Magnetic resonance perfusion imaging in the study of language

This paper provides a brief review of various uses of magnetic resonance perfusion imaging in the investigation of brain/language relationships. The reviewed studies illustrate how perfusion imaging can reveal areas of brain where dysfunction due to low blood flow is associated with specific language deficits, and where restoration of blood flow to improve the tissue function results in recovery of those deficits. This sort of evidence helps to reveal areas of the brain that are essential to a particular language task. Other studies have provided clues regarding the mechanisms of early language recovery, or have shown how perfusion imaging can identify patients with chronic hypoperfusion due to cerebrovascular stenosis in whom the BOLD effect in fMRI may be absent or reduced in areas of neural activation.     

An Introduction to Normalization and Calibration Methods in Functional MRI

In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes in the baseline neurovascular state can result in significant modulations of the BOLD signal that are independent of changes in neural activity. This paper introduces some of the normalization and calibration methods that have been proposed for making the BOLD signal a more accurate reflection of underlying brain activity for human fMRI studies.     

Pharmacologic Treatment of Attention-Deficit/Hyperactivity Disorder: Efficacy,Safety and Mechanisms of Action

Studies examining the efficacy, safety and mechanisms of action of agents for the treatment of attention-deficit/hyperactivity disorder (ADHD) are reviewed, with an emphasis on newer agents such as the long acting stimulants and atomoxetine. Recent studies of medications are characterized by large, rigorously diagnosed samples of children, adolescents and adults with ADHD, use of standardized rating scales and extensive safety data. These studies confirm a robust treatment effect for the Food and Drug Administration approved agents ranging from 0.7 to 1.5. The most common short term side effects to the most commonly used agents include insomnia, loss of appetite, and headaches. Despite public controversy and labeling changes to warn of extremely rare cardiovascular and psychiatric side effects, the evidence does not support the hypothesis that medication for ADHD increases risk for sudden death, mania or psychosis. A wide variety of neuroimaging techniques including electrocephalogram (EEG) power, event related potentials (ERP), functional magnetic resonance imaging (fMRI), and positron emission tomography (PET) are beginning to examine the mechanisms of action of medications for ADHD, and implicating the catecholamines and prefrontal and anterior cingulate cortices as prime sites of actions for these agents.     

青老年组不同难度下心算活动的脑功能磁共振成像研究

应用功能磁共振成像技术研究不同心算难度下脑区的活动以及年龄的影响。14名志愿者（20～29岁青年和60～69岁老年被试各7名）参加了该实验。实验任务为2个难度水平的连续减法心算,分别为1000—3和1000—17。结果表明：（1）心算加工激活了额叶和顶叶的许多脑区;（2）大脑左半球是心算加工的优势半球,但随着心算难度加大,大脑一侧化程度下降,而年老加剧了这一趋势;（3）青年组进行简单心算（1000—3）时,额中回未见明显激活,而老年组进行简单心算时,该脑区被明显激活。总体上,额叶和顶叶在心算活动中起着重要作用,而任务难度和年龄对心算加工时脑活动的影响以额中回区最为明显。     

Role of Functional Magnetic Resonance Imaging in Drug Discovery

In this review, we survey the state of the field of functional magnetic resonance imaging (fMRI) as it relates to drug discovery and drug development. We highlight the advantages and limitations of fMRI for this purpose and suggest ways to improve the use of fMRI for developing new therapeutics, with emphasis on treatments for anxiety disorders. Fundamentally, pharmacological studies with standard psychiatric treatments using standardized behavioral probes during fMRI will need to be carried out to determine characteristic brain signatures that could be used to predict whether novel compounds are likely to have specific therapeutic effects.     

The role of neuronal signaling in controlling cerebral blood flow

Well-regulated blood flow within the brain is vital to normal function. The brain's requirement for sufficient blood flow is ensured by a tight link between neural activity and blood flow. The link between regional synaptic activity and regional cerebral blood flow, termed functional hyperemia, is the basis for several modern imaging techniques that have revolutionized the study of human brain activity. Here, we review the mechanisms of functional hyperemia and their implications for interpreting the blood oxygen level-dependent (BOLD) contrast signal used in functional magnetic resonance imaging (fMRI).     

Operant-contingency-based preparation of children for functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) is used to study brain function during behavioral tasks. The participation of pediatric subjects is problematic because reliable task performance and control of head movement are simultaneously required. Differential reinforcement decreased head motion and improved vigilance task performance in 4 children (2 with behavioral disorders) undergoing simulated fMRI scans. Results show that behavior analysis techniques can improve child cooperation during fMRI procedures.     

Lateralized spatial and object memory encoding in entorhinal and perirhinal cortices

The perirhinal and entorhinal cortices are critical components of the medial temporal lobe (MTL) declarative memory system. Study of their specific functions using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI), however, has suffered from severe magnetic susceptibility signal dropout resulting in poor temporal signal-to-noise (tSNR) and thus weak BOLD signal detectability. We have demonstrated that higher spatial resolution in the z-plane leads to improved BOLD fMRI signal quality in the anterior medial temporal lobes when using a 16-element surface coil array at 3 T (Tesla). Using this technique, the present study investigated the roles of the anterior medial temporal lobe, particularly the entorhinal and perirhinal cortices, in both object and spatial memory. Participants viewed a series of fractal images and were instructed to encode either the object's identity or location. Object and spatial recognition memory were tested after 18-sec delays. Both the perirhinal and entorhinal cortices were active during the object and spatial encoding tasks. In both regions, object encoding was biased to the left hemisphere, whereas spatial encoding was biased to the right. A similar hemispheric bias was evident for recognition memory. Recent animal studies suggest functional dissociations among regions of the entorhinal cortex for spatial vs. object processing. Our findings suggest that this process-specific distinction may be expressed in the human brain as a hemispheric division of labor.     

Prototype-distortion category learning: a two-phase learning process across a distributed network

This paper reviews a body of work conducted in our laboratory that applies functional magnetic resonance imaging (fMRI) to better understand the biological response and change that occurs during prototype-distortion learning. We review results from two experiments (Little, Klein, Shobat, McClure, & Thulborn, 2004; Little & Thulborn, 2005) that provide support for increasing neuronal efficiency by way of a two-stage model that includes an initial period of recruitment of tissue across a distributed network that is followed by a period of increasing specialization with decreasing volume across the same network. Across the two studies, participants learned to classify patterns of random-dot distortions (Posner & Keele, 1968) into categories. At four points across this learning process subjects underwent examination by fMRI using a category-matching task. A large-scale network, altered across the protocol, was identified to include the frontal eye fields, both inferior and superior parietal lobules, and visual cortex. As behavioral performance increased, the volume of activation within these regions first increased and later in the protocol decreased. Based on our review of this work we propose that: (i) category learning is reflected as specialization of the same network initially implicated to complete the novel task, and (ii) this network encompasses regions not previously reported to be affected by prototype-distortion learning.     

Role of medial prefrontal cortex in representing one’s own subjective emotional responses: A preliminary study

The medial prefrontal cortex (mPFC) has been implicated in attending to one’s own emotional states, but the role of emotional valence in this context is not understood. We examined valence-specific BOLD activity in a previously validated functional magnetic resonance imaging (fMRI) paradigm. Ten healthy subjects viewed emotional pictures and categorized their experience as pleasant, unpleasant or neutral. All three categories activated a common region within mPFC. Subtraction of neutral from pleasant or unpleasant conditions instead revealed ventromedial PFC (vmPFC), suggesting that this region represents emotional valence. During exteroceptive attention, greater mPFC responses were observed in response to emotional relative to neutral stimuli, consistent with studies implicating mPFC in the top-down modulation of emotion-biased attention. These findings may help to integrate the two proposed roles of mPFC in emotional representation and top-down modulation of subcortical structures.     

艺术设计中创造性思维的fMRI研究：一项基于智能CAD的探索

本项工作尝试将人类思维的神经生物学基础研究与人工智能的研究成果相结合, 利用类比生成模型的原理, 开发了一个计算机辅助设计系统“多源类比人脸生成系统”, 并运用此平台开展了fMRI实验, 对人类大脑创造性思维的神经生物学机制进行了探索。实验采用open-ends模式下的“design task”和problem solving模式下的“control task”作为对照, 共采得15名健康成人被试的有效数据。数据结果显示design task与control task相比更为显著地激活了内侧前额叶、额中回、右侧颞上回、前扣带回、双侧海马、楔前叶这些脑区。综合以往研究推测, 内侧前额叶可能更多地与即兴自由创作中对自我信息的表征有关, 颞叶可能与不断产生和输出新颖性的观点有关, 边缘系统则可能主要与创造性活动中的动力驱动作用有关。总的来说, 创造性思维是多个脑区同时参与的高度分布式加工的结果。     

Are errors differentiable from deceptive responses when feigning memory impairment? An fMRI study

Previous neuroimaging studies have suggested that the neural activity associated with truthful recall, with false memory, and with feigned memory impairment are different from one another. Here, we report a functional magnetic resonance imaging (fMRI) study that addressed an important but yet unanswered question: Is the neural activity associated with intentional faked responses and with errors differentiable? Using a word list learning recognition paradigm, the findings of this mixed event-related fMRI study clearly indicated that the brain activity associated with intentional faked responses was different to the activity associated with errors committed unintentionally. For intentional faked responses, significant activation was found in the ventrolateral prefrontal cortex, the posterior cingulate region, and the precuneus. However, no significant activation was observed for unintentional errors. The results suggest that deception, in terms of feigning memory impairment, is not only more cognitively demanding than making unintentional errors but also utilizes different cognitive processes.     

Effects of motor intention on the perception of somatosensory events: A behavioural and functional magnetic resonance imaging study

The intention to execute a movement can modulate our perception of sensory events, and this modulation is observed ahead of both ocular and upper limb movements. However, theoretical accounts of these effects, and also the empirical data, are often contradictory. Accounts of “active touch”, and the premotor theory of attention, have emphasized how movement intention leads to enhanced perceptual processing at the target of a movement, or on the to-be-moved effector. By contrast, recent theories of motor control emphasize how internal “forward” model (FM) estimates may be used to cancel or attenuate sensory signals that arise as a result of self-generated movements. We used behavioural and functional brain imaging (functional magnetic resonance imaging, fMRI) to investigate how perception of a somatosensory stimulus differed according to whether it was delivered to a hand that was about to execute a reaching movement or the alternative, nonmoving, hand. The results of our study demonstrate that a somatosensory stimulus delivered to a hand that is being prepared for movement is perceived to have occurred later than when that same stimulus is delivered to a nonmoving hand. This result indicates that it takes longer for a tactile stimulus to be detected when it is delivered to a moving limb and may correspond to a change in perceptual threshold. Our behavioural results are paralleled by the results of our fMRI study that demonstrated that there were significantly reduced blood-oxygen-level-dependent (BOLD) responses within the parietal operculum and insula following somatosensory stimulation of the hand being prepared for movement, compared to when an identical stimulus was delivered to a nonmoving hand. These findings are consistent with the prediction of FM accounts of motor control that postulate that central sensory suppression of somatosensation accompanies self-generated limb movements, and with previous reports indicating that effects of sensory suppression are observed in higher order somatosensory regions.     

Prefrontal brain activity predicts temporally extended decision-making behavior

Although functional neuroimaging studies of human decision-making processes are increasingly common, most of the research in this area has relied on passive tasks that generate little individual variability. Relatively little attention has been paid to the ability of brain activity to predict overt behavior. Using functional magnetic resonance imaging (fMRI), we investigated the neural mechanisms underlying behavior during a dynamic decision task that required subjects to select smaller, short-term monetary payoffs in order to receive larger, long-term gains. The number of trials over which the longterm gains accrued was manipulated experimentally (2 versus 12). Event-related neural activity in right lateral prefrontal cortex, a region associated with high-level cognitive processing, selectively predicted choice behavior in both conditions, whereas insular cortex responded to fluctuations in amount of reward but did not predict choice behavior. These results demonstrate the utility of a functional neuroimaging approach in behavioral psychology, showing that (a) highly circumscribed brain regions are capable of predicting complex choice behavior, and (b) fMRI has the ability to dissociate the contributions of different neural mechanisms to particular behavioral tasks.     

Voluntary aspects of attentional control setting for detecting a feature‐defined target1

Abstract: Singleton targets that differ from distractors in a single salient attribute can be discerned regardless of the number of items in the display. Recent studies have indicated that the perception of singleton targets is facilitated by an attentional control setting. We focused on the voluntary aspect of the attentional control setting. Psychophysical and functional magnetic resonance imaging (fMRI) experiments examined the temporal characteristics of the attentional control setting by using an auditory cue. In both experiments, an auditorily cued feature‐search task was used. The cue validity (valid vs. neutral) and the cue lead time (CLT) were varied. In the psychophysical experiment, we established the effect of a symbolic cue on detection of a singleton. When the CLT was short or the cue was neutral, there was no facilitation, as re?ected by the slow activation of the attentional control setting. In our fMRI experiment, the brain activity indicates that this detection task activated the prefrontal cortex. These results demonstrate that the attentional control setting for facilitation of the singleton‐target perception modulates activity in regions of the prefrontal cortex.     

人脑自适应多尺度功能连接的性别差异

已有脑成像研究展示了男女脑功能差异, 但功能磁共振信号的频率划分通常基于主观经验, 使脑功能性别差异的生物学解释遭遇瓶颈。本文提出人脑自适应多尺度功能连接算法, 刻画功能连接的时空多尺度特性, 揭示出0.06~0.10 Hz的性别差异：男性较强的连接主要与边缘网络和腹侧注意网络有关, 女性较强的连接主要与腹侧注意网络、视觉网络和额顶网络有关。     

A functional MRI study of human amygdala responses to facial expressions of fear versus anger

Functional magnetic resonance imaging (fMRI) of the human brain was used to compare changes in amygdala activity associated with viewing facial expressions of fear and anger. Pictures of human faces bearing expressions of fear or anger, as well as faces with neutral expressions, were presented to 8 healthy participants. The blood oxygen-level dependent (BOLD) fMRI signal within the dorsal amygdala was significantly greater to Fear versus Anger, in a direct contrast. Significant BOLD signal changes in the ventral amygdala were observed in contrasts of Fear versus Neutral expressions and, in a more spatially circumscribed region, to Anger versus Neutral expressions. Thus, activity in the amygdala is greater to fearful facial expressions when contrasted with either neutral or angry faces. Furthermore, directly contrasting fear with angry faces highlighted involvement of the dorsal amygdaloid region.     

Event-related fMRI of category learning: differences in classification and feedback networks

Eighteen healthy young adults underwent event-related (ER) functional magnetic resonance imaging (fMRI) of the brain while performing a visual category learning task. The specific category learning task required subjects to extract the rules that guide classification of quasi-random patterns of dots into categories. Following each classification choice, visual feedback was presented. The average hemodynamic response was calculated across the eighteen subjects to identify the separate networks associated with both classification and feedback. Random-effects analyses identified the different networks implicated during the classification and feedback phases of each trial. The regions included prefrontal cortex, frontal eye fields, supplementary motor and eye fields, thalamus, caudate, superior and inferior parietal lobules, and areas within visual cortex. The differences between classification and feedback were identified as (i) overall higher volumes and signal intensities during classification as compared to feedback, (ii) involvement of the thalamus and superior parietal regions during the classification phase of each trial, and (iii) differential involvement of the caudate head during feedback. The effects of learning were then evaluated for both classification and feedback. Early in learning, subjects showed increased activation in the hippocampal regions during classification and activation in the heads of the caudate nuclei during the corresponding feedback phases. The findings suggest that early stages of prototype-distortion learning are characterized by networks previously associated with strategies of explicit memory and hypothesis testing. However as learning progresses the networks change. This finding suggests that the cognitive strategies also change during prototype-distortion learning.     

多目标追踪的神经机制

多目标追踪任务是研究动态场景中视觉注意加工机制常用的范式。自1998年开始对多目标追踪神经机制的影像学研究以来, 研究者采用ERP和fMRI等技术对多目标注意追踪所涉及的神经电生理活动和脑功能区激活方面开展了大量研究。ERP研究发现, 追踪过程持续的ERP脑电成分如N2pc、CDA的波幅与注意追踪负荷有关, 并且出现在目标与非目标上的探测刺激诱发的脑电成分如N1、P1波幅的差异可反映注意资源的分配, 具体为目标在追踪过程中得到了激活, 而非目标受到了抑制。fMRI研究比较一致地发现了顶叶(包括前顶内沟、后顶内沟、顶上小叶)、背外侧额叶皮层等在注意追踪中的强烈激活。其中顶内沟主要与注意负荷有关, 顶内沟的活动水平直接决定了观察者注意追踪的行为表现。而顶上小叶可能更多的负责注意转移。背外侧额叶皮层可能负责追踪时的感觉运动预测过程。     

Reduced right hemisphere activation in severely abused violent offenders during a working memory task: An fMRI study

This study uses functional magnetic resonance imaging (fMRI) to address two important gaps in our knowledge of brain functioning and violence: (1) What are the brain correlates of adults in the community who have suffered severe physical abuse early in life and who go on to perpetrate serious violence in adulthood? (2) What characterizes those who experience severe physical abuse but who refrain from serious violence? Four groups of participants recruited from the community (controls, severe physical child abuse only, serious violence only, and severely abused, seriously violent offenders) underwent fMRI while performing a visual/verbal working memory task. Violent offenders who had suffered severe child abuse show reduced right hemisphere functioning, particularly in the right temporal cortex. Abused individuals who refrain from serious violence showed relatively lower left, but higher right, activation of the superior temporal gyrus. Abused individuals, irrespective of violence status, showed reduced cortical activation during the working memory task, especially in the left hemisphere. Brain deficits were independent of IQ, history of head injury, task performance, cognitive strategy, and mental activity during the control task. Findings constitute the first fMRI study of brain dysfunction in violent offenders, and indicate that initial right hemisphere dysfunction, when combined with the effects of severe early physical abuse, predisposes to serious violence but that relatively good right hemisphere functioning protects against violence in physically abused children. Aggr. Behav. 27:111–129, 2001. © 2001 Wiley‐Liss, Inc.