Categorical learning revealed in activity pattern of left fusiform cortex

The brain is organized such that it encodes and maintains category information about thousands of objects. However, how learning shapes these neural representations of object categories is unknown. The present study focuses on faces, examining whether: (1) Enhanced categorical discrimination or (2) Feature analysis enhances face/non‐face categorization in the brain. Stimuli ranged from non‐faces to faces with two‐toned Mooney images used for testing and gray‐scale images used for training. The stimulus set was specifically chosen because it has a true categorical boundary between faces and non‐faces but the stimuli surrounding that boundary have very similar features, making the boundary harder to learn. Brain responses were measured using functional magnetic resonance imaging while participants categorized the stimuli before and after training. Participants were either trained with a categorization task, or with non‐categorical semblance analyzation. Interestingly, when participants were categorically trained, the neural activity pattern in the left fusiform gyrus shifted from a graded representation of the stimuli to a categorical representation. This corresponded with categorical face/non‐face discrimination, critically including both an increase in selectivity to faces and a decrease in false alarm response to non‐faces. By contrast, while activity pattern in the right fusiform cortex correlated with face/non‐face categorization prior to training, it was not affected by learning. Our results reveal the key role of the left fusiform cortex in learning face categorization. Given the known right hemisphere dominance for face‐selective responses, our results suggest a rethink of the relationship between the two hemispheres in face/non‐face categorization. Hum Brain Mapp 38:3648–3658, 2017. © 2017 Wiley Periodicals, Inc.     

5‐HTTLPR differentially predicts brain network responses to emotional faces

The effects of the 5‐HTTLPR polymorphism on neural responses to emotionally salient faces have been studied extensively, focusing on amygdala reactivity and amygdala‐prefrontal interactions. Despite compelling evidence that emotional face paradigms engage a distributed network of brain regions involved in emotion, cognitive and visual processing, less is known about 5‐HTTLPR effects on broader network responses. To address this, we evaluated 5‐HTTLPR differences in the whole‐brain response to an emotional faces paradigm including neutral, angry and fearful faces using functional magnetic resonance imaging in 76 healthy adults. We observed robust increased response to emotional faces in the amygdala, hippocampus, caudate, fusiform gyrus, superior temporal sulcus and lateral prefrontal and occipito‐parietal cortices. We observed dissociation between 5‐HTTLPR groups such that L_AL_A individuals had increased response to only angry faces, relative to neutral ones, but S′ carriers had increased activity for both angry and fearful faces relative to neutral. Additionally, the response to angry faces was significantly greater in L_AL_A individuals compared to S′ carriers and the response to fearful faces was significantly greater in S′ carriers compared to L_AL_A individuals. These findings provide novel evidence for emotion‐specific 5‐HTTLPR effects on the response of a distributed set of brain regions including areas responsive to emotionally salient stimuli and critical components of the face‐processing network. These findings provide additional insight into neurobiological mechanisms through which 5‐HTTLPR genotype may affect personality and related risk for neuropsychiatric illness. Hum Brain Mapp 36:2842–2851, 2015. © 2015 Wiley Periodicals, Inc.     

Brain functional correlates of emotion regulation across adolescence and young adulthood

Few studies have examined the neural correlates of emotion regulation across adolescence and young adulthood. Existing studies of cognitive reappraisal indicate that improvements in regulatory efficiency may develop linearly across this period, in accordance with maturation of prefrontal cortical systems. However, there is also evidence for adolescent differences in reappraisal specific to the activation of “social‐information processing network” regions, including the amygdala and temporal‐occipital cortices. Here, we use fMRI to examine the neural correlates of emotional reactivity and reappraisal in response to aversive social imagery in a group of 78 adolescents and young adults aged 15–25 years. Within the group, younger participants exhibited greater activation of temporal‐occipital brain regions during reappraisal in combination with weaker suppression of amygdala reactivity—the latter being a general correlate of successful reappraisal. Further analyses demonstrated that these age‐related influences on amygdala reactivity were specifically mediated by activation of the fusiform face area. Overall, these findings suggest that enhanced processing of salient social cues (i.e., faces) increases reactivity of the amygdala during reappraisal and that this relationship is stronger in younger adolescents. How these relationships contribute to well‐known vulnerabilities of emotion regulation during this developmental period will be an important topic for ongoing research. Hum Brain Mapp 37:7–19, 2016. © 2015 Wiley Periodicals, Inc.     

The effect of encoding strategy on the neural correlates of memory for faces

Encoding and recognition of unfamiliar faces in young adults were examined using positron emission tomography to determine whether different encoding strategies would lead to encoding/retrieval differences in brain activity. Three types of encoding were compared: a 'deep' task (judging pleasantness/unpleasantness), a 'shallow' task (judging right/left orientation), and an intentional learning task in which subjects were instructed to learn the faces for a subsequent memory test but were not provided with a specific strategy. Memory for all faces was tested with an old/new recognition test. A modest behavioral effect was obtained, with deeply-encoded faces being recognized more accurately than shallowly-encoded or intentionally-learned faces. Regardless of encoding strategy, encoding activated a primarily ventral system including bilateral temporal and fusiform regions and left prefrontal cortices, whereas recognition activated a primarily dorsal set of regions including right prefrontal and parietal areas. Within encoding, the type of strategy produced different brain activity patterns, with deep encoding being characterized by left amygdala and left anterior cingulate activation. There was no effect of encoding strategy on brain activity during the recognition conditions. Posterior fusiform gyrus activation was related to better recognition accuracy in those conditions encouraging perceptual strategies, whereas activity in left frontal and temporal areas correlated with better performance during the 'deep' condition. Results highlight three important aspects of face memory: (1) the effect of encoding strategy was seen only at encoding and not at recognition; (2) left inferior prefrontal cortex was engaged during encoding of faces regardless of strategy; and (3) differential activity in fusiform gyrus was found, suggesting that activity in this area is not only a result of automatic face processing but is modulated by controlled processes.     

Face gender modulates women’s brain activity during face encoding

Women typically remember more female than male faces, whereas men do not show a reliable own-gender bias. However, little is known about the neural correlates of this own-gender bias in face recognition memory. Using functional magnetic resonance imaging (fMRI), we investigated whether face gender modulated brain activity in fusiform and inferior occipital gyri during incidental encoding of faces. Fifteen women and 14 men underwent fMRI while passively viewing female and male faces, followed by a surprise face recognition task. Women recognized more female than male faces and showed higher activity to female than male faces in individually defined regions of fusiform and inferior occipital gyri. In contrast, men’s recognition memory and blood-oxygen-level-dependent response were not modulated by face gender. Importantly, higher activity in the left fusiform gyrus (FFG) to one gender was related to better memory performance for that gender. These findings suggest that the FFG is involved in the gender bias in memory for faces, which may be linked to differential experience with female and male faces.     

Being BOLD: The neural dynamics of face perception

According to a non‐hierarchical view of human cortical face processing, selective responses to faces may emerge in a higher‐order area of the hierarchy, in the lateral part of the middle fusiform gyrus (fusiform face area [FFA]) independently from face‐selective responses in the lateral inferior occipital gyrus (occipital face area [OFA]), a lower order area. Here we provide a stringent test of this hypothesis by gradually revealing segmented face stimuli throughout strict linear descrambling of phase information [Ales et al., 2012]. Using a short sampling rate (500 ms) of fMRI acquisition and single subject statistical analysis, we show a face‐selective responses emerging earlier, that is, at a lower level of structural (i.e., phase) information, in the FFA compared with the OFA. In both regions, a face detection response emerging at a lower level of structural information for upright than inverted faces, both in the FFA and OFA, in line with behavioral responses and with previous findings of delayed responses to inverted faces with direct recordings of neural activity were also reported. Overall, these results support the non‐hierarchical view of human cortical face processing and open new perspectives for time‐resolved analysis at the single subject level of fMRI data obtained during continuously evolving visual stimulation. Hum Brain Mapp 38:120–139, 2017. © 2016 Wiley Periodicals, Inc.     

Different fusiform activity to stranger and personally familiar faces in shy and social adults

Abstract

Although shyness is associated with deficits in different aspects of face processing including face recognition and facial emotions, we know relatively little about the neural correlates of face processing among individuals who are shy. Here we show reduced activation to stranger faces among shy adults in a key brain area involved in face processing. Event-related functional magnetic resonance imaging scans were acquired on 12 shy and 12 social young adults during the rapid presentation of stranger and personally familiar neutral faces. Shy adults exhibited significantly less bilateral activation in the fusiform face area (FFA) in response to stranger faces and significantly greater bilateral activation in the same region to personally familiar faces than their social counterparts. Shy adults also exhibited significantly greater right amygdala activation in response to stranger faces than social adults. Among social adults, stranger faces elicited greater FFA activation than personally familiar faces. Findings suggest that there are distinct patterns of neural activation in the FFA in response to viewing stranger and personally familiar faces among shy and social adults.     

Brain signatures of perceiving a smile: Time course and source localization

Facial happiness is consistently recognized faster than other expressions of emotion. In this study, to determine when and where in the brain such a recognition advantage develops, EEG activity during an expression categorization task was subjected to temporospatial PCA analysis and LAURA source localizations. Happy, angry, and neutral faces were presented either in whole or bottom‐half format (with the mouth region visible). The comparison of part‐ versus whole‐face conditions served to examine the role of the smile. Two neural signatures underlying the happy face advantage emerged. One peaked around 140 ms (left N140) and was source‐located at the left IT cortex (MTG), with greater activity for happy versus non‐happy faces in both whole and bottom‐half face format. This suggests an enhanced perceptual encoding mechanism for salient smiles. The other peaked around 370 ms (P3b and N3) and was located at the right IT (FG) and dorsal cingulate (CC) cortices, with greater activity specifically for bottom‐half happy versus non‐happy faces. This suggests an enhanced recruitment of face‐specific information to categorize (or reconstruct) facial happiness from diagnostic smiling mouths. Additional differential brain responses revealed a specific “anger effect,” with greater activity for angry versus non‐angry expressions (right N170 and P230; right pSTS and IPL); and a coarse “emotion effect,” with greater activity for happy and angry versus neutral expressions (anterior P2 and posterior N170; vmPFC and right IFG). Hum Brain Mapp 36:4287–4303, 2015. © 2015 Wiley Periodicals, Inc.     

APOE ɛ4 constrains engagement of encoding‐related compensatory networks in amnestic mild cognitive impairment

People with amnestic mild cognitive impairment (aMCI), compared to healthy older adults (HO), benefit less from semantic congruent cues during episodic encoding. The presence of the apolipoprotein E (APOE) ?4 makes this congruency benefit smaller, but the neural correlates of this deficit are unknown. Here, we estimated the source generators of EEG oscillatory activity associated with successful encoding of face‐location associations preceded by semantically congruent and incongruent cues in HO (N = 26) and aMCI subjects (N = 34), 16 of which were ?4 carriers (?4⁺) and 18 ?4 noncarriers (?4^?). Source estimation was performed in those spectrotemporal windows where the power of low‐alpha, high‐alpha, and beta oscillatory activity differed either between congruent and incongruent faces or between groups. Differences in high‐alpha and beta‐oscillatory dynamics indicated that aMCI ?4⁺ are unable to activate lateral regions of the temporal lobe involved in associative memory and congruency benefit in HO. Interestingly, and regardless of APOE genotype, aMCI activated additional regions relative to HO, through alpha oscillations. However, only activation in a distributed fronto‐temporo‐parietal network in ?4 noncarriers was paralleled by enhanced memory. On the contrary, the redundant prefrontal activation shown by aMCI ?4⁺ did not prevent performance from decreasing. These results indicate that the effect of aMCI‐related degeneracy on functional networks is constrained by the presence of APOE ?4. Whereas individuals with aMCI ?4^? activate attentional, perceptual and semantic compensatory networks, aMCI ?4⁺ show reduced processing efficiency and capacity. © 2015 Wiley Periodicals, Inc.     

Aging modulates the oscillatory dynamics underlying successful working memory encoding and maintenance

Working memory is central to the execution of many daily functions and is typically divided into three phases: encoding, maintenance, and retrieval. While working memory performance has been repeatedly shown to decline with age, less is known regarding the underlying neural processes. We examined age‐related differences in the neural dynamics that serve working memory by recording high‐density magnetoencephalography (MEG) in younger and older adults while they performed a modified, high‐load Sternberg working memory task with letters as stimuli. MEG data were evaluated in the time‐frequency domain and significant oscillatory responses were imaged using a beamformer. A hierarchical regression was performed to investigate whether age moderated the relationship between oscillatory activity and accuracy on the working memory task. Our results indicated that the spatiotemporal dynamics of oscillatory activity in language‐related areas of the left fronto‐temporal cortices were similar across groups. Age‐related differences emerged during early encoding in the right‐hemispheric homologue of Wernicke's area. Slightly later, group differences emerged in the homologue of Broca's area and these persisted throughout memory maintenance. Additionally, occipital alpha activity during maintenance was stronger, occurred earlier, and involved more cortical tissue in older adults. Finally, age significantly moderated the relationship between accuracy and neural activity in the prefrontal cortices. In younger adults, as prefrontal activity decreased, accuracy tended to increase. Our results are consistent with predictions of the compensation‐related utilization of neural circuits hypothesis (CRUNCH). Such differences in the oscillatory dynamics could reflect compensatory mechanisms, which would aid working memory performance in older age. Hum Brain Mapp 37:2348–2361, 2016. © 2016 Wiley Periodicals, Inc.     

Diminished neural sensitivity to irregular facial expression in first‐episode schizophrenia

Introduction: Blunted, inappropriate affective‐social behavior is a hallmark of early schizophrenia, possibly corresponding to reduced ability to recognize and express emotions. It is yet unknown if this affective deficiency relates to disturbed neural sensitivity to facial expressions or to overall face processing. In a previous imaging study, healthy subjects showed less suppression of the fusiform gyrus (FG) to repeated presentation of the same transfigured‐bizarre face relative to regular face. We assumed that the FG in schizophrenia will show reduced repetition related sensitivity to transfigured‐bizarre faces, while having overall normal response to faces. Methods: Ten first‐episode patients with schizophrenia and 10 controls rated the bizarreness of upright and inverted faces. In an fMRI study, another group of 17 first‐episode patients with schizophrenia and 12 controls viewed regular and transfigured‐bizarre faces in blocks. Each block contained regular‐ or transfigured‐bizarre faces of either different or same individual, presented in an upright or inverted orientation. Results: Patients in comparison with controls rated irregular faces as less bizarre. The FG, in patients and controls exhibited similar response to inverted faces, suggesting normal face processing. In contrast, the FG only in patients, showed similar suppression to repeated transfigured‐bizarre and regular faces. Finally, the FG in patients compared with controls showed reduced functional connectivity with the amygdala and prefrontal cortex. Conclusion: Patients with schizophrenia already at first‐episode, showed reduced behavioral and neural sensitivity to bizarre facial expressions. Possibly, this deficiency is related to disturbed modulations of emotion‐related face processing in the FG by the amygdala and prefrontal cortex. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

A case of persistent visual hallucinations of faces following LSD abuse: A functional Magnetic Resonance Imaging study

In this study, we report the case of a patient experiencing hallucinations of faces that could be reliably precipitated by looking at trees. Using functional Magnetic Resonance Imaging (fMRI), we found that face hallucinations were associated with increased and decreased neural activity in a number of cortical regions. Within the same fusiform face area, however, we found significant decreased and increased neural activity according to whether the patient was experiencing hallucinations or veridical perception of faces, respectively. These findings may indicate key differences in how hallucinatory and veridical perceptions lead to the same phenomenological experience of seeing faces.     

Brain activation during face perception: evidence of a developmental change

Behavioral studies suggest that children under age 10 process faces using a piecemeal strategy based on individual distinctive facial features, whereas older children use a configural strategy based on the spatial relations among the face's features. The purpose of this study was to determine whether activation of the fusiform gyrus, which is involved in face processing in adults, is greater during face processing in older children (12-14 years) than in younger children (8-10 years). Functional MRI scans were obtained while children viewed faces and houses. A developmental change was observed: Older children, but not younger children, showed significantly more activation in bilateral fusiform gyri for faces than for houses. Activation in the fusiform gyrus correlated significantly with age and with a behavioral measure of configural face processing. Regions believed to be involved in processing basic facial features were activated in both younger and older children. Some evidence was also observed for greater activation for houses versus faces for the older children than for the younger children, suggesting that processing of these two stimulus types becomes more differentiated as children age. The current results provide biological insight into changes in visual processing of faces that occur with normal development.     

The fusiform response to faces: Explicit versus implicit processing of emotion

Regions of the fusiform gyrus (FG) respond preferentially to faces over other classes of visual stimuli. It remains unclear whether emotional face information modulates FG activity. In the present study, whole‐head magnetoencephalography (MEG) was obtained from fifteen healthy adults who viewed emotionally expressive faces and made button responses based upon emotion (explicit condition) or age (implicit condition). Dipole source modeling produced source waveforms for left and right primary visual and left and right fusiform areas. Stronger left FG activity (M170) to fearful than happy or neutral faces was observed only in the explicit task, suggesting that directed attention to the emotional content of faces facilitates observation of M170 valence modulation. A strong association between M170 FG activity and reaction times in the explicit task provided additional evidence for a role of the fusiform gyrus in processing emotional information. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Amyloid-β associated cortical thinning in clinically normal elderly

Objective:

Both amyloid‐β (Aβ) deposition and brain atrophy are associated with Alzheimer's disease (AD) and the disease process likely begins many years before symptoms appear. We sought to determine whether clinically normal (CN) older individuals with Aβ deposition revealed by positron emission tomography (PET) imaging using Pittsburgh Compound B (PiB) also have evidence of both cortical thickness and hippocampal volume reductions in a pattern similar to that seen in AD.

Methods:

A total of 119 older individuals (87 CN subjects and 32 patients with mild AD) underwent PiB PET and high‐resolution structural magnetic resonance imaging (MRI). Regression models were used to relate PiB retention to cortical thickness and hippocampal volume.

Results:

We found that PiB retention in CN subjects was (1) age‐related and (2) associated with cortical thickness reductions, particularly in parietal and posterior cingulate regions extending into the precuneus, in a pattern similar to that observed in mild AD. Hippocampal volume reduction was variably related to Aβ deposition.

Interpretation:

We conclude that Aβ deposition is associated with a pattern of cortical thickness reduction consistent with AD prior to the development of cognitive impairment. ANN NEUROL 2010;     

Repetition suppression of face‐selective evoked and induced EEG recorded from human cortex

In functional MRI studies, repetition suppression refers to the reduction of hemodynamic activation to repeated stimulus presentation. For example, the repeated presentation of a face reduces the hemodynamic response evoked by faces in the fusiform gyrus. The neural events that underlie repetition suppression are not well understood. Indeed, in contrast to the hemodynamic response, the face‐specific N200 recorded from subdural electrodes on the ventral occipitotemporal cortex, primarily along the fusiform gyrus, has been reported to be insensitive to face‐identity repetition. We have previously described a face‐specific broadband gamma (30–100 Hz) response at ventral face‐specific N200 sites that is functionally dissociable from the N200. In this study, we investigate whether gamma and other components of the electroencephalogram spectrum are affected by face‐identity repetition independently of the N200. Participants viewed sequentially presented identical faces. At sites on and around the fusiform gyrus, we found that face repetition modulated alpha (8–12 Hz), low‐gamma (30–60 Hz), and high‐gamma (60–100 Hz) synchrony, but not the N200. These findings provide evidence of a spatially co‐localized progression of face processing. Whereas the N200 reflects an initial obligatory response that is less sensitive to face‐identity repetition, the subsequent spectral fluctuations reflect more elaborative face processing and are thus sensitive to face novelty. It is notable that the observed modulations were different for different frequency bands. We observed repetition suppression of broadband gamma, but repetition enhancement of alpha synchrony. This difference is discussed with regard to an existing model of repetition suppression and behavioral repetition priming. Hum Brain Mapp 35:4155–4162, 2014. © 2014 Wiley Periodicals, Inc .     

Cortical activation during cholinesterase-inhibitor treatment in Alzheimer disease: preliminary findings from a pharmaco-fMRI study.

OBJECTIVE: Cholinesterase inhibitors improve cognitive functioning in Alzheimer disease (AD). The authors studied, with functional magnetic resonance imaging (fMRI), the neural mechanism by which this cholinergic enhancement improves memory encoding in AD over longer time periods. METHODS: Brain activation was measured in 10 patients with AD and 10 healthy elderly comparison subjects with fMRI while they were encoding novel faces. Patients were scanned again after a 10-week open treatment with the cholinesterase-inhibitor donepezil. RESULTS: Neuropsychologically-tested memory performance improved during the treatment phase in the patients. During the encoding of novel faces, elderly comparison subjects showed more activation in the right fusiform gyrus than the group of AD patients. After a 10-week treatment with donepezil, the fusiform gyrus was also activated in patients, similar to the comparison group. CONCLUSIONS: The right fusiform gyrus is associated with the processing of faces. Cholinergic enhancement augments selective attention by increased selectivity of perceptual responses in patients with AD. This mechanism may contribute to a more efficient processing of the attended stimulus and thus be a mechanism underlying clinical improvement of cognitive functioning. These promising preliminary findings need to be confirmed in a larger, controlled trial in which both fMRI and attention measures serve as outcomes.     

In Pre-Clinical AD Small Vessel Disease is Associated With Altered Hippocampal Connectivity and Atrophy

ObjectiveSmall Vessel Disease (SVD) is known to be associated with higher AD risk, but its relationship to amyloidosis in the progression of AD is unclear. In this cross-sectional study of cognitively normal older adults, we explored the interactive effects of SVD and amyloid-beta (Aβ) pathology on hippocampal functional connectivity during an associative encoding task and on hippocampal volume.MethodsThis study included 61 cognitively normal older adults (age range: 65–93 years, age mean ± standard deviation: 75.8 ± 6.4, 41 [67.2%] female). PiB PET, T2-weighted FLAIR, T1-weighted and face-name fMRI images were acquired on each participant to evaluate brain Aβ, white matter hyperintensities (WMH+/- status), gray matter density, and hippocampal functional connectivity.ResultsWe found that, in WMH (+) older adults greater Aβ burden was associated with greater hippocampal local connectivity (i.e., hippocampal-parahippocampal connectivity) and lower gray matter density in medial temporal lobe (MTL), whereas in WMH (-) older adults greater Aβ burden was associated with greater hippocampal distal connectivity (i.e., hippocampal-prefrontal connectivity) and no changes in MTL gray matter density. Moreover, greater hippocampal local connectivity was associated with MTL atrophy.ConclusionThese observations support a hippocampal excitotoxicity model linking SVD to neurodegeneration in preclinical AD. This may explain how SVD may accelerate the progression from Aβ positivity to neurodegeneration, and subsequent AD.     

Age-related differences in brain regions supporting successful encoding of emotional faces

In an event-related functional Magnetic Resonance Imaging (fMRI) study, younger and older adults were presented with negative emotional (i.e., fearful) and neutral face pictures under incidental learning conditions. They were subsequently given a test of face recognition outside the scanner. Both age groups activated amygdala bilaterally as well as the right hippocampus during successful encoding of the fearful faces. Direct age comparisons revealed greater activation in right amygdala and bilateral hippocampus in the young, whereas older adults showed greater activation in the left insular and right prefrontal cortices. None of these brain areas was activated during successful encoding of neutral faces, suggesting specificity of these brain activation patterns. The results indicate an age-related shift in the neural underpinnings of negative emotional face processing from medial-temporal to neocortical regions.     

Reactivation of context-specific brain regions during retrieval

The neural correlates of recollection were examined using event-related functional MRI. We examined how the presence of different visual context information during encoding of target words influenced later recollection for the words presented alone at retrieval. Participants studied words presented with different pictures of faces or scrambled faces on each trial, and on a subsequent scanned recognition test made ‘remember’, ‘know’ or ‘new’ responses to words presented alone. Prior to the study phase, participants performed a localizer task, in which the fusiform face area (FFA) was identified. We compared brain activation patterns for remember and know responses given to words studied with faces as compared to scrambled faces. Though behaviourally participants showed no difference in memory performance depending on encoding trial type, both a group- and individual-based region-of-interest analysis showed increased activation in the functionally-defined FFA for remember responses given to words studied with faces compared to scrambled faces. A regression analysis additionally showed that activation in the right fusiform gyrus increased as the relative recollection benefit for words studied with meaningful (face) compared to non-meaningful (scrambled face) context information increased. Results suggest that context-specific brain regions implicated during encoding are recruited during retrieval, and that the degree to which participants activate context-specific brain regions during retrieval is related to a behavioural benefit in later recollection for target information presented alone.