Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter.

BACKGROUND: Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studies involving schizophrenics may be complicated by the effects of exposure to neuroleptics and chronic illness. Sharing the same genetic diathesis of schizophrenics, subjects with schizotypal personality disorder (SPD) offer a unique opportunity to evaluate commonalities between schizophrenia and SPD, particularly as SPD subjects are characterized by cognitive and perceptual distortions, an inability to tolerate close friendships, and odd behavior, but they are not psychotic and so have generally not been prescribed neuroleptics nor hospitalized. Evaluation of brain structure in SPD may thus offer insight into the "endophenotype" common to both disorders. In addition, differences between groups may suggest which are the brain structures of schizophrenics that contribute to the development of psychosis. METHODS: To test the hypothesis of whether SPD subjects might show similar STG abnormalities, STG and medial temporal lobe regions of interest (ROI) were manually drawn on high resolution coronal MRI 1.5 mm thick slices. Images were derived from 16 right-handed male SPD subjects, without regard to family history, and 14 healthy, right-handed, comparison males who did not differ from the SPD group on parental socio-economic status, age, or verbal IQ. RESULTS: As predicted, SPD subjects showed a reduction in left STG gray matter volume compared with age and gender matched comparison subjects. SPD subjects also showed reduced parahippocampal left/right asymmetry and a high degree of disordered thinking. Comparisons with chronic schizophrenics previously studied by us showed the SPD group had a similarity of left STG gray matter volume reduction, but fewer medial temporal lobe abnormalities. CONCLUSIONS: These abnormalities strengthen the hypothesis of a temporal lobe abnormality in SPD, and the similarity of STG findings in schizophrenia and SPD suggest that STG abnormalities may be part of the spectrum "endophenotype." It is also possible that presence of medial temporal lobe abnormalities may help to differentiate who will develop schizophrenia and who will develop the less severe schizophrenia spectrum disorder, SPD.     

Postictal psychosis: a retrospective study in patients with refractory temporal lobe epilepsy

Postictal psychosis (PIP) represents 25% of the psychoses seen in epileptic patients. A high frequency of bilateral independent epileptiform activity has been observed in patients with PIP. The objective of this study was to determine the frequency of PIP in patients with temporal lobe epilepsy (TLE) who underwent video-EEG monitoring and to investigate possible differences between PIP and control patients. METHODS: Clinical, electroencephalographic and neuroimaging data of 5 PIP patients with TLE were compared with data of 50 patients with TLE without psychotic antecedents. Patients with a past history of interictal psychosis were excluded. RESULTS: From 55 patients, 5 were patients with PIP and 50 controls. 31 (62%) were men, 9 (16.4%) had a previous history of encephalitis and 6 (10.9%) of status epilepticus. The mean age was 42.2 years (S.D. 12.93). Mean age at epilepsy onset was 16.95 years (S.D. 12.93) and mean seizure frequency 5seizures/month (S.D. 1.87). The frequency of PIP was 5/55 (9.1%). Previous history of status epilepticus was more frequent in PIP patients than in controls (p: 0.019). PIP patients more frequently had a non-lateralizing ictal EEG than controls (p: 0.001). Bitemporal lobe dysfunction revealed by neuropsychological studies was greater than expected by the observed lesion on MRI studies in patients with PIP. Moreover, the presurgical study was less conclusive in PIP than in control patients (p: 0.049). CONCLUSIONS: PIP is observed in up to 9% of patients with TLE undergoing video-EEG monitoring and most often develops in patients with bitemporal lobe dysfunction.     

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.     

Regional gray matter abnormalities in panic disorder: a voxel-based morphometry study

Although abnormalities in brain structures involved in the neurobiology of fear and anxiety have been implicated in the pathophysiology of panic disorder (PD), relatively few studies have made use of voxel-based morphometry (VBM) magnetic resonance imaging (MRI) to determine structural brain abnormalities in PD. We have assessed gray matter volume in 19 PD patients and 20 healthy volunteers using VBM. Images were acquired using a 1.5 T MRI scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. A relative increase in gray matter volume was found in the left insula of PD patients compared with controls. Additional structures showing differential increases were the left superior temporal gyrus, the midbrain, and the pons. A relative gray matter deficit was found in the right anterior cingulate cortex. The insula and anterior cingulate abnormalities may be relevant to the pathophysiology of PD, since these structures participate in the evaluation process that ascribes negative emotional meaning to potentially distressing cognitive and interoceptive sensory information. The abnormal brain stem structures may be involved in the generation of panic attacks.     

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.     

Extrahippocampal gray matter atrophy and memory impairment in patients with medial temporal lobe epilepsy

Memory impairment observed in patients with medial temporal lobe epilepsy (MTLE) is classically attributed to hippocampal atrophy. The contribution of extrahippocampal structures in shaping memory impairment in patients with MTLE is not yet completely understood, even though atrophy in MTLE extends beyond the hippocampus. We aimed to evaluate the neuropsychological profile of patients with MTLE focusing on memory, and to investigate whether gray matter concentration (GMC) distribution within and outside the medial portion of the temporal lobes would be associated with their neuropsychological performance. We performed a voxel based morphometry study of 36 consecutive patients with MTLE and unilateral hippocampal atrophy. We observed a significant simple regression between general and verbal memory performance based on Wechsler Memory Scale-Revised and the GMC of medial temporal and extratemporal structures in patients with left MTLE. We also performed a "regions of interest analysis" of the medial temporal lobe, and we observed that the GMC of the hippocampus, entorhinal, and perirhinal cortices were consistently associated with general and verbal memory performance in patients with MTLE. We also observed that the GMC of the cingulate and orbito-frontal cortex are independently associated with verbal and general memory performances. Our results suggest that general and verbal memory impairments in patients with left MTLE are associated with atrophy of the hippocampus, the entorhinal, and the perirhinal cortex. We also suggest that atrophy and dysfunction of limbic and frontal structures such as the cingulate and the orbito-frontal cortex contribute to memory impairment in MTLE.     

Interictal SPECT in patients with mesial temporal lobe epilepsy and psychosis: a case-control study

Assessments of the severity of vomiting (weekly frequency), depressive and eating-related psychopathology, anger level and management, and personality dimensions were used to characterize patients with bulimia nervosa binge purging type (BN-BP). The sample comprised 130 outpatients with BN and 130 control women. The Eating Disorder Inventory-2 (EDI-2), the State-Trait Anger Expression Inventory, the Beck Depression Inventory, and the Temperament and Character Inventory (TCI) were administered to all patients. The Self-Directedness dimension of the TCI and the Bulimia subscale of the EDI-2 were the strongest predictors of the severity of bulimic behavior; anger levels and anger expression were not so strongly related to illness severity. A more severe form of bulimic symptomatology probably has substrata in specific character deficits (low Self-Directedness on the TCI) and particular psychopathological features (high bulimia on the EDI-2). Patients with a high frequency of vomiting need specific therapeutic interventions to enhance the character dimension of Self-Directedness.     

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.     

Cortical abnormalities and their cognitive correlates in patients with temporal lobe epilepsy and interictal psychosis

Purpose: To determine whether cortical abnormalities are more severe and widespread in patients with temporal lobe epilepsy (TLE) and interictal psychosis (IP) compared to those with TLE only (NIP) and healthy controls (HC), and to explore the associations between cortical parameters (area, thickness and volume), psychotic symptoms, and cognitive performance. Methods: Twenty‐two patients with IP (9 male; 10 hippocampal sclerosis, HS), 23 TLE nonpsychotic (NIP) patients (11 male; 13 HS) matched for duration of epilepsy and 20 HC participated. Surface‐based morphometry (SBM) was used to measure cortical parameters. Cognition was examined in IP and NIP patients. Associations between cortical parameters and cognition were examined using linear mixed models adjusted by age, gender, and brain volume. Key Findings: IP patients had an earlier onset of epilepsy, more status epilepticus, and worse cognitive performance than NIP patients. In IP patients, cortical thickness was reduced in the inferior frontal gyrus (IFG), and their current IQ was associated with decreases in area, but not thickness, in regions of the frontotemporal cortex. Significance: IP likely reflects the interplay of psychosis‐related genetic factors and the cumulative effects of seizure activity on the brain. Cortical thinning in the IFG, a region implicated in schizophrenia, is likely to be related to seizure activity, whereas changes in IQ, associated with reductions in area of frontotemporal cortex, may be related to the presence of psychosis.     

Regional gray matter abnormalities in panic disorder: A voxel-based morphometry study

Although abnormalities in brain structures involved in the neurobiology of fear and anxiety have been implicated in the pathophysiology of panic disorder (PD), relatively few studies have made use of voxel-based morphometry (VBM) magnetic resonance imaging (MRI) to determine structural brain abnormalities in PD. We have assessed gray matter volume in 19 PD patients and 20 healthy volunteers using VBM. Images were acquired using a 1.5 T MRI scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. A relative increase in gray matter volume was found in the left insula of PD patients compared with controls. Additional structures showing differential increases were the left superior temporal gyrus, the midbrain, and the pons. A relative gray matter deficit was found in the right anterior cingulate cortex. The insula and anterior cingulate abnormalities may be relevant to the pathophysiology of PD, since these structures participate in the evaluation process that ascribes negative emotional meaning to potentially distressing cognitive and interoceptive sensory information. The abnormal brain stem structures may be involved in the generation of panic attacks.     

Postictal psychosis in temporal lobe epilepsy

PURPOSE: Postictal psychosis is a well-known complication, occurring especially in patients with temporal lobe epilepsy. It usually runs a benign course. The literature on this topic is sparse, and the underlying pathogenic mechanisms are not known. METHODS: We report five patients with temporal lobe epilepsy in whom postictal psychosis developed during the course of video-EEG monitoring; they were studied with hexamethyl-propyleneamine-oxime single-photon emission computed tomography (HMPAO-SPECT) during and after the psychotic event. RESULTS: In comparison to the interictal state, all SPECT scans obtained during postictal psychosis were remarkable for bifrontal and bitemporal hyperperfusion patterns. Some studies also demonstrated unilateral left lateral frontal hyperperfusion. These cortical blood-flow patterns appeared to be distinct from those obtained during complex partial seizures. CONCLUSIONS: Our data suggest that postictal psychoses in patients with temporal lobe epilepsy are associated with hyperactivation of both temporal and frontal lobe structures. This hyperperfusion may reflect ongoing (subcortical) discharges, active inhibitory mechanisms that terminate the seizure, or simply a dysregulation of cerebral blood flow.     

A neuropsychological study of patients with temporal lobe epilepsy and chronic interictal psychosis

PURPOSE: To characterize the pattern of cognitive deficits in patients with temporal lobe epilepsy (TLE) and interictal (schizophrenia-like) psychosis and to examine the relationship between neuropsychological deficits and Magnetization transfer imaging. METHODS: Twenty patients with TLE and interictal psychosis were compared to 20 non-psychotic TLE patients. Patients were matched with respect to premorbid IQ, age and conventional MRI findings. A battery of neuropsychological tests was administered. The neuropsychological tests which showed significant group differences were used for correlational analysis with magnetization transfer ratio (MTR) which provides a quantitative measure of macromolecular structural integrity. RESULTS: Patients with interictal psychosis were significantly more impaired on executive and semantic memory tasks than the non-psychotic TLE group. Vocabulary test scores correlated significantly with MTR reduction in the left fusiform gyrus in the psychotic but not the non-psychotic group. DISCUSSION: In this study, patients with TLE and interictal psychosis were more cognitively impaired than non-psychotic TLE patients. Our findings suggest that the cognitive deterioration in these patients may occur as the illness progresses and the causes for this are probably multifactorial. Our study also provides further evidence that MTR may be useful in investigating structural correlates of cognitive impairment.     

Neurodevelopmental disruption in early-onset temporal lobe epilepsy: evidence from a voxel-based morphometry study

Childhood onset of epilepsy has long been associated with an adverse impact on brain development and cognition. In this study it is proposed that earlier (vs later) onset of temporal lobe epilepsy (TLE) has a negative developmental impact on distant brain structures. One hundred ten patients with TLE were assigned to early (≤14 years, N=58) and late (>15 years, N=52) age at onset of epilepsy groups. Voxel-based morphometry revealed onset-dependent abnormalities (in terms of a gray matter excess in the early-onset group), which were found mainly in frontal regions. An excess of gray matter is not a usual finding in TLE. However, within a neurodevelopmental framework, retained gray matter is discussed as reflecting neurodevelopmental disruption. The findings indicate the importance of quantitative MRI for the detection of subtle secondary abnormalities in focal TLE and once more underline the importance of early seizure management in children with intractable TLE.