Neurometabolite correlates with personality and stress in healthy emerging adults: A focus on sex differences.

Personality traits have been linked with both brain structure and function. However, the exact relationship between personality traits and other behavioural measures with neurometabolites, measured with proton magnetic resonance spectroscopy, is not clear. Here we investigated the association between behavioural measures (i.e., personality traits, resilience, perceived stress, self-esteem, hopelessness, psychological distress) and metabolite ratios (i.e., of choline-containing compounds [Cho], creatine and phosphocreatine [Cr], and N-acetyl-aspartate [NAA]) in the posterior cingulate cortex (pCC) and the dorsal anterior cingulate cortex (dACC) and surrounding white matter (WM) regions in healthy emerging adults (N = 57, 26 women, mean age=23.40 years, SD=2.50). The pCC and the dACC were selected for their known involvement as important brain network hubs and their association to five factor personality dimensions and other psychological measures. Spectral analysis as well as statistics for demographic, clinical, and imaging data were performed. Correlation and multiple regression analyses were used to test the relationship between metabolite ratios and behavioural scores in the entire sample as well as in female and male participants separately. The entire sample showed significant (p<0.05) negative correlates of stress with the NAA/Cr ratio in the pCC, and of extraversion with WM metabolite ratios. In regards of sex differences, a significantly higher NAA/Cho ratio in the pCC (p<0.05), the dACC (p<0.01), and in the left and right posterior WM matter (p<0.05), and a lower Cho/Cr ratio in the dACC (p<0.01) was detected in women. Moreover, the two sexes differed in regards of metabolite correlates of openness, conscientiousness, extraversion, agreeableness, neuroticism, stress, hopelessness, and self-esteem, and in multiple regression model predictions. Our results point to a role of the ACC in conscientiousness through its involvement in higher-order cognitive control as part of the salience network and internally directed thoughts as part of the default mode network (DMN). Furthermore, the two sexes differ in terms of metabolite correlates of openness and conscientiousness in the pCC, suggesting mental process involvement through the DMN, and of agreeableness in the dACC, possibly through involvement in social cognitive processes, particularly in women. Additionally, our results suggest that the ACC is linked to the so-called Alpha-factor of personality. Our findings on stress correlates contribute to the existing literature of the involvement of the ACC as part of the limbic system. In addition, our results suggest a possible role of the pCC in stress-regulatory processes through a possible co-involvement of stress, hopelessness, and self-esteem in the pCC in men, where higher self-esteem may help to cope with stress.

Sex matters: stress perception and the relevance of resilience and perceived social support in emerging adults.

The emerging adulthood represents a vulnerable and critical turning point for the beginning of mental illnesses and is therefore of particular interest for the study of risk and resilience. The present survey investigated the impact of sex on the associations between resilience and the perception of social support and stress in students. The Resilience Scale was used to assess resilience. Stress perception and social support perception were measured using the Perceived Stress Scale and the Social Support Questionnaire FSozU k-22, respectively. Between the ages of 18 and 30, 503 subjects (59.6% female) were included into the study. We detected a significant effect of sex with markedly lower resilience and a more pronounced perception of stress and social support among females. Significant correlations between resilience, stress perception, and social support perception were found in both sexes with women showing a stronger interrelationship between stress perception and both resilience and social support perception. Mediation analysis revealed that the relationship between the perception of social support and stress was fully mediated by resilience among men and partly mediated by resilience among women. Of note, the mediation of resilience on the interrelationship between the perception of social support and stress was much stronger in women than in men. These findings suggest that sex-specific, customized interventions focusing on the strengthening of resilience and the claiming of social support are needed to promote mental health in emerging adults.

Between- and within-site variability of fMRI localizations.

This study provides first data about the spatial variability of fMRI sensorimotor localizations when investigating the same subjects at different fMRI sites. Results are comparable to a previous patient study. We found a median between-site variability of about 6 mm independent of task (motor or sensory) and experimental standardization (high or low). An intraclass correlation coefficient analysis using data quality measures indicated a major influence of the fMRI site on variability. In accordance with this, within-site localization variability was considerably lower (about 3 mm). We conclude that the fMRI site is a considerable confound for localization of brain activity. However, when performed by experienced clinical fMRI experts, brain pathology does not seem to have a relevant impact on the reliability of fMRI localizations. Hum Brain Mapp 37:2151-2160, 2016. © 2016 Wiley Periodicals, Inc.

Sonographic cross-sectional area measurement in carpal tunnel syndrome patients: can delta and ratio calculations predict severity compared to nerve conduction studies?

OBJECTIVE: To evaluate the accuracy of two different sonographic median nerve measurement calculations in predicting carpal tunnel syndrome (CTS) severity in a study population with clinically and electrophysiologically confirmed CTS. METHODS: 643 wrists of 427 patients (325 females and 102 males, age range: 17-90 years, mean ± SD: 57.9 ± 14.7) were included with CTS diagnosis based on clinical and nerve conduction studies (NCS). Cross-sectional area (CSA) measurement of the median nerve was performed at the carpal tunnel level (CSAc) and at the pronator quadratus muscle level (CSAp). Two parameters were calculated: delta (∆-CSA), which is the difference between proximal and distal measurements, and ratio (R-CSA), calculated by dividing distal over proximal measurements. RESULTS: Patients were classified into mild, moderate and severe CTS based upon NCS. The mean ∆-CSA (4.2 ± 2.6, 6.95 ± 2.2 and 10.7 ± 4.9 mm(2)) and mean R-CSA (1.5 ± 0.4, 1.95 ± 0.4 and 2.4 ± 0.7) values were significantly different between all groups (p < 0.001). Optimal cut-off values for ∆-CSA and R-CSA were 6 mm(2) and 1.7, respectively, to distinguish mild from moderate disease, and 9 mm(2) and 2.2, respectively, to distinguish moderate from severe disease. CONCLUSION: Threshold values for the calculated sonographic parameters ∆-CSA and R-CSA are useful in predicting CTS severity compared to NCS. KEY POINTS: • Two proposed parameters were calculated (∆-CSA, R-CSA) and compared to NCS. • A defined sonoanatomical proximal landmark was used for the calculation. • Both parameters showed ability to detect CTS severity comparable to NCS. • Cut-off values could be determined for both parameters.

Intracarpal tunnel contents: evaluation of the effects of corticosteroid injection with sonoelastography.

PURPOSE: To define the stiffness of the intracarpal tunnel contents and to evaluate the effect of corticosteroid injection on the intracarpal tunnel contents by using sonoelastography. MATERIALS AND METHODS: This study was conducted with the approval of the institutional review boards, and all participants provided written, informed consent. Both hands were studied in 20 healthy volunteers, including eight men (mean age, 59.6 years; range, 50-76 years) and 12 women (mean age, 61.0 years; range, 39-79 years) and 22 hands were studied in 20 patients with carpal tunnel syndrome (CTS) (five men [mean age, 49.0 years] and 15 women [mean age, 61.1 years]; range, 39-89 years) between April 2012 and August 2012. The stiffness of the intracarpal tunnel contents was estimated as the standardized acoustic coupler (AC)-to-intracarpal tunnel contents surrounding the nerve (AC/C) strain ratio, analyzed with the Mann-Whitney U test. The patients were treated with corticosteroid injections, and the strain ratio was reexamined 6 weeks later, analyzed with the Wilcoxon t test. RESULTS: The mean AC/C strain ratio in the CTS patients was 12.6 ± 4.7 (standard deviation), which was higher (stiffer) than that in the healthy volunteers with a mean strain ratio of 8.2 ± 3.5 (P = .0013). Six weeks after the injection, the mean AC/C strain ratio had decreased to 8.5 ± 4.1 (P = .00069, compared with the preinjection value) in the CTS patients. CONCLUSION: The stiffness of the intracarpal tunnel contents in untreated CTS patients is higher than that of healthy volunteers but decreases 6 weeks after corticosteroid injection.

Variability of clinical functional MR imaging results: a multicenter study.

PURPOSE: To investigate intersite variability of clinical functional magnetic resonance (MR) imaging, including influence of task standardization on variability and use of various parameters to inform the clinician whether the reliability of a given functional localization is high or low. MATERIALS AND METHODS: Local ethics committees approved the study; all participants gave written informed consent. Eight women and seven men (mean age, 40 years) were prospectively investigated at three experienced functional MR sites with 1.5- (two sites) or 3-T (one site) MR. Nonstandardized motor and highly standardized somatosensory versions of a frequently requested clinical task (localization of the primary sensorimotor cortex) were used. Perirolandic functional MR variability was assessed (peak activation variability, center of mass [COM] variability, intraclass correlation values, overlap ratio [OR], activation size ratio). Data quality measures for functional MR images included percentage signal change (PSC), contrast-to-noise ratio (CNR), and head motion parameters. Data were analyzed with analysis of variance and a correlation analysis. RESULTS: Localization of perirolandic functional MR activity differed by 8 mm (peak activity) and 6 mm (COM activity) among sites. Peak activation varied up to 16.5 mm (COM range, 0.4-16.5 mm) and 45.5 mm (peak activity range, 1.8-45.5 mm). Signal strength (PSC, CNR) was significantly lower for the somatosensory task (mean PSC, 1.0% ± 0.5 [standard deviation]; mean CNR, 1.2 ± 0.4) than for the motor task (mean PSC, 2.4% ± 0.8; mean CNR, 2.9 ± 0.9) (P < .001, both). Intersite variability was larger with low signal strength (negative correlations between signal strength and peak activation variability) even if the task was highly standardized (mean OR, 22.0% ± 18.9 [somatosensory task] and 50.1% ± 18.8 [motor task]). CONCLUSION: Clinical practice and clinical functional MR biomarker studies should consider that the center of task-specific brain activation may vary up to 16.5 mm, with the investigating site, and should maximize functional MR signal strength and evaluate reliability of local results with PSC and CNR.

A deep learning pipeline for the automated segmentation of posterior limb of internal capsule in preterm neonates.

Segmentation of specific brain tissue from MRI volumes is of great significance for brain disease diagnosis, progression assessment, and monitoring of neurological conditions. Manual segmentation is time-consuming, laborious, and subjective, which significantly amplifies the need for automated processes. Over the last decades, the active development in the field of deep learning, especially convolutional neural networks (CNNs), and the associated performance improvements have increased the demand for the application of CNN-based methods to provide consistent measurements and quantitative analyses. In this paper, we present an efficient deep learning approach for the segmentation of brain tissue. More specifically, we address the problem of segmentation of the posterior limb of the internal capsule (PLIC) in preterm neonates. To this end, we propose a CNN-based pipeline comprised of slice-selection modules and a multi-view segmentation model, which exploits the 3D information contained in the MRI volumes to improve segmentation performance. One special feature of the proposed method is its ability to identify one desired slice out of the whole image volume, which is relevant for pediatricians in terms of prognosis. To increase computational efficiency, we apply a strategy that automatically reduces the information contained in the MRI volumes to its relevant parts. Finally, we conduct an expert rating alongside standard evaluation metrics, such as dice score, to evaluate the performance of the proposed framework. We demonstrate the benefit of the multi-view technique by comparing it with its single-view counterparts, which reveals that the proposed method strikes a good balance between exploiting the available image information and reducing the required computing power compared to 3D segmentation networks. Standard evaluation metrics as, well as expert-based assessment, confirm the good performance of the proposed framework, with the latter being more relevant in terms of clinical applicability. We demonstrate that the proposed deep learning pipeline can compete with the experts in terms of accuracy. To prove the generalisability of the proposed method, we additionally assess our deep learning pipeline to data from the Developing Human Connectome Project (dHCP).

Limbic Responses to Aversive Visual Stimuli during the Acute and Recovery Phase of Takotsubo Syndrome.

The role of the limbic system in the acute phase and during the recovery of takotsubo syndrome needs further clarification. In this longitudinal study, anatomical and task-based functional magnetic resonance imaging of the brain was performed during an emotional picture paradigm in 19 postmenopausal female takotsubo syndrome patients in the acute and recovery phases in comparison to sex- and aged-matched 15 healthy controls and 15 patients presenting with myocardial infarction. Statistical analyses were performed based on the general linear model where aversive and positive picture conditions were included in order to reveal group differences during encoding of aversive versus positive pictures and longitudinal changes. In the acute phase, takotsubo syndrome patients showed a lower response in regions involved in affective and cognitive emotional processes (e.g., insula, thalamus, frontal cortex, inferior frontal gyrus) while viewing aversive versus positive pictures compared to healthy controls and patients presenting with myocardial infarction. In the recovery phase, the response in these brain regions normalized in takotsubo syndrome patients to the level of healthy controls, whereas patients 8-12 weeks after myocardial infarction showed lower responses in the limbic regions (mainly in the insula, frontal regions, thalamus, and inferior frontal gyrus) compared to healthy controls and takotsubo syndrome patients. In conclusion, compared to healthy controls and patients suffering from acute myocardial infarction, limbic responses to aversive visual stimuli are attenuated during the acute phase of takotsubo syndrome, recovering within three months. Reduced functional brain responses in the recovery phase after a myocardial infarction need further investigation.

Short-term meditation training influences brain energy metabolism: A pilot study on 31 P MR spectroscopy.

BACKGROUND: Meditation is increasingly attracting interest among neuroimaging researchers for its relevance as a cognitive enhancement technique and several cross-sectional studies have indicated cerebral changes. This longitudinal study applied a distinct and standardized meditative technique with a group of volunteers in a short-term training program to analyze brain metabolic changes. METHODS: The effect of 7 weeks of meditation exercises (focused attention meditation, FAM) was assessed on 27 healthy volunteers. Changes in cerebral energy metabolism were investigated using 31 P-MR spectroscopy. Metabolite ratios were compared before (T1) and after training (T2). Additional questionnaire assessments were included. RESULTS: The participants performed FAM daily. Depression and anxiety scores revealed a lower level of state anxiety at T2 compared to T1. From T1 to T2, energy metabolism ratios showed the following differences: PCr/ATP increased right occipitally; Pi/ATP decreased bilaterally in the basal ganglia and temporal lobe on the right; PCr/Pi increased in occipital lobe bilaterally, in the basal ganglia and in the temporal lobe on the right side. The pH decreased temporal on the left side and frontal in the right side. The observed changes in the temporal areas and basal ganglia may be interpreted as a higher energetic state, whereas the frontal and occipital areas showed changes that may be related to a down-regulation in ATP turnover, energy state, and oxidative capacity. CONCLUSIONS: The results of the current study indicate for the first time in a longitudinal study that even short-term training in FAM may have considerable effects on brain energy state with different local energy management in specific brain regions. Especially higher energetic state in basal ganglia may represent altered function in their central role in complex cerebral distributed networks including frontal and temporal areas. Further studies including different forms of relaxation techniques should be performed for more specific and reliable insights.

Emotional Recognition in Patients With Mesial Temporal Epilepsy Associated With Enlarged Amygdala.

BACKGROUND: Amygdalae play a central role in emotional processing by interconnecting frontal cortex and other brain structures. Unilateral amygdala enlargement (AE) is associated with mesial temporal lobe epilepsy (mTLE). In a relatively large sample of patients with mTLE and AE, we aimed to evaluate functional integration of AE in emotion processing and to determine possible associations between fMRI activation patterns in amygdala and deficits in emotion recognition as assessed by neuropsychological testing. METHODS: Twenty-two patients with drug resistant unilateral mTLE due to ipsilateral AE were prospectively recruited in a large epilepsy unit and compared with 17 healthy control subjects in terms of amygdala volume, fMRI activation patterns and performance in emotion recognition as assessed by comprehensive affect testing system (CATS) and Ekman faces. All patients underwent structural and functional 1.5 Tesla MRI, electro-clinical assessment and neuropsychological testing. RESULTS: We observed BOLD signal ipsilateral to AE (n = 7; group PAT1); contralateral to AE (n = 6; group PAT2) and no activation (n = 9; group PAT3). In the region of interest (ROI) analysis, beta estimates for fearful face > landscape contrast in the left amygdala region did not differ significantly in patients with left TLE vs. patients with right TLE [T (16) = -1.481; p = 0.158]. However, beta estimates for fearful face > landscape contrast in the right amygdala region were significantly reduced in patients with right TLE vs. patients with left TLE [T (16) = -2,922; p = 0.010]. Patients showed significantly lower total scores in CATS and Ekman faces compared to healthy controls. CONCLUSION: In our cohort, patients with unilateral mesial TLE and ipsilateral AE, an amygdala could display either functional integration in emotion recognition or dysfunction as demonstrated by fMRI. Perception and recognition of emotions were impaired more in right-sided mTLE as compared to left-sided mTLE. Neuropsychological tests showed deficits in emotion recognition in patients as compared to healthy controls.

Functional neuroimaging in the acute phase of Takotsubo syndrome: volumetric and functional changes of the right insular cortex.

BACKGROUND: A brain-heart interaction has been proposed in Takotsubo syndrome (TTS). Structural changes in the limbic system and hypoconnectivity between certain brain areas in the chronic phase of the disease have been reported, but little is known concerning functional neuroimaging in the acute phase. We hypothesized anatomical and functional changes in the central nervous system and investigated whole-brain volumetric and functional connectivity alterations in the acute phase TTS patients compared to controls. METHODS: Anatomical and resting-state functional magnetic resonance imaging were performed in postmenopausal females: thirteen in the acute TTS phase and thirteen healthy controls without evidence of coronary artery disease. Voxel-based morphometry and graph theoretical analysis were applied to identify anatomical and functional differences between patients and controls. RESULTS: Significantly lower gray matter volumes were found in TTS patients in the right middle frontal gyrus (p = 0.004) and right subcallosal cortex (p = 0.009) compared to healthy controls. When lower threshold was applied, volumetric changes were noted in the right insular cortex (p = 0.0113), the right paracingulate cortex (p = 0.012), left amygdala (p = 0.018), left central opercular cortex (p = 0.017), right (p = 0.013) and left thalamus (p = 0.017), and left cerebral cortex (p = 0.017). Graph analysis revealed significantly (p < 0.01) lower functional connectivity in TTS patients compared to healthy controls, particularly in the connections originating from the right insular cortex, temporal lobes, and precuneus. CONCLUSION: In the acute phase of TTS volumetric changes in frontal regions and the central autonomic network (i.e. insula, anterior cingulate cortex, and amygdala) were noted. In particular, the right insula, associated with sympathetic autonomic tone, had both volumetric and functional changes.

Language Dominance in Patients With Malformations of Cortical Development and Epilepsy.

Background: Language function may be reorganized in patients with malformations of cortical development (MCD). This prospective cohort study aimed in assessing language dominance in a large group of patients with MCD and epilepsy using functional MRI (fMRI). Methods: Sixty-eight patients (40 women) aged 10-73 years (median, 28.0; interquartile range, 19) with MCD and epilepsy underwent 1.5 T MRI and fMRI (word generation task). Single-subject image analysis was performed with statistical parametric mapping (SPM12). Language lateralization indices (LIs) were defined for statistically significantly activated voxels in Broca's and Wernicke's areas using the formula: LI = (V L - V R)/(V L + V R) × 100, where V L and V R were sets of activated voxels on the left and on the right, respectively. Language laterality was considered typical if LI was between +20 and +100 or atypical if LI was between +19 and -100. Results: fMRI signal was elicited in 55 of 68 (81%) patients. In 18 of 55 (33%) patients, language dominance was typical, and in 37 of 55 (67%) patients, atypical (in 68%, right hemispheric; in 32%, bilateral). Language dominance was not influenced by handedness, electroclinical, and imaging features. Conclusions: In this prospective study on a large group of patients with MCD and epilepsy, about two-thirds had atypical language dominance. These results may contribute to assessing risks of postsurgical language deficits and could assist in planning of "cortical mapping" with intracranial electrodes in patients who undergo presurgical assessment.

Behavioural and neural responses to aversive visceral stimuli in women with primary dysmenorrhoea.

BACKGROUND: Chronic pelvic pain, in particular dysmenorrhoea, is a significant yet unresolved healthcare problem in gynaecology. As interoceptive sensitivity and underlying neural mechanisms remain incompletely understood, this functional magnetic resonance imaging (fMRI) study assessed behavioural and neural responses to visceral stimuli in primary dysmenorrhoea (PMD). METHODS: Women with PMD (N = 19) without psychological comorbidity and healthy women (N = 20) were compared with respect to visceral sensory and pain thresholds, and to neural responses to individually calibrated mildly painful and painful rectal distensions implemented during scanning. Trial-by-trial ratings of perceived intensity were accomplished with visual analogue scales (VAS). RESULTS: Although women with dysmenorrhoea reported significantly higher chronic pain intensity and pain interference with daily life activities (p < 0.01, assessed with the West Haven-Yale Multidimensional Pain Inventory), there were no differences between groups in visceral sensitivity and mean trial-by-trial VAS ratings were virtually identical. Analysis of neural responses revealed activation in brain regions previously shown to be involved in the processing of visceral stimuli with differences between painful and mildly painful stimulation, but no group differences were found even when using a liberal statistical threshold. CONCLUSIONS: Dysmenorrhoea patients show unaltered perceptual and neural responses to experimental interoceptive stimuli. Despite limited sample size, these negative results argue against a generalized sensitization towards interoceptive stimuli in patients without psychological comorbidities. Future studies should clarify the role of psychosocial factors in central sensitization using more pain region-specific models in larger and clinically more heterogeneous samples. SIGNIFICANCE: Despite higher chronic pain and pain interference with daily life activities, women with primary dysmenorrhoea do not differ from healthy women with respect to visceral sensitivity or neural processing of aversive interoceptive stimuli induced by rectal distensions. Generalized sensitization may be present only in subgroups with pronounced psychosocial or psychiatric disturbances.

Are numbers special? Comparing the generation of verbal materials from ordered categories (months) to numbers and other categories (animals) in an fMRI study.

Months, days of the week, and numbers differ from other verbal concepts because they are ordered in a sequence, whereas no order is imposed on members of other categories, such as animals or tools. Recent studies suggest that numbers activate a representation of their quantity within the intraparietal sulcus (IPS) automatically, that is, in tasks that do not require the processing of quantity. It is unclear, however, whether ordered verbal materials in general and not only numbers activate the IPS in such tasks. In the present functional magnetic resonance imaging study word generation of months, numbers, and animals were compared. Word generation of numbers and nonnumerical materials from an ordered category (months) activated the IPS more strongly than generating items from a not-ordered category such as animals or the verbal control conditions. An ROI analysis of three subregions within the anterior IPS revealed that the most anterior and lateral of these regions, human intraparietal area hIP2, shows a greater sensitivity to ordered materials than the other two areas, hIP1 and hIP3. Interestingly, no difference in activation was observed within the IPS between numbers and months suggesting that the activation of the IPS might not be modulated by the additional quantity information carried by numbers.

An fMRI study of the numerical Stroop task in individuals with and without minimal cognitive impairment.

Aim of this functional magnetic resonance imaging (fMRI) study was to dissociate normal aging and minimal cognitive impairment (MCI) concerning magnitude processing and interference control. We examined the neural correlates of a numerical Stroop task in elderly individuals with and without MCI. Fifteen elderly participants (six patients with MCI and nine controls) were subjected to a numerical Stroop task requiring numerical/physical magnitude classifications while inhibiting task-irrelevant stimulus dimensions. Effects of distance and congruity were examined. Behaviourally, robust distance and congruity effects were observed in both groups and tasks. Imaging baseline conditions revealed stronger and more distributed activations in MCI patients relative to controls which could not be explained by the higher error rates committed by patients. Across tasks, conjunction analysis revealed highly significant activations in intra-parietal and prefrontal regions suggesting that both groups recruit comparable brain regions upon processing magnitude and interference, respectively. MCI patients exhibited stronger pre-/postcentral and thalamic activations, possibly reflecting more effortful response-selection processes or alternatively, deficient inhibitory control. Moreover, MCI patients exhibited additional activations in fronto-parietal (magnitude) and occipital/cerebellar (congruity) regions. To summarize, though MCI patients needed to recruit more distributed activation patterns conjunction analysis revealed common activation sites in response to magnitude processing and interference control.

Neural correlates of transmeatal cochlear laser (TCL) stimulation in healthy human subjects.

Transmeatal cochlear laser (TCL) treatment has recently been proposed as a therapeutic procedure for cochlear dysfunction such as chronic cochlear tinnitus or sensorineural hearing loss. The aim of this study was to investigate whether TLC has any influence on the central nervous system using functional MRI with healthy young adults. The laser stimulation device was placed on the tympanic membrane of both ears. A laser stimulation run and a placebo run were performed in random order. The participants were unable to differentiate between verum and placebo stimulation. In the comparison of verum to placebo runs, we observed significant activations within the left superior frontal gyrus, the right middle and medial frontal gyrus, the right superior parietal lobule, the left superior occipital gyrus, the precuneus and cuneus bilaterally, the right anterior and the left and right middle and posterior cingulate gyrus and the left thalamus. This network of brain areas corresponds well to results from previous PET studies of patients with tinnitus. Though TCL seems to have a clinically measurable effect on the central nervous system the neurophysiological mechanism leading to the observed activated neuronal network remains unknown.

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.

An FMRI study of episodic encoding and recognition of words in patients with schizophrenia in remission.

OBJECTIVE: Verbal memory deficits are among the most severe cognitive deficits observed in patients with schizophrenia. This study examined patterns of brain activity during episodic encoding and recognition of words in patients with schizophrenia. METHOD: Functional magnetic resonance imaging (fMRI) was used to study regional brain activation in 10 healthy male comparison subjects and 10 male outpatients with schizophrenia during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite having intact performance in word recognition, the patients with schizophrenia had less activation of the right dorsolateral and anterior prefrontal cortex, right anterior cingulate, and left lateral temporal cortex during word encoding, compared with the healthy comparison subjects. During word recognition, the patients had impairments in activation of the bilateral dorsolateral prefrontal and lateral temporal cortices. CONCLUSIONS: Schizophrenia was associated with attenuated frontotemporal activation during episodic encoding and recognition of words. These results from an fMRI study replicate earlier findings derived from a positron emission tomography study.