Altered structure and functional connectivity of the hippocampus are associated with social and mathematical difficulties in nonverbal learning disability

The hippocampus is known to play a critical role in a variety of complex abilities, including visual‐spatial reasoning, social functioning, and math. Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual‐spatial reasoning that are accompanied by impairment in social function or mathematics, as well as motor or executive function skills. Despite the overlap between behaviors supported by the hippocampus and impairments in NVLD, the structure and function of the hippocampus in NVLD has not been studied. To address this gap in the literature, we first compared hippocampal volume and resting‐state functional connectivity in children with NVLD (n = 24) and typically developing (TD) children (n = 20). We then explored associations between hippocampal structure, connectivity, and performance on measures of spatial, social, and mathematical ability. Relative to TD children, those with NVLD showed significant reductions in left hippocampal volume and greater hippocampal‐cerebellar connectivity. In children with NVLD, reduced hippocampal volume associated with worse mathematical problem solving. Although children with NVLD exhibited more social problems (social responsiveness scale [SRS]) and higher hippocampal‐cerebellar connectivity relative to TD children, greater connectivity was associated with fewer social problems among children with NVLD but not TD children. Such an effect may suggest a compensatory mechanism. These structural and functional alterations of the hippocampus may disrupt its putative role in organizing conceptual frameworks through cognitive mapping, thus contributing to the cross‐domain difficulties that characterize NVLD.     

Neural processing of social interaction: Coordinate‐based meta‐analytic evidence from human neuroimaging studies

While the action observation and mentalizing networks are considered to play complementary roles in understanding others' goals and intentions, they might be concurrently engaged when processing social interactions. We assessed this hypothesis via three activation‐likelihood‐estimation meta‐analyses of neuroimaging studies on the neural processing of: (a) social interactions, (b) individual actions by the action observation network, and (c) mental states by the mentalizing network. Conjunction analyses and direct comparisons unveiled overlapping and specific regions among the resulting maps. We report quantitative meta‐analytic evidence for a “social interaction network” including key nodes of the action observation and mentalizing networks. An action–social interaction‐mentalizing gradient of activity along the posterior temporal cortex highlighted a hierarchical processing of interactions, from visuomotor analyses decoding individual and shared intentions to in‐depth inferences on actors' intentional states. The medial prefrontal cortex, possibly in conjunction with the amygdala, might provide additional information concerning the affective valence of the interaction. This evidence suggests that the functional architecture underlying the neural processing of interactions involves the joint involvement of the action observation and mentalizing networks. These data might inform the design of rehabilitative treatments for social cognition disorders in pathological conditions, and the assessment of their outcome in randomized controlled trials.     

The assessment of nonverbal behavior in schizophrenia through the Formal Psychological Assessment

The nonverbal behavior (NVB) of people diagnosed with schizophrenia consistently interacts with their symptoms during the assessment. Previous studies frequently observed such an interaction when a prevalence of negative symptoms occurred. Nonetheless, a list of NVBs linked to negative symptoms needs to be defined. Furthermore, a list of items that can exhaustively assess such NVBs is still needed. The present study aims to introduce both lists by using the Formal Psychological Assessment. A deep analysis was performed on both the scientific literature and the DSM‐5 for constructing the set of nonverbal behaviors; similarly, an initial list of 138 items investigating the behaviors was obtained from instruments used to assess schizophrenia. The Formal Psychological Assessment was then applied to reduce the preliminary list. A final list of 23 items necessary and sufficient to investigate the NVBs emerged. The list also allowed us to analyze specific relations among items. The present study shows how it is possible to deepen a patient's negative symptomatology, starting with the relations between items and the NVBs they investigate. Finally, this study examines the advantages and clinical implications of defining an assessment tool based on the found list of items.     

Neural correlates of olfactory processing in congenital blindness

Adaptive neuroplastic changes have been well documented in congenitally blind individuals for the processing of tactile and auditory information. By contrast, very few studies have investigated olfactory processing in the absence of vision. There is ample evidence that the olfactory system is highly plastic and that blind individuals rely more on their sense of smell than the sighted do. The olfactory system in the blind is therefore likely to be susceptible to cross-modal changes similar to those observed for the tactile and auditory modalities. To test this hypothesis, we used functional magnetic resonance imaging to measure changes in the blood-oxygenation level-dependent signal in congenitally blind and blindfolded sighted control subjects during a simple odor detection task. We found several group differences in task-related activations. Compared to sighted controls, congenitally blind subjects more strongly activated primary (right amygdala) and secondary (right orbitofrontal cortex and bilateral hippocampus) olfactory areas. In addition, widespread task-related activations were found throughout the whole extent of the occipital cortex in blind but not in sighted participants. The stronger recruitment of the occipital cortex during odor detection demonstrates a preferential access of olfactory stimuli to this area when vision is lacking from birth. This finding expands current knowledge about the supramodal function of the visually deprived occipital cortex in congenital blindness, linking it also to olfactory processing in addition to tactile and auditory processing.     

Neural correlates of negative emotion processing in subthreshold depression

Subthreshold depression (SD) is regarded as a major risk factor for major depression. However, little is known about the neural mechanism of negative emotion processing in SD. The study aimed to examine the different neural correlates for negative emotion processing in SD and health controls (HCs) and to investigate changes in functional connectivity in SD compared with HC. Blood oxygenation level-dependent (BOLD) responses of SD and HC were captured while performing a passive viewing task, which comprised a negative condition and a masked condition. A total of 42 SD and 32 HC adolescents participated in the study. Between-group comparisons revealed significant reduced activations in the superior frontal gyrus (SFG), middle frontal gyrus and middle cingulate gyrus. Region of interest (ROI) analyses did not find correlations between contrast values of the ROIs and depressive symptoms. In addition, we found a significant increased functional connectivity between the SFG and caudate, pallidum and insula, which was significantly correlated with depressive symptoms in the SD group (P < 0.05). Altered functional connectivity between the SFG and caudate, pallidum and insula may underlie the pathology of SD. This is the first study to investigate neural mechanisms of negative emotion processing in SD using task-based functional magnetic resonance imaging.     

Neural correlates of self-focused attention in social anxiety

Socially anxious individuals tend to shift their attention away from external socially threatening cues and instead become highly self-focused. Such heightened self-focused attention has been suggested to be involved in the development and maintenance of social anxiety disorder. This study used functional magnetic resonance imaging to investigate the neural correlates of self-focused attention in 16 high socially anxious (HSA) and 16 low socially anxious (LSA) individuals. Participants were instructed to focus their attention either inwardly or outwardly during a simulated social situation. Results indicate hyperactivation of medial prefrontal cortex (mPFC), temporo-parietal junction (TPJ) and temporal pole during inward vs outward attention in HSA compared with LSA participants. Furthermore, activation of mPFC, right anterior insula, TPJ and posterior cingulate cortex was positively correlated with the trait of self-focused attention in HSA subjects. Results highlight the prominent role of the mPFC and other cortical structures in abnormal self-focused attention in social anxiety. Finally, findings for the insula suggest increased processing of bodily states that is related to the amount of habitual self-focused attention in social anxiety.     

Neural correlates of processing emotional prosody in unipolar depression

Major depressive disorder (MDD) is characterized by a biased emotion perception. In the auditory domain, MDD patients have been shown to exhibit attenuated processing of positive emotions expressed by speech melody (prosody). So far, no neuroimaging studies examining the neural basis of altered processing of emotional prosody in MDD are available. In this study, we addressed this issue by examining the emotion bias in MDD during evaluation of happy, neutral, and angry prosodic stimuli on a five‐point Likert scale during functional magnetic resonance imaging (fMRI). As expected, MDD patients rated happy prosody less intense than healthy controls (HC). At neural level, stronger activation in the middle superior temporal gyrus (STG) and the amygdala was found in all participants when processing emotional as compared to neutral prosody. MDD patients exhibited an increased activation of the amygdala during processing prosody irrespective of valence while no significant differences between groups were found for the STG, indicating that altered processing of prosodic emotions in MDD occurs rather within the amygdala than in auditory areas. Concurring with the valence‐specific behavioral effect of attenuated evaluation of positive prosodic stimuli, activation within the left amygdala of MDD patients correlated with ratings of happy, but not neutral or angry prosody. Our study provides first insights in the neural basis of reduced experience of positive information and an abnormally increased amygdala activity during prosody processing.     

Common neural correlates of emotion perception in humans

Whether neuroimaging findings support discriminable neural correlates of emotion categories is a longstanding controversy. Two recent meta‐analyses arrived at opposite conclusions, with one supporting (Vytal and Hamann [ 2010 ]: J Cogn Neurosci 22:2864–2885) and the other opposing this proposition (Lindquist et al. [ 2012 ]: Behav Brain Sci 35:121–143). To obtain direct evidence regarding this issue, we compared activations for four emotions within a single fMRI design. Angry, happy, fearful, sad and neutral stimuli were presented as dynamic body expressions. In addition, observers categorized motion morphs between neutral and emotional stimuli in a behavioral experiment to determine their relative sensitivities. Brain–behavior correlations revealed a large brain network that was identical for all four tested emotions. This network consisted predominantly of regions located within the default mode network and the salience network. Despite showing brain–behavior correlations for all emotions, muli‐voxel pattern analyses indicated that several nodes of this emotion general network contained information capable of discriminating between individual emotions. However, significant discrimination was not limited to the emotional network, but was also observed in several regions within the action observation network. Taken together, our results favor the position that one common emotional brain network supports the visual processing and discrimination of emotional stimuli. Hum Brain Mapp 36:4184–4201, 2015. © 2015 Wiley Periodicals, Inc.     

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.     

Neural correlates of incidental and directed facial emotion processing in adolescents and adults

Our knowledge on the development of the affective and cognitive circuitries that underlie affect regulation is still limited. This functional magnetic resonance imaging (fMRI) study examined whether there is more efficient prefrontal modulation of affective circuits with development. Ten adolescents (mean age 14 ± 2 years) and 10 adults (mean age 30 ± 6 years) underwent two scanning conditions that required different levels of cognitive control over face emotion processing. A ‘directed’ emotion processing condition required judgment of facial expressions. An ‘incidental’ emotion processing condition required an age judgment. For the incidental emotion processing condition, adolescents, compared with adults, showed less activation in right ventrolateral prefrontal cortex (VLPFC) and greater activation in paralimbic regions, suggesting greater emotional reactivity and immature prefrontal circuitries for affect regulation. For the directed emotion processing condition, adolescents, compared with adults, showed decreased recruitment of both the dorsal and pregenual right anterior cingulate cortex (ACC), suggesting immature modulatory functions of the ACC during directed face emotion processing. These results indicate that the neural circuitries for affect regulation are still developing in adolescence and have not yet reached the adult level.     

Clusters of nonverbal behavior differentiate truths and lies about future malicious intent in checkpoint screening interviews

Recent research has shown that nonverbal behavior (NVB) assessed across multiple channels can differentiate truthtellers from liars. No study, however, has examined whether or not multiple NVBs can differentiate truths from lies about intent regarding future malicious behavior, or across multiple cultural/ethnic groups. We address this gap by examining truths and lies about intent to commit a malicious act in the future in brief, checkpoint-type security screening interviews. Data from four NVB channels producing twenty-one observable NVBs were coded and analyzed using different analytic strategies. Clusters of NVB were found to differentiate truthtellers from liars at statistically significant levels, and substantially beyond the ability of human observers. The findings showed that clusters of NVB can differentiate truthtellers from liars even in brief, checkpoint-type interviews.     

Neural correlates of retrieval processing in the prefrontal cortex during recognition and exclusion tasks

Event-related fMRI was employed to contrast the neural activity elicited in prefrontal cortex during recognition memory and exclusion tests. The study phases preceding each memory test were identical, involving the presentation of study items (visually presented words) in one of two study contexts. For the recognition test subjects were required to respond positively to all old items regardless of study context, and to respond negatively to new items. For the exclusion task, positive responses were required to old items presented in one of the study contexts only; negative responses were required both to unstudied items and studied items from the alternative context (non-targets). No prefrontal region demonstrated greater activity for new items in the exclusion task. Thus, there was no evidence that retrieval cues were processed differently according to the specificity of the sought-for information. In several regions, most notably bilateral anterior prefrontal cortex, activity was greater for old than for new items regardless of task. Activity in right dorsolateral prefrontal cortex was also greater for old than for new items; these effects however were larger in the exclusion task. The findings are consistent with previous reports that activity in anterior prefrontal cortex elicited by recognition retrieval cues is sensitive to retrieval success, and extend these findings to the exclusion task. The findings for the right dorsolateral cortex add further weight to the proposal that this region supports post-retrieval monitoring of retrieved information.     

Neural correlates of pre‐attentive processing of pattern deviance in professional musicians

Pre‐attentive registration of aberrations in predictable sound patterns is attributed to the temporal cortex. However, electrophysiology suggests that frontal areas become more important when deviance complexity increases. To play an instrument in an ensemble, professional musicians have to rely on the ability to detect even slight deviances from expected musical patterns and therefore have highly trained aural skills. Here, we aimed to identify the neural correlates of experience‐driven plasticity related to the processing of complex sound features. We used functional magnetic resonance imaging in combination with an event‐related oddball paradigm and compared brain activity in professional musicians and non‐musicians during pre‐attentive processing of melodic contour variations. The melodic pattern consisted of a sequence of five tones each lasting 50 ms interrupted by silent interstimulus intervals of 50 ms. Compared to non‐musicians, the professional musicians showed enhanced activity in the left middle and superior temporal gyri, the left inferior frontal gyrus and in the right ventromedial prefrontal cortex in response to pattern deviation. This differential brain activity pattern was correlated with behaviorally tested musical aptitude. Our results thus support an experience‐related role of the left temporal cortex in fast melodic contour processing and suggest involvement of the prefrontal cortex. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Neural correlates of anticipation and processing of performance feedback in social anxiety

Fear of negative evaluation, such as negative social performance feedback, is the core symptom of social anxiety. The present study investigated the neural correlates of anticipation and perception of social performance feedback in social anxiety. High (HSA) and low (LSA) socially anxious individuals were asked to give a speech on a personally relevant topic and received standardized but appropriate expert performance feedback in a succeeding experimental session in which neural activity was measured during anticipation and presentation of negative and positive performance feedback concerning the speech performance, or a neutral feedback‐unrelated control condition. HSA compared to LSA subjects reported greater anxiety during anticipation of negative feedback. Functional magnetic resonance imaging results showed deactivation of medial prefrontal brain areas during anticipation of negative feedback relative to the control and the positive condition, and medial prefrontal and insular hyperactivation during presentation of negative as well as positive feedback in HSA compared to LSA subjects. The results indicate distinct processes underlying feedback processing during anticipation and presentation of feedback in HSA as compared to LSA individuals. In line with the role of the medial prefrontal cortex in self‐referential information processing and the insula in interoception, social anxiety seems to be associated with lower self‐monitoring during feedback anticipation, and an increased self‐focus and interoception during feedback presentation, regardless of feedback valence. Hum Brain Mapp 35:6023–6031, 2014. © 2014 Wiley Periodicals, Inc.     

Neural correlates of social cooperation and non-cooperation as a function of psychopathy.

BACKGROUND: Psychopathy is a disorder involving a failure to experience many emotions that are necessary for appropriate social behavior. In this study, we probed the behavioral, emotional, and neural correlates of psychopathic traits within the context of a dyadic social interaction. METHODS: Thirty subjects were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma game with human confederates who were outside the scanner. Subjects also completed two self-report psychopathy questionnaires. RESULTS: Subjects scoring higher on psychopathy, particularly males, defected more often and were less likely to continue cooperating after establishing mutual cooperation with a partner. Further, they experienced more outcomes in which their cooperation was not reciprocated (cooperate-defect outcome). After such outcomes, subjects scoring high in psychopathy showed less amygdala activation, suggesting weaker aversive conditioning to those outcomes. Compared with low-psychopathy subjects, subjects higher in psychopathy also showed weaker activation within orbitofrontal cortex when choosing to cooperate and showed weaker activation within dorsolateral prefrontal and rostral anterior cingulate cortex when choosing to defect. CONCLUSIONS: These findings suggest that whereas subjects scoring low on psychopathy have emotional biases toward cooperation that can only be overcome with effortful cognitive control, subjects scoring high on psychopathy have an opposing bias toward defection that likewise can only be overcome with cognitive effort.     

Neural correlates of emotional processing in depression: changes with cognitive behavioral therapy and predictors of treatment response

Major depressive disorder (MDD) is characterized by the presence of disturbances in emotional processing. However, the neural correlates of these alterations, and how they may be affected by therapeutic interventions, remain unclear. The present study addressed these issues in a preliminary investigation using functional magnetic resonance imaging (fMRI) to examine neural responses to positive, negative, and neutral pictures in unmedicated MDD patients (N = 22) versus controls (N = 14). After this initial scan, MDD patients were treated with cognitive behavioral therapy (CBT) and scanned again after treatment. Within regions that showed pre-treatment differences between patients and controls, we tested the association between pre-treatment activity and subsequent treatment response as well as activity changes from pre- to post-treatment. This study yielded three main findings. First, prior to treatment and relative to controls, patients exhibited overall reduced activity in the ventromedial prefrontal cortex (PFC), diminished discrimination between emotional and neutral items in the amygdala, caudate, and hippocampus, and enhanced responses to negative versus positive stimuli in the left anterior temporal lobe (ATL) and right dorsolateral PFC. Second, CBT-related symptom improvement in MDD patients was predicted by increased activity at baseline in ventromedial PFC as well as the valence effects in the ATL and dorsolateral PFC. Third, from pre- to post-treatment, MDD patients exhibited overall increases in ventromedial PFC activation, enhanced arousal responses in the amygdala, caudate, and hippocampus, and a reversal of valence effects in the ATL. The study was limited by the relatively small sample that was able to complete both scan sessions, as well as an inability to determine the influence of comorbid disorders within the current sample. Nevertheless, components of the neural networks corresponding to emotion processing disturbances in MDD appear to resolve following treatment and are predictive of treatment response, possibly reflecting improvements in emotion regulation processes in response to CBT.     

Neural correlates of the implicit association test: evidence for semantic and emotional processing

The implicit association test (IAT) has been widely used in social cognitive research over the past decade. Controversies have arisen over what cognitive processes are being tapped into using this task. While most models use behavioral (RT) results to support their claims, little research has examined neurocognitive correlates of these behavioral measures. The present study measured event-related brain potentials (ERPs) of participants while completing a gay-straight IAT in order to further understand the processes involved in a typical group bias IAT. Results indicated significantly smaller N400 amplitudes and significantly larger LPP amplitudes for compatible trials than for incompatible trials, suggesting that both the semantic and emotional congruence of stimuli paired together in an IAT trial contribute to the typical RT differences found, while no differences were present for earlier ERP components including the N2. These findings are discussed with respect to early and late processing in group bias IATs.