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Little is known about the neural reorganization that takes place subsequent to lesions that affect orthographic processing (reading and/or spelling). We report on an fMRI investigation of an individual with a left mid-fusiform resection that affected both reading and spelling (Tsapkini & Rapp, 2010). To investigate possible patterns of functional reorganization, we compared the behavioral and neural activation patterns of this individual with those of a group of control participants for the tasks of silent reading of words and pseudowords and the passive viewing of faces and objects, all tasks that typically recruit the inferior temporal lobes. This comparison was carried out with methods that included a novel application of Mahalanobis distance statistics, and revealed: (1) normal behavioral and neural responses for face and object processing, (2) evidence of neural reorganization bilaterally in the posterior fusiform that supported normal performance in pseudoword reading and which contributed to word reading (3) evidence of abnormal recruitment of the bilateral anterior temporal lobes indicating compensatory (albeit insufficient) recruitment of mechanisms for circumventing the word reading deficit.

Although its precise functional contribution to reading remains unclear, there is broad consensus that activity in the left mid-fusiform gyrus is highly sensitive to written words and word-like stimuli. In the current study, we take advantage of a particularity of the Chinese writing system in order to manipulate word-likeness parametrically, from real characters, to pseudo-characters that vary in whether they contain phonological and semantic cues, to artificial stimuli with varying surface similarity to real characters. In a one-back task, BOLD activity in the left mid-fusiform was inversely related to word-likeness, such that the least activity was observed in response to real characters, and the greatest to artificial stimuli that violate the orthotactic constraints of the writing system. One possible explanation for this surprising result is that the short-term memory demands of the one-back task put more pressure on the visual system when other sources of information cannot be used to aid in detecting repeated stimuli. For real characters and, to a lesser extent for pseudo-characters, information about meaning and pronunciation can contribute to performance, whereas artificial stimuli are entirely dependent on visual information. Consistent with this view, functional connectivity analyses revealed a strong positive relationship between left mid-fusiform and other visual areas, whereas areas typically involved in phonological and semantic processing for text were negatively correlated with this region.

Recent evidence suggests that the Fusiform Face Area (FFA) is not exclusively dedicated to the interactive processing of face features, but also contains neurons sensitive to local features. This suggests the existence of both interactive and local processing modes, consistent with recent behavioral findings that the strength of interactive feature processing (IFP) engages most strongly when similar features need to be disambiguated. Here we address whether the engagement of the FFA into interactive versus featural representational modes is governed by local feature discriminability. We scanned human participants while they matched target features within face pairs, independently of the context of distracter features. IFP was operationalized as the failure to match the target without being distracted by distracter features. Picture-plane inversion was used to disrupt IFP while preserving input properties. We found that FFA activation was comparably strong, irrespective of whether similar target features were embedded in dissimilar contexts(i.e., inducing robust IFP) or dissimilar target features were embedded in the same context (i.e., engaging local processing). Second, inversion decreased FFA activation to faces most robustly when similar target features were embedded in dissimilar contexts, indicating that FFA engages into IFP mainly when features cannot be disambiguated at a local level. Third, by means of Spearman rank correlation tests, we show that the local processing of feature differences in the FFA is supported to a large extent by the Occipital Face Area, the Lateral Occipital Complex, and early visual cortex, suggesting that these regions encode the local aspects of face information. The present findings confirm the co-existence of holistic and featural representations in the FFA. Furthermore, they establish FFA as the main contributor to the featural/holistic representational mode switches determined by local discriminability.

Objective

To assess the dynamic activations of the key brain areas associated with the time-course of the sexual arousal evoked by visual sexual stimuli in healthy male subjects.

Materials and Methods

Fourteen right-handed heterosexual male volunteers participated in this study. Alternatively combined rest period and erotic video visual stimulation were used according to the standard block design. In order to illustrate and quantify the spatiotemporal activation patterns of the key brain regions, the activation period was divided into three different stages as the EARLY, MID and LATE stages.

Results

For the group result (p < 0.05), when comparing the MID stage with the EARLY stage, a significant increase of the brain activation was observed in the areas that included the inferior frontal gyrus, the supplementary motor area, the hippocampus, the head of the caudate nucleus, the midbrain, the superior occipital gyrus and the fusiform gyrus. At the same time, when comparing the EARLY stage with the MID stage, the putamen, the globus pallidus, the pons, the thalamus, the hypothalamus, the lingual gyrus and the cuneus yielded significantly increased activations. When comparing the LATE stage with the MID stage, all the above mentioned brain regions showed elevated activations except the hippocampus.

Conclusion

Our results illustrate the spatiotemporal activation patterns of the key brain regions across the three stages of visual sexual arousal.

We report the results of an fMRI investigation of the neural bases of written language comprehension (reading) and production (spelling). Both tasks were examined in the same individuals, allowing greater precision in establishing the relationship between the neural underpinnings of these two cognitive functions. Also examined was the relationship between written language substrates and those involved in face and object (house) processing. The results reveal that reading and spelling share specific left hemisphere substrates in the mid-fusiform gyrus and in the inferior frontal gyrus/junction. Furthermore, the results indicate that the left mid-fusiform substrates are specifically involved in lexical orthographic processing. We also find that written language and face processing exhibit largely complementary activation patterns in both the fusiform and the inferior frontal/junction areas, with left and right lateralization, respectively. In sum, these results provide perhaps the strongest evidence to date of components that are shared by written language comprehension (reading) and production (spelling), and they further our understanding of the role of literacy within the larger repertoire of cognitive operations and their neural substrates.

The present study investigated whether emotionally expressive faces guide attention and modulate fMRI activity in fusiform gyrus in acquired prosopagnosia. Patient PS, a pure case of acquired prosopagnosia with intact right middle fusiform gyrus, performed two behavioral experiments and a functional imaging experiment to address these questions. In a visual search task involving face stimuli, PS was faster to select the target face when it was expressing fear or happiness as compared to when it was emotionally neutral. In a change detection task, PS detected significantly more changes when the changed face was fearful as compared to when it was neutral. Finally, an fMRI experiment showed enhanced activation to emotionally expressive faces and bodies in right fusiform gyrus. In addition, PS showed normal body-selective activation in right fusiform gyrus, partially overlapping the fusiform face area. Together these behavioral and neuroimaging results show that attention was preferentially allocated to emotional faces in patient PS, as observed in healthy subjects. We conclude that systems involved in the emotional guidance of attention by facial expression can function normally in acquired prosopagnosia, and can thus be dissociated from systems involved in face identification.

In fingerspelling, different hand configurations are used to represent the different letters of the alphabet. Signers use this method of representing written language to fill lexical gaps in a signed language. Using fMRI, we compared cortical networks supporting the perception of fingerspelled, signed, written, and pictorial stimuli in deaf native signers of British Sign Language (BSL). In order to examine the effects of linguistic knowledge, hearing participants who knew neither fingerspelling nor a signed language were also tested. All input forms activated a left fronto-temporal network, including portions of left inferior temporal and mid-fusiform gyri, in both groups. To examine the extent to which activation in this region was influenced by orthographic structure, two contrasts of orthographic and non-orthographic stimuli were made: one using static stimuli (text vs. pictures), the other using dynamic stimuli (fingerspelling vs. signed language). Greater activation in left and right inferior temporal and mid-fusiform gyri was found for pictures than text in both deaf and hearing groups. In the fingerspelling vs. signed language contrast, a significant interaction indicated locations within the left and right mid-fusiform gyri. This showed greater activation for fingerspelling than signed language in deaf but not hearing participants. These results are discussed in light of recent proposals that the mid-fusiform gyrus may act as an integration region, mediating between visual input and higher-order stimulus properties.

Background

Experience can alter how objects are represented in the visual cortex. But experience can take different forms. It is unknown whether the kind of visual experience systematically alters the nature of visual cortical object representations.

Methodology/Principal Findings

We take advantage of different training regimens found to produce qualitatively different types of perceptual expertise behaviorally in order to contrast the neural changes that follow different kinds of visual experience with the same objects. Two groups of participants went through training regimens that required either subordinate-level individuation or basic-level categorization of a set of novel, artificial objects, called “Ziggerins”. fMRI activity of a region in the right fusiform gyrus increased after individuation training and was correlated with the magnitude of configural processing of the Ziggerins observed behaviorally. In contrast, categorization training caused distributed changes, with increased activity in the medial portion of the ventral occipito-temporal cortex relative to more lateral areas.

Conclusions/Significance

Our results demonstrate that the kind of experience with a category of objects can systematically influence how those objects are represented in visual cortex. The demands of prior learning experience therefore appear to be one factor determining the organization of activity patterns in visual cortex.

Previous studies have shown differential responses in the fusiform and lingual gyri during reading and suggested that the former is engaged in processing local features of visual stimuli and the latter is engaged in global shape processing. We used positron emission tomography in order to investigate how these regions are modulated by two common variables in reading: word length (three, six and nine letters) and perceptive similarity to the background (high and low contrast). Increasing both word length and visual contrast had a positive monotonic effect on activation in the bilateral fusiform. However, in the lingual gyrus, activation increased with increasing word length but decreased with increasing contrast. On the basis of previous studies, we suggest that (i) increasing word length increases the demands on both local feature and global shape processing, but (ii) increasing visual contrast increases the demands on local feature processing while decreasing the demands on global shape processing.

Controversy surrounds the proposal that specific human cortical regions in the ventral occipitotemporal cortex, commonly called the fusiform face area (FFA) and occipital face area (OFA), are specialized for face processing. Here, we present findings from an fMRI study of identity discrimination of faces and objects that demonstrates the FFA and OFA are equally responsive to processing stimuli at the level of individuals (i.e., individuation), be they human faces or non-face objects. The FFA and OFA were defined via a passive viewing task as regions that produced greater activation to faces relative to non-face stimuli within the middle fusiform gyrus and inferior occipital gyrus. In the individuation task, participants judged whether sequentially presented images of faces, diverse objects, or wristwatches depicted the identical or a different exemplar. All three stimulus types produced equivalent BOLD activation within the FFA and OFA; that is, there was no face-specific or face-preferential processing. Critically, individuation processing did not eliminate an object superiority effect relative to faces within a region more closely linked to object processing in the lateral occipital complex (LOC), suggesting that individuation processes are reasonably specific to the FFA and OFA. Taken together, these findings challenge the prevailing view that the FFA and OFA are face-specific processing regions, demonstrating instead that they function to individuate – i.e., identify specific individuals – within a category. These findings have significant implications for understanding the function of brain regions widely believed to play an important role in social cognition.

Children with autism exhibit impairment in the processing of socioemotional information. The amygdala, a core structure centrally involved in socioemotional functioning, has been implicated in the neuropathology of autism. We collected structural and functional MRI images in children 8-to-12 years of age with high functioning autism (n=12) and typical development (n=15). The fMRI experiment involved matching facial expressions and people. Volumetric analysis of the amygdala was also performed. The results showed that children with autism exhibited intact emotion matching, while showing diminished activation of the fusiform gyrus (FG) and the amygdala. Conversely, the autism group showed deficits in person matching amidst some FG and variable amygdala activation. No significant between group differences in the volume of the left or right amygdala were found. There were associations between age, social anxiety and amygdala volume in the children with autism such that smaller volumes were generally associated with more anxiety and younger age. In summary, the data are consistent with abnormalities in circuits involved in emotion and face processing reported in studies of older subjects with autism showing reductions in amygdala activation related to emotion processing and reduced fusiform activation involved in face processing.

Much of the lower urinary tract, including the bladder, is lined by a stratified urothelium forming a highly differentiated, superficial umbrella cell layer. The apical plasma membrane as well as abundant cytoplasmic fusiform vesicles of the umbrella cells is covered by two-dimensional crystals that are formed by four membrane proteins named uroplakins (UPs) Ia, Ib, II, and III. UPs are synthesized on membrane-bound polysomes, and after several co- and posttranslational modifications they assemble into planar crystals in a post-Golgi vesicular compartment. Distension of the bladder may cause fusiform vesicles to fuse with the apical plasma membrane. We have investigated the early stages of uroplakin assembly by expressing the four uroplakins in 293T cells. Transfection experiments showed that, when expressed individually, only UPIb can exit from the endoplasmic reticulum (ER) and move to the plasma membrane, whereas UPII and UPIII reach the plasma membrane only when they form heterodimeric complexes with UPIa and UPIb, respectively. Heterodimer formation in the ER was confirmed by pulse-chase experiment followed by coimmunoprecipitation. Our results indicate that the initial building blocks for the assembly of crystalline uroplakin plaques are heterodimeric uroplakin complexes that form in the ER.

A number of recent studies consistently show an area, known as the visual word form area (VWFA), in the left fusiform gyrus that is selectively responsive for visual words in alphabetic scripts as well as in logographic scripts, such as Chinese characters. However, given the large difference between Chinese characters and alphabetic scripts in terms of their orthographic rules, it is not clear at a fine spatial scale, whether Chinese characters engage the same VWFA in the occipito-temporal cortex as alphabetic scripts. We specifically compared Chinese with Korean script, with Korean script serving as a good example of alphabetic writing system, but matched to Chinese in the overall square shape. Sixteen proficient early Chinese-Korean bilinguals took part in the fMRI experiment. Four types of stimuli (Chinese characters, Korean characters, line drawings and unfamiliar Chinese faces) were presented in a block-design paradigm. By contrasting characters (Chinese or Korean) to faces, presumed VWFAs could be identified for both Chinese and Korean characters in the left occipito-temporal sulcus in each subject. The location of peak response point in these two VWFAs were essentially the same. Further analysis revealed a substantial overlap between the VWFA identified for Chinese and that for Korean. At the group level, there was no significant difference in amplitude of response to Chinese and Korean characters. Spatial patterns of response to Chinese and Korean are similar. In addition to confirming that there is an area in the left occipito-temporal cortex that selectively responds to scripts in both Korean and Chinese in early Chinese-Korean bilinguals, our results show that these two scripts engage essentially the same VWFA, even at the level of fine spatial patterns of activation across voxels. These results suggest that similar populations of neurons are engaged in processing the different scripts within the same VWFA in early bilinguals.

Ventral-visual activity in older adults has been characterized by dedifferentiation, or reduced distinctiveness, of responses to different categories of visual stimuli such as faces and houses, that typically elicit highly specialized responses in the fusiform and parahippocampal brain regions respectively in young adults (Park et al., 2004). In the present study, we demonstrate that age-related neural dedifferentiation applies to within-category stimuli (different types of faces) as well, such that older adults process less distinctive representations for individual faces than young adults. We performed a functional magnetic resonance imaging adaptation experiment while young and older participants made same-different judgments to serially presented face-pairs that were Identical, Moderate in similarity through morphing, or Different. As expected, older adults showed adaptation in the fusiform face area (FFA), during the Identical as well as the Moderate conditions relative to the Different condition. Young adults showed adaptation during the Identical condition, but minimal adaptation to the Moderate condition. These results indicate that older adults’ FFA treated the morphed faces as Identical faces, reflecting decreased fidelity of neural representation of faces with age.

The tendency to perceive faces in random patterns exhibiting configural properties of faces is an example of pareidolia. Perception of ‘real’ faces has been associated with a cortical response signal arising at about 170ms after stimulus onset; but what happens when non-face objects are perceived as faces? Using magnetoencephalography (MEG), we found that objects incidentally perceived as faces evoked an early (165ms) activation in the ventral fusiform cortex, at a time and location similar to that evoked by faces, whereas common objects did not evoke such activation. An earlier peak at 130 ms was also seen for images of real faces only. Our findings suggest that face perception evoked by face-like objects is a relatively early process, and not a late re-interpretation cognitive phenomenon.

Social interaction and comprehension of non-verbal behaviour requires a representation of people’s bodies. Research into the neural underpinnings of body representation implicates several brain regions including extrastriate and fusiform body areas (EBA and FBA), superior temporal sulcus (STS), inferior frontal gyrus (IFG) and inferior parietal lobule (IPL). The different roles played by these regions in parsing familiar and unfamiliar body postures remain unclear. We examined the responses of this body observation network to static images of ordinary and contorted postures by using a repetition suppression design in functional neuroimaging. Participants were scanned whilst observing static images of a contortionist or a group of objects in either ordinary or unusual configurations, presented from different viewpoints. Greater activity emerged in EBA and FBA when participants viewed contorted compared to ordinary body postures. Repeated presentation of the same posture from different viewpoints lead to suppressed responses in the fusiform gyrus as well as three regions that are characteristically activated by observing moving bodies, namely STS, IFG and IPL. These four regions did not distinguish the image viewpoint or the plausibility of the posture. Together, these data define a broad cortical network for processing static body postures, including regions classically associated with action observation.

Decades of research have documented the specialization of fusiform gyrus (FG) for facial information processes. Recent theories indicate that FG activity is shaped by input from amygdala, but effective connectivity from amygdala to FG remains undocumented. In this fMRI study, 39 participants completed a face recognition task. 11 participants underwent the same experiment approximately four months later. Robust face-selective activation of FG, amygdala, and lateral occipital cortex were observed. Dynamic causal modeling and Bayesian Model Selection (BMS) were used to test the intrinsic connections between these structures, and their modulation by face perception. BMS results strongly favored a dynamic causal model with bidirectional, face-modulated amygdala-FG connections. However, the right hemisphere connections diminished at time 2, with the face modulation parameter no longer surviving Bonferroni correction. These findings suggest that amygdala strongly influences FG function during face perception, and that this influence is shaped by experience and stimulus salience.

Recent evidence suggests that a rapid, automatic face-detection system is supported by subcortical structures including the amygdala, pulvinar, and superior colliculus. Early emerging abnormalities in these structures may be related to reduced social orienting in children with autism, and subsequently, to aberrant development of cortical circuits involved in face processing. Our objective was to determine whether functional abnormalities in the subcortical face processing system are present in adults with autism spectrum disorders (ASD) during supraliminal fearful face processing. Participants included twenty-eight individuals with ASD and 25 controls group-matched on age, IQ, and behavioral performance. The ASD group met diagnostic criteria on the ADI-R, ADOS-G, and DSM-IV. Both the ASD and control groups showed significant activation in bilateral fusiform gyri. The control group exhibited additional significant responses in the right amygdala, right pulvinar, and bilateral superior colliculi. In the direct group comparison, the controls showed significantly greater activation in the left amygdala, bilateral fusiform gyrus, right pulvinar, and bilateral superior colliculi. No brain region showed significantly greater activation in the ASD group compared to the controls. Thus, basic rapid face identification mechanisms appear to be functional in ASD. However, individuals with ASD failed to engage the subcortical brain regions involved in face detection and automatic emotional face processing, suggesting a core mechanism for impaired socioemotional processing in ASD. Neural abnormalities in this system may contribute to early emerging deficits in social orienting and attention, the putative precursors to abnormalities in social cognition and cortical face processing specialization.

Objective

The authors examined the association between volume of the fusiform gyrus, a region involved in face processing, and the personality trait of extraversion in patients with schizophrenia.

Method

Male patients (N=24) and age-matched male comparison subjects (N=26) completed NEO Five-Factor Inventory personality measures of extraversion and underwent high-spatial-resolution magnetic resonance imaging of anterior and posterior fusiform gyrus gray matter.

Results

Low extraversion scores were significantly correlated with gray matter volume reductions in the right posterior fusiform gyrus for patients but not comparison subjects.

Conclusions

Reduced right posterior fusiform gyrus volume may contribute to disease-related social disturbances, characterized by both low extraversion and reduced sensitivity to human faces.

The current study examined the hypothesis that amygdala activation serves as a neural precondition for negative affective experience. Participants’ affective experience was measured by asking them to report on their momentary experiences several times a day over the course of a month using an electronic experience-sampling procedure. One year later, participants viewed backwardly masked depictions of fear while functional magnetic resonance imaging was used to measure their amygdala and fusiform gyrus activation. Negative affect, as measured during the experience-sampling procedure 1-year prior, was positively correlated with amygdala activation in response to these brief presentations of fear depictions. Furthermore, descriptive analyses indicated that fusiform gyrus activation and negative affective experience in the scanner were associated for participants reporting increased nervousness during the imaging procedure. The results are consistent with the interpretation that the amygdala contributes to negative affective experience by increasing perceptual sensitivity for negative stimuli.

The current study examined the hypothesis that amygdala activation serves as a neural precondition for negative affective experience. Participants’ affective experience was measured by asking them to report on their momentary experiences several times a day over the course of a month using an electronic experience-sampling procedure. One year later, participants viewed backwardly masked depictions of fear while functional magnetic resonance imaging was used to measure their amygdala and fusiform gyrus activation. Negative affect, as measured during the experience-sampling procedure 1-year prior, was positively correlated with amygdala activation in response to these brief presentations of fear depictions. Furthermore, descriptive analyses indicated that fusiform gyrus activation and negative affective experience in the scanner were associated for participants reporting increased nervousness during the imaging procedure. The results are consistent with the interpretation that the amygdala contributes to negative affective experience by increasing perceptual sensitivity for negative stimuli.

MRI diffusion-tensor tracking (DTT) was performed in 17 high-functioning adolescents/adults with autism and 17 pairwise-matched controls. White matter pathways involved in face processing were examined due to the relevance of face perception to the social symptoms of autism, and due to known behavioral and functional imaging findings in autism. The hippocampo-fusiform (HF) and amygdalo-fusiform (AF) pathways had normal size and shape but abnormal microstructure in the autism group. The right HF had reduced across-fiber diffusivity (D-min) compared with controls, opposite to the whole-brain effect of increased D-min. In contrast, left HF, right AF, and left AF had increased D-min and increased along-fiber diffusivity (D-max), more consistent with the whole-brain effect. There was a general loss of lateralization compared with controls. The right HF D-min was markedly low in the autism subgroup with lower Benton face recognition scores, compared with the lower-Benton control subgroup, and compared with the higher-Benton autism subgroup. Similar behavioral relationships were found for performance IQ. Such results suggest an early functionally-significant pathological process in right HF consistent with small-diameter axons (with correspondingly slower neural transmission) and/or higher packing density. In left AF and HF, changes were interpreted as secondary, possibly reflecting axonal loss and/or decreased myelination.

In order to probe the organization of the contractile machinery in smooth muscle, we have studied the distribution of alpha-actinin, a protein present in high concentration in dense bodies, structures apparently analogous to the Z-disks of striated muscle. Localization of alpha-actinin in single isolated smooth muscle cells of the stomach muscularis of Bufo marinus was determined by analysis of the pattern of anti-alpha-actinin staining in single fluorescence photomicrographs, stereo pair micrographs, and computerized three-dimensional reconstructions from multiple image planes. The distribution of anti- alpha-actinin and antitubulin staining was compared in contracted and relaxed cells. The studies revealed that alpha-actinin is present in high concentrations in fusiform elements (mean axial ratio = 4.82) throughout the cytoplasm and in larger, more irregularly shaped plaques along the cell margins. Many of the fusiform-stained elements are organized into stringlike arrays characterized by a regular repeating pattern (mean center-to-center interspace = 2.2 +/- 0.1 micron). These linear arrays appear to terminate at the anti-alpha-actinin stained larger plaques along the cell margin; several of these strings often run in parallel with their elements in lateral register. While this general pattern of organization is maintained in cells during contraction, the distance between successive stained elements in stringlike arrays is decreased. We suggest that the decrease in the distance between elements in these strings results from shortening of materials that constitute these linear arrays. We do not believe that the shortening within these arrays reflects compression by forces generated elsewhere within the cell, as the reorganization of noncontractile microtubules is qualitatively different from the changes in the pattern of anti-alpha-actinin staining.

Functional neuroimaging research has demonstrated that retrieving information about object-associated colors activates the left fusiform gyrus in posterior temporal cortex. Although regions near the fusiform have previously been implicated in color perception, it remains unclear whether color knowledge retrieval actually activates the color perception system. Evidence to this effect would be particularly strong if color perception cortex was activated by color knowledge retrieval triggered strictly with linguistic stimuli. To address this question, subjects performed two tasks while undergoing fMRI. First, subjects performed a property verification task using only words to assess conceptual knowledge. On each trial, subjects verified whether a named color or motor property was true of a named object (e.g., TAXI-yellow, HAIR-combed). Next, subjects performed a color perception task. A region of the left fusiform gyrus that was highly responsive during color perception also showed greater activity for retrieving color than motor property knowledge. These data provide the first evidence for a direct overlap in the neural bases of color perception and stored information about object-associated color, and they significantly add to accumulating evidence that conceptual knowledge is grounded in the brain’s modality-specific systems.

Functional neuroimaging studies of face processing deficits in autism have typically focused on visual processing regions, such as the fusiform face area (FFA), which have shown reduced activity in autism spectrum disorders (ASD), though inconsistently. We recently reported reduced activity in the inferior frontal region in ASD, implicating impaired mirror-neuron systems during face processing. In the present study, we used fMRI during a face processing task in which subjects had to match faces presented in the upright versus inverted position. Typically developing (TD) children showed a classic behavioral inversion effect, increased reaction time for inverted faces, while this effect was significantly reduced in ASD subjects. The fMRI data showed similar responses in the fusiform face area for ASD and TD children, with both groups demonstrating increased activation for inverted faces. However, the groups did differ in several brain regions implicated in social cognition, particularly prefrontal cortex and amygdala. These data suggest that the behavioral differences in processing upright versus inverted faces for TD children are related not to visual information processing but to the social significance of the stimuli. Our results are consistent with other recent studies implicating frontal and limbic dysfunction during face processing in autism.