Marcus Schmidt

Publications (7)36.13 Total impact

• Article: Evidence for intact local connectivity but disrupted regional function in the occipital lobe in children and adolescents with schizophrenia.

  Tonya White, Steen Moeller, Marcus Schmidt, Jose V Pardo, Cheryl Olman
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  ABSTRACT: It has long been known that specific visual frequencies result in greater blood flow to the striate cortex. These peaks are thought to reflect synchrony of local neuronal firing that is reflective of local cortical networks. Since disrupted neural connectivity is a possible etiology for schizophrenia, our goal was to investigate whether localized connectivity, as measured by aberrant synchrony, is abnormal in children and adolescents with schizophrenia. Subjects included 25 children and adolescents with schizophrenia and 39 controls matched for age and gender. Subjects were scanned on a Siemens 3 Tesla Trio scanner while observing flashing checkerboard presented at either 1, 4, 8, or 12 Hz. Image processing included both a standard GLM model and a Fourier transform analysis. Patients had significantly smaller volume of activation in the occipital lobe compared to controls. There were no differences in the integral or percent signal change of the hemodynamic response function for each of the four frequencies. Occipital activation was stable during development between childhood and late adolescence. Finally, both patients and controls demonstrated an increased response between 4 and 8 Hz consistent with synchrony or entrainment in the neuronal response. Children and adolescents with schizophrenia had a significantly lower volume of activation in the occipital lobe in response to the flashing checkerboard task. However, features of intact local connectivity in patients, such as the hemodynamic response function and maximal response at 8 Hz, were normal. These results are consistent with abnormalities in regional connectivity with preserved local connectivity in early-onset schizophrenia.
  Human Brain Mapping 06/2011; 33(8):1803-11. · 5.88 Impact Factor
• Article: Disrupted functional brain connectivity during verbal working memory in children and adolescents with schizophrenia.

  Tonya White, Marcus Schmidt, Dae Il Kim, Vince D Calhoun
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  ABSTRACT: Children and adolescents who develop schizophrenia tend to have greater symptom severity than adults who develop the illness. Since the brain continues to mature into early adulthood, developmental differences in brain structure and function may provide clues to the underlying neurobiology of schizophrenia. With an emerging body of evidence supporting disrupted connectivity contributing to the underlying pathophysiology of schizophrenia, it was our goal to assess differences in functional connectivity in children and adolescents who develop schizophrenia. Participants included a total of 28 children and adolescents (14 patients with schizophrenia and 14 age- and gender-matched controls). All subjects underwent a functional magnetic resonance imaging scan involving a modified Sternberg Item Recognition Paradigm with 3 working memory (WkM) loads. Patients had poorer performance at all 3 WkM loads without a load by diagnosis interaction. Functional imaging results demonstrated 3 specific brain networks disrupted in children and adolescents with schizophrenia. These networks include 1) the anterior cingulate and the temporal lobes, bilaterally; 2) the cerebellum with subcortical regions; and 3) the occipital lobe and the cerebellum. Patients with early-onset schizophrenia demonstrate abnormal functional connectivity in networks involving limbic, temporal lobe, cerebellum, and early visual processing streams.
  Cerebral Cortex 03/2011; 21(3):510-8. · 6.54 Impact Factor
• Article: Increased anterior cingulate and temporal lobe activity during visuospatial working memory in children and adolescents with schizophrenia.

  Tonya White, Donaya Hongwanishkul, Marcus Schmidt
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  ABSTRACT: Similar to adults, children and adolescents with schizophrenia present with significant working memory (WkM) deficits. However, unlike adults, findings of abnormal activity in the prefrontal cortex in early-onset schizophrenia (EOS) are not consistently reported. Since WkM continues to develop through adolescence and into early adulthood, patterns of activation in adolescents may be different than those found in adults. The goal of this study was to evaluate the functional neurobiology of WkM in patients with EOS. Participants included 22 patients with EOS (mean age 15±2.8 years) and 24 controls (mean age 15.0±3.0 years). Diagnoses were confirmed using the KIDDIE-SADS-PL. All subjects underwent a functional MRI paradigm involving a visuospatial working memory task with three separate loads. The behavioral results demonstrated deficits in EOS patients at all three WkM loads. On functional imaging, EOS patients demonstrated increased activation in the anterior cingulate cortex (ACC), medial temporal lobe structures, the insula, and bilateral lateral temporal lobes. Patients with EOS demonstrate increased activity in limbic structures and regions involved in processing primary and secondary sensory information. In addition, EOS patients had load dependent decreased activity in the parietal lobe. Unlike studies in adults, we did not find that EOS patients had activation differences in the frontal cortical regions. One possibility is that abnormalities in PFC function are related to secondary downstream or developmental processes which are 'unmasked' during development. Finally, our findings support growing evidence that EOS patients have aberrations in the limbic and temporal lobe regions.
  Biological Psychiatry 02/2011; 125(2-3):118-28. · 8.28 Impact Factor
• Article: Verbal and visuospatial working memory development and deficits in children and adolescents with schizophrenia.

  Tonya White, Marcus Schmidt, Canan Karatekin
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  ABSTRACT: Deficits in working memory are considered a core feature of schizophrenia and are present early in the course of the illness. Because working memory continues to mature through childhood and into early adulthood, it was the aim of this study to assess developmental trajectories of verbal and visuospatial working memory performance in children and adolescents with schizophrenia. Differences in the developmental trajectories in patients compared with controls may reflect differential effects within specific neural networks involved in working memory performance. Twenty-six children and adolescents with schizophrenia (age range of 8-19 years) and 37 controls matched on age and gender participated in the study. Modified versions of both a verbal and visuospatial Sternberg Item Recognition Paradigm were administered. In the three age groups studied, patients performed significantly worse than controls on the verbal working memory tasks. There were significant effects of diagnosis and load on the verbal Sternberg, with patients performing worse than controls. However, there was no diagnosis by load interactions. Similar findings were present for the visuospatial Sternberg, except for the youngest age group. The 8- to 12-year-old patients had a disproportionately lower performance on the verbal working memory task than on the visuospatial task. Our findings support disruptions in shared verbal and visuospatial working memory networks, such as those supporting encoding processes, in children and adolescents with schizophrenia. We also found specific deficits in non-shared verbal working memory performance in childhood-onset schizophrenia.
  Early Intervention in Psychiatry 11/2010; 4(4):305-13. · 0.92 Impact Factor
• Article: The development of gyrification in childhood and adolescence.

  Tonya White, Shu Su, Marcus Schmidt, Chiu-Yen Kao, Guillermo Sapiro
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  ABSTRACT: Gyrification is the process by which the brain undergoes changes in surface morphology to create sulcal and gyral regions. The period of greatest development of brain gyrification is during the third trimester of pregnancy, a period of time in which the brain undergoes considerable growth. Little is known about changes in gyrification during childhood and adolescence, although considering the changes in gray matter volume and thickness during this time period, it is conceivable that alterations in the brain surface morphology could also occur during this period of development. The formation of gyri and sulci in the brain allows for compact wiring that promotes and enhances efficient neural processing. If cerebral function and form are linked through the organization of neural connectivity, then alterations in neural connectivity, i.e., synaptic pruning, may also alter the gyral and sulcal patterns of the brain. This paper reviews developmental theories of gyrification, computational techniques for measuring gyrification, and the potential interaction between gyrification and neuronal connectivity. We also present recent findings involving alterations in gyrification during childhood and adolescence.
  Brain and Cognition 11/2009; 72(1):36-45. · 3.17 Impact Factor
• Article: White matter 'potholes' in early-onset schizophrenia: a new approach to evaluate white matter microstructure using diffusion tensor imaging.

  Tonya White, Marcus Schmidt, Canan Karatekin
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  ABSTRACT: There is considerable evidence implicating white matter abnormalities in the pathophysiology of schizophrenia. Many of the recent studies examining white matter have utilized diffusion tensor imaging (DTI) using either region of interest (ROI) or voxel-based approaches. Both voxel-based and ROI approaches are based on the assumption that the abnormalities in white matter overlap spatially. However, this is an assumption that has not been tested, and it is possible that aberrations in white matter occur in non-overlapping regions. In order to test for the presence of non-overlapping regions of aberrant white matter, we developed a novel image processing technique that evaluates for white matter 'potholes,' referring to within-subject clusters of white matter voxels that show a significant reduction in fractional anisotropy. We applied this algorithm to a group of children and adolescents with schizophrenia compared to controls and found an increased number of 'potholes' in the patient group. These results suggest that voxel-based and ROI approaches may be missing some white matter differences that do not overlap spatially. This algorithm may be also be well suited to detect white matter abnormalities in disorders such as substance abuse, head trauma, or specific neurological conditions affecting white matter.
  Psychiatry Research 11/2009; 174(2):110-5. · 2.52 Impact Factor
• Article: Limbic structures and networks in children and adolescents with schizophrenia.

  Tonya White, Kathryn Cullen, Lisa Michelle Rohrer, Canan Karatekin, Monica Luciana, Marcus Schmidt, Donaya Hongwanishkul, Sanjiv Kumra, S Charles Schulz, Kelvin O Lim
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  ABSTRACT: Studies of adults with schizophrenia provide converging evidence for abnormalities in the limbic system. Limbic structures that show consistent patient/control differences in both postmortem and neuroimaging studies include the anterior cingulate and hippocampus, although differences in the amygdala, parahippocampal gyrus, and fornix have also been observed. Studies of white matter in children and adolescents with schizophrenia tend to show findings that are more focal than those seen in adults. Interestingly, these focal abnormalities in early-onset schizophrenia tend to be more localized to limbic regions. While it is unclear if these early limbic abnormalities are primary in the etiology of schizophrenia, there is evidence that supports a developmental progression with early limbic abnormalities evolving over time to match the neuroimaging profiles seen in adults with schizophrenia. Alternatively, the aberrations in limbic structures may be secondary to a more widespread or global pathological processes occurring with the brain that disrupt neural transmission. The goal of this article is to provide a review of the limbic system and limbic network abnormalities reported in children and adolescents with schizophrenia. These findings are compared with the adult literature and placed within a developmental context. These observations from neuroimaging studies enrich our current understanding of the neurodevelopmental model of schizophrenia and raise further questions about primary vs secondary processes. Additional research within a developmental framework is necessary to determine the putative etiologic roles for limbic and other brain abnormalities in early-onset schizophrenia.
  Schizophrenia Bulletin 02/2008; 34(1):18-29. · 8.80 Impact Factor