Limbic over-activity in depression during preserved performance on the n-back task

The profile of cognitive dysfunction observed in patients with major depressive disorder (MDD) may be partially attributed to a deficit in the central executive component of working memory (WM). This could be the consequence of a functional deficit in regions of cortex that are associated with WM function in healthy adults. In order to investigate this assertion, ten patients with a diagnosis of MDD and ten matched healthy controls undertook a parametric WM task (i.e. the n-back task) during the acquisition of blood oxygen level dependent echo planar magnetic resonance images (BOLD EPI fMRI). There was no significant difference in the behavioral performance of depressed patients and controls. This was true for both accuracy and reaction time on the n-back task. Random effects analysis of the functional imaging data (using SPM99) revealed a significant difference in load-dependent activation in the medial orbitofrontal cortex/rostral anterior cingulate between patients and controls (cluster size (K(E))/volume = 128/1024 mm3, P(corrected) = 0.025). While both participant groups exhibited a significant decrease in activation in this region with increased task difficulty, the magnitude of this decrease was smaller in patients with MDD than in controls. Therefore, this study implies that the performance of WM tasks is associated with a dysfunctional activation of the medial orbitofrontal and rostral anterior cingulate cortex in MDD. The study thus offers a rationale for explaining depressive cognitive impairment by the abnormal fronto-limbic activation found in clinical depression.     

精神分裂症空间工作记忆任务的fMRI研究

目的采用fMRI技术探讨精神分裂症患者空间工作记忆损害的神经机制。方法收集18例精神分裂症患者和18名正常受试者进行空间n-back任务的fMRI扫描。采用SPM 8进行数据预处理和统计分析,单样本t-检验用于分析两组各自脑激活结果,双样本t-检验用于工作记忆相关脑激活的组间比较。采用FDR方法进行多重比较校正。利用SPSS 17.0软件对工作记忆任务中的行为学结果 (正确率和反应时间)进行组间比较。结果与对照组相比,精神分裂症患者空间工作记忆任务反应时间延长(882.00±50.31)ms,正确率下降(83.60±2.90)%(P0.05)。精神分裂症患者在n-back空间工作记忆任务时所激活的脑区分布与对照组基本一致,主要包括双侧前额皮层、颞顶叶皮层及部分基底核团。但组间比较显示精神分裂症患者多个脑区激活强度及范围明显增加,包括双侧前额皮层背外侧、双侧后顶叶皮层、右侧中央前回、左侧颞中回、右扣带回和双侧小脑(FDR校正,P0.05)。结论执行空间工作记忆任务时精神分裂症患者脑区激活增加,但行为学表现下降,提示患者脑区活动效率低下,可能是工作记忆能力损害的神经基础。     

Working memory dysfunction in schizophrenia compared to healthy controls and patients with depression: evidence from event-related fMRI

Studies on working memory (WM) dysfunction in schizophrenia have reported several functionally aberrant brain areas including the lateral prefrontal cortex, superior temporal areas and the striatum. However, less is known about the relationship of WM-dysfunction, cerebral activation, task-accuracy and diagnostic specificity. Using a novel WM-task and event-related functional magnetic resonance imaging (fMRI), we studied healthy control subjects (n=17) and partially remitted, medicated inpatients meeting DSM-IV criteria for schizophrenia (n=19) and major depressive disorder (n=12). Due to the event-related technique, we excluded incorrectly performed trials, thus controlling for accuracy-related activation confounds. Compared with controls, patients with schizophrenia showed less activation in frontoparietal and subcortical regions at high cognitive load levels. Compared with patients with depression, schizophrenic patients showed less prefrontal activation in left inferior frontal cortex and right cerebellum. In patients with schizophrenia, a lack of deactivation of the superior temporal cortex was found compared to both healthy controls and patients with depression. Thus, we could not confirm previous findings of impaired lateral prefrontal activation during WM performance in schizophrenic patients after the exclusion of incorrectly performed or omitted trials in our functional analysis. However, superior temporal cortex dysfunction in patients with schizophrenia may be regarded as schizophrenia-specific finding in terms of psychiatric diagnosis specificity.     

首发精神分裂症患者威斯康星卡片分类测验中的脑功能障碍研究

目的:探讨首发未服药精神分裂症患者进行威斯康星卡片分类测验(WCST)操作时的脑功能状态特点。方法:20名健康受试者(对照组)和20名首发未服药精神分裂症患者(患者组)操作WCST和颜色卡片分类测验(CCST)时进行脑功能磁共振成像(fMRI),比较2组激活脑区的激活体积。结果:对照组WCST和CCST功能图像相减获得的脑活动功能图像显示,激活主要分布在双侧前额叶,尤其是背外侧部以及顶叶后下部皮质和前扣带回。患者组WCST操作成绩较对照组差,有显著性差异(P<0.01)。与对照组相比,患者组的左侧前额叶背外侧部、左前扣带回皮质激活低下,左顶叶后下部皮质激活增加(P<0.01或0.05)。结论:双侧前额叶,尤其是背外侧部,以及顶叶后下部皮质和前扣带回皮质参与WCST操作的高级认知过程。精神分裂症患者在未治疗前就存在执行功能缺陷,其前额叶和扣带回功能低下,可能与患者执行功能障碍相关;后顶叶皮质功能亢进,可能对前额叶功能低下有补偿作用。     

Neural mechanism underlying impaired visual judgement in the dysmetabolic brain: an fMRI study

An altered brain metabolism in the parietal and prefrontal regions of the cerebral cortex as well as cognitive alterations have been found in patients suffering from hepatic encephalopathy. The neural mechanisms underlying these metabolically induced cognitive alterations, however, are not known. Since patients with liver cirrhosis without clinically overt encephalopathy already show an impaired performance in a flicker light test, the aim of this study was to analyze the normal and pathologically impaired neural mechanisms of these patients using functional magnetic resonance imaging (fMRI). Nine subjects at the early stage of encephalopathy [nonmanifest hepatic encephalopathy (nmHE)] and ten controls underwent scanning, while they indicated the apparent transition from a steady light to the onset of a flicker light, that is, the critical flicker frequency (CFF). Judgement-related blood oxygenation level-dependent (BOLD) activation was decreased in nmHE compared to controls in the right inferior parietal cortex (IPL). Furthermore, the analysis of psychophysiologic interaction suggests impaired neural interaction in patients with nmHE, especially between the IPL and the parietooccipital cortex (Poc), the intraparietal sulcus, the anterior cingulate cortex (ACC), the right prefrontal cortex (PFC), the medial temporal lobe, and the extrastriate cortex V5. In contrast, nonmanifest patients revealed an enhanced coupling between IPL and the postcentral cortex. Our findings provide evidence of an early-impaired and compensatory neural mechanism during visual judgement already in the earliest stages of hepatic encephalopathy and suggest an aberrant coupling between cerebral regions in the dysmetabolic brain.     

Multi-task functional MRI in multiple sclerosis patients without clinical disability

While the majority of individuals with multiple sclerosis (MS) develop significant clinical disability, a subset experiences a disease course with minimal impairment even in the presence of significant apparent tissue damage on magnetic resonance imaging (MRI). Functional magnetic resonance imaging (fMRI) in MS patients with low disability suggests that increased use of the cognitive control system may limit the clinical manifestation of the disease. The current fMRI studies tested the hypothesis that nondisabled MS patients show increased recruitment of cognitive control regions while performing sensory, motor and cognitive tasks. Twenty two patients with relapsing-remitting MS and an Expanded Disability Status Scale (EDSS) score of ≤ 1.5 and 23 matched healthy controls were recruited. Subjects underwent fMRI while observing flashing checkerboards, performing right or left hand movements, or executing the 2-back working memory task. Compared to control subjects, patients demonstrated increased activation of the right dorsolateral prefrontal cortex and anterior cingulate cortex during the performance of the working memory task. This pattern of functional recruitment also was observed during the performance of non-dominant hand movements. These results support the mounting evidence of increased functional recruitment of cognitive control regions in the working memory system of MS patients with low disability and provide new evidence for the role of increased cognitive control recruitment in the motor system.     

Distinct mechanisms of altered brain activation in patients with multiple sclerosis

Cerebral reorganization may limit the effects of central nervous system tissue damage on cognition in patients with multiple sclerosis (MS). This study investigated fMRI activation patterns in patients with relapsing-remitting MS and healthy control subjects during performance of a delayed recognition task. As intended, fMRI task performance was similar in the MS and the control group, whereas neuropsychological testing revealed reduced performance in the patient group on the Paced Serial Addition Test, a reference task for the assessment of cognitive function in MS. Patients overall showed more activation in left posterior parietal cortex than healthy control subjects. Global gray matter atrophy in the patient group was associated with low PASAT scores. In a multiple regression analysis including white matter lesion load and gray matter atrophy as covariates, PASAT performance correlated with activation in left posterior parietal cortex and right anterior midfrontal gyrus, indicating a reallocation of neuronal resources to help preserve function. Global gray matter atrophy correlated with activation in bilateral prefrontal cortex, dorsal ACC and left posterior parietal cortex and, furthermore, was associated with a low degree of deactivation in rostral ACC, suggesting neural inefficiency and consistent with a reduced capacity to modulate between frontoparietal task-associated activation and 'default network' activity. The current study provides evidence that altered brain activation in MS patients has two distinct components, one related to compensatory processes and one to neural inefficiency associated with tissue damage.     

Developmental neural networks in children performing a Categorical N-Back Task

The prefrontal and temporal networks subserving object working memory tasks in adults have been reported as immature in young children; yet children are adequately capable of performing such tasks. We investigated the basis of this apparent contradiction using a complex object working memory task, a Categorical n-back (CN-BT). We examined whether the neural networks engaged by the CN-BT in children consist of the same brain regions as those in adults, but with a different magnitude of activation, or whether the networks are qualitatively different. Event-related fMRI was used to study differences in brain activation between healthy children ages 6 and 10 years, and young adults (20-28 years). Performance accuracy and RTs in 10-year-olds and adults were comparable, but the performance in 6-year-olds was lower. In adults, the CN-BT was highly effective in engaging the bilateral (L>R) ventral prefrontal cortex, the bilateral fusiform gyrus, posterior cingulate and precuneus, thus suggesting an involvement of the ventral visual stream, with related feature extraction and semantic labeling strategies. In children, the brain networks were distinctly different. They involved the premotor and parietal cortex, anterior insula, caudate/putamen, and the cerebellum, thus suggesting a predominant involvement of the visual dorsal and sensory-motor pathways, with related visual-spatial and action cognitive strategies. The findings indicate engagement of developmental networks in children reflecting task-effective brain activation. The age-related pattern of fMRI activation suggests a working hypothesis of a developmental shift from reliance on the dorsal visual stream and premotor/striatal/cerebellar networks in young children to reliance on the ventral prefrontal and inferior temporal networks in adults.     

A developmental fMRI study of the Stroop color-word task

We used fMRI to investigate developmental changes in brain activation during a Stroop color-word interference task. A positive correlation was observed between age and Stroop-related activation (n = 30) in the left lateral prefrontal cortex, the left anterior cingulate, and the left parietal and parieto-occipital cortices. No regions showed a negative correlation between activation and age. We further investigated age-related differences by stratifying the sample into three age groups: children (ages 7-11), adolescents (ages 12-16), and young adults (ages 18-22). Young adult subjects (n = 11) displayed significant activation in the inferior and middle frontal gyri bilaterally, the left anterior cingulate, and bilateral inferior and superior parietal lobules. Between-group comparisons revealed that young adults had significantly greater activation than adolescent subjects (n = 11) in the left middle frontal gyrus and that young adults showed significantly greater activation than children (n = 8) in the anterior cingulate and left parietal and parieto-occipital regions, as well as in the left middle frontal gyrus. Compared to children, both adult and adolescent subjects exhibited significantly greater activation in the parietal cortex. Adult and adolescent groups, however, did not differ in activation for this region. Together, these data suggest that Stroop task-related functional development of the parietal lobe occurs by adolescence. In contrast, prefrontal cortex function contributing to the Stroop interference task continues to develop into adulthood. This neuromaturational process may depend on increased ability to recruit focal neural resources with age. Findings from this study, the first developmental fMRI investigation of the Stroop interference task, provide a template with which normal development and neurodevelopmental disorders of prefrontal cortex function can be assessed.     

Prefrontal direct current stimulation modulates resting EEG and event-related potentials in healthy subjects: a standardized low resolution tomography (sLORETA) study

Prefrontal transcranial direct current stimulation (tDCS) with the anode placed on the left dorsolateral prefrontal cortex (DLPFC) has been reported to enhance working memory in healthy subjects and to improve mood in major depression. However, its putative antidepressant, cognitive and behavior action is not well understood. Here, we evaluated the distribution of neuronal electrical activity changes after anodal tDCS of the left DLPFC and cathodal tDCS of the right supraorbital region using spectral power analysis and standardized low resolution tomography (sLORETA). Ten healthy subjects underwent real and sham tDCS on separate days in a double-blind, placebo-controlled cross-over trial. Anodal tDCS was applied for 20 min at 2 mA intensity over the left DLPFC, while the cathode was positioned over the contralateral supraorbital region. After tDCS, EEG was recorded during an eyes-closed resting state followed by a working memory (n-back) task. Statistical non-parametric mapping showed reduced left frontal delta activity in the real tDCS condition. Specifically, a significant reduction of mean current densities (sLORETA) for the delta band was detected in the left subgenual PFC, the anterior cingulate and in the left medial frontal gyrus. Moreover, the effect was strongest for the first 5 min (p<0.01). The following n-back task revealed a positive impact of prefrontal tDCS on error rate, accuracy and reaction time. This was accompanied by increased P2- and P3- event-related potentials (ERP) component-amplitudes for the 2-back condition at the electrode Fz. A source localization using sLORETA for the time window 250-450 ms showed enhanced activity in the left parahippocampal gyrus for the 2-back condition. These results suggest that anodal tDCS of the left DLPFC and/or cathodal tDCS of the contralateral supraorbital region may modulate regional electrical activity in the prefrontal and anterior cingulate cortex in addition to improving working memory performance.     

fMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis

Functional magnetic resonance imaging (fMRI) data on motor function have shown adaptive functional changes related to brain injury in multiple sclerosis (MS). We investigated whether patients with MS have altered fMRI activation patterns during attention and memory tasks, and whether functional changes in the brain correlate with the extent of overall tissue damage on conventional MRI. Twenty-two right-handed patients with relapsing-remitting MS (RRMS) and no or only mild deficits at neuropsychological testing and 22 matched healthy subjects were scanned during the Paced Auditory Serial Addition Test (PASAT) and a recall task. fMRI data were analyzed using Statistical Parametric Mapping (SPM99). The relation between fMRI changes during both tasks and T2 lesion load was investigated. During both tasks, patients exhibited significantly greater brain activation than controls and recruited additional brain areas. Task-related functional changes were more significant in patients whose performance matched that of controls than in patients with a lower performance. During the PASAT, brain functional changes involved the right supplementary motor area and cingulate, the bilateral prefrontal, temporal and parietal areas, whereas during the recall task they involved the prefrontal and temporal cortex and basal ganglia bilaterally, and the left thalamus. In patients, activation in specific brain areas during performance of both tasks positively correlated with T2 brain lesions. Patients with RRMS exhibit altered patterns of activation during tasks exploring sustained attention, information processing and memory. During these tasks, fMRI activity is greater in patients with better cognitive function than in those with lower cognitive function. Functional changes in specific brain areas increase with increasing tissue damage suggesting that they may also represent adaptive mechanisms that reflect underlying neural disorganization or disinhibition, possibly associated with MS.     

Limbic-frontal circuitry in major depression: a path modeling metanalysis

This paper reports the results of an across lab metanalysis of effective connectivity in major depression (MDD). Using FDG PET data and Structural Equation Modeling, a formal depression model was created to explicitly test current theories of limbic-cortical dysfunction in MDD and to characterize at the path level potential sources of baseline variability reported in this patient population. A 7-region model consisting of lateral prefrontal cortex (latF9), anterior thalamus (aTh), anterior cingulate (Cg24), subgenual cingulate (Cg25), orbital frontal cortex (OF11), hippocampus (Hc), and medial frontal cortex (mF10) was tested in scans of 119 depressed patients and 42 healthy control subjects acquired during three separate studies at two different institutions. A single model, based on previous theory and supported by anatomical connectivity literature, was stable for the three groups of depressed patients. Within the context of this model, path differences among groups as a function of treatment response characteristics were also identified. First, limbic-cortical connections (latF9-Cg25-OF11-Hc) differentiated drug treatment responders from nonresponders. Second, nonresponders showed additional abnormalities in limbic-subcortical pathways (aTh-Cg24-Cg25-OF11-Hc). Lastly, more limited limbic-cortical (Hc-latF9) and cortical-cortical (OF11-mF10) path differences differentiated responders to cognitive behavioral therapy (CBT) from responders to pharmacotherapy. We conclude that the creation of such models is a first step toward full characterization of the depression phenotype at the neural systems level, with implications for the future development of brain-based algorithms to determine optimal treatment selection for individual patients.     

缺陷型及非缺陷型精神分裂症执行功能障碍的fMRI初步研究

目的比较缺陷型、非缺陷型精神分裂症患者与执行控制功能有关的脑区激活情况,探讨精神分裂症执行功能障碍的表现规律与相应脑机制。方法缺陷型、非缺陷型精神分裂症患者各6名及与之匹配的正常对照组,在执行参量设计的倒数n项实验时进行全脑BOLD-fMRI扫描。数据处理时采用单因素方差分析进行差异检测,分离出激活强度随记忆负荷增加而增强的脑区（执行加工相关脑区）。结果正常组执行加工相关脑区主要为左侧前额叶及顶叶后部皮层,两精神分裂症组前额叶激活体积相对较小,而且涉及更多皮层下结构。其中非缺陷型组双侧前额皮层均显著激活,且背外侧前额叶（BA9/46区）激活数目较正常组明显增多。而缺陷型组无论是前额皮层激活的脑区分布范围还是体积均显著减少于其他两组。结论精神分裂症患者存在以前额叶功能失调为基础的执行功能障碍。不同亚型的患者前额叶功能失调的机制不同：缺陷型患者前额叶可能存在特异性损伤,而非缺陷型患者主要表现为前额叶的生理低效能。     

咖啡因对抗睡眠剥夺影响执行控制功能的fMRI研究

目的 研究36 h睡眠剥夺(SD)以及睡眠剥夺并服用咖啡因后脑部功能磁共振成像(fMRI)特点,探讨咖啡因对抗睡眠剥夺对大脑功能影响的可能机制.方法 13名健康男性大学生参加试验.试验采用随机、双盲自身对照设计,对受试者在清醒状态下以及36 h睡眠剥夺并随机服用咖啡因或者安慰剂后进行Go/No-go测验并使用3.0T磁共振仪进行fMRI扫描,3次fMRI扫描之间间隔3周.受试者行为学数据使用SPSS软件处理,fMRI数据使用AFNI软件包进行处理.结果 36 h睡眠剥夺后受试者前额叶皮层显著激活,前扣带回功能活动下降;服用咖啡因后双侧豆状核、丘脑、边缘系统相关脑区激活程度下降.结论 36 h睡眠剥夺可导致执行控制功能的显著下降,前额叶皮质参与功能代偿.咖啡因通过对边缘系统相关区域及纹状体系统活动的抑制来对抗睡眠剥夺对于执行控制功能的影响.     

Color-word matching stroop task: separating interference and response conflict

The Stroop interference task requires a person to respond to a specific dimension of a stimulus while suppressing a competing stimulus dimension. Previous PET and fMRI studies using the Color Stroop paradigm have shown increased activity in the "cognitive division" of the cingulate cortex. In our fMRI study with nine subjects, we used a Color-Word Matching Stroop task. A frontoparietal network, including structures in the lateral prefrontal cortex, the frontopolar region, the intraparietal sulcus, as well as the lateral occipitotemporal gyrus, was activated when contrasting the incongruent vs the neutral condition. However, no substantial activation in either the right or left hemisphere of the anterior cingulate cortex (ACC) was detected. In accordance with a series of recent articles, we argue that the ACC is not specifically involved in interference processes. The ACC seems rather involved in motor preparation processes which were controlled in the present Color-Word Matching Stroop task. We argue that the region around the banks of the inferior frontal sulcus is required to solve interference problems, a concept which can also be seen as a component of task set management.     

Activity in ventromedial prefrontal cortex covaries with sympathetic skin conductance level: a physiological account of a "default mode" of brain function

We examined neural activity related to modulation of skin conductance level (SCL), an index of sympathetic tone, using functional magnetic resonance imaging (fMRI) while subjects performed biofeedback arousal and relaxation tasks. Neural activity within the ventromedial prefrontal cortex (VMPFC) and the orbitofrontal cortex (OFC) covaried with skin conductance level (SCL), irrespective of task. Activity within striate and extrastriate cortices, anterior cingulate and insular cortices, thalamus, hypothalamus and lateral regions of prefrontal cortex reflected the rate of change in electrodermal activity, highlighting areas supporting transient skin conductance responses (SCRs). Successful performance of either biofeedback task (where SCL changed in the intended direction) was associated with enhanced activity in mid-OFC. The findings point to a dissociation between neural systems controlling basal sympathetic tone (SCL) and transient skin conductance responses (SCRs). The level of activity in VMPFC has been related to a default mode of brain function and our findings provide a physiological account of this state, indicating that activity within VMPFC and OFC reflects a dynamic between exteroceptive and interoceptive deployment of attention.     

强迫症患者fMRI Stroop试验脑功能异常

目的 应用fMRI观察强迫症(OCD)患者的脑功能异常区域。 方法 OCD患者13例(OCD组),正常对照者15名(正常对照组),按年龄、性别、受教育程度相匹配。对全部受试者行fMRI,刺激采用Stroop任务,运用SPM8软件对两组平均后的脑功能图像的激活区域进行比较分析。 结果 OCD患者需要激活更多脑区(左侧海马旁回、中央旁小叶、丘脑、距状回等)以完成相对简单的色字无干扰任务,激活减低的脑区主要有左侧前扣带回和左侧尾状核。在相对复杂的色字干扰任务时,OCD组并未出现激活高于正常对照组的脑区,激活减低的脑区主要有双侧眶额叶、左侧前扣带回以及左侧尾状核。 结论 OCD患者可能存在眶额叶、前扣带回、尾状核等区域的功能异常,这些脑区功能异常可能在OCD发病机制方面发挥作用。     

Neural basis of abnormal response to negative feedback in unmedicated mood disorders

Depressed individuals show hypersensitivity to negative feedback during cognitive testing, which can precipitate subsequent errors and thereby impair a broad range of cognitive abilities. We studied the neural mechanisms underlying this feedback hypersensitivity using functional magnetic resonance imaging (fMRI) with a reversal learning task that required subjects to ignore misleading negative feedback on some trials. Thirteen depressed subjects with major depressive disorder (MDD), 12 depressed subjects with bipolar disorder (BD) and 15 healthy controls participated. The MDD group, but not the BD group, demonstrated enhanced sensitivity to negative feedback compared to controls, as indicated by the rates of rule reversal following misleading negative feedback. In the control and BD groups, hemodynamic activity was significantly higher in the dorsomedial and ventrolateral prefrontal cortices during reversal shifting, and significantly lower in the right amygdala in response to negative feedback. The extent to which the amygdala showed less activity during negative feedback correlated inversely with the behavioral tendency to reverse after misleading feedback. This effect was not present in the MDD group, who also failed to recruit the prefrontal cortex during behavioral reversal. Hypersensitivity to negative feedback is present in unmedicated depressed patients with MDD. Disrupted top-down control by the prefrontal cortex of the amygdala may underlie this abnormal response to negative feedback in unipolar depression.     

Stroop performance in normal control subjects: an fMRI study

In an attempt to clarify regional signal intensity changes, which may accompany the performance of the Stroop Color-Word task, healthy subjects were imaged using the fMRI BOLD technique while performing a modified version of the task. Both the AAA and VOA subdivisions of the anterior cingulate cortex were significantly activated during the interference condition; however, only the signal intensity change within the VOA correlated with task performance. Additionally, signal intensity change was significantly increased in the VOA subdivision of the cingulate cortex when controlling for signal intensity change present during the performance of a color naming task. This study extends previous findings by demonstrating that in healthy adults, a subdivision of the cingulate cortex is specifically associated with the cognitive demands present in the interference condition.     

Same or different? Neural correlates of happy and sad mood in healthy males

Emotional experience in healthy men has been shown to rely on a brain network including subcortical as well as cortical areas in a complex interaction, which may be substantially influenced by many internal personal and external factors such as individuality, gender, stimulus material and task instructions. The divergent results may be interpreted by taking these considerations into account. Hence, many aspects remain to be clarified in characterizing the neural correlates underlying the subjective experience of emotion. One unresolved question refers to the influence of emotion quality on the cerebral substrates. Hence, 26 male healthy subjects were investigated with functional magnetic resonance imaging during standardized sad and happy mood induction as well as a cognitive control task to explore brain responses differentially involved in positive and negative emotional experience. Sad and happy mood in contrast to the control task produced similarly significant activations in the amygdala-hippocampal area extending into the parahippocampal gyrus as well as in the prefrontal and temporal cortex, the anterior cingulate, and the precuneus. Significant valence differences emerged when comparing both tasks directly. More activation has been demonstrated in the ventrolateral prefrontal cortex (VLPFC), the anterior cingulate cortex (ACC), the transverse temporal gyrus, and the superior temporal gyrus during sadness. Happiness, on the other hand, produced stronger activations in the dorsolateral prefrontal cortex (DLPFC), the cingulate gyrus, the inferior temporal gyrus, and the cerebellum. Hence, negative and positive moods reveal distinct cortical activation foci within a common neural network, probably making the difference between qualitatively different emotional feelings.