双相抑郁患者前额叶和前扣带回皮质氢质子波谱研究

目的:研究双相抑郁患者前额叶皮质、前扣带回皮质代谢物的相对含量。方法:对30例未服药双相抑郁患者和30名健康志愿者的前额叶皮质、前扣带回皮质进行氢质子波谱(1H-MRS)扫描,双相抑郁患者经6周药物治疗后再次做1H-MRS扫描,检测N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、谷氨酸复合物(Glx)、肌酸(Cr)4种代谢物。结果:双相抑郁组左侧前额叶皮质、双侧前扣带回皮质NAA/Cr值均显著低于正常对照组(P<0.05),Cho/Cr值、Glx/Cr值均显著高于正常对照组(P<0.05),双相抑郁组右侧前额叶皮质NAA/Cr、Cho/Cr、Glx/Cr值两组比较差异无统计学意义(P>0.05)。经药物治疗后,左侧前额叶皮质、双侧前扣带回皮质NAA/Cr值较治疗前升高,Cho/Cr值、Glx/Cr值较治疗前降低,差异有统计学意义(P<0.05)。结论:前额叶和前扣带回皮质NAA、Cho、Glx含量的改变与双相抑郁的发生和药物的疗效有关。     

Volume reduction of ventromedial prefrontal cortex in bipolar II patients with rapid cycling: a voxel-based morphometric study

Although rapid cycling (RC), a course specifier of bipolar I or II disorder, is particularly common among bipolar II patients compared with bipolar I patients, the pathophysiological lines of evidence regarding bipolar II with RC are still limited. In this preliminary study with a cross-sectional design, we examined the regional gray matter (GM) volume in 14 bipolar II patients with RC, 17 patients without RC and 84 healthy controls by whole-brain and region-of-interest (ROI) analysis methods, using magnetic resonance imaging with voxel-based morphometry. Whole-brain analysis in this study revealed that the bipolar II patients with RC showed GM volume reductions in the bilateral hemispheres of the medial orbital prefrontal cortex, ventromedial prefrontal cortex, anterior cingulate, insula and parahippocampus, in the left hemisphere of the inferior temporal cortex and cerebellum, and in the brainstem, compared with the healthy controls. Moreover, ROI analysis focusing on the ventral prefrontal cortex, i.e., Brodmann areas 10, 11 and 47, revealed that the bipolar II patients with RC showed GM volume reduction in the ventromedial prefrontal cortex, compared with the patients without RC. The findings of our pilot study suggest that the ventromedial prefrontal cortex is associated with the generation of RC in bipolar II disorder.     

Examining ventral and dorsal prefrontal function in bipolar disorder: a functional magnetic resonance imaging study.

Several lines of research suggest both dorsal and ventral prefrontal cortical dysfunction in bipolar disorder (BD). We used functional magnetic resonance imaging to compare patterns of brain activation in remitted BD patients and controls whilst performing tasks selected for their relative specificity in engaging either the dorsal (n-back sequential-letter working memory task) or ventral (gambling task) PFC. Seven BD patients were selected from participants of the Maudsley Bipolar Disorder Project on the basis of clinical remission, absence of cognitive deficits, and monotherapy with mood stabilisers. Subjects were individually matched by gender, age, and IQ to an equal number of healthy controls. In the n-back task, group differences were only present in response to increasing memory load. Patients did not show the predicted dynamic response in the dorsal PFC, but had increased activation in the parietal cortices. During the gambling task, controls showed significant activation in the ventral and dorsal PFC; this was attenuated in BD patients where increased activation was seen in lateral temporal and polar regions. Our findings suggest that there are trait abnormalities in dorsal and ventral PFC function in BD that may be more pronounced during tasks that rely on ventral-dorsal PFC interaction.     

Semantic processing in the left inferior prefrontal cortex: a combined functional magnetic resonance imaging and transcranial magnetic stimulation study

The involvement of the left inferior prefrontal cortex (LIPC) in phonological processing is well established from both lesion-deficit studies with neurological patients and functional neuroimaging studies of normals. Its involvement in semantic processing, on the other hand, is less clear. Although many imaging studies have demonstrated LIPC activation during semantic tasks, this may be due to implicit phonological processing. This article presents two experiments investigating semantic functions in the LIPC. Results from a functional magnetic resonance imaging experiment demonstrated that both semantic and phonological processing activated a common set of areas within this region. In addition, there was a reliable increase in activation for semantic relative to phonological decisions in the anterior LIPC while the opposite comparison (phonological vs. semantic decisions) revealed an area of enhanced activation within the posterior LIPC. A second experiment used transcranial magnetic stimulation (TMS) to temporarily interfere with neural information processing in the anterior portion of the LIPC to determine whether this region was essential for normal semantic performance. Both repetitive and single pulse TMS significantly slowed subjects' reactions for the semantic but not for the perceptual control task. Our results clarify the functional anatomy of the LIPC by demonstrating that anterior and posterior regions contribute to both semantic and phonological processing, albeit to different extents. In addition, the findings go beyond simply establishing a correlation between semantic processing and activation in the LIPC and demonstrate that a transient disruption of processing selectively interfered with semantic processing.     

Functional magnetic resonance imaging evidence for a hierarchical organization of the prefrontal cortex

The prefrontal cortex (PFC) is central to flexible and organized action. Recent theoretical and empirical results suggest that the rostro-caudal axis of the frontal lobes may reflect a hierarchical organization of control. Here, we test whether the rostro-caudal axis of the PFC is organized hierarchically, based on the level of abstraction at which multiple representations compete to guide selection of action. Four functional magnetic resonance imaging (fMRI) experiments parametrically manipulated the set of task-relevant (a) responses, (b) features, (c) dimensions, and (d) overlapping cue-to-dimension mappings. A systematic posterior to anterior gradient was evident within the PFC depending on the manipulated level of representation. Furthermore, across four fMRI experiments, activation in PFC subregions was consistent with the sub- and superordinate relationships that define an abstract representational hierarchy. In addition to providing further support for a representational hierarchy account of the rostro-caudal gradient in the PFC, these data provide important empirical constraints on current theorizing about control hierarchies and the PFC.     

Neurochemical metabolites in the medial prefrontal cortex in bipolar disorder A proton magnetic resonance spectroscopy study

The aim of this study was to investigate proton magnetic resonance spectroscopy metabolite values in the medial prefrontal cortex of individuals with euthymic bipolar disorder. The subjects consisted of 15 patients with euthymic bipolar disorder type Ⅰ and 15 healthy controls. We performed proton magnetic resonance spectroscopy of the bilateral medial prefrontal cortex and measured levels of N-acetyl aspartate, choline and creatine. Levels of these three metabolites in the medial prefrontal cortex were found to be lower in patients with bipolar disorder compared with healthy controls. A positive correlation was found between illness duration and choline levels in the right medial prefrontal cortex. Our study suggests that during the euthymic period, there are abnormalities in cellular energy and membrane phospholipid metabolism in the medial prefrontal cortex, and that this may impair neuronal activity and integrity.     

A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices

BACKGROUND: Abnormalities in prefrontal and anterior cingulate cortices are implicated in disturbances of attention, cognition, and impulse regulation in bipolar disorder. Acute episodes have been associated with dysfunction in these brain regions, and more enduring trait-related dysfunction has been implicated by volumetric and cellular abnormalities in these regions. The relative contributions of prefrontal regions to state and trait disturbances in bipolar disorder, however, have not been defined. We sought to characterize state- and trait-related functional impairment in frontal systems in bipolar disorder. METHODS: Thirty-six individuals with bipolar disorder I (11 with elevated, 10 with depressed, and 15 with euthymic mood states) and 20 healthy control subjects matched for handedness and sex participated in an event-related functional magnetic resonance imaging study of the color-word Stroop to determine mean percentage of regional task-related signal change. RESULTS: Signal increased during the Stroop task similarly across diagnostic groups in a distribution that included dorsal anterior cingulate and prefrontal cortices, consistent with previously reported activations in this task. Signal changes associated with specific mood states in bipolar disorder were detected in ventral prefrontal cortex, with a blunted increase in signal on the right side in the elevated mood group (P =.005) and an exaggerated increase in signal on the left side in the depressed group (P =.02) compared with the euthymic group. Patients (vs healthy controls) demonstrated blunted activation in a spatially distinct, rostral region of left ventral prefrontal cortex that was independent of mood state (P<.005). CONCLUSIONS: Bipolar disorder is associated with a trait abnormality in left ventral prefrontal cortex. Additional ventral prefrontal abnormalities may be associated with specific acute mood states. The hemispheric laterality of the abnormality and the directions of signal change may relate to the valence of the mood episode.     

The role of the right prefrontal cortex in self-evaluation of the face: a functional magnetic resonance imaging study

Individuals can experience negative emotions (e.g., embarrassment) accompanying self-evaluation immediately after recognizing their own facial image, especially if it deviates strongly from their mental representation of ideals or standards. The aim of this study was to identify the cortical regions involved in self-recognition and self-evaluation along with self-conscious emotions. To increase the range of emotions accompanying self-evaluation, we used facial feedback images chosen from a video recording, some of which deviated significantly from normal images. In total, 19 participants were asked to rate images of their own face (SELF) and those of others (OTHERS) according to how photogenic they appeared to be. After scanning the images, the participants rated how embarrassed they felt upon viewing each face. As the photogenic scores decreased, the embarrassment ratings dramatically increased for the participant's own face compared with those of others. The SELF versus OTHERS contrast significantly increased the activation of the right prefrontal cortex, bilateral insular cortex, anterior cingulate cortex, and bilateral occipital cortex. Within the right prefrontal cortex, activity in the right precentral gyrus reflected the trait of awareness of observable aspects of the self; this provided strong evidence that the right precentral gyrus is specifically involved in self-face recognition. By contrast, activity in the anterior region, which is located in the right middle inferior frontal gyrus, was modulated by the extent of embarrassment. This finding suggests that the right middle inferior frontal gyrus is engaged in self-evaluation preceded by self-face recognition based on the relevance to a standard self.     

Grey matter abnormalities in trichotillomania: morphometric magnetic resonance imaging study

BACKGROUND: Trichotillomania (repetitive hair-pulling) is an Axis I psychiatric disorder whose neurobiological basis is incompletely understood. Whole-brain trichotillomania neuroimaging studies are lacking. AIMS: To investigate grey and white matter abnormalities over the whole brain in patients with trichotillomania. METHOD: Eighteen patients with DSM-IV trichotillomania and 19 healthy controls undertook structural magnetic resonance imaging after providing written informed consent. Differences in grey and white matter were investigated using computational morphometry. RESULTS: Patients with trichotillomania showed increased grey matter densities in the left striatum, left amygdalo-hippocampal formation, and multiple (including cingulate, supplementary motor, and frontal) cortical regions bilaterally. CONCLUSIONS: Trichotillomania was associated with structural grey matter changes in neural circuitry implicated in habit learning, cognition and affect regulation. These findings inform animal models of the disorder and highlight key regions of interest for future translational research.     

双相抑郁患者前额叶及海马磁共振质子波谱成像研究

目的探讨双相抑郁患者前额叶及海马磁共振质子波谱(proton magnetic resonance spectroscopy,1H-MRS)的代谢物变化特点,为其神经生物学研究提供线索。方法应用磁共振质子波谱成像技术检测26例双相抑郁患者(患者组)和26例单相抑郁患者及13例健康志愿者(对照组)双侧前额叶白质、前扣带回皮质、海马N-乙酰天门冬氨酸(N-Acetylaspartate,NAA)、胆碱(choline,Cho)、肌酸(creatine,Cr)3种代谢物,以Cr为参照物,分别计算双侧NAA/Cr和Cho/Cr比值。采用SPSS 13.0进行统计处理。结果患者组左侧前额叶白质NAA/Cr(1.65±0.31)低于对照组(2.37±0.36),左侧前额叶白质Cho/Cr(1.35±0.27)低于对照组(1.65±0.21),差异有统计学意义(P<0.05);右侧前额叶白质NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组双侧前扣带回NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组双侧海马NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组与单相抑郁组的双侧额叶白质、双侧前扣带回皮质、双侧海马NAA/Cr、Cho/Cr值差异均无统计学意义。结论双相抑郁患者可能存在左侧前额叶神经元功能下降和膜磷脂代谢异常,其代谢物特点存在偏侧化。     

Insular cortex abnormalities in schizophrenia: a structural magnetic resonance imaging study of first-episode patients

The insular cortex is a limbic integration region that is engaged in emotional and cognitive functions. To investigate possible insular cortex abnormalities in schizophrenia, we measured insular gray matter volume and cortical surface size in drug-naive first-episode patients. Magnetic resonance images were used to explore the morphology of the insular cortex of 25 healthy male volunteers, and 25 male schizophrenic patients. Groups were matched for age, sex, height, and parental socio-economic status. Clinical dimension scores were correlated with insular gray matter volume and cortical surface area.Patients had a significant reduction in cortical surface area [patients=2020 (206); controls=2142 (204); F=5.83, df=1, 47; P=0.01] and gray matter volume [patients=8.12 (0.77); controls=8.57 (0.94); F=3.93, df=1,47; P=0.05] in the left insular cortex. Insular gray matter volume and cortical surface size correlated negatively and significantly with the psychotic symptom dimension. Schizophrenic patients show morphological abnormalities in the insular cortex at early stages of the illness. These abnormalities are related to the severity of psychotic symptoms. Further investigations are needed to evaluate the role of the insula in the pathophysiology of schizophrenia.     

Spatial inhibition and the visual cortex: a magnetic resonance spectroscopy imaging study

Introduction

Deficits in processing spatial information have been observed in clinical populations who have abnormalities within the dopamine (DA) system. As psychostimulants such as methamphetamine (MA) are particularly neurotoxic to the dopaminergic system it was of interest to examine the performance of MA-dependent individuals on a task of spatial attention.

Method

51 MA-dependent subjects and 22 age-matched non-substance abusing control subjects were tested on a Spatial Stroop attention test. MR Spectroscopy (MRS) imaging data were analyzed from 32 MA abusers and 13 controls.

Results

No group differences in response time or accuracy emerged on the behavioral task with both groups exhibiting equivalent slowing when the word meaning and the spatial location of the word were in conflict. MRS imaging data from the MA abusers revealed a strong inverse correlation between NAA/Cr ratios in the Primary Visual Cortex (PVC) and spatial interference (p = 0.0001). Moderate inverse correlations were also seen in the Anterior Cingulate Cortex (ACC) (p = 0.02). No significant correlations were observed in the controls, perhaps due to the small sample of imaging data available (n = 13).

Discussion

The strong correlation between spatial conflict suppression and NAA/Cr levels within the PVC in the MA-dependent individuals suggests that preserved neuronal integrity within the PVC of stimulant abusers may modulate cognitive mechanisms that process implicit spatial information.     

Choline, myo-inositol and mood in bipolar disorder: a proton magnetic resonance spectroscopic imaging study of the anterior cingulate cortex

Objectives: Alterations in choline and myo-inositol metabolism have been noted in bipolar disorder, and the therapeutic efficacy of lithium in mania may be related to these effects. We wished to determine the relationship between anterior cingulate cortex choline and myo-inositol levels, assessed using proton magnetic resonance spectroscopic imaging (MRSI), and mood state in subjects with bipolar disorder.

Methods: Serial assessments of anterior cingulate cortex choline and myo-inositol metabolism were performed in nine subjects with bipolar disorder, taking either lithium or valproate, and 14 controls. Each bipolar subject was examined between one and four times (3.1±1.3). On the occasion of each examination, standardized ratings of both depression and mania were recorded.

Results: In the left cingulate cortex, the bipolar subjects' depression ratings correlated positively with MRSI measures of Cho/Cr-PCr. In the right cingulate cortex, the Cho/Cr-PCr ratio was significantly higher in subjects with bipolar disorder compared with control subjects. In addition, bipolar subjects not taking antidepressants had a significantly higher right cingulate cortex Cho/Cr-PCr ratio compared with patients taking antidepressants or controls. No clinical or drug-related changes were observed for the Ino/Cr-PCr ratio.

Conclusions: The results of this study suggest that bipolar disorder is associated with alterations in the metabolism of cytosolic, choline-containing compounds in the anterior cingulate cortex. As this resonance arises primarily from phosphocholine and glycerophosphocholine, both of which are metabolites of phosphatidylcholine, these results are consistent with impaired intraneuronal signaling mechanisms.     

Diffusion-weighted magnetic resonance imaging of white matter in bipolar disorder: a pilot study

OBJECTIVE: Diffusion-weighted magnetic resonance imaging (MRI) has shown increased sensitivity in detecting brain white matter disease compared to traditional T2-weighted MRI. Diffusion-weighted imaging (DWI) can quantitatively assess the microstructural integrity of white matter using the average apparent diffusion coefficient (ADC(av)), a measure of the extent to which water molecules move freely within tissue. On the basis of numerous studies suggesting white matter disease in bipolar patients, particularly patients with more severe illness, this study aimed to test the utility of DWI in assessing the white matter integrity of bipolar patients with severe illness. METHODS: The existing MRI scans of eight bipolar patients and eight age-matched controls with neurological illness were examined retrospectively. ADC(av) values for pixels within white matter regions of interest (ROIs) were calculated and used to plot ADC(av) frequency histograms for each ROI. Mean ADC(av) values for the two groups were then compared by ANCOVA. RESULTS: The bipolar mean ADC(av) (0.855 +/- 0.051 x 10(-3) mm2/s) for combined white matter ROIs significantly exceeded that of controls (0.799 +/- 0.046 x 10(-3) mm2/s), while covarying for age (F = 4.47, df = 3, p = 0.025). CONCLUSIONS: This is the first report of an elevated ADC(av) in the white matter of a group of patients with bipolar disorder. In this group of patients with severe illness, increased white matter ADC(av) suggests microstructural changes consistent with decreased white matter integrity. DWI may be an additional, useful tool to assess white matter abnormalities in bipolar disorder.     

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.     

Decreased GABA concentrations in left prefrontal cortex of methamphetamine dependent patients: A proton magnetic resonance spectroscopy study

Increasing evidence suggested the dorsolateral prefrontal cortex (DLPFC) is implicated in the pathogenesis of methamphetamine use disorder. Metabolites changes of DLPFC may mediate the progression of addiction. We used proton magnetic resonance spectroscopy (¹H-MRS) to examine the changes of metabolites in the left DLPFC in individuals with methamphetamine dependence compared to healthy controls. Fifty patients and twenty age-matched healthy controls participated in this study. The ¹H MRS data were automatically fit with linear combination model for quantification of metabolite levels of γ-aminobutyric acid (GABA), glutamate + glutamine (Glx) and other metabolites across groups. The GABA and Glx levels were calculated with the unsuppressed water signal as reference. Methamphetamine users showed reduced GABA and GABA/Glx in left DLPFC than healthy controls. Furthermore, the concentration of GSH, GPC, Ins, NAA, GPC + PCh, NAA + NAAG, Cr + PCr were lower in individuals with methamphetamine dependence compared with controls. The patients group's relative GABA and Glx metabolite concentrations were significantly correlated with age and duration of withdrawal. Our preliminary findings provide the first report of abnormal levels of GABA in left DLPFC of patients with methamphetamine use disorder, indicating that dysregulation of the GABAergic neurotransmitter system may be an important neurobiological mechanism in the pathogenesis of methamphetamine dependence.     

Metabolic alterations in medication-free patients with bipolar disorder: a 3T CSF-corrected magnetic resonance spectroscopic imaging study

The objective of this study was to determine whether cerebrospinal fluid(CSF)-corrected concentrations of N-acetylaspartate are lower in several brain regions of drug- and medication-free subjects with bipolar disorder as compared with matched healthy controls. Bipolar subjects (n=21) and age- and sex-matched healthy control (n=21) were studied using proton magnetic resonance spectroscopic imaging on a 3T magnetic resonance (MR) scanner. Spectra were quantified using the LCModel, and metabolite values were CSF-corrected to yield metabolite concentrations. Fourteen regions of interest and five metabolite concentrations in each subject were selected for statistical analysis. We found that bipolar subjects had significantly decreased N-acetylaspartate concentrations in both caudate heads and the left lentiform nucleus. Choline and creatine in the head of the right caudate were also significantly decreased in bipolar subjects. Significantly increased myo-inositol was found in the left caudate head in bipolar subjects. Bipolar subjects showed significantly decreased glutamate/glutamine concentrations in the frontal white matter bilaterally and in the right lentiform nucleus. No differences were found for other metabolites examined. These preliminary findings suggest decreased neuronal density or viability in the basal ganglia and neurometabolic abnormalities in the frontal lobes of subjects with bipolar disorder.     

Paracingulate morphologic differences in males with established schizophrenia: a magnetic resonance imaging morphometric study.

BACKGROUND: Our previous work on sulcal-gyral brain morphology in healthy volunteers revealed that males were characterized by greater cortical folding in the left versus right anterior cingulate cortex. Given the evidence showing an absence or reversal of normal anatomical asymmetries in patients with schizophrenia, the current study examined the anterior cingulate cortex sulcal-gyral patterns in patients with schizophrenia. METHODS: Using high-resolution magnetic resonance imaging, we examined anterior cingulate cortex surface morphology in a group of 55 patients with established schizophrenia and 75 healthy controls. All subjects were male and right-handed. Depending on the presence of a paracingulate sulcus and its antero-posterior extent, three types of anterior cingulate cortex sulcal patterns were identified: "prominent," "present," and "absent." Measures of overall cerebral hemispheric folding were used as independent variables and as covariates to ascertain the specificity of the findings to the anterior cingulate cortex. RESULTS: Examination of anterior cingulate cortex morphology showed that, compared with controls, patients with schizophrenia lacked the leftward anterior cingulate cortex sulcal asymmetry, which was explained by reduced folding in the left anterior cingulate cortex. These differences were over and above differences in cortical folding across the entire left hemisphere. CONCLUSIONS: These findings suggest that, in male patients with schizophrenia, there is a disturbance in the neurodevelopment of the left anterior cingulate cortex, as well as a more general aberration of left hemisphere development.