Sex differences in functional connectivity during fetal brain development.

Sex-related differences in brain and behavior are apparent across the life course, but the exact set of processes that guide their emergence in utero remains a topic of vigorous scientific inquiry. Here, we evaluate sex and gestational age (GA)-related change in functional connectivity (FC) within and between brain wide networks. Using resting-state functional magnetic resonance imaging we examined FC in 118 human fetuses between 25.9 and 39.6 weeks GA (70 male; 48 female). Infomap was applied to the functional connectome to identify discrete prenatal brain networks in utero. A consensus procedure produced an optimal model comprised of 16 distinct fetal neural networks distributed throughout the cortex and subcortical regions. We used enrichment analysis to assess network-level clustering of strong FC-GA correlations separately in each sex group, and to identify network pairs exhibiting distinct patterns of GA-related change in FC between males and females. We discovered both within and between network FC-GA associations that varied with sex. Specifically, associations between GA and posterior cingulate-temporal pole and fronto-cerebellar FC were observed in females only, whereas the association between GA and increased intracerebellar FC was stronger in males. These observations confirm that sexual dimorphism in functional brain systems emerges during human gestation.

Within-subject neural reactivity to reward and threat is inverted in young adolescents.

BACKGROUND: As children mature, they become increasingly independent and less reliant on caregiver support. Changes in brain systems are likely to stimulate and guide this process. One mechanistic hypothesis suggests that changes in neural systems that process reward and threat support the increase in exploratory behavior observed in the transition to adolescence. This study examines the basic tenets of this hypothesis by performing functional magnetic resonance imaging (fMRI) during well-established reward and threat processing tasks in 40 children and adolescents, aged 9-15 years. METHOD: fMRI responses in the striatum and amygdala are fit to a model predicting that striatal reward and amygdala threat-responses will be unrelated in younger participants (aged 9-12 years), while older participants (aged 13-15 years) will differentially engage these structures. RESULTS: Our data are consistent with this model. Activity in the striatum and amygdala are comparable in younger children, but in older children, they are inversely related; those more responsive to reward show a reduced threat-response. Analyses testing age as a continuous variable yield consistent results. In addition, the proportion of threat to reward-response relates to self-reported approach behavior in older but not younger youth, exposing behavioral relevance in the relative level of activity in these structures. CONCLUSIONS: Results are consistent with the notion that both individual and developmental differences drive reward-seeking behavior in adolescence. While these response patterns may serve adaptive functions in the shift to independence, skew in these systems may relate to increased rates of emotional psychopathology and risk-taking observed in adolescence.

You say 'prefrontal cortex' and I say 'anterior cingulate': meta-analysis of spatial overlap in amygdala-to-prefrontal connectivity and internalizing symptomology.

Connections between the amygdala and medial prefrontal cortex (mPFC) are considered critical for the expression and regulation of emotional behavior. Abnormalities in frontoamygdala circuitry are reported across several internalizing conditions and associated risk factors (for example, childhood trauma), which may underlie the strong phenotypic overlap and co-occurrence of internalizing conditions. However, it is unclear if these findings converge on the same localized areas of mPFC or adjacent anterior cingulate cortex (ACC). Examining 46 resting-state functional connectivity magnetic resonance imaging studies of internalizing conditions or risk factors (for example, early adversity and family history), we conducted an activation likelihood estimation meta-analysis of frontoamygdala circuitry. We included all reported amygdala to frontal coordinate locations that fell within a liberal anatomically defined frontal mask. Peak effects across studies were centered in two focal subareas of the ACC: pregenual (pgACC) and subgenual (sgACC). Using publicly available maps and databases of healthy individuals, we found that observed subareas have unique connectivity profiles, patterns of neural co-activation across a range of neuropsychological tasks, and distribution of tasks spanning various behavioral domains within peak regions, also known as 'functional fingerprints'. These results suggest disruptions in unique amygdala-ACC subcircuits across internalizing, genetic and environmental risk studies. Based on functional characterizations and the studies contributing to each peak, observed amygdala-ACC subcircuits may reflect separate transdiagnostic neural signatures. In particular, they may reflect common neurobiological substrates involved in developmental risk (sgACC), or the broad expression of emotional psychopathology (pgACC) across disease boundaries.

Investigating neural primacy in Major Depressive Disorder: multivariate Granger causality analysis of resting-state fMRI time-series data.

Major Depressive Disorder (MDD) has been conceptualized as a neural network-level disease. Few studies of the neural bases of depression, however, have used analytical techniques that are capable of testing network-level hypotheses of neural dysfunction in this disorder. Moreover, of those that have, fewer still have attempted to determine the directionality of influence within functionally abnormal networks of structures. We used multivariate GC analysis, a technique that estimates the extent to which preceding neural activity in one or more seed regions predicts subsequent activity in target brain regions, to analyze blood-oxygen-level-dependent (BOLD) data collected during eyes-closed rest from depressed and never-depressed persons. We found that activation in the hippocampus predicted subsequent increases in ventral anterior cingulate cortex (vACC) activity in depression, and that activity in the medial prefrontal cortex and vACC were mutually reinforcing in MDD. Hippocampal and vACC activation in depressed participants predicted subsequent decreases in dorsal cortical activity. This study shows that, on a moment-by-moment basis, there is increased excitatory activity among limbic and paralimbic structures, as well as increased inhibition in the activity of dorsal cortical structures, by limbic structures in depression; these aberrant patterns of effective connectivity implicate disturbances in the mesostriatal dopamine system in depression. These findings advance the neural theory of depression by detailing specific patterns of limbic excitation in MDD, by making explicit the primary role of limbic inhibition of dorsal cortex in the cortico-limbic relation posited to underlie depression, and by presenting an integrated neurofunctional account of altered dopamine function in this disorder.

An impairment in sniffing contributes to the olfactory impairment in Parkinson's disease.

Although the presence of an olfactory impairment in Parkinson's disease (PD) has been recognized for 25 years, its cause remains unclear. Here we suggest a contributing factor to this impairment, namely, that PD impairs active sniffing of odorants. We tested 10 men and 10 women with clinically typical PD, and 20 age- and gender-matched healthy controls, in four olfactory tasks: (i) the University of Pennsylvania smell identification test; (ii and iii) detection threshold tests for the odorants vanillin and propionic acid; and (iv) a two-alternative forced-choice detection paradigm during which sniff parameters (airflow peak rate, mean rate, volume, and duration) were recorded with a pneomatotachograph-coupled spirometer. An additional experiment tested the effect of intentionally increasing sniff vigor on olfactory performance in 20 additional patients. PD patients were significantly impaired in olfactory identification (P < 0.0001) and detection (P < 0.007). As predicted, PD patients were also significantly impaired at sniffing, demonstrating significantly reduced sniff airflow rate (P < 0.01) and volume (P < 0.002). Furthermore, a patient's ability to sniff predicted his or her performance on olfactory tasks, i.e., the more poorly patients sniffed, the worse their performance on olfaction tests (P < 0.009). Finally, increasing sniff vigor improved olfactory performance in those patients whose baseline performance had been poorest (P < 0.05). These findings implicate a sniffing impairment as a component of the olfactory impairment in PD and further depict sniffing as an important component of human olfaction.

Work-related musculoskeletal disorders among physical therapists.

BACKGROUND AND PURPOSE: Increasing evidence suggests that musculoskeletal disorders are common in workers in the United States health care industry. Physical therapists, who commonly treat patients with these disorders, are also at risk for work-related musculoskeletal disorders (WMD) in the upper limbs and low back. The purpose of this study was to determine the prevalence of WMD during a 12-month period and the job factors that may be associated with these disorders in physical therapists. SUBJECTS: A four-page questionnaire was mailed to physical therapists (N = 1,160) who attended The University of Iowa between 1943 and 1993. Nine hundred twenty-eight questionnaires were returned (80% response rate) from physical therapists in 46 states. METHODS: Based on a literature review and pilot study of physical therapists, a survey instrument was constructed consisting of a symptom survey, a job-factor survey, and various demographic information. RESULTS: The highest prevalences of WMD among physical therapists were in the following anatomical areas: low back (45%), wrist/hand (29.6%), upper back (28.7%), and neck (24.7%). The job factor rated most likely to contribute to job-related musculoskeletal disorders was "lifting or transferring dependent patients." The prevalence of WMD in physical therapists also was affected by work setting, practice specialty, age of patient, and gender of therapist. CONCLUSION AND DISCUSSION: Specific strategies should be developed to reduce WMD in the practice of physical therapy.

Correlates of preoperative hematocrit value in patients undergoing coronary artery bypass.

The patient's preoperative red cell volume and hematocrit value are among the strongest predictors of need for postoperative transfusion. We have determined the factors that correlate with preoperative hematocrit value. We performed multiple regression analysis with preoperative hematocrit value as the dependent variable. The factors that were significantly correlated with preoperative hematocrit value, in order of their decreasing contribution to variability, were sex, date of operation, preoperative hospital stay, weight, left ventricular end-diastolic pressure, age, smoking history, and recent myocardial infarction (less than 6 weeks). Factors that did not contribute significantly to predicting preoperative hematocrit value included ejection fraction, emergency operation, previous streptokinase use, number of coronary arteries diseased, body mass index (obesity), diabetes, height, body surface area, and history of percutaneous transluminal coronary angioplasty. The patient most likely to have a low preoperative hematocrit value can be characterized as a small, elderly, female nonsmoker with a recent myocardial infarction and elevated left ventricular end-diastolic pressure. The prevalence of low preoperative hematocrit value is increasing with time independent of other factors.

Preoperative correlates of impaired wound healing after saphenous vein excision.

Although major wound complications after saphenous vein excision are infrequent, we have found broadly defined impairment in leg wound healing to be relatively common. Wound healing impairment is defined in this study as inflammation, separation, cellulitis, lymphangitis, drainage, necrosis, or abscess necessitating dressing, antibiotics, or débridement before wound healing with complete epithelialization without eschar. Healing was impaired in 245 of 1047 patients (24.3%). Significant correlations were found between impaired wound healing and female sex (p less than 0.005), body mass index (obesity) (p less than 0.005), diabetes mellitus (p less than 0.005), left ventricular end-diastolic pressure greater than 15 mm Hg (p = 0.0074), arterial occlusive disease of the legs (p = 0.0124), and preoperative hematocrit value (p = 0.0491).