Benedicto Crespo-Facorro

Insular cortex abnormalities in schizophrenia: a structural magnetic resonance imaging study of first-episode patients

The insular cortex is a limbic integration region that is engaged in emotional and cognitive functions. To investigate possible insular cortex abnormalities in schizophrenia, we measured insular gray matter volume and cortical surface size in drug-naive first-episode patients. Magnetic resonance images were used to explore the morphology of the insular cortex of 25 healthy male volunteers, and 25 male schizophrenic patients. Groups were matched for age, sex, height, and parental socio-economic status. Clinical dimension scores were correlated with insular gray matter volume and cortical surface area. Patients had a significant reduction in cortical surface area [patients=2020 (206); controls=2142 (204); F=5.83, df=1, 47; P=0.01] and gray matter volume [patients=8.12 (0.77); controls=8.57 (0.94); F=3.93, df=1,47; P=0.05] in the left insular cortex. Insular gray matter volume and cortical surface size correlated negatively and significantly with the psychotic symptom dimension. Schizophrenic patients show morphological abnormalities in the insular cortex at early stages of the illness. These abnormalities are related to the severity of psychotic symptoms. Further investigations are needed to evaluate the role of the insula in the pathophysiology of schizophrenia.

An MRI-based parcellation method for the temporal lobe.

The temporal lobe has long been a focus of attention with regard to the underlying pathology of several major psychiatric illnesses. Previous postmortem and imaging studies describing regional volume reductions or perfusion defects in temporal subregions have shown inconsistent findings, which are in part due to differences in the definition of the subregions and the methodology of measurement. The development of precise reproducible parcellation systems on magnetic resonance images may help improve uniformity of results in volumetric MR studies and unravel the complex activation patterns seen in functional neuroimaging studies. The present study describes detailed guidelines for the parcellation of the temporal neocortex. It parcels the entire temporal neocortex into 16 subregions: temporal pole, heschls gyrus, planum temporale, planum polare, superior temporal gyrus (rostral and caudal), middle temporal gyrus (rostral, intermediate, and caudal), inferior temporal gyrus (rostral, intermediate, and caudal), occipitotemporal gyrus (rostral and caudal), and parahippocampal gyrus (rostral and caudal). Based upon topographic landmarks of individual sulci, every subregion was consecutively traced on a set of serial coronal slices. In spite of the huge variability of sulcal topography, the sulcal landmarks could be identified reliably due to the simultaneous display of three orthogonal (transaxial, coronal, and sagittal) planes, triangulated gray matter isosurface, and a 3-D-rendered image. The reliability study showed that the temporal neocortex could be parceled successfully and reliably; intraclass correlation coefficient for each subregion ranged from 0.62 to 0.99. Ultimately, this method will permit us to detect subtle morphometric impairments or to find abnormal patterns of functional activation in the temporal subregions that might reflect underlying neuropathological processes in psychiatric illnesses such as schizophrenia.

Human Frontal Cortex: An MRI-Based Parcellation Method

The frontal lobe is not a single anatomical and functional brain region. Several lines of research have demonstrated that particular subregions within the frontal lobe are associated with specific motor and cognitive functions in the human being. Our main purpose is to develop a magnetic resonance image (MRI)-based parcellation method of the frontal lobe that permits us to explore plausible abnormalities in functionally relevant frontal subregions in brain illnesses. We describe a procedure using MRI for subdividing the entire frontal cortex into 11 subregions: supplementary motor area (SMA), rostral anterior cingulate gyrus (r-ACiG), caudal anterior cingulate gyrus (c-ACiG), superior cingulate gyrus (SCiG), medial frontal cortex (MFC), straight gyrus (SG), orbitofrontal cortex (OFC), precentral gyrus (PCG), superior frontal gyrus (SFG), inferior frontal gyrus (IFG), and middle frontal gyrus (MFG). Our method posits to conserve the topographic uniqueness of individual brains and is based on our ability to visualize both the three-dimensional (3D) rendered brain and the three orthogonal planes simultaneously. The reliability study for gray matter volume and surface area of each subregion was performed on a set of 10 MR scans by two raters. The intraclass R coefficients for gray matter volume of each subregion ranged between 0.86 and 0.99. We describe here a reproducible and reliable topography-based parcellation method of the frontal lobe that will allow us to use new approaches to understand the role of particular frontal cortical subregions in schizophrenia and other brain illnesses.

Regional frontal abnormalities in schizophrenia: a quantitative gray matter volume and cortical surface size study.

BACKGROUND Previous structural studies of the frontal lobe in schizophrenia have had somewhat inconsistent results, but most of them have measured the frontal lobe as a single brain structure. To investigate more specific abnormalities in frontal subregions, we measured gray matter volume and cortical surface size in 10 subregions in drug-naive patients during the early stages of the illness. METHODS Magnetic resonance imaging was used to measure frontal subregions in 34 healthy male volunteers, and 26 male, drug-naive schizophrenia patients at early stages of the illness. Frontal subregions were manually traced using our locally developed parcellation method. RESULTS Patients with schizophrenia had a significant deficit in cortical surface size in the right straight gyrus and left orbitofrontal cortex. No differences were found in gray matter volumes. CONCLUSIONS Frontal structural abnormalities found in drug-naive schizophrenic patients appear to be subtle and circumscribed to ventral portions. Anomalies in the cortical surface size suggest neurodevelopmental abnormalities might occur during the early stages of the gyrogenesis. Further investigations are needed to explore the implications of paralimbic ventral frontal regions (i.e., straight gyrus and orbitofrontal cortex) in the pathophysiology of schizophrenia.

Cerebral cortex: a topographic segmentation method using magnetic resonance imaging

Remarkable developments in magnetic resonance imaging (MRI) technology provide a broad range of potential applications to explore in vivo morphological characteristics of the human cerebral cortex. MR-based parcellation methods of the cerebral cortex may clarify the structural anomalies in specific brain subregions that reflect underlying neuropathological processes in brain illnesses. The present study describes detailed guidelines for the parcellation of the cerebral cortex into 41 subregions. Our method conserves the topographic uniqueness of individual brains and is based on our ability to visualize the three orthogonal planes, the triangulated gray matter isosurface and the three-dimensional (3D) rendered brain simultaneously. Based upon topographic landmarks of individual sulci, every subregion was manually segmented on a set of serial coronal or transaxial slices consecutively. The reliability study indicated that the cerebral cortex could be parcelled reliably; intraclass correlation coefficients for each subregion ranged from 0.60 to 0.99. The validity of the method is supported by the fact that gyral subdivisions are similar to regions delineated in functional imaging studies conducted in our center. Ultimately, this method will permit us to detect subtle morphometric impairments or to find abnormal patterns of functional activation in circumscribed cortical subregions. The description of a thorough map of regional structural and functional cortical abnormalities will provide further insight into the role that different subregions play in the pathophysiology of brain illnesses.

Neural basis of novel and well-learned recognition memory in schizophrenia: a positron emission tomography study.

The level of familiarity of a given stimulus plays an important role in memory processing. Indeed, the novelty/familiarity of learned material has been proven to affect the pattern of activations during recognition memory tasks. We used visually presented words to investigate the neural basis of recognition memory for relatively novel and familiar stimuli in schizophrenia. Subjects were 34 healthy volunteers and 19 schizophrenia spectrum patients. Two experimental cognitive conditions were used: 1 week and again 1 day prior to the PET imaging subjects had to thoroughly learn a list of 18 words (well‐learned memory). Subjects were also asked to learn another set of 18 words presented 1 min before the PET experiment (novel memory). During the PET session, subjects had to recognize the list of 18 words among 22 new (distractor) words. Subjects also performed a control task (reading words). A nonparametric randomization test and a statistical t‐mapping method were used to determine between‐ and within‐group differences. In patients the recognition of novel material produced relatively less flow in several frontal areas, superior temporal gyrus, insular cortex, and parahippocampal areas, and relatively higher activity in parietal areas, visual cortex, and cerebellum, compared to controls. No significant differences in flow were seen when comparing well‐learned memory activations between groups. These results suggest that different neural pathways are engaged during novel recognition memory in patients with schizophrenia compared to healthy individuals. During recognition of novel material, patients failed to activate frontal/limbic regions, recruiting a set of posterior perceptual brain regions instead. Hum. Brain Mapping 12:219–231, 2001.

Morphology of the ventral frontal cortex in schizophrenia: relationship with social dysfunction

BACKGROUND Studies have reported premorbid as well as postonset social dysfunction in schizophrenia. This impairment has also been observed to emerge after lesions in the ventral aspect of the frontal cortex (i.e., straight gyrus and orbitofrontal cortex). METHODS Magnetic resonance imaging scans were obtained from 45 male patients with schizophrenia and 45 matched control subjects. Cortical gray matter volume and surface area were determined for the ventral frontal cortex (VFC), subdivided into the orbitofrontal cortex (OFC) and the straight gyrus (SG). RESULTS The global measures of gray matter volume and surface area in the VFC was not significantly different between patients and control subjects; however, there was a regional difference, with the right SG volume and surface area being smaller in patients compared with control subjects. Volume of the VFC had an inverse correlation with measurements of both premorbid and postdiagnosis social function. The smaller the gray matter in these regions, the greater the social dysfunction. There was no relationship between morphology of this brain region and any other clinical variable. CONCLUSIONS Morphology of the VFC is directly related to abnormal social function in schizophrenia, including measures of social dysfunction that predate the onset of illness.

Novel vs. Well-learned Memory for Faces: A Positron Emission Tomography Study

Previous work has suggested that familiarity/novelty of learned materials affects the circuitry involved in memory, primarily in the size of activations rather than the pattern of activation. Although this work has examined both recall and recognition, it has been limited to verbal material. In this study, we set out to determine if the same result applies to nonverbal memory. We used the same experimental design, but used faces as the memory task. Healthy volunteers thoroughly learned a set of 18 faces a week prior to the Positron Emission Tomography (PET) experiment (well-learned memory) and were asked to remember another set of 18 faces, to which they were exposed 1 min before the PET experiment (novel memory). During the PET session, their task was to recognize the faces learned a week before and the faces seen a minute before; the remembered faces were interspersed among entirely new (distractor) faces. We found that, unlike for verbal material, the retention interval and the familiarity level of the faces affected both the pattern and the size of activations. Comparing the novel and well-learned recognition tasks revealed that novel memory for faces is primarily a frontallobe task, while well-learned recognition memory for faces utilizes a more distributed neural circuit, including visual areas, which appear to serve as memory-storage sites.

Temporal pole morphology and psychopathology in males with schizophrenia

A dysfunction of the paralimbic system has been implicated in the pathophysiology of schizophrenia. The temporal pole (TP) is a relevant component of the paralimbic circuit. Functional and structural imaging studies have shown circumscribed abnormalities in the TP. Subjects were 30 controls and 30 schizophrenia patients. Cortical surface size and gray matter volume of the TP were accurately measured to explore the morphology of the TP cortex and the relationship of TP measures to clinical variables in patients with schizophrenia. Correlations between structural measures and clinical dimensions, duration of illness, and cumulative neuroleptic exposure were determined. Neither macroscopic abnormalities in the TP nor differences in the pattern of asymmetry were demonstrated. The TP volume was correlated negatively to the psychotic and disorganized dimension scores. No other significant correlations were found. No morphological abnormalities in the TP were found in patients with schizophrenia. Interestingly, a reduction in the TP volume, a higher-order multimodal association cortex, was associated with the severity of disorganized and psychotic symptoms.

Sex differences in the absence of massa intermedia in patients with schizophrenia versus healthy controls

OBJECTIVE To evaluate sexual dimorphism and incidence of absent massa intermedia (MI), a midline thalamic structure, in patients with schizophrenia and healthy controls. METHODS Thin slice magnetic resonance images of the brain were obtained. The presence of MI was determined by viewing sagittal, coronal, and axial planes. RESULTS In healthy controls, females had a significantly lower incidence of absent MI (13.56%) compared with males (32.08%). In patients with schizophrenia, there was a sex by diagnosis interaction. Female patients had significantly higher incidence of absent MI (32.76%) compared with their healthy controls (13.56%), whereas the male patients showed no difference in incidence of absent MI compared with their controls. CONCLUSION The MI, a sexually dimorphic midline structure, is more commonly absent in female patients with schizophrenia. These results support the growing literature reporting structural aberration of the thalamus, as well as other midline structures in the brains of patients with schizophrenia.