Levels of word processing and incidental memory: dissociable mechanisms in the temporal lobe.

Word recall is facilitated when deep (e.g. semantic) processing is applied during encoding. This fact raises the question of the existence of specific brain mechanisms supporting different levels of information processing that can modulate incidental memory performance. In this study we obtained spatiotemporal brain activation profiles, using magnetic source imaging, from 10 adult volunteers as they performed a shallow (phonological) processing task and a deep (semantic) processing task. When phonological analysis of the word stimuli into their constituent phonemes was required, activation was largely restricted to the posterior portion of the left superior temporal gyrus (area 22). Conversely, when access to lexical/semantic representations was required, activation was found predominantly in the left middle temporal gyrus and medial temporal cortex. The differential engagement of each mechanism during word encoding was associated with dramatic changes in subsequent incidental memory performance.     

Matching is not naming: A direct comparison of lexical manipulations in explicit and implicit reading tasks

The neurobiological basis of reading is of considerable interest, yet analyzing data from subjects reading words aloud during functional MRI data collection can be difficult. Therefore, many investigators use surrogate tasks such as visual matching or rhyme matching to eliminate the need for spoken output. Use of these tasks has been justified by the presumption of “automatic activation” of reading‐related neural processing when a word is viewed. We have tested the efficacy of using a nonreading task for studying “reading effects” by directly comparing blood oxygen level dependent (BOLD) activity in subjects performing a visual matching task and an item naming task on words, pseudowords (meaningless but legal letter combinations), and nonwords (meaningless and illegal letter combinations). When compared directly, there is significantly more activity during the naming task in “reading‐related” regions such as the inferior frontal gyrus (IFG) and supramarginal gyrus. More importantly, there are differing effects of lexicality in the tasks. A whole‐brain task (matching vs. naming) by string type (word vs. pseudoword vs. nonword) by BOLD timecourse analysis identifies regions showing this three‐way interaction, including the left IFG and left angular gyrus (AG). In the majority of the identified regions (including the left IFG and left AG), there is a string type × timecourse interaction in the naming but not the matching task. These results argue that the processing performed in specific regions is contingent on task, even in reading‐related regions and is thus nonautomatic. Such differences should be taken into consideration when designing studies intended to investigate reading. Hum Brain Mapp 34:2425–2438, 2013. © 2012 Wiley Periodicals, Inc.     

Characterising comprehension difficulties after right brain damage: Attentional demands of suppression function

Background: Comprehension deficits that typify adults with right brain damage (RBD) have been linked to considerations of processing capacity and processing demands, as well as to ineffective suppression of mental activation that is incompatible with a contextually intended interpretation. Aims: As a first step in investigating how processing resource factors and more specific difficulties like suppression deficits interact to yield characteristic RBD comprehension patterns, the current study was designed to assess whether suppression function consumes attention. Methods & Procedures: A total of 28 RBD and 22 non-brain-damaged adults listened to sentence stimuli that biased the meaning of a sentence-final lexical ambiguity (e.g., “spade”). The suppression task involved speeded judgements of whether a subsequent spoken probe word fitted the overall sentence meaning. In experimental stimuli, the probe word (e.g., “cards”) was unrelated to the biased meaning of the ambiguity. Comparison stimuli ended in an unambiguous word (e.g., “shovel”) that was clearly unrelated to the spoken probe. Thus, slowness after an experimental sentence, relative to its comparison sentence, indicated that the contextually inappropriate meaning of the experimental ambiguity interfered with the probesentence relatedness judgement (i.e., had not been suppressed). In two dual-task conditions, participants allocated 20% or 50% of their “brain power” to a concurrent secondary task, reporting orally whether the probe word consisted of one or two syllables. Outcomes & Results: For both groups, suppression of contextually unintended meanings of lexical ambiguities was more effective in a single-task condition than when attention was shared with a secondary task. The secondary syllable-counting task also suffered when allocated less attention. Conclusions: Effective suppression consumes finite processing capacity. As elaborated in the paper, several combinations of these variables could underlie relatively good and poor comprehension after RBD. Researchers and clinicians need to keep in mind such potential interactions of ineffective comprehension mechanisms, stimulus/task processing demands, and processing capacity.     

Cortical dynamics of word recognition

While functional neuroimaging studies have helped elucidate major regions implicated in word recognition, much less is known about the dynamics of the associated activations or the actual neural processes of their functional network. We used intracerebral electroencephalography recordings in 10 patients with epilepsy to directly measure neural activity in the temporal and frontal lobes during written words' recognition, predominantly in the left hemisphere. The patients were presented visually with consonant strings, pseudo-words, and words and performed a hierarchical paradigm contrasting semantic processes (living vs. nonliving word categorization task), phonological processes (rhyme decision task on pseudo-words), and visual processes (visual analysis of consonant strings). Stimuli triggered a cascade of modulations in the gamma-band (>40 Hz) with reproducible timing and task-sensitivity throughout the functional reading network: the earliest gamma-band activations were observed for all stimuli in the mesial basal temporal lobe at 150 ms, reaching the word form area in the mid fusiform gyrus at 200 ms, evidencing a superiority effect for word-like stimuli. Peaks of gamma-band activations were then observed for word-like stimuli after 400 ms in the anterior and middle portion of the superior temporal gyrus (BA 38 and BA 22 respectively), in the pars triangularis of Broca's area for the semantic task (BAs 45 and 47), and in the pars opercularis for the phonological task (BA 44). Concurrently, we observed a two-pronged effect in the prefrontal cortex (BAs 9 and 46), with nonspecific sustained dorsal activation related to sustained attention and, more ventrally, a strong reflex deactivation around 500 ms, possibly due to semantic working memory reset.     

An fMRI Study of the Neural Correlates of Incidental Versus Directed Emotion Processing in Pediatric Bipolar Disorder

ObjectiveTo use functional neuroimaging to probe the affective circuitry dysfunctions underlying disturbances in emotion processing and emotional reactivity in pediatric bipolar disorder (PBD).MethodEqual numbers of controls (HC) and unmedicated patients with euthymia and PBD were matched for age, sex, race, socioeconomic status, and IQ (n = 10 per group; mean age 14.2 years [SD 2.0 years]). The task consisted of a “directed” emotion processing condition where subjects judged whether emotion in facial expression was positive or negative and an “incidental” condition where subjects judged whether faces expressing similar affect were older or younger than 35 years.ResultsRelative to the directed condition, the incidental condition elicited greater activation in the right amygdala and the right insula, the left middle frontal gyrus, and the left posterior cingulate cortex in patients with PBD, in contrast to the HC that showed greater activation in the right superior frontal gyrus. In both incidental and directed conditions, relative to visual fixation, patients with PBD showed less activation in the right prefrontal cortex (superior, middle, and inferior frontal gyri) and the pregenual anterior cingulate cortex and greater activation in the posterior visual and face-processing regions (i.e., right precuneus/cuneus, fusiform gyrus).ConclusionsIncreased amygdala activation observed in patients with PBD elicited by incidental emotional processing relative to directed emotional processing may indicate more intense automatic emotional reactivity. Furthermore, the right prefrontal systems that are believed to modulate affect seem to be less engaged in patients with PBD regardless of whether the emotion processing is incidental or directed, which may signify reduced top-down control of emotional reactivity in PBD.     

The visual word form area: a prelexical representation of visual words in the fusiform gyrus

Event-related fMRI was used to test the hypothesis that the visual word form area in the left fusiform gyrus holds a modality-specific and prelexical representation of visual words. Subjects were engaged in a repetition-detection task on pairs of words or pronounceable pseudo-words that could be written or spoken. The visual word form area responded only to written stimuli, not to spoken stimuli, independently of their semantic content. We propose that the occasional activation of the fusiform gyrus when listening to spoken words is due to the topdown recruitment of visual orthographic or object representations.     

The effect of word imagery on priming effect under a preconscious condition: An fMRI study

Semantic priming is affected by the degree of association and how readily a word is imagined. In the association effect, activity in the perisylvian structures including the bilateral inferior frontal gyrus, the left middle temporal gyrus, and the supramarginal gyrus was correlated. However, little is known about the brain regions related to the effect of imagery word under the preconscious condition. Forty word pairs for high (HA)‐, low (LA)‐, and nonassociation (NA), nonword (NW) conditions were presented. Each 40 association word pairs (HA and LA) included 20 high (HI) and 20 low (LI) imagery prime stimuli, using a visually presented lexical decision task. A trial consisted of 30 ms prime, 30 ms mask, 500 ms probe, and 2–8 s stimulus onset asynchrony. Brain activation was measured using functional magnetic resonance imaging during word discrimination. Behavioral data indicated that the shortest response time (RT) was given for HA words, followed by LA and NA, and NW showed the longest RT (P < 0.01). RT was faster in HI than LI within HA, but not LA conditions (P < 0.01). Functional neuroimaging showed that differential brain regions for high imagery (HI) and low imagery (LI) words within low prime‐target word association were observed in the left precuneus, left posterior cingulate gyrus, and right cuneal cortex. The present findings demonstrate that the effect of the degree of imagery on semantic priming occurs during the early stage of language processing, indicating an “automatic imagery priming effect.” Our paradigm may be useful to explore semantic deficit related to imagery in various psychiatric disorders. Hum Brain Mapp 35:4795–4804, 2014. © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.     

Temporal lobe abnormalities in semantic processing by criminal psychopaths as revealed by functional magnetic resonance imaging

We tested the hypothesis that psychopathy is associated with abnormalities in semantic processing of linguistic information. Functional magnetic resonance imaging (fMRI) was used to elucidate and characterize the neural architecture underlying lexico-semantic processes in criminal psychopathic individuals and in a group of matched control participants. Participants performed a lexical decision task in which blocks of linguistic stimuli alternated with a resting baseline condition. In each lexical decision block, the stimuli were either concrete words and pseudowords or abstract words and pseudowords. Consistent with our hypothesis, psychopathic individuals, relative to controls, showed poorer behavioral performance for processing abstract words. Analysis of the fMRI data for both groups indicated that processing of word stimuli, compared with the resting baseline condition, was associated with neural activation in bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. Analyses confirmed our prediction that psychopathic individuals would fail to show the appropriate neural differentiation between abstract and concrete stimuli in the right anterior temporal gyrus and surrounding cortex. The results are consistent with other studies of semantic processing in psychopathy and support the theory that psychopathy is associated with right hemisphere abnormalities for processing conceptually abstract material.     

Q:] When would you prefer a SOSSAGE to a SAUSAGE? [A:] At about 100 msec. ERP correlates of orthographic typicality and lexicality in written word recognition

Using a speeded lexical decision task, event-related potentials (ERPs), and minimum norm current source estimates, we investigated early spatiotemporal aspects of cortical activation elicited by words and pseudo-words that varied in their orthographic typicality, that is, in the frequency of their component letter pairs (bi-grams) and triplets (tri-grams). At around 100 msec after stimulus onset, the ERP pattern revealed a significant typicality effect, where words and pseudo-words with atypical orthography (e.g., yacht, cacht) elicited stronger brain activation than items characterized by typical spelling patterns (cart, yart). At approximately 200 msec, the ERP pattern revealed a significant lexicality effect, with pseudo-words eliciting stronger brain activity than words. The two main factors interacted significantly at around 160 msec, where words showed a typicality effect but pseudo-words did not. The principal cortical sources of the effects of both typicality and lexicality were localized in the inferior temporal cortex. Around 160 msec, atypical words elicited the stronger source currents in the left anterior inferior temporal cortex, whereas the left perisylvian cortex was the site of greater activation to typical words. Our data support distinct but interactive processing stages in word recognition, with surface features of the stimulus being processed before the word as a meaningful lexical entry. The interaction of typicality and lexicality can be explained by integration of information from the early form-based system and lexicosemantic processes.     

Temporal lobe abnormalities in semantic processing by criminal psychopaths as revealed by functional magnetic resonance imaging

We tested the hypothesis that psychopathy is associated with abnormalities in semantic processing of linguistic information. Functional magnetic resonance imaging (fMRI) was used to elucidate and characterize the neural architecture underlying lexico-semantic processes in criminal psychopathic individuals and in a group of matched control participants. Participants performed a lexical decision task in which blocks of linguistic stimuli alternated with a resting baseline condition. In each lexical decision block, the stimuli were either concrete words and pseudowords or abstract words and pseudowords. Consistent with our hypothesis, psychopathic individuals, relative to controls, showed poorer behavioral performance for processing abstract words. Analysis of the fMRI data for both groups indicated that processing of word stimuli, compared with the resting baseline condition, was associated with neural activation in bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. Analyses confirmed our prediction that psychopathic individuals would fail to show the appropriate neural differentiation between abstract and concrete stimuli in the right anterior temporal gyrus and surrounding cortex. The results are consistent with other studies of semantic processing in psychopathy and support the theory that psychopathy is associated with right hemisphere abnormalities for processing conceptually abstract material.     

Neural correlates of semantic and morphological processing of Hebrew nouns and verbs

Neuropsychological evidence regarding grammatical category suggests that deficits affecting verbs tend to localize differently from those affecting nouns, but previous functional imaging studies on healthy subjects fail to show consistent results that correspond to the clinical dissociation. In the current imaging study, we addressed this issue by manipulating not only the grammatical category but also the processing mode, using auditory presentation of Hebrew words. Subjects were presented with verbs and nouns and were instructed to make either a semantic decision (“Does the word belong to a given semantic category?”) or a morphological decision (“Is the word inflected in plural?”). The results showed different patterns of activation across distinct regions of interest. With respect to grammatical category effects, we found increased activation for verbs in the posterior portion of the left superior temporal sulcus, left dorsal premotor area, and posterior inferior frontal gyrus. In each of these regions, the effect was sensitive to task. None of the ROIs showed noun advantage. With respect to task effects, we found a semantic advantage in left anterior inferior frontal gyrus, as well as in left posterior middle temporal gyrus. The results suggest that cerebral verb‐noun dissociation is a result of localized and subtle processes that take place in a set of left frontal and temporal regions, and that the cognitive and neural processes involved in analyzing grammatical category depend on the lexical characteristics of the stimuli, as well as on task requirements. The discrepancy between functional imaging and patient data is also discussed. Hum. Brain Mapp, 2007. © 2006 Wiley‐Liss, Inc.     

The left fusiform area is affected by written frequency of words

The recent neuroimaging literature gives conflicting evidence about whether the left fusiform gyrus (FG) might recognize words as unitary visual objects. The sensitivity of the left FG to word frequency might provide a neural basis for the orthographic input lexicon theorized by reading models [Patterson, K., Marshall, J. C., & Coltheart, M. (1985). Surface dyslexia: Cognitive and neuropsychological studies of phonological reading. London: Lawrence Erlbaum]. The goal of this study was to investigate the time course and neural correlates of word processing in right-handed readers engaged in an orthographic decision task. Three hundred and twenty Italian words of high and low written frequency and 320 non-derived legal pseudo-words were presented for 250ms in the central visual field. ERPs were recorded from 128 scalp sites in 10 Italian University students. Behavioural data showed a word superiority effect, with faster RTs to words than pseudo-words. Left occipito/temporal N2 (240ms) was greater to high-frequency than low-frequency words and pseudo-words. According to the swLORETA inverse solution, the underlying neural source of this effect was located in the left fusiform gyrus of the occipital lobe (X=-29, Y=-66, Z=-10, BA19) and the right superior temporal gyrus (X=51, Y=6, Z=-5, BA22), which are probably involved in word recognition and semantic representation, respectively. Later frontal ERP components, LPN (300-350) and P3 (400-500), also showed strong lexical sensitivity, thus suggesting implicit semantic processes. The results shed some light on the possible neural substrate of visual reading disabilities such as developmental surface dyslexia or pure alexia.     

Dynamic and strategic aspects of executive processing

Executive cognitive functions have been postulated to include both dynamic behavioral selection and strategic goal-setting or response preparation. To investigate the relation between these aspects of executive processing, we embedded an event-related oddball paradigm within a blocked design. Subjects responded to infrequent targets presented within a series of standard stimuli that required no response; this task alternated with a visually similar nontask condition. Using functional magnetic resonance imaging (fMRI), we found that a set of brain regions including dorsolateral prefrontal cortex (dlPFC), insular cortex, cingular cortex, and the basal ganglia demonstrated transient activation both to target stimuli and to the onset of task blocks. Within the parietal cortex, there was a dissociation such that the supramarginal gyrus exhibited greater activity to the target stimuli than to block onsets, while the converse pattern was observed in the intraparietal sulcus. Sustained positive activity during task blocks was present in the caudate and supplementary motor area, while sustained negative activity was present in the precuneus and medial parietal cortex. We conclude that dlPFC and related brain regions mediate both dynamic and strategic processing, through the preparation and selection of rules for behavior.     

抑郁症患者脑功能偏侧化的分听研究

目的 探讨抑郁症患者大脑半球机能不对称的特点,以及抗抑郁药治疗后半球机能不对称性的变化。方法 用集中注意法及两种押韵词,对115例抑郁症患者进行耳优势测试,其中34例在服药6周后再次测定;并与58例健康者进行对照分析。结果 健康组真词测听未见耳优势而假词测听则呈现右耳(左半球)优势;抑郁症组真词测听未见耳优势而假词测听呈增强的右耳(左半球)优势;服药前后抑郁症患者的大脑半球机能不对称性无变化。结论 抑郁症组对汉字词的加工与认知,表现出较健康组强的右耳(左半球)优势;患者的言语偏侧化指数与症状严重程度无相关性;假词为较为理想的分听材料。     

Neural pathways involved in the processing of concrete and abstract words.

The purpose of this study was to delineate the neural pathways involved in processing concrete and abstract words using functional magnetic resonance imaging (fMRI). Word and pseudoword stimuli were presented visually, one at a time, and the participant was required to make a lexical decision. Lexical decision epochs alternated with a resting baseline. In each lexical decision epoch, the stimuli were either concrete words and pseudowords, or abstract words and pseudowords. Behavioral data indicated that, as with previous research, concrete word stimuli were processed more efficiently than abstract word stimuli. Analysis of the fMRI data indicated that processing of word stimuli, compared to the baseline condition, was associated with neural activation in the bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. A direct comparison between the abstract and concrete stimuli epochs yielded a significant area of activation in the right anterior temporal cortex. The results are consistent with recent positron emission tomography work showing right hemisphere activation during processing of abstract representations of language. The results are interpreted as support for a right hemisphere neural pathway in the processing of abstract word representations.     

Altered brain activity during emotional empathy in somatoform disorder

Somatoform disorder patients suffer from impaired emotion recognition and other emotional deficits. Emotional empathy refers to the understanding and sharing of emotions of others in social contexts. It is likely that the emotional deficits of somatoform disorder patients are linked to disturbed empathic abilities; however, little is known so far about empathic deficits of somatoform patients and the underlying neural mechanisms. We used fMRI and an empathy paradigm to investigate 20 somatoform disorder patients and 20 healthy controls. The empathy paradigm contained facial pictures expressing anger, joy, disgust, and a neutral emotional state; a control condition contained unrecognizable stimuli. In addition, questionnaires testing for somatization, alexithymia, depression, empathy, and emotion recognition were applied. Behavioral results confirmed impaired emotion recognition in somatoform disorder and indicated a rather distinct pattern of empathic deficits of somatoform patients with specific difficulties in “empathic distress.” In addition, somatoform patients revealed brain areas with diminished activity in the contrasts “all emotions”–“control,” “anger”–“control,” and “joy”–“control,” whereas we did not find brain areas with altered activity in the contrasts “disgust”–“control” and “neutral”–“control.” Significant clusters with less activity in somatoform patients included the bilateral parahippocampal gyrus, the left amygdala, the left postcentral gyrus, the left superior temporal gyrus, the left posterior insula, and the bilateral cerebellum. These findings indicate that disturbed emotional empathy of somatoform disorder patients is linked to impaired emotion recognition and abnormal activity of brain regions responsible for emotional evaluation, emotional memory, and emotion generation. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Word and picture matching: a PET study of semantic category effects

We report two positron emission tomography (PET) studies of cerebral activation during picture and word matching tasks, in which we compared directly the processing of stimuli belonging to different semantic categories (animate and inanimate) in the visual (pictures) and verbal (words) modality. In the first experiment, brain activation was measured in eleven healthy adults during a same/different matching task for textures, meaningless shapes and pictures of animals and artefacts (tools). Activations for meaningless shapes when compared to visual texture discrimination were localized in the left occipital and inferior temporal cortex. Animal picture identification, either in the comparison with meaningless shapes and in the direct comparison with non-living pictures, involved primarily activation of occipital regions, namely the lingual gyrus bilaterally and the left fusiform gyrus. For artefact picture identification, in the same comparison with meaningless shape-baseline and in the direct comparison with living pictures, all activations were left hemispheric, through the dorsolateral frontal (Ba 44/6 and 45) and temporal (Ba 21, 20) cortex. In the second experiment, brain activation was measured in eight healthy adults during a same/different matching task for visually presented words referring to animals and manipulable objects (tools); the baseline was a pseudoword discrimination task. When compared with the tool condition, the animal condition activated posterior left hemispheric areas, namely the fusiform (Ba 37) and the inferior occipital gyrus (Ba 18). The right superior parietal lobule (Ba 7) and the left thalamus were also activated. The reverse comparison (tools vs animals) showed left hemispheric activations in the middle temporal gyrus (Ba 21) and precuneus (Ba 7), as well as bilateral activation in the occipital regions. These results are compatible with different brain networks subserving the identification of living and non-living entities; in particular, they indicate a crucial role of the left fusiform gyrus in the processing of animate entities and of the left middle temporal gyrus for tools, both from words and pictures. The activation of other areas, such as the dorsolateral frontal cortex, appears to be specific for the semantic access of tools only from pictures.     

Cognitive processing in Chinese literate and illiterate subjects: an fMRI study

Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) were used to map brain activation during language tasks. While previous studies have compared performance between alphabetic literate and illiterate subjects, there have been no such data in Chinese-speaking individuals. In this study, we used fMRI to examine the effects of education on neural activation associated with silent word recognition and silent picture-naming tasks in 24 healthy right-handed Chinese subjects (12 illiterates and 12 literates). There were 30 single Chinese characters in the silent word recognition task and 30 meaningful road-signs in the silent picture-naming task. When we compared literate and illiterate subjects, we observed education-related differences in activation patterns in the left inferior/middle frontal gyrus and both sides of the superior temporal gyrus for the silent word recognition task and in the bilateral inferior/middle frontal gyrus and left limbic cingulated gyrus for the silent picture-naming task. These results indicate that the patterns of neural activation associated with language tasks are strongly influenced by education. Education appears to have enhanced cognitive processing efficiency in language tasks.     

Processing complex pseudo-words in mild cognitive impairment: The interaction of preserved morphological rule knowledge with compromised cognitive ability

Mild cognitive impairment (MCI) affects the cognitive performance of elderly adults. However, the level of severity is not high enough to be diagnosed with dementia. Previous research reports subtle language impairments in individuals with MCI specifically in domains related to lexical meaning. The present study used both off-line (grammaticality judgment) and on-line (lexical decision) tasks to examine aspects of lexical processing and how they are affected by MCI. 21 healthy older adults and 23 individuals with MCI saw complex pseudo-words that violated various principles of word formation in Slovenian and decided if each letter string was an actual word of their language. The pseudo-words ranged in their degree of violability. A task effect was found, with MCI performance to be similar to that of healthy controls in the off-line task but different in the on-line task. Overall, the MCI group responded slower than the elderly controls. No significant differences were observed in the off-line task, while the on-line task revealed a main effect of Violation type, a main effect of Group and a significant Violation × Group interaction reflecting a difficulty for the MCI group to process pseudo-words in real time. That is, while individuals with MCI seem to preserve morphological rule knowledge, they experience additional difficulties while processing complex pseudo-words. This was attributed to an executive dysfunction associated with MCI that delays the recognition of ungrammatical formations.     

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.