Brain activation patterns during a selective attention test--a functional MRI study in healthy volunteers and unmedicated patients during an acute episode of schizophrenia.

In a previous functional magnetic resonance imaging (fMRI) study of high functioning outpatients with remitted schizophrenia, we found increased activity compared with healthy subjects across multiple areas of the brain, including the dorsolateral frontal cortex and the anterior cingulate, during a modified Stroop task. The same fMRI procedure was used in this subsequent study to investigate eight unmedicated patients during an acute episode of schizophrenia and eight healthy control subjects. Patients showed a reduced activation in dorsolateral prefrontal, anterior cingulate and parietal regions and a higher activation in temporal regions and posterior cingulate compared to healthy controls. Healthy controls showed a trend towards higher accuracy in the modified Stroop task compared to schizophrenia patients. Treatment with second generation antipsychotics may improve executive performance in patients with schizophrenia and facilitate a normalization of functional hypofrontality after symptomatic improvement.

Neural correlates of the number-size interference task in children.

In this functional magnetic resonance imaging study, 17 children were asked to make numerical and physical magnitude classifications while ignoring the other stimulus dimension (number-size interference task). Digit pairs were either incongruent (3 8) or neutral (3 8). Generally, numerical magnitude interferes with font size (congruity effect). Moreover, relative to numerically adjacent digits far ones yield quicker responses (distance effect). Behaviourally, robust distance and congruity effects were observed in both tasks. Imaging baseline contrasts revealed activations in frontal, parietal, occipital and cerebellar areas bilaterally. Different from results usually reported for adults, smaller distances activated frontal, but not (intra-)parietal areas in children. Congruity effects became significant only in physical comparisons. Thus, even with comparable behavioural performance, cerebral activation patterns may differ substantially between children and adults.

Language lateralization in unmedicated patients during an acute episode of schizophrenia: a functional MRI study.

In a previous fMRI study of high-functioning outpatients with remitted schizophrenia, we found that healthy subjects and schizophrenia patients showed similar patterns of activation during a verbal fluency task. However, the activation in controls was primarily in Broca's area on the left, while it was more bilateral for schizophrenia patients, implicating a reduced language lateralization in schizophrenia patients. The same fMRI procedure was used in this subsequent study to investigate unmedicated patients during an acute episode of schizophrenia. Schizophrenia patients showed reduced language lateralization in the frontal cortex, because of a more bilateral activation of Broca's area compared with a primarily left hemisphere activation in healthy controls. Furthermore decreased lateralization was correlated to the severity of hallucinations. Although patients with schizophrenia showed a significantly reduced performance on the verbal fluency task when compared with healthy subjects, we were not able to find evidence of decreased language-related activity in the left hemisphere. These results suggest that decreased language lateralization is also evident in unmedicated patients experiencing an acute episode of schizophrenia.

Olfactory functions and volumetric measures of orbitofrontal and limbic regions in schizophrenia.

OBJECTIVE: Olfactory deficits in schizophrenia patients have been suggested to reflect medial temporal and/or prefrontal brain abnormalities. In this study, we examined the relationship between different olfactory functions and volumes of the hippocampus-amygdala complex (HAC) and the orbitofrontal brain region using magnetic resonance imaging (MRI). METHODS: Thirty-three young men with schizophrenia (DSM-IV) and 40 healthy controls performed unirhinal olfactory assessment including the main olfactory functions (threshold, discrimination, and identification), and odor judgements (intensity, edibility, familiarity, and pleasantness). Volumes of regions in the medial temporal lobe (hippocampus and amygdala) and the prefrontal region (orbitofrontal gray and white matter) were measured on MRI scans. RESULTS: Compared with controls, patients showed bilaterally impaired thresholds, quality discrimination and identification, as well as edibility judgements. Olfactory deficits were not attributable to smoking, premorbid intelligence, or impaired thresholds. Relative to controls, patients had bilateral reduced hippocampus and amygdala volumes. In patients, smaller hippocampus volumes were associated with poorer olfactory discrimination ability. CONCLUSIONS: Olfactory deficits in schizophrenia appear to be associated with morphometric abnormalities in the medial temporal rather than the orbitofrontal region (OFR). These results indicate that olfactory quality discrimination deficits are related to structural hippocampus abnormalities. Future studies of genetic and behavioral high-risk samples seem warranted.

Longitudinal volumetric MRI study in first- and multiple-episode male schizophrenia patients.

In this longitudinal study we compared brain volume changes in first- and multiple-episode patients with schizophrenia to normal aging changes observed in healthy control subjects scanned at comparable times. Two to four years after an initial examination including MRI volumetry, we followed up 21 first episode patients, 17 patients after multiple episodes of schizophrenia, and 20 healthy controls. Volumetric measurements of left and right hemispheres, total brain volume, lateral ventricles, hippocampus and amygdala as well as a clinical evaluation were performed. Patients with schizophrenia showed significant ventricular enlargement and volume reduction of the hippocampus-amygdala complex compared with healthy control subjects both at baseline and follow-up. While there were no differences between patients and controls with respect to mean annual volume changes in the measured regions, patients with schizophrenia showed higher between-subject variability in ventricular volume change. These data are consistent with cross-sectional studies demonstrating ventricular enlargement and hippocampal volume deficits in schizophrenia. However, we were not able to demonstrate a difference in the rate of volume changes over time that distinguished patients with schizophrenia from healthy controls for any of the brain structures measured. Drawbacks of the study are that the follow-up was done after a relatively short interval and that there was a difference in time to follow-up and age between patients and controls. Our results do not support the hypothesis that schizophrenia leads to progressive volume reduction in these areas, although there may be a subset of patients with morphologically visible disease progression.

Brain activation patterns during a verbal fluency test-a functional MRI study in healthy volunteers and patients with schizophrenia.

FMRI was used to study cortical activation patterns in nine healthy male subjects and nine high-functioning male schizophrenia patients during a letter verbal fluency task. Both groups showed similar patterns of activation, however, in controls the activation was primarily in the left broca area, while for schizophrenia patients, it was more bilateral. These data indicate that high-functioning schizophrenia patients show a reduced language lateralization of the frontal cortex compared to healthy controls.

How specifically do we learn? Imaging the learning of multiplication and subtraction.

The present functional magnetic resonance imaging (fMRI) study investigates modifications of brain activation patterns related to the training of two different arithmetic operations, multiplication and subtraction. Healthy young adults were trained in five sessions to answer multiplication and subtraction problems. In the following fMRI session, trained and new untrained problems closely matched for difficulty were presented in blocked order. Contrasts between untrained and trained operations showed stronger activation of inferior frontal and parietal regions, especially along the banks of the intraparietal sulcus. The reverse contrasts, trained minus untrained operations, yielded significantly higher activation in the left angular gyrus for multiplication but no significantly activated area for subtraction. This suggests that training leads to a reduction of general purpose processes, such as working memory and executive control in both operations, indicated by the decrease of activation in inferior frontal areas. For multiplication, however, the increase of activation in the left angular gyrus indicates a switching of cognitive processes. Trained subtraction therefore seems to lead to faster and more efficient strategies, while trained multiplication showed a shift from quantity-based processing (supported by the areas along the intraparietal sulci) to more automatic retrieval (supported by the left angular gyrus). The same training method caused changes in brain activation patterns that depended on the given operation. The effects of learning on the brain therefore seem not only to depend on the method of learning but also on its content.

Yellow teeth, seizures, and mental retardation: a less severe case of Kohlschütter-Tönz syndrome.

We describe an 11-year-old boy with hypoplastic amelogenesis imperfecta, yellow teeth, seizures, and developmental delay, which are the hallmarks of Kohlschütter-Tönz syndrome. Compared to other reported cases of the syndrome, our patient had less severe developmental delay. Also, spasticity and loss of mental capacity should not be considered obligatory manifestations of the syndrome because they are not present in half of reported patients, as well as in our family. Origin of the parents of our patient from neighboring villages supports autosomal recessive inheritance of Kohlschütter-Tönz syndrome.

Neural correlates of distance and congruity effects in a numerical Stroop task: an event-related fMRI study.

This study aimed at investigating the neural correlates of a number-size congruity task. Using an event-related fMRI design, we presented one-digit number pairs to 17 participants in a number-size interference task that required subjects to focus on one stimulus property (e.g., numerical size) and to ignore the other (physical size). In different blocks, participants were asked to decide which digit of a digit pair was numerically larger (numerical comparison task) or physically larger (physical comparison task). Stimuli were classified into three categories: (a) congruent: physical and numerical comparison leads to the same response; (b) incongruent: physical and numerical comparison leads to different responses; (c) neutral: the stimuli differ only with regard to the task-relevant stimulus property. Behavioral results reflect robust distance effects (quicker reaction times for long distances relative to short ones) and size congruity effects (longer reaction times for incongruent relative to congruent stimuli) in both tasks. Imaging results reveal that-compared to congruent trials-incongruent trials led to a stronger activation in the dorsolateral prefrontal cortex and the anterior cingulate cortex, areas associated with attentional control. The distance effect (neutral condition only) led to a stronger activation in bilateral parietal areas including the intraparietal sulcus (IPS).