Functional Diffusion Tensor Imaging: Measuring Task-Related Fractional Anisotropy Changes in the Human Brain along White Matter Tracts

Functional neural networks in the human brain can be studied from correlations between activated gray matter regions measured with fMRI. However, while providing important information on gray matter activation, no information is gathered on the co-activity along white matter tracts in neural networks.We report on a functional diffusion tensor imaging (fDTI) method that measures task-related changes in fractional anisotropy (FA) along white matter tracts. We hypothesize that these fractional anisotropy changes relate to morphological changes of glial cells induced by axonal activity although the exact physiological underpinnings of the measured FA changes remain to be elucidated. As expected, these changes are very small as compared to the physiological noise and a reliable detection of the signal change would require a large number of measurements. However, a substantial increase in signal-to-noise ratio was achieved by pooling the signal over the complete fiber tract. Adopting such a tract-based statistics enabled us to measure the signal within a practically feasible time period. Activation in the sensory thalamocortical tract and optic radiation in eight healthy human subjects was found during tactile and visual stimulation, respectively.The results of our experiments indicate that these FA changes may serve as a functional contrast mechanism for white matter. This noninvasive fDTI method may provide a new approach to study functional neural networks in the human brain

Cerebellar Asymmetry and Cortical Connectivity in Monozygotic Twins with Discordant Handedness

Handedness differentiates patterns of neural asymmetry and interhemispheric connectivity in cortical systems that underpin manual and language functions. Contemporary models of cerebellar function incorporate complex motor behaviour and higher-order cognition, expanding upon earlier, traditional associations between the cerebellum and motor control. Structural MRI defined cerebellar volume asymmetries and correlations with corpus callosum (CC) size were compared in 19 pairs of adult female monozygotic twins strongly discordant for handedness (MZHd). Volume and asymmetry of cerebellar lobules were obtained using automated parcellation.CC area and regional widths were obtained from midsagittal planimetric measurements. Within the cerebellum and CC, neurofunctional distinctions were drawn between motor and higher-order cognitive systems. Relationships amongst regional cerebellar asymmetry and cortical connectivity (as indicated by CC widths) were investigated. Interactions between hemisphere and handedness in the anterior cerebellum were due to a larger right-greater-than-left hemispheric asymmetry in right-handed (RH) compared to left-handed (LH) twins. In LH twins only, anterior cerebellar lobule volumes (IV, V) for motor control were associated with CC size, particularly in callosal regions associated with motor cortex connectivity. Superior posterior cerebellar lobule volumes (VI, Crus I, Crus II, VIIb) showed no correlation with CC size in either handedness group. These novel results reflected distinct patterns of cerebellar-cortical relationships delineated by specific CC regions and an anterior-posterior cerebellar topographical mapping. Hence, anterior cerebellar asymmetry may contribute to the greater degree of bilateral cortical organisation of frontal motor function in LH individuals

Arcuate Fasciculus Abnormalities and Their Relationship with Psychotic Symptoms in Schizophrenia

Disruption of fronto-temporal connections involving the arcuate fasciculus (AF) may underlie language processing anomalies and psychotic features such as auditory hallucinations in schizophrenia. No study to date has specifically investigated abnormalities of white matter integrity at particular loci along the AF as well as its regional lateralization in schizophrenia. We examined white matter changes (fractional anisotropy (FA), axial diffusivity (AD), asymmetry indices) along the whole extent of the AF and their relationship with psychotic symptoms in 32 males with schizophrenia and 44 healthy males. Large deformation diffeomorphic metric mapping and Fiber Assignment Continuous Tracking were employed to characterize FA and AD along the geometric curve of the AF. Our results showed that patients with schizophrenia had lower FA in the frontal aspects of the left AF compared with healthy controls. Greater left FA and AD lateralization in the temporal segment of AF were associated with more severe positive psychotic symptoms such as delusions and hallucinations in patients with schizophrenia. Disruption of white matter integrity of the left frontal AF and accentuation of normal left greater than right asymmetry of FA/AD in the temporal AF further support the notion of aberrant fronto-temporal connectivity in schizophrenia. AF pathology can affect corollary discharge of neural signals from frontal speech/motor initiation areas to suppress activity of auditory cortex that may influence psychotic phenomena such as auditory hallucinations and facilitate elaboration of delusional content

Oscillatory Cortical Network Involved in Auditory Verbal Hallucinations in Schizophrenia

Auditory verbal hallucinations (AVH), a prominent symptom of schizophrenia, are often highly distressing for patients. Better understanding of the pathogenesis of hallucinations could increase therapeutic options. Magnetoencephalography (MEG) provides direct measures of neuronal activity and has an excellent temporal resolution, offering a unique opportunity to study AVH pathophysiology.Twelve patients (10 paranoid schizophrenia, 2 psychosis not otherwise specified) indicated the presence of AVH by button-press while lying in a MEG scanner. As a control condition, patients performed a self-paced button-press task. AVH-state and non-AVH state were contrasted in a region-of-interest (ROI) approach. In addition, the two seconds before AVH onset were contrasted with the two seconds after AVH onset to elucidate a possible triggering mechanism.AVH correlated with a decrease in beta-band power in the left temporal cortex. A decrease in alpha-band power was observed in the right inferior frontal gyrus. AVH onset was related to a decrease in theta-band power in the right hippocampus.These results suggest that AVH are triggered by a short aberration in the theta band in a memory-related structure, followed by activity in language areas accompanying the experience of AVH itself

Efficacy of typical and atypical antipsychotic medication on hostility in patients with psychosis-spectrum disorders: a review and meta-analysis

As violence against self and others is an important outcome in the treatment of patients with psychosis-spectrum disorders and hostility is an important indicator for violence, we set out to evaluate the effects of different types of antipsychotic agents in reducing hostility. We performed a systematic literature search, which provided 18 suitable randomized studies comparing typical to atypical antipsychotics for at least 4 weeks in patients with psychotic disorders. Results showed a small (0.26) but significant effect for atypical as compared to typical antipsychotics, with high heterogeneity, even though the mean dose of typical antipsychotics was higher. This effect size remained similar when separately analyzing sponsored and non-sponsored studies. When differentiating between high and low-dose studies, the high-dose group showed a significant difference between typical and atypical antipsychotics whereas the low-dose group did not. An analysis comparing clozapine to typical antipsychotics showed a moderate effect size (0.415), with low heterogeneity. These results are important for clinicians to help their shared decision making with patients when choosing maintenance treatment, as next to efficacy for psychosis and tolerability, safety for the patient and their environment is an important outcome

Combined analysis of language tasks in fMRI improves assessment of hemispheric dominance for language functions in individual subjects

Recent advances in functional neuroimaging techniques have prompted an increase in the number of studies investigating lateralization of language functions. One of the problems in relating findings of various studies to one another is the diversity of reported results. This may be due to differences in the tasks that are used to stimulate language processing regions and in the control tasks, as well as differences in the way imaging data are analyzed, in particular the threshold for significance of signal change. We present a simple method to assess language lateralization that allows for some variation of tasks and statistical thresholding, but at the same time yields reliable and reproducible results. Images acquired during a set of word-comprehension and -production tasks are analyzed conjointly. As opposed to the use of any one particular task, this combined task analysis (CTA) approach is geared toward identifying language regions that are involved in generic language functions rather than regions that are involved in functions that are specific to a single task. In two experiments CTA is compared to single-task analysis in healthy right-handed males. In a third experiment left-handed males were examined. Results indicate that CTA: (1) improves detection of language-related brain activity in individual subjects and (2) yields a high language laterality index (LI) in right-handed males with a small variance across subjects. The high LI matches the strong left-hemisphere dominance for language that is typical for these subjects as reported in neuropsychological and clinical tests in other studies. In the left-handed subjects dominance was found either in the left (n = 4) or the right (n = 1) hemisphere or was absent (n = 3). The LI derived from CTA is more consistent across statistical thresholds for significance of signal change in fMRI analysis than in individual-task analysis. Also, the CTA results are very similar to those obtained with conjunction analysis of the same data. (C) 2001 Academic Press