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Reduced frontal white matter integrity in early-onset schizophrenia: a preliminary study.

BACKGROUND: Research suggests that brain frontal white matter (WM) might be qualitatively altered in adolescents with early onset schizophrenia (EOS). Diffusion tensor imaging provides a relatively new approach for quantifying possible connectivity of WM in vivo. METHODS: Diffusion tensor imaging was used to examine the WM integrity of frontal regions at seven levels from 25 mm above to 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. Three other regions were examined: the occipital region at the AC-PC plane and the genu and splenium of the corpus callosum. Fractional anisotropy was compared between 12 adolescents (nine male, 3 female) with EOS (onset of psychotic symptoms by age 18 years) and nine age-similar healthy comparison subjects (six male, 3 female). RESULTS: Adolescents with EOS had significantly reduced fractional anisotropy in the frontal WM at the AC-PC plane in both hemispheres and in the occipital WM at the AC-PC plane in the right hemisphere. CONCLUSIONS: These preliminary data support a hypothesis that alterations in brain WM integrity occur in adolescents with EOS. Abnormalities found in this study were similar to those reported in adults with chronic schizophrenia. Additional studies are needed to assess whether there is progression of WM abnormalities in schizophrenia.

Adolescent↗

Frontopolar cortex mediates abstract integration in analogy.

Integration of abstractly similar relations during analogical reasoning was investigated using functional magnetic resonance imaging. Activation elicited by an analogical reasoning task that required both complex working memory and integration of abstractly similar relations was compared to activation elicited by a non-analogical task that required complex working memory in the absence of abstract relational integration. A left-sided region of the frontal pole of the brain (BA 9/10) was selectively active for the abstract relational integration component of analogical reasoning. Analogical reasoning also engaged a left-sided network of parieto-frontal regions. Activity in this network during analogical reasoning is hypothesized to reflect categorical alignment of individual component terms that make up analogies. This parieto-frontal network was also engaged by the complex control task, which involved explicit categorization, but not by a simpler control task, which did not involve categorization. We hypothesize that frontopolar cortex mediates abstract relational integration in complex reasoning while parieto-frontal regions mediate working memory processes, including manipulation of terms for the purpose of categorical alignment, that facilitate this integration.

Adult↗

Information processing of geometrical features of a surface based on binocular disparity cues: an fMRI study.

Cortical areas related to the information processing of binocular disparity-defined geometrical features of a surface, such as depth, orientation and shape are examined by functional magnetic resonance imaging while subjects discriminated these three types of geometrical feature in random dot stereograms. Results indicate that disparity-defined information of depth and that of orientation are processed in the parietal area. Furthermore, the visual system for 3D vision in the parietal area may be organized in a hierarchical manner and the posterior part of the right intraparietal sulcus may be involved in cognitive process of 3D vision. On the other hand, disparity-defined shape information seems to be processed in the occipital visual areas and the crucial involvement of human LOS for this process is suggested.

Adult↗

Two brain pathways for attended and ignored words.

The dependency of word processing on spare attentional resources has been debated for several decades. Recent research in the study of selective attention has emphasized the role of task load in determining the fate of ignored information. In parallel to behavioral evidence, neuroimaging data show that the activation generated by unattended stimuli is eliminated in task-relevant brain regions during high attentional load tasks. We conducted an fMRI experiment to explore how word encoding proceeds in a high load situation. Participants saw a rapid series of stimuli consisting of overlapping drawings and letter strings (words or nonwords). In different blocks, task instructions directed attention to either the drawings or the letters, and subjects responded to immediate repetition of items in the attended dimension. To look at the effect of attention on word processing, we compared brain activations for words and nonwords under the two attentional conditions. As compared to nonwords, word stimuli drove responses in left frontal, left temporal and parietal areas when letters were attended. However, although the behavioral measures suggested that ignored words were not analyzed when drawings were attended, a comparison of ignored words to ignored nonwords indicated the involvement of several regions including left insula, right cerebellum and bilateral pulvinar. Interestingly, word-specific activations found when attended and ignored words were compared showed no anatomical overlap, suggesting a change in processing pathways for attended and ignored words presented in a high attentional load task.

Adult↗

Social contracts and precautions activate different neurological systems: an fMRI investigation of deontic reasoning.

We conducted an event-related, functional MRI investigation of 12 male's and 12 female's reasoning about conditional deontic rules, rules regulating people's behavior. We employed two different types of rules: social contracts and nonsocial, precautionary rules. Although the rules and the demands of the task were matched in terms of their logical structure, reasoning about social contracts and precautions activated a different constellation of neurological structures. The regions differentially activated by social contracts included dorsomedial PFC (BA 6/8), bilateral ventrolateral PFC (BA 47), the left angular gyrus (BA 39), and left orbitofrontal cortex (BA 10). The regions differentially activated by precautions included bilateral insula, the left lentiform nucleus, posterior cingulate (BA 29/31), anterior cingulate (BA 24) and right postcentral gyrus (BA 3). Collectively, reasoning about prescriptive rules activated the dorsomedial PFC (BA 6/8). The results reinforce the view that human reasoning is not a unified phenomenon, but is content-sensitive.

Adult↗

Evidence for developmental changes in the visual word processing network beyond adolescence.

Late development of specialization in the visual word processing system was examined using event-related potentials (ERP) and functional magnetic resonance imaging (fMRI) of word and symbol string processing in groups of adolescents (15.2-17.3 years) and adults (19.8-30.8 years). We focused our ERP analyses on fast visual activity: the occipital P1 (82-131 ms) modulated by physical stimulus characteristics and the occipito-temporal N1 (132-256 ms) reflecting visual tuning for print. Our fMRI analyses concentrated on basal occipito-temporal activations in the visual word form area VWFA. For words, the correlation of fMRI activation in the VWFA and N1 amplitude confirmed the close relationship of the electrophysiological N1 with metabolic activity in the VWFA. Further support for this relationship came from low resolution electromagnetic tomography localizing the word-specific N1 near the VWFA. Both imaging techniques revealed age-independent differences between words and symbol strings. Late development, however, was preferentially detected with ERPs. Decreases of P1 and N1 amplitudes with age were not limited to words and suggested further maturation of the underlying brain microstructure and function. Following adolescence, decreasing N1 latencies specific to words point to continued specialization of the visual word processing system. Both N1 and fMRI measures correlated with reading performance. In summary, the similarity of global fMRI activation patterns between groups suggests a fully established distribution of the reading network in adolescence, while the decreasing N1 latencies for words indicate protracted fine tuning after adolescence.

Adolescent↗

Making sense of discourse: an fMRI study of causal inferencing across sentences.

To build up coherence between sentences (comprehend discourse), we must draw inferences, i.e. activate and integrate information that is not actually stated. We used event-related fMRI to determine the localization and extent of brain activity mediating causal inferencing across short, three-sentence scenarios. Participants read and made causal coherence judgments to sentences that were highly causally related, intermediately related or unrelated to their preceding two-sentence contexts. The highly related and intermediately related scenarios were matched in terms of semantic similarities between their individual component words. A pre-rating study established that causal inferences were generated to the intermediately related but not to the highly related or unrelated scenarios. In the scanner, sentences that were intermediately related (relative to highly related or unrelated) to their preceding contexts were associated with longer judgment reaction times and sustained increases in hemodynamic activity within left lateral temporal/inferior parietal/prefrontal cortices, the right inferior prefrontal gyrus and bilateral superior medial prefrontal cortices. In contrast, sentences that were unrelated (relative to highly related) to their preceding contexts were associated with only transient increases in activity (at, but not after, the peak of the hemodynamic response) within the right lateral temporal cortex and the right inferior prefrontal gyrus. These data suggest that, to make sense of discourse, we activate a large bilateral cortical network in response to what is not explicitly stated. We suggest that this network reflects the activation, retrieval and integration of information from long-term semantic memory into incoming discourse structure during causal inferencing.

Adult↗

Numerical magnitude in the human parietal lobe; tests of representational generality and domain specificity.

Behavioral evidence suggests that human adults have a single system for representing the numerical magnitude of both symbolic numbers (e.g., Arabic digits) and nonsymbolic number stimuli (e.g., dot arrays). Brain imaging studies have implicated a specific parietal region in symbolic number processing, leading to the influential hypothesis that this region is the locus of a dedicated, domain-specific number system. Here we evaluated a prediction of this hypothesis, that this region should be activated not only by symbolic but also nonsymbolic number processing. Using nonsymbolic stimuli, we tested for higher parietal activations for number than for nonnumber comparison tasks (experiment 1), fMRI adaptation for numerosity repetition (experiment 2), and greater fMRI increases with increasing task difficulty for number than nonnumber tasks (experiment 3). None of these predictions were supported by the data, posing a serious challenge to the hypothesis that a single, domain-specific parietal region underlies both symbolic and nonsymbolic number representation.

Brain Mapping↗

Neural signatures of economic preferences for risk and ambiguity.

People often prefer the known over the unknown, sometimes sacrificing potential rewards for the sake of surety. Overcoming impulsive preferences for certainty in order to exploit uncertain but potentially lucrative options may require specialized neural mechanisms. Here, we demonstrate by functional magnetic resonance imaging (fMRI) that individuals' preferences for risk (uncertainty with known probabilities) and ambiguity (uncertainty with unknown probabilities) predict brain activation associated with decision making. Activation within the lateral prefrontal cortex was predicted by ambiguity preference and was also negatively correlated with an independent clinical measure of behavioral impulsiveness, suggesting that this region implements contextual analysis and inhibits impulsive responses. In contrast, activation of the posterior parietal cortex was predicted by risk preference. Together, this novel double dissociation indicates that decision making under ambiguity does not represent a special, more complex case of risky decision making; instead, these two forms of uncertainty are supported by distinct mechanisms.

Adolescent↗

Isolation of a central bottleneck of information processing with time-resolved FMRI.

When humans attempt to perform two tasks at once, execution of the first task usually leads to postponement of the second one. This task delay is thought to result from a bottleneck occurring at a central, amodal stage of information processing that precludes two response selection or decision-making operations from being concurrently executed. Using time-resolved functional magnetic resonance imaging (fMRI), here we present a neural basis for such dual-task limitations, e.g. the inability of the posterior lateral prefrontal cortex, and possibly the superior medial frontal cortex, to process two decision-making operations at once. These results suggest that a neural network of frontal lobe areas acts as a central bottleneck of information processing that severely limits our ability to multitask.

Acoustic Stimulation↗

The special involvement of the rostrolateral prefrontal cortex in planning abilities: an event-related fMRI study with the Tower of London paradigm.

Planning abilities are essential for the successful management of everyday life activities. Although several neuroimaging studies provide evidence that the prefrontal cortex is crucially involved in planning, the differential roles of its subregions are still a matter of debate. The aim of this study was to investigate the neural correlates of planning by focusing on the functional differentiation between the dorsolateral and rostrolateral prefrontal cortex using the Tower of London (ToL) task and a parametric event-related functional MRI design. In order to control for activations unspecific to planning, two control conditions were presented, which were matched for the length of single events in the ToL task. Seventeen right-handed healthy subjects participated in this study. All statistics were reported with corrections for multiple comparisons (p < 0.05). Compared to control conditions, activations in the ToL task were observed in the dorsolateral prefrontal cortex bilaterally, the right ventrolateral and left rostrolateral prefrontal cortex along with the thalamus, as well as in the parietal and premotor cortex bilaterally. Task complexity dependent analyses revealed that only the left rostrolateral prefrontal cortex showed a BOLD signal increase over the four planning levels, which could not be observed in the control conditions. Hence, current findings suggest that planning involves an extensive fronto-parieto-thalamic network. Within this network, the rostrolateral prefrontal cortex seems to be the only region that is exclusively reactive to planning specific processes, which we described in terms of simultaneous monitoring of internally generated and externally presented information.

Adult↗

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.

Adult↗

Relationship between information processing speed in temporal lobe epilepsy and white matter volume.

Abnormalities in white matter have been linked to processing speed impairment in clinical populations (e.g., multiple sclerosis, closed head injury). Recent studies indicate the presence of significant reduction in cerebral white matter volume in some patients with chronic temporal lobe epilepsy (TLE). The objective of this study was to examine the relationship between white matter volume and processing speed and performance efficiency on the Sternberg Memory Scanning Test (SMST). The study groups included TLE subjects with white matter volume reduction (n=13), TLE subjects with normal white matter volume (n=14), and healthy controls (n=18). The groups did not differ in total cerebral gray matter volume. Compared with the controls, the reduced white matter volume TLE group exhibited a significantly steeper slope on the SMST. This was characterized by a disproportionate increase in reaction time with increased processing demands (set size), particularly for negative probe trials. In contrast, no significant differences on the SMST were evident between controls and the normal white matter volume TLE group. These findings suggest the presence of information processing speed and efficiency impairment in TLE and its relationship with white matter volume integrity.

Adolescent↗