Regional brain changes in bipolar I depression: a functional magnetic resonance imaging study

Objective:  To investigate neural activity in prefrontal cortex and amygdala during bipolar depression.
Methods:  Eleven bipolar I depressed and 17 normal subjects underwent functional magnetic resonance imaging (fMRI) while performing a task known to activate prefrontal cortex and amygdala. Whole brain activation patterns were determined using statistical parametric mapping (SPM) when subjects matched faces displaying neutral or negative affect (match condition) or matched a geometric form (control condition). Contrasts for each group for the match versus control conditions were used in a second-level random effects analysis.
Results:  Random effects between-group analysis revealed significant attenuation in right and left orbitofrontal cortex (BA47) and right dorsolateral prefrontal cortex (DLPFC) (BA9) in bipolar depressed subjects. Additionally, random effects analysis showed a significantly increased activation in left lateral orbitofrontal cortex (BA10) in the bipolar depressed versus control subjects. Within-group contrasts demonstrated significant amygdala activation in the controls and no significant amygdala activation in the bipolar depressed subjects. The amygdala between-group difference, however, was not significant.
Conclusions:  Bipolar depression is associated with attenuated bilateral orbitofrontal (BA47) activation, attenuated right DLPFC (BA9) activation and heightened left orbitofrontal (BA10) activation. BA47 attenuation has also been reported in mania and may thus represent a trait feature of the disorder. Increased left prefrontal (BA10) activation may be a state marker to bipolar depression. Our findings suggest dissociation between mood-dependent and disease-dependent functional brain abnormalities in bipolar disorder.     

Tactile-visual integration in the posterior parietal cortex: a functional magnetic resonance imaging study

To explore the neural substrates of visual-tactile crossmodal integration during motion direction discrimination, we conducted functional magnetic resonance imaging with 15 subjects. We initially performed independent unimodal visual and tactile experiments involving motion direction matching tasks. Visual motion discrimination activated the occipital cortex bilaterally, extending to the posterior portion of the superior parietal lobule, and the dorsal and ventral premotor cortex. Tactile motion direction discrimination activated the bilateral parieto-premotor cortices. The left superior parietal lobule, intraparietal sulcus, bilateral premotor cortices and right cerebellum were activated during both visual and tactile motion discrimination. Tactile discrimination deactivated the visual cortex including the middle temporal/V5 area. To identify the crossmodal interference of the neural activities in both the unimodal and the multimodal areas, tactile and visual crossmodal experiments with event-related designs were also performed by the same subjects who performed crossmodal tactile-visual tasks or intramodal tactile-tactile and visual-visual matching tasks within the same session. The activities detected during intramodal tasks in the visual regions (including the middle temporal/V5 area) and the tactile regions were suppressed during crossmodal conditions compared with intramodal conditions. Within the polymodal areas, the left superior parietal lobule and the premotor areas were activated by crossmodal tasks. The left superior parietal lobule was more prominently activated under congruent event conditions than under incongruent conditions. These findings suggest that a reciprocal and competitive association between the unimodal and polymodal areas underlies the interaction between motion direction-related signals received simultaneously from different sensory modalities.     

Orbitofrontal dysfunction in a monozygotic twin discordant for postpartum affective psychosis: a functional magnetic resonance imaging study

BACKGROUND: Incomplete concordance for psychosis in monozygotic (MZ) twins has been interpreted as indicative of non-genetic cofactors in transmission of the illness. In this case study, we consider childbirth a landmark in the onset of psychotic symptoms, leading to the diagnosis of puerperal psychosis and then to bipolar/schizoaffective disorder. At the end of the third trimester, there is a sudden drop in estrogen, which exerts prominent effects on the serotonergic system in the orbitofrontal cortex (OFC). OBJECTIVES: The purpose of the present study was to investigate OFC activation during emotional processing in MZ twins discordant for affective psychosis. METHODS: Blood-oxygen-level-dependent activation using functional magnetic resonance imaging was measured during the passive viewing of emotional film excerpts. RESULTS: Consistent with our hypothesis, a significant locus of activation was found in the left OFC in the normal MZ twin, but not in the psychosis MZ twin. CONCLUSIONS: The personality changes noted in the psychosis MZ twin (postpartum psychosis) may be related to dysfunctional OFC. Ms J's childbirth may have triggered the onset of psychotic symptoms, leading to the diagnosis of bipolar or schizoaffective disorder.     

Abnormal prefrontal cortex function during response inhibition in Turner syndrome: functional magnetic resonance imaging evidence.

BACKGROUND: Turner syndrome (TuS) arises from the partial or complete absence of one X chromosome. Although neuropsychological studies report impaired attentional function and response inhibition in TuS, the neural correlates of these cognitive problems are unknown. METHODS: Eleven female subjects with TuS and 11 individually matched normal control subjects were imaged using functional magnetic resonance imaging while performing a Go/NoGo task. RESULTS: Groups did not differ on accuracy or reaction time; however, the TuS group activated more in the bilateral superior and middle frontal gyri than control subjects. Control subjects did not activate more than the TuS group in any region. CONCLUSION: These findings suggest that female subjects with TuS compensate for executive dysfunction via recruitment of additional prefrontal cortex regions involved in inhibition, attention, and working memory, functions necessary for successful performance of Go/NoGo tasks. Elucidating brain function in TuS will advance our understanding of the influence of X-chromosome genes on neurodevelopment and brain function and contribute to planning future intervention strategies.     

Sex and performance level effects on brain activation during a verbal fluency task: A functional magnetic resonance imaging study

Neuroimaging studies investigating the neural correlates of verbal fluency (VF) focused on sex differences without taking into account behavioural variation. Nevertheless, group differences in this verbal ability might account for neurocognitive differences elicited between men and women. The aim of this study was to test sex and performance level effects and the combination of these on cerebral activation. Four samples of 11 healthy students (N = 44) selected on the basis of sex and contrasted VF scores, high fluency (HF) versus low fluency (LF), performed a covert phonological VF task during scans. Within- and between-group analyses were conducted. Consistent with previous studies, for each sample, the whole-group analysis reported activation in the inferior frontal gyrus (IFG), insula, anterior cingulate cortex (ACC), medial frontal gyrus (mFG), superior (SPL) and inferior parietal lobules (IPL), inferior visual areas, cerebellum, thalamus and basal ganglia. Between-group analyses showed an interaction between sexes and performances in the right precuneus, left ACC, right IFG and left dorsolateral prefrontal cortex (dlPFC). HF men showed more activation than LF ones in the right precuneus and left dlPFC. LF men showed more activation in the right IFG than HF ones and LF women elicited more activation in the left ACC than HF ones. A sex main effect was found regardless of performance in the left inferior temporal gyrus (ITG), cerebellum, anterior and posterior cingulate cortexes and in the right superior frontal gyrus (SFG) and dlPFC, lingual gyrus and ACC, with men eliciting significantly greater activations than women. A performance main effect was found for the left ACC and the left cerebellum regardless of sex. LF subjects had stronger activations than HF ones in the ACC whereas HF subjects showed stronger activations in the cerebellum. Activity in three discrete subregions of the ACC is related to sex, performance and their interaction, respectively. Our findings emphasize the need to consider sex and performance level in functional imaging studies of VF.     

Cerebral activation patterns in patients with writer's cramp: a functional magnetic resonance imaging study

Functional MRI (fMRI), visualizing changes in cerebral blood oxygenation, has to date not been performed either in patients with writer's cramp or in healthy subjects during writing. We compared the cerebral and cerebellar activation pattern of 12 patients with writer's cramp during writing with a group of 10 healthy subjects performing the same tasks over 30-s periods of rest or writing. Sixty echo planar imaging multi-slice datasets were analysed using SPM96 software. Data were analysed for each subject individually and groupwise for patients vs. controls. Healthy subjects showed a significant activation of the ipsilateral dentate nucleus, contralateral cerebellar hemisphere, contralateral primary sensorimotor cortex, and contralateral precentral gyrus during writing. Patients with writer's cramp showed significantly greater activation of the ipsilateral cerebellar hemisphere than controls. Also the activation in the primary sensorimotor cortex extended further caudally and anteriorly towards the premotor association area. Activation was observed in the thalamus during writing only among the patients. Our results indicate an increased basal ganglia output via the thalamus to the motor and premotor cortical areas in dystonia patients and support the notion of disinhibition of the motor cortex leading to coconcentrations and dystonic postures. Received: 10 November 1999 / Received in revised form: 4 April 2000 / Accepted: 26 April 2000     

Relation of bimanual coordination to activation in the sensorimotor cortex and supplementary motor area: analysis using functional magnetic resonance imaging

The aim of this study was to analyze how functional activation in the supplementary motor area (SMA) and sensorimotor cortex (SMC) is related to bimanual coordination using functional magnetic resonance imaging. Subjects included 24 healthy volunteers, 15 of whom were right-handed and 9 left-handed. Three kinds of activation tasks, all of which required the repetitive closing and opening of a fist, were performed: unimanual movement of the nonpreferred hand (task A); simultaneous, agonistic movement of both hands (task B); simultaneous, antagonistic movement of both hands (task C). The SMA activation during task C was more pronounced than that during the other two tasks for right and left handers. The results suggested that the activation of the SMA, at least during a simple motion used in the present study, was little influenced by whether the motion was unimanual or bimanual but instead how the bimanual motion was composed of the motion element of a single hand. The SMC activation during task C was significantly larger than that during task B, whereas hemispheric differences in the activation were not found. This indicated that the complexity of the bimanual movement also affected the SMC activation.     

抑郁症患者眶额叶皮层功能连接偏离的研究

目的 通过功能磁共振成像技术,研究抑郁症患者和健康对照组在情感处理时眶额叶皮层的功能连接偏离,为抑郁症的早期诊断和疗效评估提供影像学依据.方法 对25例重度抑郁症患者和15名健康对照组在执行面貌一致性任务时进行功能性磁共振成像.结果 和健康对照组相比重度抑郁症患者的背侧前扣带回皮层、楔前叶、小脑与眶额叶的活动连接减少;抑郁症患者的眶额叶皮层和背外侧前额叶皮层、右额叶岛盖部、左运动区之间的功能连接比健康对照组有所增加.结论 眶额叶皮层在抑郁症的病理生理学机制中发挥着关键作用.眶额叶皮层连接的失衡似乎代表加工偏离的神经机制.从神经生物学的角度来看,楔前叶和扣带回的连接解离活动与眶额叶皮层的自我架构规则的问题相关,而背外侧前额叶皮层到眶额叶的连接增加可能代表更高消极刺激的神经反应.     

功能磁共振成像在植物状态研究中的应用

一、植物状态及其研究历程随着现代医疗技术的进步,危重患者的死亡率明显降低,临床上可以见到越来越多的意识障碍患者.1972年由Jennett和Plum在Lancet上首次提出持续性植物状态(vegetative state,VS)的概念,用以取代当时混杂应用的各类名词,如极深度昏迷,运动不能性缄默,永久性、不可逆性或稽延性昏迷、去大脑或去皮层状态等,这一见解以后逐渐为各国学者所采纳.1994年美国PVS多学科专责小组对VS下的定义为:“患者完全失去对自身及周围环境的认知,有睡眠一觉醒周期,下丘脑及脑干的自主功能完全或部分保存”.此类患者死亡率高,致残严重且缺乏有效治疗,给社会及家庭造成沉重的负担,引起了医学界和全社会的广泛关注.     

Plasticity of the human motor system following muscle reconstruction: a magnetic stimulation and functional magnetic resonance imaging study

OBJECTIVE: Although motor system plasticity in response to neuromuscular injury has been documented, few studies have examined recovered and functioning muscles in the human. We examined brain changes in a group of patients who had a muscle transfer. METHODS: Transcranial magnetic stimulation (TMS) was used to study a unique group of 9 patients who had upper extremity motor function restored using microneurovascular transfer of the gracilis muscle. The findings from the reconstructed muscle were compared to the homologous muscle of the intact arm. One patient was also studied with functional magnetic resonance imaging (fMRI). RESULTS: TMS showed that the motor threshold and short interval intracortical inhibition was reduced on the transplanted side while at rest but not during muscle activation. The difference in motor threshold decreased with the time since surgery. TMS mapping showed no significant difference in the location and size of the representation of the reconstructed muscle in the motor cortex compared to the intact side. In one patient with reconstructed biceps muscle innervated by the intercostal nerves, both TMS mapping and fMRI showed that the upper limb area rather than the trunk area of the motor cortex controlled the reconstructed muscle. CONCLUSIONS: Plasticity occurs in cortical areas projecting to functionally relevant muscles. Changes in the neuronal level are not necessarily accompanied by changes in motor representation. Brain reorganization may involve multiple processes mediated by different mechanisms and continues to evolve long after the initial injury. SIGNIFICANCE: Central nervous system plasticity following neuromuscular injury may have functional relevance.     

Abnormal functional connectivity in patients with vascular cognitive impairment, no dementia: a resting-state functional magnetic resonance imaging study

The functional connectivity (FC) method was used to investigate the changes in the resting state of patients with vascular cognitive impairment, no dementia (VCIND). Resting-state functional magnetic resonance images (fMRIs) were acquired from 16 patients with subcortical ischemic vascular disease (SIVD) who fulfilled the criteria for VCIND, as well as 18 age- and sex-matched subjects with SIVD with no cognitive impairment (control group). Posterior cingulate cortex connectivity was gathered by investigating synchronic low-frequency fMRI signal fluctuations with a temporal correlation method. Compared with the control group, the patients showed FC decrease in the left middle temporal gyrus, the left anterior cingulate/left middle frontal gyrus, the right caudate, the right middle frontal gyrus, and the left medial frontal gyrus/paracentral lobule. There were also some regions that showed increased connectivity. These regions included the right inferior temporal gyrus, the left middle temporal gyrus, the left precentral gyrus, and the left superior parietal lobule. Our findings revealed the change in resting-state patterns of neuronal activity in patients with VCIND. This change may be caused by subcortical white matter lesions that destroyed direct and indirect fiber tract connectivity across the cerebral white matter and influenced the cortical FC and hypoperfusion resulted from small vascular disease. The results of the increased connectivity may be evoked by the compensatory recruitment and plasticity mechanism. Our findings suggest that the simplicity and noninvasiveness of this method makes it a potential tool to help thoroughly understand the pathogenesis of VCIND.     

Motor representation in patients rapidly recovering after stroke: a functional magnetic resonance imaging and transcranial magnetic stimulation study

OBJECTIVE: Neuroimaging studies have suggested an evolution of the brain activation pattern in the course of motor recovery after stroke. Initially poor motor performance is correlated with an recruitment of the uninjured hemisphere that continuously vanished until a nearly normal (contralateral) activation pattern is achieved and motor performance is good. Here we were interested in the early brain activation pattern in patients who showed a good and rapid recovery after stroke. METHODS: Ten patients with first-ever ischemic stroke affecting motor areas had to perform self-paced simple or more complex movements with the affected or the unaffected hand during functional magnetic resonance imaging (fMRI). The location and number of activated voxels above threshold were determined. To study possible changes in the cortical motor output map the amplitude of the motor evoked potentials (MEP) and the extent of the excitable area were determined using transcranial magnetic stimulation (TMS). RESULTS: The pattern of activation observed with movements of the affected and the unaffected hand was similar. In the simple motor task significant (P<0.05) increases were found in the primary motor cortex ipsilateral to the movement, the supplementary motor area and the cerebellar hemisphere contralateral to the movement during performance with the affected hand compared to movements with the unaffected hand. When comparing simple with more complex movements performed with either the affected or the unaffected hand, a further tendency to increased activation in motor areas was observed. The amplitude of MEPs obtained from the affected hemisphere was smaller and the extent of cortical output maps was decreased compared to the unaffected hemisphere; but none of the patients showed MEPs at the affected hand when the ipsilateral unaffected motor cortex was stimulated. CONCLUSIONS: Despite a rapid and nearly complete motor recovery the brain activation pattern was associated with increased activity in (bilateral) motor areas as revealed with fMRI. TMS revealed impaired motor output properties, but failed to demonstrate ipsilateral motor pathways. Successful recovery in our patients may therefore rely on the increased bilateral activation of existing motor networks spared by the injury.     

Increased amygdala activation during mania: a functional magnetic resonance imaging study

OBJECTIVE: This study sought to investigate neural activity in the amygdala during episodes of mania. METHOD: Nine manic subjects and nine healthy comparison subjects underwent functional magnetic resonance imaging (fMRI) while performing a neuropsychological paradigm known to activate the amygdala. Subjects viewed faces displaying affect (experimental task) and geometric forms (control task) and matched them to one of two simultaneously presented similar images. RESULTS: Manic subjects had significantly increased activation in the left amygdala and reduced bilateral activation in the lateral orbitofrontal cortex relative to the comparison subjects. CONCLUSIONS: Increased activation in the amygdala and decreased activation in the orbitofrontal cortex may represent disruption of a specific neuroanatomic circuit involved in mania. These brain regions may be implicated in disorders involving regulation of affect.     

Longitudinal functional magnetic resonance imaging of cognition in preclinical Huntington's disease

Neuropsychological and functional neuroimaging studies have revealed early changes of cognition and brain function in individuals with the Huntington's disease (HD) gene mutation who are presymptomatic for the motor symptoms of the disease (preHD). However, little is known about whether changes of neural function progress over time. In this study, we used neuropsychological tests of attention, working memory and executive function, functional magnetic resonance imaging and voxel-based analyses of high-resolution structural data to explore the temporal dynamics of potential cognitive, functional and structural biomarkers in far from onset preHD (n = 13, mean time to the estimated motor symptom onset = 19.5 years) and healthy controls (n = 13) followed over a 2-year period. Behavioral measures were similar in preHD individuals and controls at baseline and remained normal 2 years later. At both time points, the left dorsolateral prefrontal cortex was less active in preHD than in controls during working memory performance. The left dorsolateral prefrontal cortex did not exhibit further loss of activity over time. Regions showing less gray matter volume in preHD at baseline did not show further volume loss over time. These data indicate that the activity in brain regions contributing to working memory processing differs consistently in HD expansion mutation carriers while cognitive performance remains normal. However, the present data do not support the notion of a progressive decline of left prefrontal cortex activity in far from onset preHD followed over a 2-year period.     

Visual hallucinations in schizophrenia investigated with functional magnetic resonance imaging

We investigated a 27-year old patient with paranoid schizophrenia. Brain activity related to visual hallucinations was found in higher visual areas corresponding to the content of the hallucinations (faces, bodies, scenes) and the hippocampus. We assume that the hippocampal activity is related to the retrieval of visual images from memory and that sensory cortex activity is related to the vividness of the perceptual experience.     

大鼠视觉皮层动态锰离子增强磁共振功能成像研究

目的 应用动态锰离子增强磁共振技术行大鼠视觉皮层功能成像,为神经系统功能的研究提供方法.方法 成年雄性Wistar大鼠6只,右颈外动脉插管后于连续的4个时段分别进行不同处理,第一时段(5 min)不给予药物,无视觉刺激;第二时段(10 min)经右颈外动脉注射甘露醇和氯化锰,无视觉刺激;第三时段(15 min)仅注射氯化锰,给予视觉刺激;第四时段(5 min)注射氯化锰与谷氨酸混合液,无视觉刺激.每一时段处理后立即进行大鼠头颅磁共振成像,应用SPM软件进行图像的配准和平滑处理,应用Matlab软件得出图像的配色图及等高线图;选取视觉皮层进行兴趣区(ROI)分析,观察不同处理后磁共振图像中脑内特异性增强区域并比较大鼠视觉皮层的信号强度.结果 磁共振图像分析显示第一、二时段处理后大鼠脑内未发现特异性增强区域,第三时段处理后大鼠右侧视觉皮层特异性增强,第四时段处理后大鼠右侧脑内多个核团特异性增强;ROI分析显示第三时段处理后的视觉皮层信号强度(1.897±0.172)明显强于第二时段(1.549±0.163),差异有统计学意义(P<0.05).结论 动态锰离子增强磁共振成像技术能分析大鼠视觉皮层功能活动,可做为研究神经系统功能的新方法.     

Posterior orbitofrontal sulcogyral pattern associated with orbitofrontal cortex volume reduction and anxiety trait in panic disorder

Aims: The posterior region of the orbitofrontal cortex (OFC), which forms its sulcogyral pattern during neurodevelopment, receives multisensory inputs. The purpose of the present study was to assess the relationship between posterior OFC sulcogyral pattern and OFC volume difference in patients with panic disorder. Methods: The anatomical pattern of the posterior orbital sulcus (POS) was classified into three subtypes (absent POS, single POS, double POS) using 3‐D high‐spatial resolution magnetic resonance images obtained from 28 patients with panic disorder and 28 age‐ and gender‐matched healthy controls. Optimized voxel‐based morphometry (VBM) was performed to assess OFC volume differences between the two groups by subtype. Categorical regression analysis was applied to examine the association of POS subtypes with State–Trait Anxiety Inventory and Revised Neuroticism‐Extraversion‐Openness Personality Inventory scores. Results: No significant difference was found in POS subtype distribution between control subjects and patients with panic disorder. VBM, however, indicated volume reduction in the right posterior–medial OFC region in panic disorder patients with absent POS and single POS. Single POS was positively associated with Trait‐Anxiety (β = 0.446, F = 6.409, P = 0.020), and absent POS was negatively associated with Trait‐Anxiety (β = ?0.394, F = 5.341, P = 0.032) and Neuroticism trait (β = ?0.492, F = 6.989, P = 0.017). Conclusions: POS subtypes may be relevant to volume reduction in OFC and the anxiety trait in patients with panic disorder. These findings suggest that volume reduction in OFC in panic disorder may be associated with neurodevelopment.     

Meta-analysis of magnetic resonance imaging brain morphometry studies in bipolar disorder.

BACKGROUND: Several studies assessing volumetric measurements of regional brain structure in bipolar disorder have been published in recent years, but their results have been inconsistent. Our aim was to complete a meta-analysis of regional morphometry in bipolar disorder as assessed using magnetic resonance imaging (MRI). METHODS: We conducted a systematic literature search of MRI studies of bipolar disorder and identified studies which reported volume measurements in a selected number of regions. Twenty-six studies comprising volumetric measurements on up to 404 independent patients with bipolar disorder were included. A meta-analysis was carried out comparing the volumes of regions in bipolar disorder to comparison subjects using a random effects model. RESULTS: Patients with bipolar disorder had enlargement of the right lateral ventricle, but no other regional volumetric deviations which reached significance. Strong heterogeneity existed for several regions, including the third ventricle, left subgenual prefrontal cortex, bilateral amygdala and thalamus. CONCLUSIONS: Regional volume of most structures we studied is preserved in bipolar disorder as a whole, which was significantly associated only with right-sided ventricular enlargement. However the extensive heterogeneity detected indicates the need for further studies to establish if consistent regional brain volume deviation exists in bipolar disorder or in specific clinical subsets of the illness.     

Brain activation associated with visual motion studied by functional magnetic resonance imaging in humans

Localized brain activation in response to moving visual stimuli was studied by functional magnetic resonance imaging (fMRI). Stimuli were 100 small white dots randomly arranged on a visual display. During the Motion condition, the dots moved along random, noncoherent linear trajectories at different velocities. During the Blink condition, the dots remained stationary but blinked on and off every 500 ms. The Motion and Blink conditions continuously alternated with 10 cycles per run and 6–8 runs per experiment. In half of the runs, the starting stimulus condition was Motion, while in the remaining runs it was Blink. A series of 128 gradient echo echoplanar images were acquired from 5–7 slices during each run using a 1.5 T GE Signa with an Advanced NMR echoplanar subsystem. The time series for each voxel were analyzed in the frequency domain. Voxels which demonstrated a significant spectral peak at the alternation frequency and whose phase changed in response to stimulus order were considered activated. These activated voxels were displayed upon high resolution anatomical images to determine the sites of activation and were also transformed into the coordinates of Talairach and Tournoux ([1988] Co-planar Stereotaxic Atlas of the Human Brain, New York: Thieme) for comparison to prior neuroimaging studies. Seven of ten subjects showed clusters of activation bilaterally at the junction of the temporal and occipital lobes (area 37) in response to moving stimuli. Most activated voxels were located within or adjacent to a region designated the parietal-temporal-occipital fossa, or PTOF. Five subjects also showed activation to moving stimuli in midline occipital cortex. The activated voxels in midline cortex had a significantly shorter phase delay in their MR signal change relative to voxels in PTOF. © 1995 Wiley-Liss, Inc. 1

1 This article is a US Government work and, as such, is in the public domain in the United States of America