Monoamine oxidase-a genetic variations influence brain activity associated with inhibitory control: new insight into the neural correlates of impulsivity.

BACKGROUND: Previous evidence has shown that genetic variations in the serotonergic system contribute to individual differences in personality traits germane to impulse control. The monoamine oxidase-A (MAO-A) gene, coding for an enzyme primarily involved in serotonin and noradrenaline catabolism, presents a well-characterized functional polymorphism consisting of a variable number of tandem repeats in the promoter region, with high-activity and low-activity variants. High-activity allele carriers have higher enzyme expression, lower amine concentration, and present higher scores on behavioral measures of impulsivity than low-activity allele carriers. METHODS: We studied the relationship of this polymorphism to brain activity elicited by a response inhibition task (Go/NoGo task), using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging in 24 healthy men. RESULTS: Direct comparison between groups revealed a greater BOLD response in the right ventrolateral prefrontal cortex (Brodmann's area [BA] 45/47) in high-activity allele carriers, whereas a greater response in the right superior parietal cortex (BA 7) and bilateral extrastriate cortex (BA 18) was found in low-activity allele carriers. CONCLUSIONS: These data suggest that a specific genetic variation involving serotonergic catabolism can modulate BOLD response associated with human impulsivity.     

No altered dorsal anterior cingulate activation in bipolar II disorder patients during a Go/No-go task: an fMRI study

Objectives:  It has been reported that one of the core features in patients with bipolar disorder II (BD II) is increased impulsivity. The aim of this study was to investigate whether patients with BD II showed decreased activation in the dorsal anterior cingulate cortex (dACC) as compared to healthy controls when performing a task sensitive to impulsivity.
Methods:  Twenty-seven BD II patients and 28 healthy controls performed a Go/No-go task during a functional magnetic resonance imaging (fMRI) session. Eleven of the patients were unmedicated, and possible group differences between medicated and unmedicated patients were also assessed.
Results:  The groups did not differ in behavioral performance on the Go/No-go task.
Both BD II subjects and healthy controls demonstrated dACC activity during the task, and analyses revealed no statistically significant group differences. Medicated and unmedicated patients also did not differ in the degree of fMRI activation.
Conclusions:  These findings do not support the hypothesis of abnormal dACC activity during a Go/No-go task in BD II patients.     

Dieting tendency and eating behavior problems in eating disorder correlate with right frontotemporal and left orbitofrontal cortex: A near-infrared spectroscopy study

Frontal lobe dysfunctions have been implicated as one of the pathophysiological bases in eating disorder (ED). Neural substrates of ED have been examined in neuroimaging studies employing symptom-related stimuli, such as food and body-image distortion, but with inconsistent results because of differences in study design, task, and stimulus used. In order to elucidate frontal lobe dysfunction correlates of clinical symptoms in ED, we examined the frontal lobe function during a cognitive task, not a symptom-related task, using near-infrared spectroscopy (NIRS), which is suitable for the functional neuroimaging study of ED because of its complete noninvasiveness and natural measurement setting. Regional hemodynamic changes were monitored during a verbal fluency task (letter version) using a 52-channel NIRS apparatus in 27 female ED patients and 27 matched healthy controls, and their correlations with clinical symptoms assessed using the Eating Attitude Scale (EAT-26) were examined. Regional hemodynamic changes were significantly smaller in the ED group than in the control group in the bilateral orbitofrontal and right frontotemporal regions, and negatively correlated with dieting tendency scores in EAT-26 in the right frontotemporal regions and with the eating restriction and binge eating scores in the left orbitofrontal regions. The clinical symptoms of ED are considered to consist of two components: dieting tendency that correlates with the right frontotemporal cortex and eating behavior problems that correlate with left the orbitofrontal cortex.     

额前皮质内侧区和眶回损伤后恐惧情绪管理改变的初步分析

目的 探讨额前皮质内侧区和眶回局限性损伤后恐惧情绪控制的变化模式及其神经结构基础.方法 对7例额前皮质内侧区和眶回损伤的病例进行MRI影像和心理测评比对分析,并进行统计描述.对照组为5例MRI影像正常的轻度颅脑创伤患者.结果 所有7例额前皮质内侧区和眶回损伤后患者均表现有情绪控制力下降,明显的反社会人格,对死亡的恐惧几近下降,攻击性显著增强,尤以2例眶回局限性损伤的患者表现突出.对照组中所有病例的情感等高级认知功能均正常,无反社会人格表现,恐惧管理表现正常,图片知觉整合能力正常,自我控制能力正常,无恐惧情绪控制异常.结论 额前皮质内侧区和眶回负责恐惧信息的评价,该部位损伤后可导致异常的主观情感状态和社会行为,因而额前皮质内侧区和眶回可能与恐惧信息的评价有关.     

The dynamic approach to neurodevelopmental psychiatric disorders: use of fMRI combined with neuropsychology to elucidate the dynamics of psychiatric disorders, exemplified in ADHD and schizophrenia

The paper discusses the application of fMRI in combination with neuropsychology to neurodevelopmental psychiatric disorders, exemplified on the case of attention deficit hyperactivity disorder (ADHD) in comparison with schizophrenia. The view is presented that ADHD, rather than being a compound of unrelated co-existing deficits, is a pervasive disorder of impulsiveness, which manifests at the motor, emotional, social and cognitive domain. Neuropsychology needs to refine the psychological measurements of these impulsivity symptoms and, in combination with fMRI, provide new insights into the interrelationship between brain and dysfunction and its bi-directional causalities. The suitability of the dynamic technique of functional MRI to assess the dynamic nature of developmental neuropsychiatric disorders is discussed. Brain activation can inform about strategy and compensatory mechanisms at a neuroanatomical level, which are not observable at a psychological level, providing insight into the underlying neurocognitive mechanisms of psychiatric disorders. Data are presented and discussed on opposing neurocognitive activation patterns for patients with ADHD and those with schizophrenia while performing a stop task. Comparisons between patient groups will be essential to address the specificity of neurocognitive mechanisms corresponding to specific neurodevelopmental psychiatric disorders.     

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.     

Mental state attribution and the temporoparietal junction: An fMRI study comparing belief, emotion, and perception

By age 2, children attribute referential mental states such as perceptions and emotions to themselves and others, yet it is not until age 4 that they attribute representational mental states such as beliefs. This raises an interesting question: is attribution of beliefs different from attribution of perceptions and emotions in terms of its neural substrate? To address this question with a high degree of anatomic specificity, we partitioned the TPJ, a broad area often found to be recruited in theory of mind tasks, into 2 neuroanatomically specific regions of interest: Superior Temporal Sulcus (STS) and Inferior Parietal Lobule (IPL). To maximize behavioral specificity, we designed a tightly controlled verbal task comprised of sets of single sentences - sentences identical except for the type of mental state specified in the verb (belief, emotion, perception, syntax control). Results indicated that attribution of beliefs more strongly recruited both regions of interest than did emotions or perceptions. This is especially surprising with respect to STS, since it is widely reported in the literature to mediate the detection of referential states - among them emotions and perceptions - rather than the inference of beliefs. An explanation is offered that focuses on the differences between verbal stimuli and visual stimuli, and between a process of sentence comprehension and a process of visual detection.     

Motor imagery in chronic neglect: An fMRI pilot study

Aim. Previous studies indicate the effectiveness of motor imagery training in stroke patients. To determine whether patients showing chronic visuospatial neglect symptoms may profit from motor imagery training, it is important to assess how the brain implements motor imagery when cortical systems involved in attentional control are impaired.

Method. Therefore, in this pilot study, nine chronic neglect patients with right-hemispheric stroke performed motor imagery of a finger opposition task during functional magnetic resonance imaging (fMRI).

Results. Imagery of unaffected hand movements was related to activations in the left primary somatosensory and premotor cortices as well as in the left supplementary motor area. During the imagery of the affected hand, patients displayed activations in the left premotor cortex and supplementary motor area as well as left dorsolateral prefrontal cortex. Furthermore, time since onset and visual imagery capacity were negatively related to activation in the supplementary motor area during the imagery of the affected hand.

Conclusions. These initial results demonstrate motor imagery capacity in patients with chronic neglect via compensatory neural processing during motor imagery of the affected hand in ipsilateral brain regions, since we found that the supplementary motor area appears to be specifically related to neglect severity. Although our results must be treated with caution due to the small sample size and missing control group, they indicate that neglect is not necessarily an exclusion criterion for motor imagery training per se.     

Trait impulsivity and response inhibition in antisocial personality disorder

Background

Impulsive behavior is a prominent characteristic of antisocial personality disorder. Impulsivity is a complex construct, however, representing distinct domains of cognition and action. Leading models refer to impulsivity as an inability to evaluate a stimulus fully before responding to it (rapid-response impulsivity), and as an inability to delay responding despite a larger reward (reward-delay impulsivity). We investigated these models in terms of the diagnosis and severity of antisocial personality disorder.

Methods

Thirty-four male subjects on probation/parole who met DSM-IV criteria for ASPD, and 30 male healthy comparison subjects, matched by ethnicity, were recruited from the community. The Barratt Impulsiveness Scale (BIS-11) provided an integrated measure of trait impulsivity. Rapid-response impulsivity was assessed using the Immediate Memory Task (IMT), a continuous performance test. Reward delay impulsivity was assessed using the Two-choice Impulsivity Paradigm (TCIP), where subjects had the choice of smaller-sooner or larger-delayed rewards, and the Single Key Impulsivity Paradigm (SKIP), a free-operant responding task.

Results

Compared to controls, subjects with ASPD had higher BIS-11 scores (Effect Size (E.S.) = 0.95). They had slower reaction times to IMT commission errors (E.S. = 0.45). Correct detections, a measure of attention, were identical to controls. On the SKIP, they had a shorter maximum delay for reward (E.S. = 0.76), but this was not significant after correction for age and education. The groups did not differ on impulsive choices on the TCIP (E.S. < 0.1). On probit analysis with age and education as additional independent variables, BIS-11 score, IMT reaction time to a commission error, and IMT positive response bias contributed significantly to diagnosis of ASPD; SKIP delay for reward did not. Severity of ASPD, assessed by the number of ASPD symptoms endorsed on the SCID-II, correlated significantly with commission errors (impulsive responses) on the IMT, and with liberal IMT response bias. This relationship persisted with correction for age and education.

Discussion

These results suggest that ASPD is characterized by increased rapid-response impulsivity. Aspects of impulsivity related to reward-delay or attention appear relatively intact.     

Implications of fMRI and genetics for the law and the routine practice of forensic psychiatry

This review outlines recent neurobiological findings in humans relevant for the practice of law and forensic psychiatry. We focus on offenders with antisocial personality disorder and on sex offenders. In addition, the impact of risk polymorphisms in monoamine oxidase A (MAO-A), previously related to violence in interaction with the environment, on brain structure and function and on personality traits in healthy persons are presented. While increasing knowledge of functional and structural alterations provides a better understanding of the neurobiological underpinnings of delinquent behaviour, antisocial and violent behaviour arises from a complex pattern of biological, psychological, social and situational factors, precluding a stance of simple biological reductionism. Rather, optimal integration of neurobiological findings requires cooperation among many disciplines such as medicine, criminology, sociology, psychology, politics and neuroscience.     

静息态脑功能成像与皮层电刺激定位皮质运动区的对照研究

目的 以术中皮层电刺激为对照,评价运动区附近脑肿瘤患者术前运用基于血氧水平依赖(BOLD)的静息态功能磁共振成像(rs-fMRI)方法定位皮质运动区的准确性.方法 选取18例运动区脑肿瘤患者,手术前采用rs-fMRI定位皮质运动区,以术中皮层电刺激作为皮质运动区定位的标准技术,比较两种技术的符合度,以评价rs-fMRI定位皮质运动区的准确性.结果 rs-fMRI与术中皮层电刺激的吻合率为92.9％,肿瘤全切率为77.8％,11例术后肌力不变,4例术后肌力好转,3例术后肌力下降.结论 rs-fMRI具有较高的敏感性和精确度,可作为术前皮质运动区定位的新方法,为手术方案的制定及预后评估提供有价值的信息.     

Memory in frontal lobe epilepsy: An fMRI study

Purpose: Focal epilepsies are often associated with structural and functional changes that may extend beyond the area of seizure onset. In this study we investigated the functional anatomy of memory in patients with frontal lobe epilepsy (FLE), focusing on the local and remote effects of FLE on the networks supporting memory encoding. Methods: We studied 32 patients with drug‐resistant FLE and 18 controls using a functional magnetic resonance imaging (fMRI) memory encoding paradigm. Key Findings: During encoding of stimuli, patients with FLE recruited more widely distributed areas than healthy controls, in particular within the frontal lobe contralateral to the seizure onset. Normal memory performance was associated with increased recruitment of frontal areas, and conversely a poor performance was associated with an absence of this increased recruitment and decreased activation in mesial temporal lobe areas. Significance: In patients with FLE, recruitment of wider areas, particularly in the contralateral frontal lobe, appears to be an effective compensatory mechanism to maintain memory function. Impaired hippocampal activation is relatively rare and, in turn, associated with poor recognition memory.     

Corticostriatal functional connectivity in non-medicated patients with obsessive-compulsive disorder

The basal ganglia represents a key component of the pathophysiological model for obsessive-compulsive disorder (OCD). This brain region is part of several neural circuits, including the orbitofronto-striatal circuit and dorsolateral prefronto-striatal circuit. There are, however, no published studies investigating those circuits at a network level in non-medicated patients with OCD. Resting state functional magnetic resonance imaging scans were obtained from 20 non-medicated patients with OCD and 23 matched healthy volunteers. Voxelwise statistical parametric maps testing strength of functional connectivity of three striatal seed regions of interest (ROIs) with remaining brain regions were calculated and compared between groups. We performed additional correlation analyses between strength of connectivity and the severity scores for obsessive-compulsive symptoms, depression, and anxiety in the OCD group. Positive functional connectivity with the ventral striatum was significantly increased (P_corrected <.05) in the orbitofrontal cortex, ventral medial prefrontal cortex and dorsal lateral prefrontal cortex of subjects with OCD. There was no significant correlation between measures of symptom severity and the strength of connectivity (P_uncorrected <.001). This is the first study to investigate the corticostriatal connectivity in non-medicated patients with OCD. These findings provide the first direct evidence supporting a pathophysiological model involving basal ganglia circuitry in OCD.     

Reading embossed capital letters: an fMRI study in blind and sighted individuals

Reading Braille activates visual cortex in blind people [Burton et al., J Neurophysiol 2002;87:589-611; Sadato et al., Nature 1996;380:526-528; Sadato et al., Brain 1998;121:1213-1229]. Because learning Braille requires extensive training, we had sighted and blind people read raised block capital letters to determine whether all groups engage visual cortex similarly when reading by touch. Letters were passively rubbed across the right index finger at 30 mm/s using an MR-compatible drum stimulator. Age-matched sighted, early blind (lost sight 0-5 years), and late blind (lost sight >5.5 years) volunteers performed three tasks: stating an identified letter, stating a verb containing an identified letter, and feeling a moving smooth surface. Responses were voiced immediately after the drum stopped moving across the fingertip. All groups showed increased activity in visual areas V1 and V2 during both letter identification tasks. Blind compared to sighted participants showed greater activation increases predominantly in the parafoveal-peripheral portions of visuotopic areas and posterior parts of BA 20 and 37. Sighted participants showed suppressed activity in most of the same areas except for small positive responses bilaterally in V1, left V5/MT+, and bilaterally in BA 37/20. Blind individuals showed suppression of the language areas in the frontal cortex, while sighted individuals showed slight positive responses. Early blind showed a more extensive distribution of activity in superior temporal sulcal multisensory areas. These results show cross-modal reorganization of visual cortex and altered response dynamics in nonvisual areas that plausibly reflect mechanisms for adaptive plasticity in blindness.     

网络游戏成瘾者相关脑区功能定位的fMRI研究

目的 采取线索--反应模式,利用功能磁共振成像(fMRI)技术探索与网络游戏成瘾相关的脑区功能定位.方法 网络游戏成瘾者和对照者各20例,在观看相关网络游戏视频录像和日常生活视频录像的同时进行fMRI扫描,进行问卷调查了解受试者观看视频录像后的心理状态并采集脑血氧水平依赖(BOLD)信号得到网络游戏和日常生活视频录像刺激的脑区激活数据,利用相减原则进行相关性分析产生相应的激活区,进行激活脑区的定位并比较激活强度.结果 成瘾者观看网络游戏和日常生活视频录像时所产生的情绪状态、渴望程度、喜欢程度和希望再次观看程度差异均有统计学意义(P<0.05),而对照者仅希望再次观看程度差异有统计学意义(P<0.05);与生活视频比较,对照者观看游戏视频时顶叶(左)和颞叶视皮层(左)的激活强度较高,差异有统计学意义(P<0.05),而成瘾者除伏核(左)和尾状核(左)外,余脑区观看观看游戏视频和生活视频时激活强度差异均有统计学意义(P<0.05).结论 利用fMRI技术可以对网络游戏成瘾者相关脑区进行功能定位,这些脑区可能参与了网络游戏成瘾的产生与维持.     

Dysfunction in the Fronto-Parietal Network in Attention Deficit Hyperactivity Disorder (ADHD): An fMRI Study

ADHD is associated with spatial working memory deficits, thought to be subserved by dysfunction of neural circuits. In this study we aimed to further examine fronto-parietal dysfunction in ADHD by examining brain activation associated with the Raven’s Progressive Matrices task, a visuo-spatial pattern sequencing task involving relational reasoning and thereby placing high-demand loading on the prefrontal cortex. Functional MRI was conducted on twelve right-handed 8–12 year old boys with ADHD-combined type and 12 right-handed, age and performance IQ-matched, healthy boys as they completed items from the Raven’s Progressive Matrices. Our findings further confirm striatum and parietal lobe dysfunction in ADHD. Furthermore, dysfunction in lateral prefrontal regions was found. In addition to lateral prefrontal, striatum and posterior parietal regions, the temporal lobe was also less active. These findings suggest deficits in a widespread ‘functional network’ in ADHD that may be fundamental for visuo-spatial information processing and relational reasoning.     

Cortical activity to vibrotactile stimulation: an fMRI study in blind and sighted individuals

Blind individuals show visual cortex activity during Braille reading. We examined whether such cross-modal activations reflect processing somatosensory stimuli independent of language by identifying cortical activity during a one-back vibrotactile matching task. Three groups (sighted, early-onset, and late-onset [>12 years] blind) detected whether paired vibrations (25 and 100 Hz), delivered to the right index finger, differed in frequency. Three successive paired vibrations, followed by a no-stimulation interval, were presented in a long event-related design. A fixed effects average z-score analysis showed increased activity throughout the visuotopic visual cortex, where it was mostly restricted to foveal and parafoveal eccentricities. Early blind showed the most extensive distribution of activity. Late blind exhibited activity mostly in similar regions but with declining response magnitudes with age of blindness onset. Three sighted individuals had suprathreshold activity in V1 but negative responses elsewhere in visual cortex. Mixed effects ANOVA confirmed group distinctions in defined regions (V1, V3, V4v, V7, LOC, and MT). These results suggest cross-modal adaptation to tactile stimulation in visual cortex independent of language processes. All groups showed increased activity in left primary (S1) and bilateral second somatosensory areas, but without response magnitude differences between groups throughout sensorimotor cortex. Early blind showed the greatest spatial extent of S1 activity. Blind participants had more extensive bilateral activity in anterior intraparietal sulcus and supramarginal gyrus. Extensive usage of touch in Braille reading may underlie observed S1 expansions in the reading finger representation. In addition, learned attentiveness to touch may explain similar expansion of parietal tactile attention regions.     

Left-sided interictal epileptic activity induces shift of language lateralization in temporal lobe epilepsy: an fMRI study

PURPOSE: By using speech-activated functional MRI (fMRI), we investigated whether the frequency of left-sided interictal epileptic activity (IED: spikes or sharp waves on the EEG) is associated with atypical speech lateralization. METHODS: We investigated 28 patients (13 men, aged 17-59 years) with left-sided mesial temporal lobe epilepsy (MTLE) and 11 patients with right-sided MTLE as a control population. Only patients with unilateral hippocampal sclerosis with unilateral IED were included. For fMRI of individual patients, we contrasted images sampled during covert word generation with a low-level rest condition. With SPM99, an individual comparison for the contrast "word generation versus resting inactivity" was conducted. To characterize speech lateralization in individual patients, we calculated asymmetry indexes (AIs): the difference between activated left-sided and right-sided voxels was divided by all activated voxels. Analyzing long-term EEG, the first 2 min of each hour were evaluated for the frequency of IED. Univariate associations with AIs were assessed by Pearson's correlation and by t test. When testing the independent associations, multivariate linear regression was performed. RESULTS: The AIs in patients with left-sided MTLE were 0.40 +/- 0.53 on average (range, -0.83 to +1.0), whereas in right-sided MTLE, they were 0.78 +/- 0.15 (p = 0.029). For the further investigations, we included left-sided MTLE patients only. The median frequency of IED was six per hour (range, 0-240). Higher IED frequency was correlated with left-right shift of lateralization of speech fMRI activity (p = 0.002). CONCLUSIONS: Higher left-sided spike frequency in MTLE was associated with a left-right shift of speech representation, suggesting that chronic frequent interictal activity may induce a reorganization of speech lateralization.     

The use of neuroimaging to study behavior in patients with epilepsy

Structural and functional neuroimaging continues to play an increasing role in the presurgical evaluation of patients with epilepsy. In addition to its value in localizing the epileptogenic zone and eloquent cortex, neuroimaging is contributing to our understanding of mood comorbidity in epilepsy. Although the vast majority of research has focused on patients with temporal lobe epilepsy (TLE), neuroimaging studies of patients with extratemporal epilepsy and primary generalized epilepsy are increasing in number. In this review, structural and functional imaging modalities that have received considerable research attention in recent years are reviewed, and their strengths and limitations for understanding behavior in epilepsy are assessed. In addition, advances in multimodal imaging are discussed along with their potential application to the presurgical evaluation of patients with seizure disorders.     

Cerebral changes and cognitive dysfunctions in medication-free schizophrenia - an fMRI study

Proposing cognitive impairment in working memory (wm) functions as a cognitive core deficit in schizophrenia, 23 first episode, medication-free schizophrenic patients in a comparison of healthy adults have been investigated by fMRI. Additionally, the effects of different attentional demands in wm tasks were analysed. A wm paradigm was applied, in which stimuli were presented in a 2-back and a 0-back condition in a non-degraded and degraded version. As hypothesized in healthy controls increased activity during both 2-back tasks was found in the ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), parietal regions, the thalamus and the cerebellum. Different activation patterns were found for the cingulate cortex in the 2-back degraded conditions. The comparison between healthy controls and schizophrenic patients revealed decreased activity in the right VLPFC in patients as well as increased activity in temporal regions. Furthermore patients' task performance quality was significantly lower for 2-back conditions. Schizophrenic patients use different cognitive strategies to solve working memory tasks, reflected in significantly altered cerebral activity. However, the different fMRI working memory correlates found in schizophrenic patients seem to be insufficient in terms of overall task performance.