Stress and the healthy adolescent brain: evidence for the neural embedding of life events.

Little is known about the long-term neural consequences of adverse life events for healthy adolescents, and this is particularly the case for events that occur after a putative stress-sensitive period in early childhood. In this functional magnetic resonance imaging study of healthy adolescents, we found that prior exposure to severe adverse life events was associated with current anxiety and with increased amygdala reactivity to standardized emotional stimuli (viewing of fearful faces relative to calm ones). Conjunction analyses identified multiple regions, including the amygdala, insula, and prefrontal cortex, in which reactivity to emotional faces covaried with life events as well as with current anxiety. Our morphometric analyses suggest systemic alterations in structural brain development with an association between anxiety symptoms and global gray matter volume. No life events were reported for the period before 4 years of age, suggesting that these results were not driven by exposure to stress during an early sensitive period in development. Overall, these data suggest systemic effects of traumatic events on the dynamically developing brain that are present even in a nonclinical sample of adolescents.

Understanding less than nothing: neural distance effects for negative numbers.

Little work has examined how the mental number system accommodates counterintuitive quantities such as negative numbers, which seem to extend the left end of the mental number line and reverse the established relationship between digit magnitude and value; even less research has been conducted on the neural systems supporting negative number understanding. This study aimed to determine whether adult behavioral and neural responses to negative number paired comparisons were similar to those expected for positive numbers. Mixed pairs (with one positive and one negative number) were also included. Negative number responses demonstrated an increased typical distance effect relative to that for positives, with decreasing response times and intraparietal sulcus activity for comparisons farther apart than those closer together. Negative pairs also showed more activity than positive comparisons across distances in the occipital lobe, inferior and superior parietal lobule, and bilateral caudate and putamen. Mixed pair effect direction varied based on polarity sensitivity, or whether attention to the negative sign was needed for accurate responses, indicating differences in processing strategy. Adults thus draw on brain areas important in numeric processing when dealing with negatives, but also recruit further areas and strategies to support the unique features of negative numbers. The increased distance effect seen may reflect a less mature understanding of negatives. This work expands our knowledge of the flexibility of the mental number system and its ability to represent difficult quantities.

Are historic years understood as numbers or events? An fMRI study of numbers with semantic associations.

While numbers generally cue processing of quantity or order, they can also contain semantic information, as in the case of historic years (e.g., "1492" calls forth associations of Columbus sailing the ocean blue). Whether these dates are processed as quantities or events may depend on the context in which they occur. We examined such "ambiguous number" processing in two different contexts using a paired-comparison task, recording both behavioral responses and brain activity. Participants were either asked to think of all items as numbers and to choose the larger number, or were told to treat the comparators as events and to choose the later event. Behaviorally, all events showed a normal distance effect, establishing that they may be understood and compared in an ordinal sequence. Functional magnetic resonance imaging (fMRI) demonstrated significant differences between years when treated as numbers versus as events. Dates in both contexts shared activity in parietal lobe regions previously implicated in number processing. Dates as numbers showed no extra-numeric activity, while dates thought of as events evoked activity in temporal semantic processing and frontal semantic retrieval areas. These differences suggest that extra-numeric information may be easily accessed and incorporated during processing when supported by even a weak context. This work supports previous studies showing a dissociation between quantity and meaning, and illustrates the brain areas involved in these different aspects.

Cultural effects on the neural basis of theory of mind.

"Theory of mind" has been described as the ability to attribute and understand other people's desires and intentions as distinct from one's own. It has been found to develop as early as between 3 and 4 years old, with precursor abilities possibly developing much earlier. There has been debate about the extent to which the developmental trajectory of theory of mind may differ across cultures or language systems. Although very few neuroimaging studies have directly compared different groups from different culture and language systems, across studies of a number of cultural/language groups have been used to explore the neural correlates of theory of mind. A summary of these findings suggests that there may be both universal and culture or language-specific neural correlates related to theory of mind. These studies, while still preliminary in many ways, illustrate the importance of taking into account the cultural background of participants. Furthermore these results suggest that there may be important cultural influence on theory of mind and the neural correlates associated with this ability.

Switching language switches mind: linguistic effects on developmental neural bases of 'Theory of Mind'.

Theory of mind (ToM)--our ability to predict behaviors of others in terms of their underlying intentions--has been examined through false-belief (FB) tasks. We studied 12 Japanese early bilingual children (8-12 years of age) and 16 late bilingual adults (18-40 years of age) with FB tasks in Japanese [first language (L1)] and English [second language (L2)], using fMRI. Children recruited more brain regions than adults for processing ToM tasks in both languages. Moreover, children showed an overlap in brain activity between the L1 and L2 ToM conditions in the medial prefrontal cortex (mPFC). Adults did not show such a convergent activity in the mPFC region, but instead, showed brain activity that varied depending on the language used in the ToM task. The developmental shift from more to less ToM specific brain activity may reflect increasing automatization of ToM processing as people age. These results also suggest that bilinguals recruit different resources to understand ToM depending on the language used in the task, and this difference is greater later in life.

Resilience after 9/11: multimodal neuroimaging evidence for stress-related change in the healthy adult brain.

Exposure to psychological trauma is common and predicts long-term physical and mental health problems, even in those who initially appear resilient. Here, we used multimodal neuroimaging in healthy adults who were at different distances from the World Trade Center on 9/11/01 to examine the neural mechanisms that may underlie this association. More than 3 years after 9/11/01, adults with closer proximity to the disaster had lower gray matter volume in amygdala, hippocampus, insula, anterior cingulate, and medial prefrontal cortex, with control for age, gender, and total gray matter volume. Further analysis showed a nonlinear (first-order quadratic) association between total number of traumas in lifetime and amygdala gray matter volume and function in the whole group. Post hoc analysis of subgroups with higher versus lower levels of lifetime trauma exposure revealed systematic associations between amygdala gray matter volume, amygdala functional reactivity, and anxiety that suggest a nonlinear trajectory in the neural response to accumulated trauma in healthy adults.

Salivary cortisol levels and mood vary by lifetime trauma exposure in a sample of healthy women.

The authors examined the effects of lifetime trauma exposure on salivary cortisol and mood in a sample of women (N = 37) over 25 days before and after a stressful event. The sample excluded posttraumatic stress disorder (PTSD) and major depression and was divided into three groups: (a) no trauma, (b) prior trauma with no peritraumatic symptoms of acute distress, and (c) prior trauma with peritraumatic symptoms. Because results indicated no significant differences between groups one and two, they were combined for analysis. Women reporting prior trauma with symptoms had lower afternoon cortisol levels across time, with sustained negative mood relative to the comparison group. These data suggest the presence of long-term psychophysiological effects of trauma exposure in healthy women.

Cultural and linguistic effects on neural bases of 'Theory of Mind' in American and Japanese children.

Theory of Mind (ToM) has been defined as our ability to predict behaviors of others in terms of their underlying intentions. While the developmental trajectory of ToM had been thought to be invariant across cultures, several ToM studies conducted outside the Anglo-American cultural or linguistic milieus have obtained mixed results. To examine effects of culture/language on the development of neural bases of ToM, we studied 12 American monolingual children and 12 Japanese bilingual children with second-order false-belief story and cartoon tasks, using functional magnetic resonance imaging (fMRI). While a few brain regions such as ventro-medial prefrontal cortex (vmPFC) and precuneus were recruited by both cultural/linguistic groups, several brain areas including inferior frontal gyrus (IFG) and temporo-parietal junction (TPJ) were employed in a culture/language-dependent manner during the ToM tasks. These results suggest that the neural correlates of ToM may begin to vary depending upon cultural/linguistic background from early in life.

The aftermath of 9/11: effect of intensity and recency of trauma on outcome.

Does trauma exposure have a long-term impact on the brain and behavior of healthy individuals? The authors used functional magnetic resonance imaging to assess the impact of proximity to the disaster of September 11, 2001, on amygdala function in 22 healthy adults. More than three years after the terrorist attacks, bilateral amygdala activity in response to viewing fearful faces compared to calm ones was higher in people who were within 1.5 miles of the World Trade Center on 9/11, relative to those who were living more than 200 miles away (all were living in the New York metropolitan area at time of scan). This activity mediated the relationship between group status and current symptoms of posttraumatic stress disorder. In turn, the effect of group status on both amygdala activation (fearful vs. calm faces) and current symptoms was statistically explained by time since worst trauma in lifetime and intensity of worst trauma, as indicated by reported symptoms at time of the trauma. These data are consistent with a model of heightened amygdala reactivity following high-intensity trauma exposure, with relatively slow recovery.

Children's and adults' neural bases of verbal and nonverbal 'theory of mind'.

Theory of mind (ToM) - our ability to predict behaviors of others in terms of their underlying intentions - has been examined through verbal and nonverbal false-belief (FB) tasks. Previous brain imaging studies of ToM in adults have implicated medial prefrontal cortex (mPFC) and temporo-parietal junction (TPJ) for adults' ToM ability. To examine age and modality related differences and similarities in neural correlates of ToM, we tested 16 adults (18-40 years old) and 12 children (8-12 years old) with verbal (story) and nonverbal (cartoon) FB tasks, using functional magnetic resonance imaging (fMRI). Both age groups showed significant activity in the TPJ bilaterally and right inferior parietal lobule (IPL) in a modality-independent manner, indicating that these areas are important for ToM during both adulthood and childhood, regardless of modality. We also found significant age-related differences in the ToM condition-specific activity for the story and cartoon tasks in the left inferior frontal gyrus (IFG) and left TPJ. These results suggest that depending on the modality adults may utilize different brain regions from children in understanding ToM.

Cultural and linguistic influence on neural bases of 'Theory of Mind': an fMRI study with Japanese bilinguals.

Theory of mind (ToM)-our ability to predict behaviors of others in terms of their underlying intentions-has been thought to be universal and invariant across different cultures. However, several ToM studies conducted outside the Anglo-American cultural or linguistic boundaries have obtained mixed results. To examine the influence of culture/language on neural bases of ToM, we studied 16 American English-speaking monolinguals and 16 Japanese-English bilinguals with second-order false-belief story tasks, using functional magnetic resonance imaging (fMRI). Several neural correlates of ToM including medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) were recruited by both cultural/linguistic groups. However, some other brain areas including inferior frontal gyrus (IFG) were employed in a culture/language-specific manner, during the ToM tasks. These results suggest that the ways in which adults understand ToM are not entirely universal.

Neural deficits in children with dyslexia ameliorated by behavioral remediation: evidence from functional MRI.

Developmental dyslexia, characterized by unexplained difficulty in reading, is associated with behavioral deficits in phonological processing. Functional neuroimaging studies have shown a deficit in the neural mechanisms underlying phonological processing in children and adults with dyslexia. The present study examined whether behavioral remediation ameliorates these dysfunctional neural mechanisms in children with dyslexia. Functional MRI was performed on 20 children with dyslexia (8-12 years old) during phonological processing before and after a remediation program focused on auditory processing and oral language training. Behaviorally, training improved oral language and reading performance. Physiologically, children with dyslexia showed increased activity in multiple brain areas. Increases occurred in left temporo-parietal cortex and left inferior frontal gyrus, bringing brain activation in these regions closer to that seen in normal-reading children. Increased activity was observed also in right-hemisphere frontal and temporal regions and in the anterior cingulate gyrus. Children with dyslexia showed a correlation between the magnitude of increased activation in left temporo-parietal cortex and improvement in oral language ability. These results suggest that a partial remediation of language-processing deficits, resulting in improved reading, ameliorates disrupted function in brain regions associated with phonological processing and produces additional compensatory activation in other brain regions.

Brain mechanisms in normal and dyslexic readers.

Developmental dyslexics, individuals with an unexplained difficulty reading, have been shown to have deficits in phonological processing -- the awareness of the sound structure of words -- and, in some cases, a more fundamental deficit in rapid auditory processing. In addition, dyslexics show a disruption in white matter connectivity between posterior and frontal regions. These results give continued support for a neurobiological etiology of developmental dyslexia. However, more research will be required to determine the possible causal relationships between these neurobiological disruptions and dyslexia.