Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensity

Neuroimaging studies of painful stimuli in humans have identified a network of brain regions that is more extensive than identified previously in electrophysiological and anatomical studies of nociceptive pathways. This extensive network has been described as a pain matrix of brain regions that mediate the many interrelated aspects of conscious processing of nociceptive input such as perception, evaluation, affective response, and emotional memory. We used functional magnetic resonance imaging in healthy human subjects to distinguish brain regions required for pain sensory encoding from those required for cognitive evaluation of pain intensity. The results suggest that conscious cognitive evaluation of pain intensity in the absence of any sensory stimulation activates a network that includes bilateral anterior insular cortex/frontal operculum, dorsal lateral prefrontal cortex, bilateral medial prefrontal cortex/anterior cingulate cortex, right superior parietal cortex, inferior parietal lobule, orbital prefrontal cortex, and left occipital cortex. Increased activity common to both encoding and evaluation was observed in bilateral anterior insula/frontal operculum and medial prefrontal cortex/anterior cingulate cortex. We hypothesize that these two regions play a crucial role in bridging the encoding of pain sensation and the cognitive processing of sensory input.     

Dissociation of inhibition from error processing using a parametric inhibitory task during functional magnetic resonance imaging

Inhibition, the process that overrides and reverses the execution of a thought, action, or emotion, is important in daily life. Sixteen healthy volunteers performed a parametrically modulated motor inhibition task during functional magnetic resonance imaging. Two results were observed: (1) increased error-related anterior cingulate cortex activation and, (2) increased inferior frontal gyrus and medial prefrontal cortex activation during inhibition, irrespective of errors. Thus, the parametric nature of the task elucidated a functional dissociation of brain structures involved in motor inhibition from those involved in error processing. Additionally, this task allowed the identification of unique areas of increased activation within specific subregions of the anterior cingulate cortex related to errors made during trials with a high (dorsal anterior cingulate cortex) and low (ventral anterior cingulate cortex) inhibitory load.     

Acupuncture at the Taixi （KI3） acupoint activates cerebral neurons in elderly patients with mild cognitive impairment

Our previous ifndings have demonstrated that acupuncture at the Taixi （KI3） acupoint in healthy youths can activate neurons in cognitive-related cerebral cortex. Here, we investigated whether acupuncture at this acupoint in elderly patients with mild cognitive impairment can also activate neurons in these regions. Resting state and task-related functional magnetic resonance imaging showed that the pinprick senstation of acupuncture at the Taixi acupoint differed signiifcantly between elderly patients with mild cognitive impairment and healthy elderly controls. Results showed that 20 brain regions were activated in both groups of participants, including the bi-lateral anterior cingulate gyrus （Brodmann areas [BA] 32, 24）, left medial frontal cortex （BA 9, 10, 11）, left cuneus （BA 19）, left middle frontal gyrus （BA 11）, left lingual gyrus （BA 18）, right medial frontal gyrus （BA 11）, bilateral inferior frontal gyrus （BA 47）, left superior frontal gyrus （BA11）, right cuneus （BA 19, 18）, right superior temporal gyrus （BA 38）, left subcallosal gyrus （BA 47）, bilateral precuneus （BA 19）, right medial frontal gyrus （BA 10）, right superior frontal （BA 11）, left cingulate gyrus （BA 32）, left precentral gyrus （BA 6）, and right fusiform gyrus （BA 19）. These results suggest that acupuncture at the Taixi acupoint in elderly patients with mild cogni-tive impairment can also activate some brain regions.     

Relative Changes in Regional Cerebral Blood Flow During Spinal Cord Stimulation in Patients with Refractory Angina Pectoris

Spinal cord stimulation applied at thoracic level 1 (T1) has a neurally mediated anti-anginal effect based on anti-ischaemic action in the myocardium. Positron emission tomography was used to study which higher brain centres are influenced by spinal cord stimulation. Nine patients with a spinal cord stimulator for angina pectoris were studied using H₂¹⁵O as a flow tracer. Relative changes in regional cerebral blood flow related to stimulation compared with non-stimulation were assessed and analysed using the method of statistical parametric mapping. Increased regional cerebral blood flow was observed in the left ventrolateral periaqueductal grey, the medial prefrontal cortex [Brodmann area (BA) 9/10], the dorsomedial thalamus bilaterally, the left medial temporal gyrus (BA 21), the left pulvinar of the thalamus, bilaterally in the posterior caudate nucleus, and the posterior cingulate cortex (BA 30). Relative decreases in rCBF were noticed bilaterally in the insular cortex (BA 20/21 and BA 38), the right inferior temporal gyrus (BA 19/37), the right inferior frontal gyrus (BA 45), the left inferior parietal lobulus (BA 40), the medial temporal gyrus (BA 39) and the right anterior cingulate cortex (BA 24). It is concluded that spinal cord stimulation used as an additional treatment for angina applied at TI modulates regional cerebral blood flow in brain areas known to be associated with nociception and in areas associated with cardiovascular control.     

Representation of attitudinal knowledge: role of prefrontal cortex, amygdala and parahippocampal gyrus

It has been proposed that behavior is influenced by representations of different types of knowledge: action representations, event knowledge, attitudes and stereotypes. Attitudes (representations of a concept or object and its emotional evaluation) allow us to respond quickly to a given stimulus. In this study, we explored the representation and inhibition of attitudes. We show that right dorsolateral prefrontal cortex mediates negative attitudes whereas left ventrolateral prefrontal cortex mediates positive attitudes. Parahippocampal regions and amygdala mediate evaluative processing. Furthermore, anxiety modulates right dorsolateral prefrontal activation during negative attitude processing. Inhibition of negative attitudes activates left orbitofrontal cortex: a region that when damaged is associated with socially inappropriate behavior in patients. Inhibition of positive attitudes activates a brain system involving right inferior frontal gyrus and bilateral anterior cingulate. Thus, we show that there are dissociable networks for the representation and inhibition of attitudes.     

Compensatory brain activation in children with attention deficit/hyperactivity disorder during a simplified Go/No-go task

Given that a number of recent studies have shown attenuated brain activation in prefrontal regions in children with ADHD, it has been recognized as a disorder in executive function. However, fewer studies have focused exclusively on the compensatory brain activation in ADHD. The present study objective was to investigate the compensatory brain activation patterns during response inhibition (RI) processing in ADHD children. In this study, 15 ADHD children and 15 sex-, age-, and IQ-matched control children were scanned with a 3-T MRI equipment while performing a simplified letter Go/No-go task. The results showed more brain activation in the ADHD group compared with the control group, whereas the accuracy and reaction time of behavioral performance were the same. Children with ADHD did not activate the normal RI brain circuits, which are thought to be predominantly located in the right middle/inferior frontal gyrus (BA46/44), right inferior parietal regions (BA40), and pre-SMA(BA6), but instead, activated brain regions, such as the left inferior frontal cortex, the right inferior temporal cortex, the right precentral gyrus, the left postcentral gyrus, the inferior occipital cortex, the middle occipital cortex, the right calcarine, the right hippocampus, the right midbrain, and the cerebellum. Our conclusion is that children with ADHD tend to compensatorily use more posterior and diffusive brain regions to sustain normal RI function.     

The brain basis of piano performance

Performances of memorized piano compositions unfold via dynamic integrations of motor, perceptual, cognitive, and emotive operations. The functional neuroanatomy of such elaborately skilled achievements was characterized in the present study by using (15)0-water positron emission tomography to image blindfolded pianists performing a concerto by J.S. Bach. The resulting brain activity was referenced to that for bimanual performance of memorized major scales. Scales and concerto performances both activated primary motor cortex, corresponding somatosensory areas, inferior parietal cortex, supplementary motor area, motor cingulate, bilateral superior and middle temporal cortex, right thalamus, anterior and posterior cerebellum. Regions specifically supporting the concerto performance included superior and middle temporal cortex, planum polare, thalamus, basal ganglia, posterior cerebellum, dorsolateral premotor cortex, right insula, right supplementary motor area, lingual gyrus, and posterior cingulate. Areas specifically implicated in generating and playing scales were posterior cingulate, middle temporal, right middle frontal, and right precuneus cortices, with lesser increases in right hemispheric superior temporal, temporoparietal, fusiform, precuneus, and prefrontal cortices, along with left inferior frontal gyrus. Finally, much greater deactivations were present for playing the concerto than scales. This seems to reflect a deeper attentional focus in which tonically active orienting and evaluative processes, among others, are suspended. This inference is supported by observed deactivations in posterior cingulate, parahippocampus, precuneus, prefrontal, middle temporal, and posterior cerebellar cortices. For each of the foregoing analyses, a distributed set of interacting localized functions is outlined for future test.     

Nonlinear Responses Within the Medial Prefrontal Cortex Reveal When Specific Implicit Information Influences Economic Decision Making

BACKGROUND AND PURPOSE: The authors used functional magnetic resonance imaging (fMRI) to investigate how individual economic decisions are influenced by implicit memory contributions. METHODS: Twenty-two participants were asked to make binary decisions between different brands of sensorily nearly undistinguishable consumer goods. Changes of brain activity comparing decisions in the presence or absence of a specific target brand were detected by fMRI. RESULTS: Only when the tar get brand was the participant's favorite one did the authors find reduced activation in the dorsolateral prefrontal, posterior parietal, and occipital cortices and the left premotor area (Brodmann areas [BA] 9, 46, 7/19, and 6). Simultaneously, activity was increased in the inferior precuneus and posterior cingulate (BA 7), right superior frontal gyrus (BA 10), right supramarginal gyrus (BA 40), and, most pronounced, in the ventromedial prefrontal cortex (BA 10). CONCLUSIONS: For products mainly distinguishable by brand information, the authors revealed a nonlinear winner-take-all effect for a participant's favorite brand characterized, on one hand, by reduced activation in brain areas associated with working memory and reasoning and, on the other hand, increased activation in areas involved in processing of emotions and self-reflections during decision making.     

Alterations in amplitude of low frequency fluctuation in treatment‐naïve major depressive disorder measured with resting‐state fMRI

There are limited resting‐state functional magnetic resonance imaging (fMRI) studies in major depressive disorder (MDD). Of these studies, functional connectivity analyses are mostly used. However, a new method based on the magnitude of low frequency fluctuation (LFF) during resting‐state fMRI may provide important insight into MDD. In this study, we examined the amplitude of LFF (ALFF) within the whole brain during resting‐state fMRI in 30 treatment‐naïve MDD subjects and 30 healthy control (HC) subjects. When compared with HC, MDD subjects showed increased ALFF in the frontal cortex (including the bilateral ventral/dorsal anterior cingulate cortex, orbitofrontal cortex, premotor cortex, ventral prefrontal cortex, left dorsal lateral frontal cortex, left superior frontal cortex), basal ganglia (including the right putamen and left caudate nucleus), left insular cortex, right anterior entorhinal cortex and left inferior parietal cortex, together with decreased ALFF in the bilateral occipital cortex, cerebellum hemisphere, and right superior temporal cortex. These findings may relate to characteristics of MDD, such as excessive self‐referential processing and deficits in cognitive control of emotional processing, which may contribute to the persistent and recurrent nature of the disorder. Hum Brain Mapp 35:4979–4988, 2014. © 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

难治性癫痫患者楔前叶功能连接的静息态功能磁共振成像研究

目的应用静息态功能磁共振成像(rs-f MRI)探讨难治性癫痫患者楔前叶与全脑功能连接的改变及其意义。方法对23例难治性癫痫患者(癫痫组)及23名健康人(对照组)进行rs-f MRI检查,采集数据后采用功能连接的方法,分别计算以左侧楔前叶和右侧楔前叶为感兴趣区与全脑的功能连接,运用双样本t检验的统计学方法发现两组的显著性差异并进行分析。结果癫痫组左侧楔前叶与双侧顶下小叶、双侧岛叶、右侧缘上回、右侧额中回和双侧额下回的功能连接较对照组减弱(均P0.05);癫痫组左侧楔前叶与双侧海马旁回、双侧额上回、左侧后扣带回的功能连接较对照组增强(均P0.05)。癫痫组右侧楔前叶与左侧顶下小叶、右侧缘上回、右侧额中回、右侧额下回的功能连接较对照组减弱(均P0.05);癫痫组右侧楔前叶与双侧楔叶、左侧后扣带回的功能连接较对照组增强(均P0.05)。结论难治性癫痫患者静息状态下楔前叶与全脑的功能连接存在异常,"默认网络"功能的抑制可能是癫痫患者意识及认知等功能损害的重要原因。     

Increased Cognition Connectivity Network in Major Depression Disorder: A fMRI Study

ObjectiveEvidence of the brain network involved in cognitive dysfunction has been inconsistent for major depressive disorder (MDD), especially during early stage of MDD. This study seeks to examine abnormal cognition connectivity network (CCN) in MDD within the whole brain.MethodsSixteen patients with MDD and 16 health controls were scanned during resting-state using 3.0 T functional magnetic resonance imaging (fMRI). All patients were first episode without any history of antidepressant treatment. Both the left and right dorsolateral prefrontal cortex (DLPFC) were used as individual seeds to identify CCN by the seed-target correlation analysis. Two sample t test was used to calculate between-group differences in CCN using fisher z-transformed correlation maps.ResultsThe CCN was constructed by bilateral seed DLPFC in two groups separately. Depressed subjects exhibited significantly increased functional connectivity (FC) by left DLPFC in one cluster, overlapping middle frontal gyrus, BA7, BA43, precuneus, BA6, BA40, superior temporal gyrus, BA22, inferior parietal lobule, precentral gyrus, BA4 and cingulate gyrus in left cerebrum. Health controls did not show any cluster with significantly greater FC compared to depressed subjects in left DLPFC network. There was no significant difference of FC in right DLPFC network between depressed subjects and the health controls.ConclusionThere are differences in CCN during early stage of MDD, as identified by increased FCs among part of frontal gyrus, parietal cortex, cingulate cortex, and BA43, BA22, BA4 with left DLPFC. These brain areas might be involved in the underlying mechanisms of cognitive dysfunction in MDD.     

长期海洛因依赖者前额叶功能连接的变化

以前额叶为种子点,利用静息态fMRI进行全脑时域相关的功能连接分析,观察长期海洛因成瘾者前额叶功能连接的变化。结果发现相比于正常对照,以左侧前额叶为种子点进行功能连接分析,海洛因成瘾者左侧前额叶与左侧海马、右侧前扣带回、左侧额中回、右侧额中回、右侧楔前叶功能连接明显降低;以右侧前额叶为种子点进行功能连接分析,海洛因成瘾者右侧前额叶与左侧眶额叶、左侧额中回功能连接明显降低。提示长期海洛因成瘾者前额叶与相关脑区的功能连接减弱,可能与海洛因成瘾的维持与戒断后复吸相关。     

Neural processes of preparatory control for stop signal inhibition

This study investigated the preparatory control of motor inhibition and motor execution using a stop signal task (SST) and functional magnetic resonance imaging (fMRI). In the SST, a frequent “go” signal triggered a prepotent response and a less frequent “stop” signal prompted the inhibition of this response. Preparatory control of motor inhibition and execution in the stop signal trials were examined by contrasting brain activation between stop success and stop error trials during the fore‐period, in which participants prepared to respond to go or to stop. Results from 91 healthy adults showed greater activation in the right prefrontal cortex and inferior parietal lobule during preparatory motor inhibition. Preparatory motor execution activated bilateral putamen, primary motor cortices, posterior cingulate cortex, ventromedial prefrontal cortex, and superior temporal/intraparietal sulci. Furthermore, the extents of these inhibition and execution activities were inversely correlated across subjects. On the basis of a median split of the stop signal reaction time (SSRT), subjects with short SSRT showed greater activity in the right orbital frontal cortex during preparatory inhibition. These new findings suggest that the go and stop processes interact prior to target presentation in the SST, in accord with recent computational models of stop signal inhibition. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

How does the brain mediate interpretation of incongruent auditory emotions? The neural response to prosody in the presence of conflicting lexico‐semantic cues

We frequently encounter conflicting emotion cues. This study examined how the neural response to emotional prosody differed in the presence of congruent and incongruent lexico-semantic cues. Two hypotheses were assessed: (i) decoding emotional prosody with conflicting lexico-semantic cues would activate brain regions associated with cognitive conflict (anterior cingulate and dorsolateral prefrontal cortex) or (ii) the increased attentional load of incongruent cues would modulate the activity of regions that decode emotional prosody (right lateral temporal cortex). While the participants indicated the emotion conveyed by prosody, functional magnetic resonance imaging data were acquired on a 3T scanner using blood oxygenation level-dependent contrast. Using SPM5, the response to congruent cues was contrasted with that to emotional prosody alone, as was the response to incongruent lexico-semantic cues (for the 'cognitive conflict' hypothesis). The right lateral temporal lobe region of interest analyses examined modulation of activity in this brain region between these two contrasts (for the 'prosody cortex' hypothesis). Dorsolateral prefrontal and anterior cingulate cortex activity was not observed, and neither was attentional modulation of activity in right lateral temporal cortex activity. However, decoding emotional prosody with incongruent lexico-semantic cues was strongly associated with left inferior frontal gyrus activity. This specialist form of conflict is therefore not processed by the brain using the same neural resources as non-affective cognitive conflict and neither can it be handled by associated sensory cortex alone. The recruitment of inferior frontal cortex may indicate increased semantic processing demands but other contributory functions of this region should be explored.     

Brain activity during expectancy of emotional stimuli: an fMRI study

We studied the neural activation associated with the expectancy of emotional stimuli using whole brain fMRI. Fifteen healthy subjects underwent fMRI scanning during which they performed a warned reaction task using emotional pictures carrying pleasant, unpleasant, or neutral content. The task involved an expected or unexpected condition. Data were analyzed by comparing the images acquired under the different conditions. In the expected condition, compared with the unexpected condition, significant activation was observed in the medial, inferior and dorsolateral prefrontal cortex. Whereas the expectancy of pleasant stimuli produced activation in the left dorsolateral and left medial prefrontal cortex as well as in the right cerebellum, the expectancy of unpleasant stimuli produced activation in the right inferior and right medial prefrontal cortex, the right amygdala, the left anterior cingulate cortex, and bilaterally in the visual cortex. These results suggest that the expectancy of emotional stimuli is mediated by the prefrontal area including the medial, inferior, and dorsolateral prefrontal cortex. Furthermore, our data suggest that left frontal activation is associated with the expectancy of pleasant stimuli and that right frontal activation is associated with the expectancy of unpleasant stimuli. Finally, our findings suggest that the amygdala and anterior cingulate cortex may play an important role in the expectancy of unpleasant stimuli and that the input of this negative information is modulated by these specific brain areas.     

STN stimulation alters pallidal-frontal coupling during response selection under competition.

To investigate the effects of bilateral subthalamic nucleus (STN) stimulation on patterns of brain activation during random number generation (RNG), a task that requires suppression of habitual counting and response selection under competition. We used H(2)(15)O positron emission tomography to investigate the changes of regional cerebral blood flow (rCBF) induced by bilateral STN stimulation during a RNG task, in six patients with Parkinson's disease. Paced RNG at 1 Hz was compared with a control counting task. Both tasks were performed off medication with deep brain stimulation on and off. Subthalamic nucleus stimulation had a negative effect on performance of fast-paced RNG, leading to reduced randomness and increased habitual counting. Subthalamic nucleus stimulation also induced a reduction of rCBF in the left dorsal frontal gyrus, inferior frontal gyrus, dorsolateral prefrontal cortex, posterior and right anterior cingulate, and an increase of rCBF in the right internal globus pallidum (GPi) during RNG. Stimulation of the STN significantly altered pallidal coupling with frontal and temporal areas compared with when the stimulators were off. In conclusion, during RNG: (i) STN stimulation activates its output neurons to the GPi; (ii) STN stimulation induces increased inhibition of a prefrontal-cingulate network. This is the first direct evidence that STN stimulation significantly alters pallidal coupling with prefrontal, cingulate, and temporal cortices during performance of a task that requires response selection under competition.     

Color Stroop and negative priming in schizophrenia: An fMRI study

Disturbances in selective attention represent a core characteristic of schizophrenia, whose neural underpinnings have yet to be fully elucidated. Consequently, we recorded brain activation using functional magnetic resonance imaging (fMRI) while 15 patients with schizophrenia and 15 age-matched controls performed a well-established measure of selective attention—the color Stroop negative priming task. We focused on two aspects of performance: overriding pre-potent responses (Stroop effect) and inhibition of prior negatively primed trials (negative priming effect). Behaviorally, controls demonstrated both significant Stroop and negative priming effects, while schizophrenic subjects only showed the Stroop effect. For the Stroop effect, fMRI indicated significantly greater activation in frontal regions–medial frontal gyrus/anterior cingulate gyrus and middle frontal gyrus for controls–but greater activation in medial parietal regions (posterior cingulate gyrus/precuneus) for patients. Negative priming elicited significant activation in right dorsolateral prefrontal cortex for both groups, but also in left dorsolateral prefrontal cortex for patients. These different patterns of fMRI activation may reflect faulty interaction in schizophrenia within networks of brain regions that are vital to selective attention.     

偏头痛与静息态脑功能连接研究

目的本文研究采用静息态功能磁共振成像(rfMRI)技术描述偏头痛患者静息态脑功能连接改变,为探索偏头痛的发病机制提供影像学资料。方法收集16例偏头痛患者与16例健康对照,采集rfMRI成像,计算低频振幅,找出感兴趣区做功能连接进行统计分析。结果偏头痛患者左侧岛叶、左侧额下回低频振幅显著低于对照组,右侧视觉皮质低频振幅显著高于对照组;以左侧额下回、右侧枕中回为感兴趣区,发现左侧额下回与脑干之间的功能连接增强,与双侧枕叶之间的功能连接减弱;右侧枕中回与双侧楔前叶延伸至扣带回中部区域之间的功能连接增强,与双侧中央前回、双侧缘上回、双侧颞上回及双侧额下回之间的功能连接减弱。结论偏头痛患者无头痛发作时神经元活动强度改变,大脑功能连接异常,这导致大脑整合信息过程改变,并与偏头痛发病相关。     

Cerebral blood flow in the ventromedial prefrontal cortex correlates with treatment response to low-frequency right prefrontal repetitive transcranial magnetic stimulation in the treatment of depression

Aims: Low‐frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) is effective in treating depression, and its antidepressant effects have proven to correlate with decreases in cerebral blood flow (CBF) in the orbitofrontal cortex and subgenual cingulate cortex. However, a predictor of treatment response to low‐frequency right prefrontal rTMS in depression has not been identified yet. The aim of this study was to estimate regional CBF in the frontal regions and investigate the correlation with treatment response to low‐frequency right prefrontal rTMS in depression. Methods: We examined 26 depressed patients for the correlation between treatment response to rTMS and regional CBF in the frontal regions, by analyzing their brain scans with ^99mTc‐ethyl cysteinate dimer before rTMS treatment. CBF in 16 brain regions was estimated using fully automated region of interest analysis software. Two principal components were extracted from CBF in 16 brain regions by factor analysis with maximum likelihood method and Promax rotation with Kaiser normalization. Results: Sixteen brain regions were divided into two groups: dorsolateral prefrontal cortex (superior frontal, medial frontal, middle frontal, and inferior frontal regions) and ventromedial prefrontal cortex (anterior cingulate, subcallosal, orbital, and rectal regions). Treatment response to rTMS was not correlated with CBF in the dorsolateral prefrontal cortex, but it was correlated with CBF in the ventromedial prefrontal cortex. Conclusion: These findings suggest that CBF in the ventromedial prefrontal cortex may be a potential predictor of low‐frequency right prefrontal rTMS, and depressed patients with increased CBF in the ventromedial prefrontal cortex may show a better response.     

Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder: fMRI outcomes

The aim of this research was to determine the relative effects of risperidone and divalproex on brain function in pediatric mania. This is a double-blind 6-week functional magnetic resonance imaging trial with 24 unmedicated manic patients randomized to risperidone or divalproex, and 14 healthy controls (HCs) matched for IQ and demographic factors (mean age: 13.1 ± 3.3 years). A pediatric affective color matching task, in which subjects matched the color of a positive, negative or neutral word with one of two colored circles, was administered. The primary clinical measure was the Young Mania Rating Scale (YMRS). The risperidone group, relative to HC, showed an increase in activation from pre- to post-treatment in right pregenual and subgenual anterior cingulate cortex and decreased activation in bilateral middle frontal gyrus during the negative condition; and decreased activation in left inferior and medial, and right middle frontal gyri, left inferior parietal lobe, and right striatum with positive condition. In the divalproex group, relative to HC, there was an increased activation in right superior temporal gyrus in the negative condition; and in left medial frontal gyrus and right precuneus with the positive condition. Greater pre-treatment right amygdala activity with negative and positive condition in the risperidone group, and left amygdala activity with positive condition in divalproex group, predicted poor response on YMRS. Risperidone and divalproex yield differential patterns of prefrontal activity during an emotion processing task in pediatric mania. Increased amygdala activity at baseline is a potential biomarker predicting poor treatment response to both the risperidone and divalproex.