Absence of cortical gray matter abnormalities in psychosis of epilepsy: a voxel-based MRI study in patients with temporal lobe epilepsy

The authors retrospectively explored cortical differences between 26 patients with temporal lobe epilepsy and psychosis of epilepsy (POE), 24 patients with temporal lobe epilepsy (TLE) alone, and 20 healthy comparison subjects. Using voxel-based morphometry based on statistical parametric mapping (SPM99), which is an unbiased and fully automated technique to test for morphometric differences, magnetic resonance imaging (MRI) 3D-datasets were acquired and analyzed. There were no significant cortical gray matter differences between the POE and the TLE group. Since cortical pathology is prominent in schizophrenia, POE may be a clinical entity separate from schizophrenia.     

White matter microstructural abnormalities in the frontal lobe of adults with antisocial personality disorder

Antisocial personality disorder (ASPD) and psychopathy involve significant interpersonal and behavioural impairments. However, little is known about their underlying neurobiology and in particular, abnormalities in white matter (WM) microstructure. A preliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of adult psychopaths employing tractography revealed abnormalities in the right uncinate fasciculus (UF) (Craig et al., 2009), indicating fronto-limbic disconnectivity. However, it is not clear whether WM abnormalities are restricted to this tract or are or more widespread, including other tracts which are involved in connectivity with the frontal lobe.We performed whole brain voxel-based analyses on WM fractional anisotropy (FA) and mean diffusivity (MD) maps acquired with DT-MRI to compare 15 adults with ASPD and healthy age, handedness and IQ-matched controls. Also, within ASPD subjects we related differences in FA and MD to measures of psychopathy.Significant WM FA reduction and MD increases were found respectively in ASPD subjects relative to controls. FA was bilaterally reduced in the genu of corpus callosum while in the right frontal lobe FA reduction was found in the UF, inferior fronto-occipital fasciculus (IFOF), anterior corona radiata and anterior limb and genu of the internal capsule. These differences negatively correlated with measures of psychopathy. Also in the right frontal lobe, increased MD was found in the IFOF and UF, and the corpus callosum and anterior corona radiata. There was a significant positive correlation between MD and psychopathy scores.ConclusionsThe present study confirms a previous report of reduced FA in the UF. Additionally, we report for the first time, FA deficits in tracts involved in interhemispheric as well as frontal lobe connectivity in conjunction with MD increases in the frontal lobe. Hence, we provide evidence of significant WM microstructural abnormalities in frontal brain regions in ASPD and psychopathy.     

Regional prefrontal gray and white matter abnormalities in bipolar disorder.

BACKGROUND: Previous magnetic resonance imaging (MRI) studies indicate that compared with healthy volunteers, patients with bipolar disorder have structural and functional abnormalities in the prefrontal cortex. The aim of this study was to investigate differences in prefrontal subregions between bipolar patients and healthy subjects. METHODS: Bipolar patients hospitalized for a manic episode (n = 17), and demographically matched healthy volunteers (n = 12) were recruited. Contiguous 1-mm coronal T1-weighted MRI slices were obtained using a Picker 1.5 Tesla scanner. The gray and white matter volumes of five prefrontal subregions of interest were measured: superior, middle, inferior, cingulate, and orbital. RESULTS: Bipolar patients had smaller left prefrontal gray matter volumes, specifically in the middle and superior subregions and smaller right prefrontal gray matter volumes, specifically in the inferior and middle subregions. White matter differences were not observed in any of the prefrontal subregions. CONCLUSIONS: The results suggest that bipolar patients have subregion-specific gray matter volume reductions in the prefrontal cortex as compared to healthy subjects. Further investigations into the role of specific prefrontal subregions in bipolar disorder are warranted.     

Frontal lobe gray matter density decreases in bipolar I disorder.

BACKGROUND: This study was conducted to explore differences in gray and white matter density between bipolar and healthy comparison groups using voxel-based morphometry (VBM). METHODS: Brain magnetic resonance imaging was performed for 39 subjects with bipolar I disorder and 43 comparison subjects. Images were registered into a proportional stereotaxic space and segmented into gray matter, white mater, and cerebrospinal fluid. Statistical parametric mapping was used to calculate differences in gray and white matter density between groups. RESULTS: Bipolar subjects had decreased gray matter density in left anterior cingulate gyrus (Brodmann's area [BA] 32, 7.3% decrease), an adjacent left medial frontal gyrus (BA 10, 6.9% decrease), right inferior frontal gyrus (BA 47, 9.2% decrease), and right precentral gyrus (BA 44, 6.2% decrease), relative to comparison subjects. CONCLUSIONS: The observation of a gray matter density decrease in the left anterior cingulate, which processes emotions, in bipolar subjects is consistent with prior reports that used region-of-interest analytic methods. Decreased gray matter density in the right inferior frontal gyrus, which processes nonverbal and intrinsic functions, supports nondominant hemisphere dysfunction as a component of bipolar disorder.     

Reduced anterior and posterior cingulate gray matter in borderline personality disorder.

BACKGROUND: Structural abnormalities in prefrontal and cingulate gyrus regions-important in affective processing, impulse control and cognition may contribute to the psychopathology of borderline personality disorder (BPD). Previous MRI studies examining volume have reported that compared with healthy controls, BPD patients have decreases in right anterior cingulate, no differences in dorsolateral prefrontal cortex, and mixed findings for prefrontal cortex. We extended this investigation by examining gray and white matter volume of frontal and cingulate gyrus Brodmann areas (BAs) in a large group of patients and healthy controls. METHODS: MRI scans were acquired in 50 BPD patients (n = 13 with comorbid diagnosis of BPD and Schizotypal Personality Disorder (SPD) and n = 37 without SPD) and 50 healthy controls, and gray/white matter volume in cingulate gyrus and frontal lobe BAs were assessed. Normal BPD and BPD subgroup comparisons were conducted. RESULTS: Compared with controls, BPD patients showed reduced gray matter volume in BA 24 and 31 of the cingulate. BPD patients without comorbid SPD had isolated gray matter volume loss in BA 24, but were spared for BA 31 in contrast to BPD patients with SPD. There were no group differences in whole cingulate or frontal lobe volume. CONCLUSIONS: The finding of more pervasive cingulate shrinkage in the patients with BPD and SPD comorbidity resembles recent observations with the same methods in patients with schizophrenia. The pattern of reduced anterior and posterior cingulate gray matter volume in BPD patients, particularly those comorbid for SPD is consistent with the affective and attentional deficits observed in these personality disorders.     

Middle and inferior temporal gyrus gray matter volume abnormalities in chronic schizophrenia: an MRI study

OBJECTIVE: The middle temporal gyrus and inferior temporal gyrus subserve language and semantic memory processing, visual perception, and multimodal sensory integration. Functional deficits in these cognitive processes have been well documented in patients with schizophrenia. However, there have been few in vivo structural magnetic resonance imaging (MRI) studies of the middle temporal gyrus and inferior temporal gyrus in schizophrenia. METHOD: Middle temporal gyrus and inferior temporal gyrus gray matter volumes were measured in 23 male patients diagnosed with chronic schizophrenia and 28 healthy male subjects by using high-spatial-resolution MRI. For comparison, superior temporal gyrus and fusiform gyrus gray matter volumes were also measured. Correlations between these four regions and clinical symptoms were also investigated. RESULTS: Relative to healthy subjects, the patients with chronic schizophrenia showed gray matter volume reductions in the left middle temporal gyrus (13% difference) and bilateral inferior temporal gyrus (10% difference in both hemispheres). In addition, the patients showed gray matter volume reductions in the left superior temporal gyrus (13% difference) and bilateral fusiform gyrus (10% difference in both hemispheres). More severe hallucinations were significantly correlated with smaller left hemisphere volumes in the superior temporal gyrus and middle temporal gyrus. CONCLUSIONS: These results suggest that patients with schizophrenia evince reduced gray matter volume in the left middle temporal gyrus and bilateral reductions in the inferior temporal gyrus. In conjunction with findings of left superior temporal gyrus reduction and bilateral fusiform gyrus reductions, these data suggest that schizophrenia may be characterized by left hemisphere-selective dorsal pathophysiology and bilateral ventral pathophysiology in temporal lobe gray matter.     

Middle and inferior temporal gyrus gray matter volume abnormalities in first-episode schizophrenia: an MRI study

OBJECTIVE: Magnetic resonance imaging (MRI) studies of schizophrenia reveal temporal lobe structural brain abnormalities in the superior temporal gyrus and the amygdala-hippocampal complex. However, the middle and inferior temporal gyri have received little investigation, especially in first-episode schizophrenia. METHOD: High-spatial-resolution MRI was used to measure gray matter volume in the inferior, middle, and superior temporal gyri in 20 patients with first-episode schizophrenia, 20 patients with first-episode affective psychosis, and 23 healthy comparison subjects. RESULTS: Gray matter volume in the middle temporal gyrus was smaller bilaterally in patients with first-episode schizophrenia than in comparison subjects and in patients with first-episode affective psychosis. Posterior gray matter volume in the inferior temporal gyrus was smaller bilaterally in both patient groups than in comparison subjects. Among the superior, middle, and inferior temporal gyri, the left posterior superior temporal gyrus gray matter in the schizophrenia group had the smallest volume, the greatest percentage difference, and the largest effect size in comparisons with healthy comparison subjects and with affective psychosis patients. CONCLUSIONS: Smaller gray matter volumes in the left and right middle temporal gyri and left posterior superior temporal gyrus were present in schizophrenia but not in affective psychosis at first hospitalization. In contrast, smaller bilateral posterior inferior temporal gyrus gray matter volume is present in both schizophrenia and affective psychosis at first hospitalization. These findings suggest that smaller gray matter volumes in the dorsal temporal lobe (superior and middle temporal gyri) may be specific to schizophrenia, whereas smaller posterior inferior temporal gyrus gray matter volumes may be related to pathology common to both schizophrenia and affective psychosis.     

Localized gray matter volume abnormalities in generalized anxiety disorder

Generalized anxiety disorder (GAD) is characterized by excessive and persistent worrying. Neural substrates of this disorder are insufficiently understood, which relates to functional as well as to structural brain abnormalities. Especially, findings on the neuroanatomy of GAD have been inconsistent and were predominantly derived from pediatric samples. Therefore, we studied adult patients. Thirty-one women (16 patients with GAD and 15 healthy control participants) underwent structural MRI scanning. Gray matter volumes for specific brain regions involved in worrying, anticipatory anxiety, and emotion regulation were analyzed by means of voxel-based morphometry. Relative to controls, patients with GAD had larger volumes of the amygdala and the dorsomedial prefrontal cortex (DMPFC). Moreover, patients’ self-reports on symptom severity were positively correlated with volumes of the DMPFC and the anterior cingulate cortex. Patients with GAD show localized gray matter volume differences in brain regions associated with anticipatory anxiety and emotion regulation. This abnormality may represent either a predisposition for GAD or a consequence of disorder-specific behavior, such as chronic worrying. This issue should be addressed in future MRI studies.     

Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

OBJECTIVE: The goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE. METHODS: Children with symptomatic TLE (n=14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n=14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery. RESULTS: Children with MTLE with unilateral hippocampal atrophy (n=9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n=14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex. CONCLUSIONS: Similar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

ObjectiveThe goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE.MethodsChildren with symptomatic TLE (n = 14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n = 14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery.ResultsChildren with MTLE with unilateral hippocampal atrophy (n = 9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n = 14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex.ConclusionsSimilar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

Gray matter abnormalities in patients with narcissistic personality disorder

Background

Despite the relevance of narcissistic personality disorder (NPD) in clinical settings, there is currently no empirical data available regarding the neurobiological correlates of NPD. In the present study, we performed a voxel-based morphometric analysis to provide initial insight into local abnormalities of gray matter (GM) volume.

Methods

Structural brain images were obtained from patients with NPD (n = 17) and a sample of healthy controls (n = 17) matched regarding age, gender, handedness, and intelligence. Groups were compared with regard to global brain tissue volumes and local abnormalities of GM volume. Regions-of-interest analyses were calculated for the anterior insula.

Results

Relative to the control group, NPD patients had smaller GM volume in the left anterior insula. Independent of group, GM volume in the left anterior insula was positively related to self-reported emotional empathy. Complementary whole-brain analyses yielded smaller GM volume in fronto-paralimbic brain regions comprising the rostral and median cingulate cortex as well as dorsolateral and medial parts of the prefrontal cortex.

Conclusion

Here we provide the first empirical evidence for structural abnormalities in fronto-paralimbic brain regions of patients with NPD. The results are discussed in the context of NPD patients' restricted ability for emotional empathy.     

Regional gray matter abnormalities in obsessive-compulsive disorder: a voxel-based morphometry study.

BACKGROUND: Several structural magnetic resonance imaging (MRI) studies have investigated the presence of brain abnormalities in obsessive-compulsive disorder (OCD) but have not produced consistent findings. This might be partly related to their use of a regions-of-interest approach. We assessed gray matter volumes in 19 OCD subjects and 15 healthy volunteers, using voxel-based morphometry (VBM). METHODS: Images were acquired with a 1.5-T MRI scanner, spatially normalized, and segmented with optimized VBM. Statistical comparisons were performed with the general linear model. RESULTS: Significant findings were detected in regions predicted a priori to be implicated in OCD, including increased gray matter in OCD subjects relative to control subjects in posterior orbitofrontal and parahippocampal regions; decreased gray matter in OCD patients in the left anterior cingulate cortex; and inverse correlations between obsessive-compulsive symptom severity and gray matter in the medial thalamus (p < .001, uncorrected for multiple comparisons). Also, an unpredicted site of gray matter reduction in OCD patients in the right parietal associative cortex approached significance (p = .052, corrected for multiple comparisons). CONCLUSIONS: Our findings are consistent with previous studies implicating dysfunction of orbitofrontal, cingulate, thalamic, and temporolimbic regions in OCD and suggest that the involvement of the parietal cortex in the pathophysiology of OCD warrants further investigation.     

Differences and similarities in insular and temporal pole MRI gray matter volume abnormalities in first-episode schizophrenia and affective psychosis

CONTEXT: Whether psychoses associated with schizophrenia and affective disorder represent manifestations of different disorders or the same disorder is an important but unresolved question in psychiatry. Results of previous volumetric magnetic resonance imaging investigations indicate that gray matter volume reductions in neocortical regions may be specific to schizophrenia. OBJECTIVE: To simultaneously evaluate multiple olfactocentric paralimbic regions, which play crucial roles in human emotion and motivation, in first-episode patients with schizophrenia and affective psychosis. DESIGN: A cross-sectional study using high-spatial resolution magnetic resonance imaging in patients with schizophrenia and affective psychosis at their first hospitalization. SETTING: Inpatient units at a private psychiatric hospital. PARTICIPANTS: Fifty-three first-episode patients, 27 with schizophrenia and 26 with affective (mainly manic) psychosis, and 29 control subjects. MAIN OUTCOME MEASURES: Using high-spatial resolution magnetic resonance imaging, the gray matter volumes of 2 olfactocentric paralimbic regions of interest, the insular cortex and the temporal pole, were evaluated. RESULTS: A bilateral volume reduction in insular cortex gray matter was specific to first-episode patients with schizophrenia. In contrast, both first-episode psychosis groups showed a volume reduction in left temporal pole gray matter and an absence of normal left-greater-than-right asymmetry. Region of interest correlations showed that only patients with schizophrenia lacked a positive correlation between left temporal pole and left anterior amygdala-hippocampal complex gray matter volumes, whereas both psychosis groups were similar in lacking normal positive correlations between left temporal pole and left anterior superior temporal gyrus gray matter volumes. CONCLUSIONS: These partially different and partially similar patterns of structural abnormalities in olfactocentric paralimbic regions and their associated abnormalities in other temporolimbic regions may be important factors in the differential and common manifestations of the 2 psychoses.     

Schizotypal personality disorder inside and outside the schizophrenic spectrum

The concept of schizotypal personality disorder has been heavily discussed since its introduction into the official classification of mental disorders in DSM-III. The aim of this study was to investigate the difference between schizotypal personality disorder within and outside the genetic spectrum of schizophrenia. Schizotypals with and without schizophrenic cotwins and first-degree relatives were compared, with individuals with other mental disorders and no mental disorders as controls. It appeared that only inadequate rapport and odd communication were more pronounced among schizotypals within, compared to schizotypals outside the schizophrenic spectrum. Schizotypals outside the schizophrenic spectrum, however, scored higher than schizotypals inside the schizophrenic spectrum on ideas of reference, suspiciousness, paranoia, social anxiety, self-damaging acts, chronic anger, free-floating anxiety and sensitivity to rejection. Interestingly, the four last features are seldom observed among schizotypals inside the schizophrenic spectrum. Monozygotic non-schizophrenic cotwins of schizophrenics score high on inadequate rapport, odd communication, social isolation and delusions/hallucinations. Monozygotic non-schizophrenic cotwins of schizotypals outside the schizophrenic genetic spectrum score high on illusions, depersonalization, derealization and magical thinking. Negative schizotypal features appear to be inside the schizophrenic spectrum, while positive borderline-like features are outside having another genetic endowment.     

Grey and white matter abnormalities in temporal lobe epilepsy with and without mesial temporal sclerosis

Temporal lobe epilepsy with (TLE-mts) and without (TLE-no) mesial temporal sclerosis display different patterns of cortical neuronal loss, suggesting that the distribution of white matter damage may also differ between the sub-groups. The purpose of this study was to examine patterns of white matter damage in TLE-mts and TLE-no and to determine if identified changes are related to neuronal loss at the presumed seizure focus. The 4 T diffusion tensor imaging (DTI) and T1-weighted data were acquired for 22 TLE-mts, 21 TLE-no and 31 healthy controls. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) maps and voxel-based morphometry (VBM) was used to identify grey matter (GM) volume atrophy. Correlation analysis was conducted between the FA maps and neuronal loss at the presumed seizure focus. In TLE-mts, reduced FA was identified in the genu, body and splenium of the corpus callosum, bilateral corona radiata, cingulum, external capsule, ipsilateral internal capsule and uncinate fasciculus. In TLE-no, FA decreases were identified in the genu, the body of the corpus callosum and ipsilateral anterior corona radiata. The FA positively correlated with ipsilateral hippocampal volume. Widespread extra-focal GM atrophy was associated with both sub-groups. Despite widespread and extensive GM atrophy displaying different anatomical patterns in both sub-groups, TLE-mts demonstrated more extensive FA abnormalities than TLE-no. The microstructural organization in the corpus callosum was related to hippocampal volume in both patients and healthy subjects demonstrating the association of these distal regions.     

Extrahippocampal gray matter loss and hippocampal deafferentation in patients with temporal lobe epilepsy

Purpose: Medial temporal epilepsy (MTLE) is associated with extrahippocampal brain atrophy. The mechanisms underlying brain damage in MTLE are unknown. Seizures may lead to neuronal damage, but another possible explanation is deafferentation from loss of hippocampal connections. This study aimed to investigate the relationship between hippocampal deafferentation and brain atrophy in MTLE. Methods: Three different MRI studies were performed involving 23 patients with unilateral MTLE (8 left and 15 right) and 34 healthy controls: (1) voxel‐based morphometry (VBM), (2) diffusion tensor imaging (DTI) and (3) probabilistic tractography (PT). VBM was employed to define differences in regional gray matter volume (GMV) between controls and patients. Voxel‐wise analyses of DTI evaluated differences in fractional anisotropy (FA), mean diffusivity (MD) and hippocampal PT. Z‐scores were computed for regions‐of‐interest (ROI) GMV and peri‐hippocampal FA and MD (to quantify hippocampal fiber integrity). The relationship between hippocampal deafferentation and regional GMV was investigated through the association between ROI Z scores and hippocampal fiber integrity. Results: Patients with MTLE exhibited a significant reduction in GMV and FA in perihippocampal and limbic areas. There was a decrease in hippocampal PT in patients with MTLE in limbic areas. A significant relationship between loss of hippocampal connections and regional GMV atrophy was found involving the putamen, pallidum, middle and inferior temporal areas, amygdala and ceberellar hemisphere. Discussion: There is a relationship between hippocampal disconnection and regional brain atrophy in MTLE. These results indicate that hippocampal deafferentation plays a contributory role in extrahippocampal brain damage in MTLE.