The Function and Organization of Lateral Prefrontal Cortex: A Test of Competing Hypotheses

The present experiment tested three hypotheses regarding the function and organization of lateral prefrontal cortex (PFC). The first account (the information cascade hypothesis) suggests that the anterior-posterior organization of lateral PFC is based on the timing with which cue stimuli reduce uncertainty in the action selection process. The second account (the levels-of-abstraction hypothesis) suggests that the anterior-posterior organization of lateral PFC is based on the degree of abstraction of the task goals. The current study began by investigating these two hypotheses, and identified several areas of lateral PFC that were predicted to be active by both the information cascade and levels-of-abstraction accounts. However, the pattern of activation across experimental conditions was inconsistent with both theoretical accounts. Specifically, an anterior area of mid-dorsolateral PFC exhibited sensitivity to experimental conditions that, according to both accounts, should have selectively engaged only posterior areas of PFC. We therefore investigated a third possible account (the adaptive context maintenance hypothesis) that postulates that both posterior and anterior regions of PFC are reliably engaged in task conditions requiring active maintenance of contextual information, with the temporal dynamics of activity in these regions flexibly tracking the duration of maintenance demands. Activity patterns in lateral PFC were consistent with this third hypothesis: regions across lateral PFC exhibited transient activation when contextual information had to be updated and maintained in a trial-by-trial manner, but sustained activation when contextual information had to be maintained over a series of trials. These findings prompt a reconceptualization of current views regarding the anterior-posterior organization of lateral PFC, but do support other findings regarding the active maintenance role of lateral PFC in sequential working memory paradigms

Amygdala Atrophy and Its Functional Disconnection with the Cortico-Striatal-Pallidal-Thalamic Circuit in Major Depressive Disorder in Females

Background Major depressive disorder (MDD) is approximately twice as common in females than males. Furthermore, female patients with MDD tend to manifest comorbid anxiety. Few studies have explored the potential anatomical and functional brain changes associated with MDD in females. Therefore, the purpose of the present study was to investigate the anatomical and functional changes underlying MDD in females, especially within the context of comorbid anxiety. Methods In this study, we recruited antidepressant-free females with MDD (N = 35) and healthy female controls (HC; N = 23). The severity of depression and anxiety were evaluated by the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Structural and resting-state functional images were acquired on a Siemens 3.0 Tesla scanner. We compared the structural volumetric differences between patients and HC with voxel-based morphometry (VBM) analyses. Seed-based voxel-wise correlative analyses were used to identify abnormal functional connectivity. Regions with structural deficits showed a significant correlation between gray matter (GM) volume and clinical variables that were selected as seeds. Furthermore, voxel-wise functional connectivity analyses were applied to identify the abnormal connectivity relevant to seed in the MDD group. Results Decreased GM volume in patients was observed in the insula, putamen, amygdala, lingual gyrus, and cerebellum. The right amygdala was selected as a seed to perform connectivity analyses, since its GM volume exhibited a significant correlation with the clinical anxiety scores. We detected regions with disrupted connectivity relevant to seed primarily within the cortico-striatal-pallidal-thalamic circuit. Conclusions Amygdaloid atrophy, as well as decreased functional connectivity between the amygdala and the cortico-striatal-pallidal-thalamic circuit, appears to play a role in female MDD, especially in relation to comorbid anxiety

Dynamical Principles of Emotion-Cognition Interaction: Mathematical Images of Mental Disorders

The key contribution of this work is to introduce a mathematical framework to understand self-organized dynamics in the brain that can explain certain aspects of itinerant behavior. Specifically, we introduce a model based upon the coupling of generalized Lotka-Volterra systems. This coupling is based upon competition for common resources. The system can be regarded as a normal or canonical form for any distributed system that shows self-organized dynamics that entail winnerless competition. Crucially, we will show that some of the fundamental instabilities that arise in these coupled systems are remarkably similar to endogenous activity seen in the brain (using EEG and fMRI). Furthermore, by changing a small subset of the system's parameters we can produce bifurcations and metastable sequential dynamics changing, which bear a remarkable similarity to pathological brain states seen in psychiatry. In what follows, we will consider the coupling of two macroscopic modes of brain activity, which, in a purely descriptive fashion, we will label as cognitive and emotional modes. Our aim is to examine the dynamical structures that emerge when coupling these two modes and relate them tentatively to brain activity in normal and non-normal states

Reconstruction of the Core and Extended Regulons of Global Transcription Factors

The processes underlying the evolution of regulatory networks are unclear. To address this question, we used a comparative genomics approach that takes advantage of the large number of sequenced bacterial genomes to predict conserved and variable members of transcriptional regulatory networks across phylogenetically related organisms. Specifically, we developed a computational method to predict the conserved regulons of transcription factors across α-proteobacteria. We focused on the CRP/FNR super-family of transcription factors because it contains several well-characterized members, such as FNR, FixK, and DNR. While FNR, FixK, and DNR are each proposed to regulate different aspects of anaerobic metabolism, they are predicted to recognize very similar DNA target sequences, and they occur in various combinations among individual α-proteobacterial species. In this study, the composition of the respective FNR, FixK, or DNR conserved regulons across 87 α-proteobacterial species was predicted by comparing the phylogenetic profiles of the regulators with the profiles of putative target genes. The utility of our predictions was evaluated by experimentally characterizing the FnrL regulon (a FNR-type regulator) in the α-proteobacterium Rhodobacter sphaeroides. Our results show that this approach correctly predicted many regulon members, provided new insights into the biological functions of the respective regulons for these regulators, and suggested models for the evolution of the corresponding transcriptional networks. Our findings also predict that, at least for the FNR-type regulators, there is a core set of target genes conserved across many species. In addition, the members of the so-called extended regulons for the FNR-type regulators vary even among closely related species, possibly reflecting species-specific adaptation to environmental and other factors. The comparative genomics approach we developed is readily applicable to other regulatory networks

Resting-State Quantitative Electroencephalography Reveals Increased Neurophysiologic Connectivity in Depression

Symptoms of Major Depressive Disorder (MDD) are hypothesized to arise from dysfunction in brain networks linking the limbic system and cortical regions. Alterations in brain functional cortical connectivity in resting-state networks have been detected with functional imaging techniques, but neurophysiologic connectivity measures have not been systematically examined. We used weighted network analysis to examine resting state functional connectivity as measured by quantitative electroencephalographic (qEEG) coherence in 121 unmedicated subjects with MDD and 37 healthy controls. Subjects with MDD had significantly higher overall coherence as compared to controls in the delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), and beta (12–20 Hz) frequency bands. The frontopolar region contained the greatest number of “hub nodes” (surface recording locations) with high connectivity. MDD subjects expressed higher theta and alpha coherence primarily in longer distance connections between frontopolar and temporal or parietooccipital regions, and higher beta coherence primarily in connections within and between electrodes overlying the dorsolateral prefrontal cortical (DLPFC) or temporal regions. Nearest centroid analysis indicated that MDD subjects were best characterized by six alpha band connections primarily involving the prefrontal region. The present findings indicate a loss of selectivity in resting functional connectivity in MDD. The overall greater coherence observed in depressed subjects establishes a new context for the interpretation of previous studies showing differences in frontal alpha power and synchrony between subjects with MDD and normal controls. These results can inform the development of qEEG state and trait biomarkers for MDD