• Objective. —This synthetic review was performed to demonstrate the utility of frontal-subcortical circuits in the explanation of a wide range of human behavioral disorders. Data Sources. —Reports of patients with degenerative disorders or focal lesions involving frontal lobe or linked subcortical structures were chosen from the English literature. Individual case reports and group investigations from peer-reviewed journals were evaluated. Study Selection. —Studies were included if they described patient behavior in detail or reported pertinent neuropsychological findings and had compelling evidence of a disorder affecting frontal-subcortical circuits. Data Extraction. —Information was used if the report from which it was taken met study selection criteria. Data Synthesis. —Five parallel segregated circuits link the frontal lobe and subcortical structures. Clinical syndromes observed with frontal lobe injury are recapitulated with lesions of subcortical member structures of the circuits. Each prefrontal circuit has a signature behavioral syndrome: executive function deficits occur with lesions of the dorsolateral prefrontal circuit, disinhibition with lesions of the orbitofrontal circuit, and apathy with injury to the anterior cingulate circuit. Depression, mania, and obsessivecompulsive disorder may also be mediated by frontalsubcortical circuits. Movement disorders identify involvement of the basal ganglia component of frontal-subcortical circuits. Conclusions. —Frontal-subcortical circuits mediate many aspects of human behavior.

Frontal-subcortical circuits and human behavior.

Exposure to arsenic has long been known to have neurologic consequences in adults, but to date there are no well-controlled studies in children. We report results of a cross-sectional investigation of intellectual function in 201 children 10 years of age whose parents participate in our ongoing prospective cohort study examining health effects of As exposure in 12,000 residents of Araihazar, Bangladesh. Water As and manganese concentrations of tube wells at each child’s home were obtained by surveying all wells in the study region. Children and mothers came to our field clinic, where children received a medical examination in which weight, height, and head circumference were measured. Children’s intellectual function on tests drawn from the Wechsler Intelligence Scale for Children, version III, was assessed by summing weighted items across domains to create Verbal, Performance, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and creatinine and were asked to provide blood samples for measuring blood lead and hemoglobin concentrations. Exposure to As from drinking water was associated with reduced intellectual function after adjustment for sociodemographic covariates and water Mn. Water As was associated with reduced intellectual function, in a dose–response manner, such that children with water As levels > 50 μg/L achieved significantly lower Performance and Full-Scale scores than did children with water As levels < 5.5 μg/L. The association was generally stronger for well-water As than for urinary As.

/pdf/water-manganese-exposure-and-children-s-intellectual-24ejtst0fo.pdf

Water Manganese Exposure and Children's Intellectual Function in Araihazar, Bangladesh

Five parallel anatomic circuits link regions of the frontal cortex to the striatum, globus pallidus/substantia nigra, and thalamus. The circuits originate in the supplementary motor area, frontal eye fields, dorsolateral prefrontal region, lateral orbito-frontal area, and anterior cingulate cortex. Open loop structures that provide input to or receive output from specific circuits share functions, cytoarchitectural features, and phylogenetic histories with the relevant circuits. The circuits mediate motor and oculomotor function as well as executive functions, socially responsive behavior, and motivation. Neuropsychiatric disorders of frontal-subcortical circuits include impaired executive function, disinhibition, and apathy; indicative mood disorders include depression, mania, and lability. Transmitters, modulators, receptor subtypes, and second messengers within the circuits provide a chemoarchitecture that can inform pharmacotherapy.

Frontal-subcortical circuits and neuropsychiatric disorders.

Exposure to manganese (Mn) causes clinical signs and symptoms resembling, but not identical to, Parkinson's disease. Since our last review on this subject in 2004, the past decade has been a thriving period in the history of Mn research. This report provides a comprehensive review on new knowledge gained in the Mn research field. Emerging data suggest that beyond traditionally recognized occupational manganism, Mn exposures and the ensuing toxicities occur in a variety of environmental settings, nutritional sources, contaminated foods, infant formulas, and water, soil, and air with natural or man-made contaminations. Upon fast absorption into the body via oral and inhalation exposures, Mn has a relatively short half-life in blood, yet fairly long half-lives in tissues. Recent data suggest Mn accumulates substantially in bone, with a half-life of about 8-9 years expected in human bones. Mn toxicity has been associated with dopaminergic dysfunction by recent neurochemical analyses and synchrotron X-ray fluorescent imaging studies. Evidence from humans indicates that individual factors such as age, gender, ethnicity, genetics, and pre-existing medical conditions can have profound impacts on Mn toxicities. In addition to body fluid-based biomarkers, new approaches in searching biomarkers of Mn exposure include Mn levels in toenails, non-invasive measurement of Mn in bone, and functional alteration assessments. Comments and recommendations are also provided with regard to the diagnosis of Mn intoxication and clinical intervention. Finally, several hot and promising research areas in the next decade are discussed.

https://link.springer.com/content/pdf/10.1007%2Fs40572-015-0056-x.pdf

G. M. Umarji

Papers

Chronic manganese poisoning.

Chronic manganese poisoning. A case report.