Christian Gaser

Neuroplasticity: Changes in grey matter induced by training

Does the structure of an adult human brain alter in response to environmental demands? Here we use whole-brain magnetic-resonance imaging to visualize learning-induced plasticity in the brains of volunteers who have learned to juggle. We find that these individuals show a transient and selective structural change in brain areas that are associated with the processing and storage of complex visual motion. This discovery of a stimulus-dependent alteration in the brains macroscopic structure contradicts the traditionally held view that cortical plasticity is associated with functional rather than anatomical changes.

Use of Neuroanatomical Pattern Classification to Identify Subjects in At-Risk Mental States of Psychosis and Predict Disease Transition

CONTEXTnIdentification of individuals at high risk of developing psychosis has relied on prodromal symptomatology. Recently, machine learning algorithms have been successfully used for magnetic resonance imaging-based diagnostic classification of neuropsychiatric patient populations.nnnOBJECTIVEnTo determine whether multivariate neuroanatomical pattern classification facilitates identification of individuals in different at-risk mental states (ARMS) of psychosis and enables the prediction of disease transition at the individual level.nnnDESIGNnMultivariate neuroanatomical pattern classification was performed on the structural magnetic resonance imaging data of individuals in early or late ARMS vs healthy controls (HCs). The predictive power of the method was then evaluated by categorizing the baseline imaging data of individuals with transition to psychosis vs those without transition vs HCs after 4 years of clinical follow-up. Classification generalizability was estimated by cross-validation and by categorizing an independent cohort of 45 new HCs.nnnSETTINGnDepartments of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.nnnPARTICIPANTSnThe first classification analysis included 20 early and 25 late at-risk individuals and 25 matched HCs. The second analysis consisted of 15 individuals with transition, 18 without transition, and 17 matched HCs.nnnMAIN OUTCOME MEASURESnSpecificity, sensitivity, and accuracy of classification.nnnRESULTSnThe 3-group, cross-validated classification accuracies of the first analysis were 86% (HCs vs the rest), 91% (early at-risk individuals vs the rest), and 86% (late at-risk individuals vs the rest). The accuracies in the second analysis were 90% (HCs vs the rest), 88% (individuals with transition vs the rest), and 86% (individuals without transition vs the rest). Independent HCs were correctly classified in 96% (first analysis) and 93% (second analysis) of cases.nnnCONCLUSIONSnDifferent ARMSs and their clinical outcomes may be reliably identified on an individual basis by assessing patterns of whole-brain neuroanatomical abnormalities. These patterns may serve as valuable biomarkers for the clinician to guide early detection in the prodromal phase of psychosis.

Functional anatomy of pitch memory—an fMRI study with sparse temporal sampling

Auditory functional magnetic resonance imaging tasks are challenging since the MR scanner noise can interfere with the auditory stimulation. To avoid this interference a sparse temporal sampling method with a long repetition time (TR = 17 s) was used to explore the functional anatomy of pitch memory. Eighteen right-handed subjects listened to a sequence of sine-wave tones (4.6 s total duration) and were asked to make a decision (depending on a visual prompt) whether the last or second to last tone was the same or different as the first tone. An alternating button press condition served as a control. Sets of 24 axial slices were acquired with a variable delay time (between 0 and 6 s) between the end of the auditory stimulation and the MR acquisition. Individual imaging time points were combined into three clusters (0-2, 3-4, and 5-6 s after the end of the auditory stimulation) for the analysis. The analysis showed a dynamic activation pattern over time which involved the superior temporal gyrus, supramarginal gyrus, posterior dorsolateral frontal regions, superior parietal regions, and dorsolateral cerebellar regions bilaterally as well as the left inferior frontal gyrus. By regressing the performance score in the pitch memory task with task-related MR signal changes, the supramarginal gyrus (left>right) and the dorsolateral cerebellum (lobules V and VI, left>right) were significantly correlated with good task performance. The SMG and the dorsolateral cerebellum may play a critical role in short-term storage of pitch information and the continuous pitch discrimination necessary for performing this pitch memory task.

Detecting structural changes in whole brain based on nonlinear deformations-application to schizophrenia research

This paper describes a new method for detecting structural brain differences based on the analysis of deformation fields. Deformations are obtained by an intensity-based nonlinear registration routine that transforms one brain onto another one. We present a general multivariate statistical approach to analyze deformation fields in different subjects. This method was applied to the brains of 85 schizophrenic patients and 75 healthy volunteers to examine whether low frequency deformations are sufficiently sensitive to detect regional deviations in the brains of both groups. We observed significant changes caused by volume reduction in brains of schizophrenics bilaterally in the thalamus and in the superior temporal gyrus. On the left side, the superior frontal gyrus and precentral gyrus are found to be changed, while on the right side, the middle frontal gyrus was altered. In addition, there were significant changes in the occipital lobe (left lingual gyrus) and in the left cerebellum. Volume enlargement in brains of schizophrenics was observed in the right putamen and in the adjacent white matter of the thalamic region. Our data suggest a disturbance in the nodes of a prefrontal-thalamic-cerebellar circuitry. This provides further support for the model of cognitive dysmetria, which postulates a disruption in these nodes. We have demonstrated the application of deformation-based morphometry by detecting structural changes in the whole brain. This technique is fully automatic, thus allowing for the inclusion of large samples, with no user bias or a priori-defined regions of interest.

Decreased frontal activation in schizophrenics during stimulation with the continuous performance test--a functional magnetic resonance imaging study.

Summary ‐ The Continuous Performance Test (CPT) has become an essential constituent of the neuropsychological investigation of schizophrenia. Also, a vast number of brain imaging studies, mostly PET investigations, have employed the CPT as a cognitive challenge and established a relative hypofrontality in schizophrenics compared to controls. The aim of the present investigation was to clarify whether this predescribed hypofrontality could also be verified using functional magnetic resonance imaging (fMRI). 20 healthy volunteers and 14 schizophrenics on stable neuroleptic medication were included. Imaging was performed using the CPT-double-T-version and a clinical 1.5 T MRI-scanner with a single slice technique and a T2*-weighted gradient-echo-sequence. The schizophrenics exhibited a decreased activation in the right mesial prefrontal cortex, the right cingulate and the left thalamus compared to controls. These results obtained by fMRI are discussed in relation to published findings using PET.

Brain activation during cognitive stimulation with the Wisconsin Card Sorting Test--a functional MRI study on healthy volunteers and schizophrenics.

It has been demonstrated by single photon emission computed tomography (SPECT) and positron emission tomography (PET) that frontal brain regions are stimulated during performance of the Wisconsin Card Sorting Test (WCST). The WCST is also regarded as one of the standard tests for the assessment of frontal activity in brain imaging studies of schizophrenia. In this study cerebral activation was assessed by means of functional magnetic resonance imaging (fMRI). In healthy volunteers WCST stimulation resulted in a right lateralized frontal activation. In 13 chronic schizophrenics on stable neuroleptic medication, a lack of activation in the right prefrontal cortex and--as a trend--an increased left temporal activity during execution of the WCST was noted compared to controls. Since a one-slice technique was used, no information about the activation pattern in adjacent brain regions was obtained. However, as fMRI possesses a superior spatial resolution compared to SPECT and PET, the anatomical localization of the activation effect in the measured slice can be defined more precisely. Beside these methodological considerations, the results are discussed in relation to prior findings of a reduced ability of schizophrenics to coordinate cerebral function.

Challenging the anterior attentional system with a continuous performance task: a functional magnetic resonance imaging approach

Abstract Combining the Continuous Performance Test (CPT) with a modern functional imaging technique provides a powerful tool for investigating neurophysiological processes in the human brain. There is increasing evidence from single photon emission tomography (SPECT), positron emission tomography (PET) and presently also functional magnetic resonance imaging (fMRI) studies proposing the existence of a distributed large-scale attentional network, mediated by the dorsolateral prefrontal and mesial frontal cortex, thalamus, basal ganglia and posterior parietal and superior temporal lobe. The aim of this study is to show that fMRI is a useful tool for in vivo localization of attentional tasks and to compare the results with established imaging techniques. Functional MRI was performed on a clinical 1.5-T system using gradient-echo acquisition. For data processing, the Statistical Parametric Mapping (SPM96) package was used. A right lateralized activation pattern in the dorsolateral prefrontal and mesial frontal cortex, the thalamus and the basal ganglia was found in a group of 12 male subjects. These findings support theories suggesting right hemispheric dominance of human attention.

Neuroanatomical correlates of different vulnerability states for psychosis and their clinical outcomes.

BACKGROUNDnStructural brain abnormalities have been described in individuals with an at-risk mental state for psychosis. However, the neuroanatomical underpinnings of the early and late at-risk mental state relative to clinical outcome remain unclear.nnnAIMSnTo investigate grey matter volume abnormalities in participants in a putatively early or late at-risk mental state relative to their prospective clinical outcome.nnnMETHODnVoxel-based morphometry of magnetic resonance imaging data from 20 people with a putatively early at-risk mental state (ARMS-E group) and 26 people with a late at-risk mental state (ARMS-L group) as well as from 15 participants with at-risk mental states with subsequent disease transition (ARMS-T group) and 18 participants without subsequent disease transition (ARMS-NT group) were compared with 75 healthy volunteers.nnnRESULTSnCompared with healthy controls, ARMS-L participants had grey matter volume losses in frontotemporolimbic structures. Participants in the ARMS-E group showed bilateral temporolimbic alterations and subtle prefrontal abnormalities. Participants in the ARMS-T group had prefrontal alterations relative to those in the ARMS-NT group and in the healthy controls that overlapped with the findings in the ARMS-L group.nnnCONCLUSIONSnBrain alterations associated with the early at-risk mental state may relate to an elevated susceptibility to psychosis, whereas alterations underlying the late at-risk mental state may indicate a subsequent transition to psychosis.

Auditory hallucinations and brain structure in schizophrenia: voxel-based morphometric study

We applied voxel-based morphometry to high-resolution magnetic resonance images of 99 participants with schizophrenia. Voxel-wise correlations with a score of auditory hallucination severity identified areas in the left and right superior temporal cortex (including Heschls gyrus), left supramarginal/angular gyrus, left postcentral gyrus and left posterior cingulate cortex. This study extends previous region-of-interest studies demonstrating main effects of auditory hallucinations related to modality-specific superior temporal areas including primary and secondary auditory cortices.

Distinct pattern of brain structural deficits in subsyndromes of schizophrenia delineated by psychopathology

Brain morphological changes are among the best-studied potential endophenotypes in schizophrenia and linked to genetic liability and expression of disease phenotype. Yet, there is considerable heterogeneity across individual subjects making its use as a disease-specific marker difficult. In this study we consider psychopathological variability of disease phenotype to delineate subsyndromes of schizophrenia, link them to distinct brain morphological patterns, and use a classification approach to test specificity of achieved discrimination. We first applied voxel-based morphometry (VBM) to compare 99 patients with DSM-IV schizophrenia (stable psychopathology and antipsychotic medication) with 113 matched healthy controls, then delineated three subgroups within the patient cohort based on psychopathology pattern and compared differential patterns of grey matter abnormalities. Finally, we tested accuracy of assigning any individual MRI scan to either the control group or any of the three patient subgroups. While VBM analysis showed overlap of brain structural deficits mostly in prefrontal areas, the disorganised subsyndrome showed stronger deficits in medial temporal and cerebellar regions, the paranoid/hallucinatory subsyndrome showed additional effects in the superior temporal cortex, and the negative subsyndrome showed stronger deficits in the thalamus. Using an automated algorithm, we achieved 95.8% accuracy classifying any given scan to one of the subgroups. Patterns of psychopathology are meaningful parameters in reducing heterogeneity of brain morphological endophenotypes in schizophrenia.