Comparable fMRI activity with differential behavioural performance on mental rotation and overt verbal fluency tasks in healthy men and women

To explicate the neural correlates of sex differences in visuospatial and verbal fluency tasks, we examined behavioural performance and blood-oxygenation-level-dependent (BOLD) regional brain activity, using functional magnetic resonance imaging, during a three-dimensional (3D) mental rotation task and a compressed sequence overt verbal fluency task in a group of healthy men (n=9) and women (n=10; tested during the low-oestrogen phase of the menstrual cycle). Men outperformed women on the mental rotation task, and women outperformed men on the verbal fluency task. For the mental rotation task, men and women activated areas in the right superior parietal lobe and the bilateral middle occipital gyrus in association with the rotation condition. In addition, men activated the left middle temporal gyrus and the right angular gyrus. For verbal fluency, men activated areas in the bilateral superior frontal gyrus, right cingulate gyrus, left precentral gyrus, left medial frontal gyrus, left inferior frontal gyrus, thalamus, left parahippocampal gyrus and bilateral lingual gyrus, and women activated areas in the bilateral inferior frontal gyrus and left caudate. Despite observing task related activation in the hypothesised areas in men and women, no areas significantly differentiated the two sexes. Our results demonstrate comparable brain activation in men and women in association with mental rotation and verbal fluency function with differential performance, and provide support for sex differences in brain–behaviour relationships.     

Comparable cortical activation with inferior performance in women during a novel cognitive inhibition task

Men are hypothesised to perform better than women at tasks requiring cognitive inhibition. The present study applied whole-brain functional magnetic resonance imaging to investigate the neural correlates of cognitive inhibition using a novel task, requiring detection of numbers decreasing in numerical order, in relation to sex. The study involved 19 young healthy subjects (9 men, 10 women). Behavioural sex differences favouring men were found on the inhibition, but not on the automatization (i.e. detection of numbers increasing in numerical order), condition of the task. Significant areas of activation associated with cognitive inhibition included the right inferior prefrontal and bilateral dorsolateral prefrontal cortices, left inferior and superior parietal lobes, and bilateral temporal regions across men and women. No brain region was significantly differently activated in men and women. Our findings demonstrate that (a) cognitive inhibition is dependent on intact processes within frontal and parietal regions, and (b) women show inferior cognitive inhibition despite of comparable activation to men in relevant regions. Equated behavioural performance may elicit sex differences in brain activation.     

The relationship of structural alterations to cognitive deficits in schizophrenia: a voxel-based morphometry study.

BACKGROUND: Region of interest studies have identified a number of structure-cognition associations in schizophrenia and revealed alterations in structure-cognition relationship in this population. METHODS: We examined the relationship of structural brain alterations, identified using voxel-based morphometry, to cognitive deficits in 45 schizophrenia patients relative to 43 healthy control subjects and tested the hypothesis that structure-cognition relationship is altered in schizophrenia. RESULTS: Patients had smaller total brain, gray matter, and white matter volumes. Regional alterations were left-hemisphere specific, including: gray matter reduction of inferior frontal, lingual, and anterior superior temporal gyri; white matter reduction of posterior and occipital lobes; and gray matter increase of the putamen and the precuneus. Smaller whole brain and gray matter volumes were associated with lower premorbid intelligence quotient (IQ) and poorer performance on IQ-dependent cognitive measures in patients and to a similar extent in control subjects. Larger precuneus was associated with better immediate verbal memory in patients, whereas verbal and nonverbal memory were positively associated with inferior frontal gyrus volume in control subjects. Smaller occipital white matter volume was associated with slower information processing speed in patients but not in control subjects. CONCLUSIONS: Regional volume alterations are associated with specific cognitive deficits in schizophrenia. Some structure-cognition relationships differentiate this population from healthy control subjects.     

Determination of plasma 3-methoxy-4-hydroxyphenyl-glycol by pulsed electron capture gas chromatography.

An improved method is described for determining picogram quantities of 3-methoxy-4-hydroxyphenylglycol (MHPG) in plasma of humans and of other species. The method makes use of gas-liquid chromatography and electron capture detection. Low level nonlinearity of detector response was corrected by operating the detector in the pulsed rather then the customary steady state mode. Detector overloading was prevented by heat coagulation of plasma proteins and subsequent ultrafiltration. Sensitivity was significantly enhanced by utilizing a derivatizing agent carrying a higher number of electrophores. Baseline conditions are described and control values for plasma MHPG of human volunteers, Rhesus monkeys and rats are presented.     

Cognitive impairment but preservation of sexual dimorphism in cognitive abilities in chronic schizophrenia

Neurocognitive impairment in schizophrenia is well established, though sex differences on cognitive tasks have produced equivocal findings. The present study was designed to examine performance of schizophrenia patients on a sexually dimorphic cognitive battery. The cognitive battery comprising tests of spatial (mental rotation, computerized version of the Benton Judgment of Line Orientation) and verbal abilities (phonological and semantic fluency) was administered to men (n = 22) and women (n = 21) with schizophrenia and healthy controls (n = 21 men and 21 women). A series of multivariate analyses showed that the patient group performed worse than controls on all the cognitive tasks. Cognitive sexual dimorphism on all spatial tasks favoring men and verbal tasks favoring women remained. Within the patient sample, correlational data demonstrated that earlier age at onset of illness related to poorer spatial performance. It is concluded that normal sexual dimorphism is undisturbed on both spatial and verbal tasks by the schizophrenia disease process.     

A review of fronto-striatal and fronto-cortical brain abnormalities in children and adults with Attention Deficit Hyperactivity Disorder (ADHD) and new evidence for dysfunction in adults with ADHD during motivation and attention

Attention Deficit Hyperactivity Disorder (ADHD) has long been associated with abnormalities in frontal brain regions. In this paper we review the current structural and functional imaging evidence for abnormalities in children and adults with ADHD in fronto-striatal, fronto-parieto-temporal, fronto-cerebellar and fronto-limbic regions and networks. While the imaging studies in children with ADHD are more numerous and consistent, an increasing number of studies suggests that these structural and functional abnormalities in fronto-cortical and fronto-subcortical networks persist into adulthood, despite a relative symptomatic improvement in the adult form of the disorder.We furthermore present new data that support the notion of a persistence of neurofunctional deficits in adults with ADHD during attention and motivation functions. We show that a group of medication-naïve young adults with ADHD behaviours who were followed up 20 years from a childhood ADHD diagnosis show dysfunctions in lateral fronto-striato-parietal regions relative to controls during sustained attention, as well as in ventromedial orbitofrontal regions during reward, suggesting dysfunctions in cognitive-attentional as well as motivational neural networks. The lateral fronto-striatal deficit findings, furthermore, were strikingly similar to those we have previously observed in children with ADHD during the same task, reinforcing the notion of persistence of fronto-striatal dysfunctions in adult ADHD. The ventromedial orbitofrontal deficits, however, were associated with comorbid conduct disorder (CD), highlighting the potential confound of comorbid antisocial conditions on paralimbic brain deficits in ADHD.Our review supported by the new data therefore suggest that both adult and childhood ADHD are associated with brain abnormalities in fronto-cortical and fronto-subcortical systems that mediate the control of cognition and motivation. The brain deficits in ADHD therefore appear to be multi-systemic and to persist throughout the lifespan.     

Disorder‐specific inferior prefrontal hypofunction in boys with pure attention‐deficit/hyperactivity disorder compared to boys with pure conduct disorder during cognitive flexibility

Background. Problems with cognitive flexibility have been observed in patients with attention deficit hyperactivity disorder (ADHD) and in patients with conduct disorder (CD), characterized by the violation of societal rules and the rights of others. Functional magnetic resonance imaging (fMRI) of cognitive switching, however, has only been investigated in patients with ADHD, including comorbidity with CD, finding frontostriatal and temporoparietal underactivation. This study investigates disorder‐specific functional abnormalities during cognitive flexibility between medication‐naïve children and adolescents with noncomorbid CD and those with noncomorbid ADHD compared to healthy controls. Methods. Event‐related fMRI was used to compare brain activation of 14 boys with noncomorbid, childhood‐onset CD, 14 boys with noncomorbid ADHD, and 20 healthy comparison boys during a visual–spatial Switch task. Results. Behaviorally, children with ADHD compared to children with CD had significantly slower reaction times to switch compared to repeat trials. The fMRI comparison showed that the patients with ADHD compared to both controls and patients with CD showed underactivation in right and left inferior prefrontal cortex. No disorder‐specific brain underactivation was observed in patients with CD. Only when compared with controls alone, the disruptive behavior group showed reduced activation in bilateral temporoparietal and occipital brain regions. Conclusions. The findings extend previous evidence for disorder‐specific underactivation in patients with ADHD compared to patients with CD in inferior prefrontal cortex during tasks of inhibitory control to the domain of cognitive flexibility. Inferior prefrontal underactivation thus appears to be a disorder‐specific neurofunctional biomarker for ADHD when compared with patients with CD. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

The relationship of sex hormones and cortisol with cognitive functioning in Schizophrenia

Gonadal as well as stress hormones have recently been implicated in pathophysiology and sex differences in onset, prognosis and treatment of schizophrenia. The present study investigated the effects of serum levels of oestrogen, progesterone, testosterone and cortisol on neuropsychological functioning and psychopathology in a group of 37 patients (17 women, 20 men) with schizophrenia. Neuropsychological measures included tests of attention, verbal abilities, language, memory, executive functioning, motor and speed of information processing. The results showed that oestrogen and age was associated with low positive symptom scores, and within gender, cortisol predicted poor performance on the information processing domain in men. These findings demonstrate that cortisol, in addition to the commonly reported effects of oestrogen, influences neuropsychological functioning in schizophrenia with differential effects on specific domains of cognitive functioning and underscore the need for further investigation of the modulating role of hormones on neuropsychological functioning in schizophrenia.     

Interaction between organochlorines and the AHR gene, and risk of non-Hodgkin lymphoma

Background

Plasma organochlorines have been implicated to increase the risk of non-Hodgkin lymphoma (NHL), and interaction with the aryl hydrocarbon receptor gene (AHR) may modify this risk.

Methods

In this case–control study conducted in British Columbia, Canada, five single nucleotide polymorphisms (SNPs) of AHR were genotyped in 422 NHL cases and 459 controls to measure the association between individual SNPs, haplotypes, and risk of NHL. Pre-chemotherapy organochlorine levels were measured and gene–environment interaction analysis was performed.

Results

The IVS1 + 4640G/A SNP was significantly associated with NHL risk, with an odds ratio of 1.32 (95% CI = 1.05–1.65) for G/A or A/A genotypes compared to the G/G genotype. Interactions were observed with PCB 118, a known inducer of AHR, and chlordane-related analytes oxychlordane and trans-nonachlor, although no interactions were statistically significant after controlling for multiple comparisons. The observed interactions were consistent across NHL subtypes.

Conclusion

Results suggest that the AHR gene may play a role in determining the risk of NHL with exposure to organochlorines, and highlight the importance of understanding gene-environment interactions.