照的RCT研究9项,其中低频r TMS组156例抑郁症患者,无效刺激组162例,meta分析显示低频r TMS刺激右侧DLPFC治疗抑郁症,其治疗应答率相比无效刺激组,差异有统计学意义RR=2.15(95%CI:1.57~2.95,P0.01);纳入以高频r TMS刺激左侧DLPFC为对照的RCT研究11项,其中低频r TMS组178例患者,高频r TMS组200例,meta分析表明两组间应答率差异无统计学意义(RR=0.80,95%CI:0.63~1.02,P=0.07)。结论低频r TMS刺激右侧DLPFC治疗抑郁症有效,但相比高频r TMS刺激左侧DLPFC方法而言,不具有疗效优势。     

老年遗忘型轻度认知损害患者语言工作记忆损害特点

目的 探讨老年遗忘型轻度认知损害(aMCI)患者语言工作记忆损害的特点及机制.方法 采用语言工作记忆检查软件对30例老年aMCI患者进行视觉语言工作记忆及词语流畅性和数字广度测试等神经心理学检查,并选择30名健康老人作对照.结果 aMCI患者的视觉语义工作记忆测试成绩正确率低于对照组,差异具有统计学意义(79.83%±3.22%与87.00%±1.93%,t=-1.03,P=0.002);视觉语音工作记忆测试成绩也低于对照组,但差异无统计学意义(78.92%±8.60%与86.80%±2.14%,t=-2.34,P=0.060);逆序数字广度测试(1.53±0.86与3.63±0.56,t=-1.23,P=0.027)和词语流畅性测试分值均低于对照组(22.96±2.31与31.53±3.72,t=-1.08,P=0.004),差异具有统计学意义.结论 老年aMCI患者的视觉语义性语言工作记忆受损,语音性语言工作记忆相对保留;逆序数字广度和词语流畅性测试成绩亦显著降低.     

Attention and executive functions profile in drug naive ADHD subtypes

Attention deficit hyperactivity disorder (ADHD) has been associated with executive functioning and sustained and divided attention deficits. In order to clarify the questions on neurocognitive impairment in ADHD, we investigated the presence of specific executive functions (EFs) and attention deficit patterns in ADHD clinical subtypes. 50 patients with ADHD and 44 controls were evaluated. All subjects were boys and performed a clinical-psychopathological and neuropsychological battery. Five main domains of EFs and attention were studied. Executive functions-related neurocognitive abilities were used as control tasks. ADHD patients, inattentive and combined subtypes differ from controls on response inhibition, divided attention, phonological, and visual object working memory and on variability of reaction times measured with CPT. Comparison of ADHD subtypes, in five main domains of EFs, did not show evidence of different executive functioning profiles. Response inhibition can predict performance on working memory tests but it cannot predict performance on divided attention/set shifting and on sustained attention. ADHD boys exhibit a selective impairment on executive functions and attention tasks. These data suggest the involvement of partially independent neural circuits which control inhibition and divided attention in ADHD. Since right prefrontal cortex seems to be crucial in controlling response inhibition, while left dorsolateral prefrontal cortex seems important in modulating divided attention, these areas are deputated to be involved in the pathogenesis of neuropsychological deficits in ADHD subtypes. In addition, this study candidates the impairment in phonological and visual-object working memory as a possible neuropsychological trait in ADHD males with inattentive or combined subtypes.     

Transcranial magnetic stimulation of left prefrontal cortex impairs working memory.

OBJECTIVES: Several lines of evidence suggest that the prefrontal cortex is involved in working memory. Our goal was to determine whether transient functional disruption of the dorsolateral prefrontal cortex (DLPFC) would impair performance in a sequential-letter working memory task. METHODS: Subjects were shown sequences of letters and asked to state whether the letter just displayed was the same as the one presented 3-back. Single-pulse transcranial magnetic stimulation (TMS) was applied over the DLPFC between letter presentations. RESULTS: TMS applied over the left DLPFC resulted in increased errors relative to no TMS controls. TMS over the right DLPFC did not alter working memory performance. CONCLUSION: Our results indicate that the left prefrontal cortex has a crucial role in at least one type of working memory.     

Frontal lobe involvement in spatial span: converging studies of normal and impaired function

Although monkey lesion studies involving the prefrontal cortex commonly report working memory deficits, and neuroimaging studies consistently show prefrontal involvement in such tasks, patients with damage to this region commonly fail to show any working memory impairment. Such a discrepancy may be due to insensitive testing measures for patients, as well as small, yet critical differences between working memory tasks in imaging and patient studies. The current study utilised a more sensitive measure of spatial working memory spans, based either on structured or unstructured spatial arrays. A PET study in normal subjects confirmed that both variants did indeed activate prefrontal cortex. The same tasks were given to frontal lobe patients and closely matched controls. Patients with large frontal lesions were significantly impaired on this task, with those patients with damage to the right dorsolateral prefrontal cortex appearing particularly impaired. This result demonstrates that prefrontal cortex is necessary for normal working memory, even in simple tasks, such as spatial span. It is suggested, however, that the patient deficit reflects strategic or goal-based dysfunction, rather than storage limitations.     

Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression.

BACKGROUND: A large number of studies suggest the presence of deficits in dorsolateral prefrontal cortex function during performance of working memory tasks in individuals with schizophrenia. However, working memory deficits may also present in other psychiatric disorders, such as major depression. It is not clear whether people with major depression also demonstrate impaired prefrontal activation during performance of working memory tasks. METHODS: We used functional magnetic resonance imaging to assess the patterns of cortical activation associated with the performance of a 2-back version of the N-Back task (working memory) in 38 individuals with schizophrenia and 14 with major depression. RESULTS: We found significant group differences in the activation of dorsolateral prefrontal cortex associated with working memory performance. Consistent with prior research, participants with schizophrenia failed to show activation of right dorsolateral prefrontal cortex in response to working memory tasks demands, whereas those with major depression showed clear activation of right and left dorsolateral prefrontal cortex as well as bilateral activation of inferior and superior frontal cortex. CONCLUSIONS: During performance of working memory tasks, deficits in prefrontal activation, including dorsolateral regions, are more severe in participants with schizophrenia (most of whom were recently released outpatients) than in unmedicated outpatients with acute nonpsychotic major depression.     

Reduced neural connectivity but increased task‐related activity during working memory in de novo Parkinson patients

Objective: Patients with Parkinson's disease (PD) often suffer from impairments in executive functions, such as working memory deficits. It is widely held that dopamine depletion in the striatum contributes to these impairments through decreased activity and connectivity between task‐related brain networks. We investigated this hypothesis by studying task‐related network activity and connectivity within a sample of de novo patients with PD, versus healthy controls, during a visuospatial working memory task. Methods: Sixteen de novo PD patients and 35 matched healthy controls performed a visuospatial n‐back task while we measured their behavioral performance and neural activity using functional magnetic resonance imaging. We constructed regions‐of‐interest in the bilateral inferior parietal cortex (IPC), bilateral dorsolateral prefrontal cortex (DLPFC), and bilateral caudate nucleus to investigate group differences in task‐related activity. We studied network connectivity by assessing the functional connectivity of the bilateral DLPFC and by assessing effective connectivity within the frontoparietal and the frontostriatal networks. Results: PD patients, compared with controls, showed trend‐significantly decreased task accuracy, significantly increased task‐related activity in the left DLPFC and a trend‐significant increase in activity of the right DLPFC, left caudate nucleus, and left IPC. Furthermore, we found reduced functional connectivity of the DLPFC with other task‐related regions, such as the inferior and superior frontal gyri, in the PD group, and group differences in effective connectivity within the frontoparietal network. Interpretation: These findings suggest that the increase in working memory‐related brain activity in PD patients is compensatory to maintain behavioral performance in the presence of network deficits. Hum Brain Mapp 36:1554–1566, 2015. © 2015 Wiley Periodicals, Inc.     

Contributions of subregions of the prefrontal cortex to working memory: evidence from brain lesions in humans

We investigated working memory in patients with focal brain damage involving subregions of the prefrontal cortex (PFC). Lesions in the dorsal portion of lateral PFC or the ventromedial portion of orbital PFC did not impair performance in tasks that required maintenance and monitoring of object or spatial information. Larger lesions involving both ventral and dorsal parts of the lateral PFC impaired maintenance and monitoring of spatial and object information, with more severe deficits observed in the spatial tasks. The results support a distributed localization of function in lateral PFC during working memory.     

Disrupted functional connectivity for controlled visual processing as a basis for impaired spatial working memory in schizophrenia

Although regional brain abnormalities underlying spatial working memory (SWM) deficits in schizophrenia have been identified, little is known about which brain circuits are functionally disrupted in the SWM network in schizophrenia. We investigated SWM-related interregional functional connectivity in schizophrenia using functional magnetic resonance imaging (fMRI) data collected during a memory task that required analysis of spatial information in object structure. Twelve schizophrenia patients and 11 normal control subjects participated. Patients had SWM performance deficits and deficient neural activation in various brain areas, especially in the high SWM load condition. Examination of the covariation of regional brain activations elicited by the SWM task revealed evidence of functional disconnection between prefrontal and posterior visual association areas in schizophrenia. Under low SMW load, we found reduced functional associations between dorsolateral prefrontal cortex (DLPFC) and inferior temporal cortex (ITC) in the right hemisphere in patients. Under high SWM load, we found evidence for further functional disconnection in patients, including additional reduced functional associations between left DLPFC and right visual areas, including the posterior parietal cortex (PPC), fusiform gyrus, and V1, as well as between right inferior frontal cortex and right PPC. Greater prefrontal-posterior cortical functional connectivity was associated with better SWM performance in controls, but not in patients. These results suggest that prefrontal-posterior functional connectivity associated with the maintenance and control of visual information is central to SWM, and that disruption of this functional network underlies SWM deficits in schizophrenia.     

How cognitive performance‐induced stress can influence right VLPFC activation: An fMRI study in healthy subjects and in patients with social phobia

The neural bases of interactions between anxiety and cognitive control are not fully understood. We conducted an fMRI study in healthy participants and in patients with an anxiety disorder (social phobia) to determine the impact of stress on the brain network involved in cognitive control. Participants performed two working memory tasks that differed in their level of performance‐induced stress. In both groups, the cognitive tasks activated a frontoparietal network, involved in working memory tasks. A supplementary activation was observed in the right ventrolateral prefrontal cortex (VLPFC) in patients during the more stressful cognitive task. Region of interest analyses showed that activation in the right VLPFC decreased in the more stressful condition as compared to the less stressful one in healthy subjects and remain at a similar level in the two cognitive tasks in patients. This pattern was specific to the right when compared to the left VLPFC activation. Anxiety was positively correlated with right VLPFC activation across groups. Finally, left dorsolateral prefrontal cortex (DLPFC) activation was higher in healthy subjects than in patients in the more stressful task. These findings demonstrate that in healthy subjects, stress induces an increased activation in left DLPFC, a critical region for cognitive control, and a decreased activation in the right VLPFC, an area associated with anxiety. In patients, the differential modulation between these dorsal and ventral PFC regions disappears. This absence of modulation may limit anxious patients' ability to adapt to demanding cognitive control tasks. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc