Cognitive Function and Neuropsychological Comorbidities in Children with Newly Diagnosed Idiopathic Epilepsy.

BACKGROUND: In this study, we aimed to identify cognitive function and neuropsychological comorbidities in children with newly diagnosed idiopathic epilepsy. METHODS: We retrospectively reviewed the records of 97 antiepileptic drug-naïve children (9.7 ± 2.9 years; 54 males and 43 females) with newly diagnosed idiopathic epilepsy, all of whom underwent a neuropsychological battery. The battery consisted of the Korean Wechsler Intelligence Scale, Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale, ADHD Diagnostic System, Children's Depression Inventory, and State-Trait Anxiety Inventory for Children. We investigated association between scores of the neuropsychological battery and epilepsy classification, lateralization of interictal epileptiform discharges (IEDs) on electroencephalography (EEG), and variables related to seizures. RESULTS: Thirteen patients (14.3%) had ADHD symptoms. Three patients (4.1%) had depressive symptoms, and 9 (12.3%) had anxiety symptoms. Patients with idiopathic generalized epilepsy (IGE) had significantly lower full-scale intelligence and performance intelligence quotient scores than patients with idiopathic localization-related epilepsy (ILRE) (89.0 ± 17.6 vs. 96.3 ± 14.8; P = 0.030 and 88.9 ± 16.3 vs. 97.0 ± 16.4; P = 0.016, respectively). Patients with ILRE having unilateral IEDs had significantly higher full-scale intelligence quotient scores than patients with ILRE having bilateral IEDs and patients with IGE (99.9 ± 12.2 vs. 93.7 ± 16.1 vs. 89.0 ± 17.6; P = 0.039, respectively). CONCLUSION: Our results suggest that idiopathic epilepsy may be accompanied by various neuropsychological comorbidities even at initial diagnosis. Patients with IGE and ILRE having bilateral IEDs on EEG appear more likely to be at high risk of decreased cognitive function.

Altered executive function in the welders: A functional magnetic resonance imaging study.

Chronic exposure to manganese (Mn) can lead to impairments in motor and cognitive functions. Several recent studies reported Mn-induced executive dysfunction. The present study compared the neural correlates of ongoing executive function of welders and healthy controls. Fifty-three welders and 44 healthy controls were enrolled. Participants were given functional magnetic resonance imaging (fMRI) scans and performed two modified versions of the Wisconsin Card Sorting Task (WCST) that differed in cognitive demand, and a task that established a high-level baseline (HLB) condition. Card Sorting Test and Word-Color Test were also used to assess executive performance. Neural activation of the bilateral superior-frontal cortex, right-inferior parietal cortex, and bilateral insula cortex were greater in healthy controls than in welders when contrasting the difficult version of the WCST with the HLB. There were also correlations between executive functions by the Card Sorting Test and Word-Color Test, and brain activation in the insula cortex using the WCST. Our results indicated that welders had altered neural processing related to executive function in the prefrontal cortex under conditions of high cognitive demand. Welders also had less activation of the insula cortex, a part of a larger network comprising the lateral prefrontal cortex and parietal cortex.

Altered executive function in the lead-exposed brain: A functional magnetic resonance imaging study.

INTRODUCTION: It is well known that lead exposure induces neurotoxic effects, which can result in dysfunction in a variety of cognitive capacities including executive function. However, few studies have used fMRI to examine the direct neural correlates of executive function in participants with past lead exposure. Therefore, this study aimed to investigate possible alterations in the neural correlates of executive function in the previously lead-exposed brain. METHODS: Forty-three lead-exposed and 41 healthy participants were enrolled. During the fMRI scans, participants performed two modified versions of the Wisconsin Card Sorting Task (WCST) differing in cognitive demand, and a task that established a high-level baseline condition (HLB). RESULTS: The neural activation of left dorsolateral prefrontal cortex was greater in healthy controls than in participants with lead exposure when contrasting the difficult version of the WCST with the HLB. Moreover, cortical activation was found to be inversely associated with blood lead concentration after controlling for covariates. DISCUSSION: These data suggest that lead exposure can induce functional abnormalities in distributed cortical networks related to executive function, and that lead-induced neurotoxicity may be persistent rather than transient.

Lead-induced impairments in the neural processes related to working memory function.

BACKGROUND: It is well known that lead exposure induces neurotoxic effects, which can result in a variety of neurocognitive dysfunction. Especially, occupational lead exposures in adults are associated with decreases in cognitive performance including working memory. Despite recent advances in human neuroimaging techniques, the neural correlates of lead-exposed cognitive impairment remain unclear. Therefore, this study was aimed to compare the neural activations in relation to working memory function between the lead-exposed subjects and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-one lead-exposed subjects and 34 healthy subjects performed an n-back memory task during MRI scan. We performed fMRI using the 1-back and 2-back memory tasks differing in cognitive demand. Functional MRI data were analyzed using within- and between-group analysis. We found that the lead-exposed subjects showed poorer working memory performance during high memory loading task than the healthy subjects. In addition, between-group analyses revealed that the lead-exposed subjects showed reduced activation in the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, pre supplementary motor areas, and inferior parietal cortex. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that functional abnormalities in the frontoparietal working memory network might contribute to impairments in maintenance and manipulation of working memory in the lead-exposed subjects.

Decreased brain volumes in manganese-exposed welders.

BACKGROUND: A great deal of research has been devoted to identifying subclinical functional brain abnormalities in manganese (Mn)-exposed welders. However, no previous study has investigated morphological brain abnormalities, such as changes in brain volume, in welders. This study evaluates morphological changes in brain volume among welders, and investigates the relationship between structural brain abnormalities and subclinical dysfunction in this population. METHODS: We used voxel-based morphometry (VBM) to assess differences in gray and white matter brain volumes between 40 welders with chronic Mn exposure and 26 age-matched control subjects. Correlation analyses were used to investigate the relationship between brain volume changes and decreased performance on neurobehavioral tests. RESULTS: Brain volumes in the globus pallidus and cerebellar regions were significantly diminished in welders with chronic Mn exposure compared to controls (FDR-corrected P<0.05). These changes in brain volume were negatively correlated with cognitive performance and grooved pegboard scores. CONCLUSION: There are measurable brain volume reductions in the globus pallidus and cerebellum of welders chronically exposed to Mn, and these volume reductions correlate with cognitive and motor neurobehavioral deficits. Our findings therefore indicate that volumetric measurement could be a useful subclinical marker among welders that show no signs of manganism.

Altered white matter microstructural integrity revealed by voxel-wise analysis of diffusion tensor imaging in welders with manganese exposure.

Chronic exposure to manganese (Mn), which can be an occupational hazard or can result from liver failure, is associated with adverse motor and cognitive outcomes. Evidence from previous neuroimaging and magnetic resonance spectroscopy studies suggested alteration of function in Mn-exposed brains. However, the effect of chronic exposure of the human brain to Mn on white matter (WM) structure has not yet been determined. In the present study, we used diffusion tensor imaging (DTI) to investigate whether welders exposed to Mn demonstrate differences in WM integrity, compared with control subjects. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on a voxel-wise basis in 30 male welders with exposure to Mn and in 19 age- and gender-matched control subjects. Direct comparison between welders and controls using investigator-independent Statistical Parametric Mapping (SPM) voxel-wise analysis of DTI metrics revealed a reduction of FA in the corpus callosum (CC) and frontal WM in Mn-exposed welders. Further, marked increases in RD and negligible changes in AD suggested that the microstructural changes in the CC and frontal WM result from compromised radial directionality of fibers in these areas, caused primarily by demyelination. Correlation analysis with neurobehavioral performance also suggested that the microstructural abnormalities were associated with subtle motor and cognitive differences in welders.

Neuroplastic changes within the brains of manganese-exposed welders: recruiting additional neural resources for successful motor performance.

BACKGROUND: In a previous study, regional delivery of manganese (Mn)ions within the brain revealed that the metal accumulates in the basal ganglia, where it induces degeneration of the globus pallidus. Degeneration of the basal ganglia impairs motor ability by compromising an important neural circuit involved in the regulation of motor control. Therefore, much research has been devoted to identifying a sensitive and non-invasive imaging marker to evaluate the functional correlates of Mn-related brain dysfunction. METHODS: We performed the first-ever sequential finger-tapping functional MRI (fMRI) experiment to investigate the behavioural significance of additionally recruited brain regions in welders with chronic Mn exposure. RESULTS: During the finger tapping task, activation of the bilateral primary sensorimotor cortex (SM1), bilateral supplementary motor area (SMA), bilateral dorsolateral premotor cortex, bilateral superior parietal cortex and ipsilateral dentate nucleus was higher in the welding group (42 welders) than in the control group (26 controls). The pallidal index correlated with the activation observed in the contralateral SM1 for the finger tapping task of the left hand. The fMRI variables correlated with motor behaviour. Grooved Pegboard performances (right hand) correlated with activation, as seen in the ipsilateral and contralateral SMAs obtained during the finger tapping task of the right hand. CONCLUSION: Our findings suggest that increased brain activation results from the compensational activation of ancillary cortical pathways, which ensures adequate motor function.

Altered working memory process in the manganese-exposed brain.

Chronic manganese (Mn) exposure often leads to impairments in fine motor and cognitive functions, particularly memory. However, the neural correlates of Mn-induced alterations in memory remain unclear. In the present study, we performed functional MRI (fMRI) with 2-back memory tests to assess the neural correlates of Mn-induced memory impairment in response to subclinical dysfunction in the working memory networks in welders exposed to Mn for extended periods of time. Within-group and between-group analyses revealed that brain activity in working memory networks was increased in welders with chronic Mn exposure during the 2-back verbal working memory task compared to healthy control individuals. Therefore, our fMRI findings indicate that welders might require more neural resources in working memory networks to compensate for subtle deficits in working memory and altered working memory processes, even if they performed the tasks at the same level as healthy control individuals.

Pallidal index measured with three-dimensional T1-weighted gradient echo sequence is a good predictor of manganese exposure in welders.

PURPOSE: To evaluate which T1-wieghted technique between 3D gradient-echo (FSPGR) and conventional spin-echo (SE) sequence is more sensitive predictor of neurobehavioral dysfunction found in welders with chronic manganese (Mn) acquired at 3 Tesla. MATERIALS AND METHODS: Forty-three current male welders and 29 age- and gender-matched, nonwelding production workers (control individuals) were recruited to the present study. Each subject underwent neurological examination, blood sample collection, and neurobehavioral tests, in addition to magnetic resonance imaging (MRI) examination. The MRI examinations were performed using a 3.0 Tesla whole-body scanner. T1-weighted axial images were obtained using SE and FSPGR with a 180 degrees inversion recovery prepared pulse, and the corresponding pallidal indices (PI), PI (SE), and PI (FSPGR), were calculated. RESULTS: Both PI (SE) and PI (FSPGR) were well correlated with blood Mn level, but only PI (FSPGR) was significantly correlated with air Mn concentration (P = 0.007). Of the neurobehavioral performance indicators, after controlling for covariates, PI (FSPGR) was significantly associated with cognitive components, such as the digit symbol score, the digit span backward score, the Stroop test score and also with the grooved pegboard (dominant hand) score, whereas PI (SE) was associated only with grooved pegboard (dominant hand) score. CONCLUSION: PI using a T1-weighted 3D FSPGR sequence shows the best correlation with neurobehavioral performance indicators and is the best measure for detection of blood and airborne Mn concentrations in welders exposed to excessive occupational Mn.

Neurochemical changes in welders revealed by proton magnetic resonance spectroscopy.

BACKGROUND: Occupational and environmental exposure to manganese (Mn) is associated with various neurobehavioral and movement dysfunctions. However, few studies have systemically examined the neurochemical effects of Mn exposure. OBJECTIVES: We examined typical changes in cerebral metabolite ratios in welders chronically exposed to Mn, compared with control individuals, using proton magnetic resonance spectroscopy (MRS), investigated whether an abnormality in brain metabolism is associated with neurobehavioral changes, and assessed possible implications of chronic Mn exposure. METHODS: Thirty-five welders chronically exposed to Mn and 20 age-matched healthy subjects underwent single-voxel MRS at short echo time to assess the N-acetylaspartate (NAA), myoinositol (mI), total choline (tCho), and glutamine plus glutamate (Glx) levels, each of which was expressed as a ratio to total creatine (tCr). Neurobehavioral tests were also performed to define cognitive status. RESULTS: NAA/tCr, Glx/tCr, and tCho/tCr ratios in the frontal gray matter (anterior cingulate cortex; ACC) and parietal white matter did not differ significantly between welders and control subjects. These metabolite ratios did not correlate significantly with blood Mn concentration or neurobehavioral parameters. However, mI levels in the ACC, but not in the parietal white matter, were significantly reduced in welders compared with control individuals (P<0.01). Furthermore, in the frontal lobe of the brain, the mI/tCr ratio was significantly correlated with verbal memory scores as well as blood Mn concentration (P<0.05). CONCLUSIONS: The cognitive decline observed in welders exposed to Mn was associated with a decreased mI/tCr ratio in the ACC. The depletion of mI in welders may reflect possible glial cell swelling and/or detoxification processes associated with long-term exposure to Mn.

High signal intensity on magnetic resonance imaging is a better predictor of neurobehavioral performances than blood manganese in asymptomatic welders.

OBJECTIVES: The aim of the study was to evaluate subclinical neurological effects in welders, using an extensive list of neurobehavioral batteries and determine if there is a link between pallidal index (PI) and subclinical neurobehavioral effects in the spectrum of manganese (Mn) symptomatology. METHODS: A total of 43 asymptomatic male welders and 29 age- and sex-matched healthy control individuals completed questionnaires, and underwent blood examinations, brain magnetic resonance imaging (MRI) scans, and a wide range of neurobehavioral examinations. RESULTS: Digit symbol, auditory verbal learning test (delayed recall), complex figure test (copy and immediate recall), digit span, verbal fluency test, Stroop test, grooved pegboard, finger tapping, frequency dispersion and harmonic index of tremor, and maximum frequency of hand coordination showed differences between welders and control individuals. No differences were noted for simple reaction time, postural sway, smell test, and profile of mood states (POMS). Blood Mn levels were shown to be significantly associated with grooved pegboard (dominant hand) and complex figure test (copy) results. PI was significantly associated with digit symbol, digit span backward, Stroop Word and Stroop error index, and grooved pegboard (dominant hand) results. CONCLUSIONS: The present findings that there were significant correlations between several neurobehavioral deficits and PI as well as blood Mn suggest that they may be attributed to Mn exposure in welding fumes. The present study also shows that PI is a better predictor of neurobehavioral performance than blood Mn levels in asymptomatic welders.