Parietal abnormalities are related to avoidance in social anxiety disorder: a study using voxel-based morphometry and manual volumetry.

Evidence is accumulating that various mental disorders are related to neural abnormalities in the parietal cortices that are associated with the default mode network (DMN). Participants comprised 67 persons with social anxiety disorder (SAD) and 64 matched healthy controls who underwent structural magnetic resonance imaging (MRI) and a comprehensive clinical assessment. Voxel-based morphometry (VBM) across the entire brain and manual volumetry of the parietal cortices were performed. The results indicate abnormal manually segmented volumes or gray matter (GM) volumes within the precuneus, postcentral gyrus and inferior parietal cortex, as well as in the premotor cortices including the supplementary motor cortex. Significant negative correlations were obtained between parietal, especially precuneus, abnormalities and social avoidance severity, indicating stronger avoidance in SAD participants with smaller volumes or less GM. We conclude that pathological avoidance behaviors in SAD are associated with structural deficits of parietal regions that are associated with the DMN, which has been shown to mediate introspection and reflection upon one's own mental state in healthy humans.

Egocentric virtual maze learning in adult survivors of childhood abuse with dissociative disorders: evidence from functional magnetic resonance imaging.

Present neuroimaging findings suggest two subtypes of trauma response, one characterized predominantly by hyperarousal and intrusions, and the other primarily by dissociative symptoms. The neural underpinnings of these two subtypes need to be better defined. Fourteen women with childhood abuse and the current diagnosis of dissociative amnesia or dissociative identity disorder but without posttraumatic stress disorder (PTSD) and 14 matched healthy comparison subjects underwent functional magnetic resonance imaging (fMRI) while finding their way in a virtual maze. The virtual maze presented a first-person view (egocentric), lacked any topographical landmarks and could be learned only by using egocentric navigation strategies. Participants with dissociative disorders (DD) were not impaired in learning the virtual maze when compared with controls, and showed a similar, although weaker, pattern of activity changes during egocentric learning when compared with controls. Stronger dissociative disorder severity of participants with DD was related to better virtual maze performance, and to stronger activity increase within the cingulate gyrus and the precuneus. Our results add to the present knowledge of preserved attentional and visuospatial mnemonic functioning in individuals with DD.

Impaired egocentric memory and reduced somatosensory cortex size in temporal lobe epilepsy with hippocampal sclerosis.

Recent research indicates that longstanding temporal lobe epilepsy (TLE) is associated with extratemporal, i.e. parietal cortex damage. We investigated egocentric and allocentric memory by use of first-person large-scale virtual reality environments in patients with TLE. We expected that TLE patients with parietal cortex damage were impaired in the egocentric memory task. Twenty-two TLE patients with hippocampal sclerosis (HS) and 22 TLE patients without HS were compared with 42 healthy matched controls on two virtual reality tasks affording to learn a virtual park (allocentric memory) and a virtual maze (egocentric memory). Participants further received a neuropsychological investigation and MRI volumetry at the time of the assessment. When compared with controls, TLE patients with HS had significantly reduced size of the ipsilateral and contralateral somatosensory cortex (postcentral gyrus). When compared with controls or TLE patients without HS, TLE patients with HS were severely impaired learning the virtual maze. Considering all participants, smaller volumes of the left-sided postcentral gyrus were related to worse performance on the virtual maze. It is concluded that the paradigm of egocentric navigation and learning in first-person large-scale virtual environments may be a suitable tool to indicate significant extratemporal damage in individuals with TLE.

Egocentric spatial learning in schizophrenia investigated with functional magnetic resonance imaging.

Psychotic symptoms in schizophrenia are related to disturbed self-recognition and to disturbed experience of agency. Possibly, these impairments contribute to first-person large-scale egocentric learning deficits. Sixteen inpatients with schizophrenia and 16 matched healthy comparison subjects underwent functional magnetic resonance imaging (fMRI) while finding their way in a virtual maze. The virtual maze presented a first-person view, lacked any topographical landmarks and afforded egocentric navigation strategies. The participants with schizophrenia showed impaired performance in the virtual maze when compared with controls, and showed a similar but weaker pattern of activity changes during egocentric learning when compared with controls. Especially the activity of task-relevant brain regions (precuneus and posterior cingulate and retrosplenial cortex) differed from that of controls across all trials of the task. Activity increase within the right-sided precuneus was related to worse virtual maze performance and to stronger positive symptoms in participants with schizophrenia. We suggest that psychotic symptoms in schizophrenia are related to aberrant neural activity within the precuneus. Possibly, first-person large-scale egocentric navigation and learning designs may be a feasible tool for the assessment and treatment of cognitive deficits related to self-recognition in patients with schizophrenia.

Hippocampal size in women but not men with schizophrenia relates to disorder duration.

Longitudinal studies have failed to find progressive hippocampal size reduction in schizophrenia. However, negative results may have been due to follow-up intervals at disease stages where no significant progressive brain changes occur. Furthermore, only male or mixed gender samples have been studied. Forty-six patients with schizophrenia (23 females) and 46 healthy controls (23 females) underwent three-dimensional structural magnetic resonance imaging of the hippocampus and a clinical investigation. Compared with controls, male but not female participants with schizophrenia displayed hippocampal size reduction. Hippocampal size of female but not male schizophrenia patients was related to disorder duration, indicating smaller hippocampal size in female patients with longer disorder duration. Female schizophrenia patients displayed normal hippocampal size at the onset of disorder, but similarly reduced hippocampal size as male schizophrenia patients after some years of illness had passed. Our results suggest preserved hippocampal size in women with schizophrenia during the first years of illness.

Egocentric and allocentric memory as assessed by virtual reality in individuals with amnestic mild cognitive impairment.

Present evidence suggests that medial temporal cortices subserve allocentric representation and memory, whereas egocentric representation and memory also depends on parietal association cortices and the striatum. Virtual reality environments have a major advantage for the assessment of spatial navigation and memory formation, as computer-simulated first-person environments can simulate navigation in a large-scale space. Twenty-nine patients with amnestic MCI (aMCI) were compared with 29 healthy matched controls on two virtual reality tasks affording to learn a virtual park (allocentric memory) and a virtual maze (egocentric memory). Participants further received a neuropsychological investigation and MRI volumetry at the time of the assessment. Results indicate that aMCI patients had significantly reduced size of the hippocampus bilaterally and the right-sided precuneus and inferior parietal cortex. aMCI patients were severely impaired learning the virtual park and the virtual maze. Smaller volumes of the right-sided precuneus were related to worse performance on the virtual maze. Participants with striatal lacunar lesions committed more errors than participants without such lesions on the virtual maze but not on the virtual park. aMCI patients later converting to dementia (n=15) had significantly smaller hippocampal size when compared with non-converters (n=14). However, both groups did not differ on virtual reality task performance. Our study clearly demonstrates the feasibility of virtual reality technology to study spatial memory deficits of persons with aMCI. Future studies should try to design spatial virtual reality tasks being specific enough to predict conversion from MCI to dementia and conversion from normal to MCI.

Reduced amygdalar and hippocampal size in adults with generalized social phobia.

BACKGROUND: Structural and functional brain imaging studies suggest abnormalities of the amygdala and hippocampus in posttraumatic stress disorder and major depressive disorder. However, structural brain imaging studies in social phobia are lacking. METHODS: In total, 24 patients with generalized social phobia (GSP) and 24 healthy controls underwent 3-dimensional structural magnetic resonance imaging of the amygdala and hippocampus and a clinical investigation. RESULTS: Compared with controls, GSP patients had significantly reduced amygdalar (13%) and hippocampal (8%) size. The reduction in the size of the amygdala was statistically significant for men but not women. Smaller right-sided hippocampal volumes of GSP patients were significantly related to stronger disorder severity. LIMITATIONS: Our sample included only patients with the generalized subtype of social phobia. Because we excluded patients with comorbid depression, our sample may not be representative. CONCLUSION: We report for the first time volumetric results in patients with GSP. Future assessment of these patients will clarify whether these changes are reversed after successful treatment and whether they predict treatment response.

The human parahippocampal cortex subserves egocentric spatial learning during navigation in a virtual maze.

BACKGROUND: Present evidence suggests that the hippocampus (HC) and the parahippocampal cortex (PHC) are involved in allocentric (world-centered) spatial memory. However, the putative role of the PHC in egocentric (body-centered) spatial learning has received only limited systematic investigation. METHODS: To examine the role of the PHC in egocentric learning, 19 healthy volunteers learned to find their way in a virtual maze during functional magnetic resonance imaging (fMRI). The virtual maze presented a first-person view, lacked any topographical landmarks and could be learned only using egocentric navigation strategies. RESULTS: During learning, increased medial temporal lobe activity was observed in the PHC bilaterally. Activity was also observed in cortical areas known to project to the PHC and proposed to contribute to egocentric spatial navigation and memory. CONCLUSIONS: Our results point to a role of the PHC for the representation and storage of egocentric information. It seems possible that the PHC contributes to egocentric memory by its feedback projections to the posterior parietal cortex. Moreover, access to allocentric and egocentric streams of spatial information may enable the PHC to construct a global and comprehensive representation of spatial environments and to promote the construction of stable cognitive maps by translating between egocentric and allocentric frames of memory.

Reduced amygdala and hippocampus size in trauma-exposed women with borderline personality disorder and without posttraumatic stress disorder.

BACKGROUND: Individuals with posttraumatic stress disorder (PTSD) display reduced hippocampus size and impaired cognition. However, studies on individuals with borderline personality disorder (BPD) are rare, and studies on trauma-exposed patients with BPD but without PTSD are lacking. METHODS: Twenty-four trauma-exposed women with BPD (10 with PTSD and 14 without) and 25 healthy controls underwent 3-dimensional structural magnetic resonance imaging of the amygdala and hippocampus and a clinical and neuropsychological investigation. RESULTS: Compared with controls, patients with BPD and PTSD displayed significantly reduced amygdala (34%) and hippocampus (12%) size and significantly impaired cognition. Trauma-exposed patients with BPD but without PTSD also showed significantly reduced amygdala (22%) and hippocampus (11%) size but normal cognition. Amygdala and hippocampus size did not differ significantly between patients with and without PTSD. LIMITATIONS: The sample sizes of trauma-exposed groups are relatively small. A larger sample size may have revealed statistically significant differences in amygdala size between those with and without PTSD. CONCLUSION: Our results demonstrate strong amygdala size reduction in trauma-exposed patients with BPD with or without PTSD, much exceeding that reported for trauma-exposed individuals without BPD. Our data suggest that BPD is associated with small amygdala size. Furthermore, evidence is increasing that amygdala and hippocampus size reduction is not only due to PTSD, but also to traumatic exposure.

[SOPHO-NET - a research network on psychotherapy for social phobia]. / SOPHO-NET - Forschungsverbund zur Psychotherapie der Sozialen Phobie.

This paper presents the Social Phobia Psychotherapy Research Network (SOPHO-NET). SOPHO-NET is among the five research networks on psychotherapy funded by "Bundesministerium für Bildung und Forschung". The research program encompasses a coordinated group of studies of social phobia. In the central project (Study A), a multi-center randomized controlled trial, refined models of manualized cognitive-behavioral therapy (CBT) and manualized short-term psychodynamic psychotherapy (STPP) are compared in the treatment of social phobia. A sample of n=512 outpatients will be randomized to either CBT, STPP or wait list. For quality assurance and treatment integrity, a specific project has been established (Project Q). Study A is complemented by four interrelated projects focusing on attachment style (Study B1), cost-effectiveness (Study B2), polymorphisms in the serotonin transporter gene (Study C1) and on structural and functional deviations of hippocampus and amygdala (Study C2). Thus, the SOPHO-NET program allows for a highly interdisciplinary research of psychotherapy in social phobia.

Impaired implicit learning and reduced pre-supplementary motor cortex size in early-onset major depression with melancholic features.

BACKGROUND: Major depression is a heterogeneous disorder. Biological markers and cognitive tasks have been employed to distinguish clinical subtypes but results have been inconclusive. METHODS: The current study assessed implicit learning with the Serial Reaction Time Task (SRTT) known to be sensitive to frontostriatal dysfunctions and regional brain volumes of the anterior supplementary motor area (pre-SMA) in participants with early-onset major depression (MD) of either melancholic (n=26) or non-melancholic (n=9) subtype, and 26 matched controls. RESULTS: Depressive subjects with melancholic features but not those with non-melancholic depression showed implicit learning deficits. This deficit could not be explained in terms of more severe depression or psychomotor retardation. Regional volumes of the right pre-SMA were reduced in depressive subjects with melancholic features. LIMITATIONS: Medication effects in depressive subjects and the small size of the non-melancholic sample should be taken into consideration when reviewing the implications of these results. CONCLUSIONS: Deficits in implicit motor sequence learning seem to be an additional characteristic of the melancholic subtype of depression. It might be linked to dysfunction within structural or functionally altered frontostriatal circuits. Use of implicit sequence learning tasks could offer useful diagnostic and aetiological cues for future research.

Serum 24S-hydroxycholesterol and hippocampal size in middle-aged normal individuals.

The present study assessed the association between serum 24S-hydroxycholesterol (24S-OH-Chol) and 27-hydroxycholesterol (27-OH-Chol) and hippocampal volumes in 69 middle-aged cognitively normal individuals. Results showed that subjects with high levels of oxysterols had significantly larger hippocampal volumes than subjects with low levels of oxysterols. Multiple regression analysis revealed that 24S-OH-Chol, but not 27-OH-Chol or cholesterol, was able to significantly predict hippocampal size. Future studies should elucidate whether high brain cholesterol metabolism in the middle age is protective against hippocampal atrophy and cognitive decline.

Egocentric memory impaired and allocentric memory intact as assessed by virtual reality in subjects with unilateral parietal cortex lesions.

Present evidence suggests that medial temporal cortices subserve allocentric representation and memory, whereas egocentric representation and memory mainly depends on inferior and superior parietal cortices. Virtual reality environments have a major advantage for the assessment of spatial navigation and memory formation, as computer-simulated first-person environments can simulate navigation in a large-scale space. However, virtual reality studies on allocentric memory in subjects with cortical lesions are rare, and studies on egocentric memory are lacking. Twenty-four subjects with unilateral parietal cortex lesions due to infarction or intracerebral haemorrhage (14 left-sided, 10 right-sided) were compared with 36 healthy matched control subjects on two virtual reality tasks affording to learn a virtual park (allocentric memory) and a virtual maze (egocentric memory). Subjects further received a comprehensive clinical and neuropsychological investigation, and MRI lesion assessment using T(1), T(2) and FLAIR sequences as well as 3D MRI volumetry at the time of the assessment. Results indicate that left- and right-sided lesioned subjects did not differ on task performance. Compared with control subjects, subjects with parietal cortex lesions were strongly impaired learning the virtual maze. On the other hand, performance of subjects with parietal cortex lesions on the virtual park was entirely normal. Volumes of the right-sided precuneus of lesioned subjects were significantly related to performance on the virtual maze, indicating better performance of subjects with larger volumes. It is concluded that parietal cortices support egocentric navigation and imagination during spatial learning in large-scale environments.

Allocentric memory impaired and egocentric memory intact as assessed by virtual reality in recent-onset schizophrenia.

Present evidence suggests that schizophrenia is associated with explicit memory deficits, whereas implicit memory seems to be largely preserved. Virtual reality studies on declarative allocentric memory in schizophrenia are rare, and studies on implicit egocentric memory in schizophrenia are lacking. However, virtual realities have a major advantage for the assessment of spatial navigation and memory formation, as computer-simulated first-person environments can simulate navigation in a large-scale space. Twenty-five subjects with recent-onset schizophrenia were compared with 25 healthy matched control subjects on two virtual reality tasks affording the navigation and learning of a virtual park (allocentric memory) and a virtual maze (egocentric memory). Compared with control subjects, schizophrenia subjects were significantly impaired in learning the virtual park. However, schizophrenia subjects were as able as control subjects to learn the virtual maze. Stronger disorganized symptoms of schizophrenia subjects were significantly related to more errors on the virtual maze. It is concluded that egocentric spatial learning adds to the many other implicit cognitive skills being largely preserved in schizophrenia. Possibly, the more global neural network supporting egocentric spatial learning is less affected than the declarative hippocampal memory system in early stages of schizophrenia and may offer opportunities for compensation in the presence of focal deficits.

Improved functional mapping of the human amygdala using a standard functional magnetic resonance imaging sequence with simple modifications.

As the amygdala is involved in various aspects of emotional processing, its characterization using neuroimaging modalities, such as functional magnetic resonance imaging (fMRI), is of great interest. However, in fMRI, the amygdala region suffers from susceptibility artifacts that are composed of signal dropouts and image distortions. Various technically demanding approaches to reduce these artifacts have been proposed, and most require alterations beyond a mere change of the acquisition parameters and cannot be easily implemented by the user without changing the MR sequence code. In the present study, we therefore evaluated the impact of simple alterations of the acquisition parameters of a standard gradient-echo echo-planar imaging technique at 3 T composed of echo times (TEs) of 27 and 36 ms as well as section thicknesses of 2 and 4 mm while retaining a section orientation parallel to the intercommissural plane and an in-plane resolution of 2x2 mm(2). In contrast to previous studies, we based our evaluation on the resulting activation maps using an emotional stimulation paradigm rather than on MR raw image quality only. Furthermore, we tested the effects of spatial smoothing of the functional raw data in the course of postprocessing using spatial filters of 4 and 8 mm. Regarding MR raw image quality, a TE of 27 ms and 2-mm sections resulted in the least susceptibility artifacts in the anteromedial aspect of the temporal lobe. The emotional stimulation paradigm resulted in robust bilateral amygdala activation for the approaches with 2-mm sections only -- but with larger activation volumes for a TE of 36 ms as compared with that of 27 ms. Moderate smoothing with a 4-mm spatial filter represented a good compromise between increased sensitivity and preserved specificity. In summary, we showed that rather than applying advanced modifications of the MR sequence, a simple increase in spatial resolution (i.e., the reduction of section thickness) is sufficient to improve the detectability of amygdala activation.

Size abnormalities of the superior parietal cortices are related to dissociation in borderline personality disorder.

Recent evidence suggests that borderline personality disorder (BPD) is related to reduced size of the parietal lobe. Dissociative symptoms occur in the majority of individuals with BPD. Structural magnetic resonance imaging (3D-MRI) was used to assess volumes of the superior (precuneus, postcentral gyrus) and inferior parietal cortices in 30 young women with BPD who had been exposed to severe childhood sexual and physical abuse and 25 healthy control subjects. Compared with control subjects, BPD subjects had significantly smaller right-sided precuneus (-9%) volumes. The left postcentral gyrus of BPD subjects with the comorbid diagnosis of dissociative amnesia (DA) or dissociative identity disorder (DID) was significantly increased compared with controls (+13%) and compared with BPD subjects without these disorders (+11%). In BPD subjects, stronger depersonalization was significantly related to larger right precuneus size. Possibly, larger precuneus size in BPD is related to symptoms of depersonalization. Increased postcentral gyrus size in BPD may be related to the development of DA or DID in the presence of severe childhood abuse.

Posterior parahippocampal gyrus lesions in the human impair egocentric learning in a virtual environment.

Functional imaging studies have shown that the posterior parahippocampal gyrus (PHG) is involved in allocentric (world-centered) object and scene recognition. However, the putative role of the posterior PHG in egocentric (body-centered) spatial memory has received only limited systematic investigation. Thirty-one subjects with pharmacoresistant medial temporal lobe epilepsy (TLE) and temporal lobe removal were compared with 19 matched healthy control subjects on a virtual reality task affording the navigation in a virtual maze (egocentric memory). Lesions of the hippocampus and PHG of TLE subjects were determined by three-dimensional magnetic resonance imaging volumetric assessment. The results indicate that TLE subjects with right-sided posterior PHG lesions were impaired on virtual maze acquisition when compared with controls and TLE subjects with anterior PHG lesions. Larger posterior PHG lesions were significantly related to stronger impairments in virtual maze performance. Our results point to a role of the right-sided posterior PHG for the representation and storage of egocentric information. Moreover, access to both allocentric and egocentric streams of spatial information may enable the posterior PHG to construct a global and comprehensive representation of spatial environments.

Abnormal size of the amygdala predicts impaired emotional memory in major depressive disorder.

BACKGROUND: Amygdala and hippocampus show significant structural abnormalities in major depressive disorder (MDD). Individuals with MDD have difficulties in emotional memory. A relationship between emotional memory deficits and structural abnormalities of amygdala and hippocampus in MDD has been proposed but not shown, yet. METHODS: The current study assessed memory for emotional faces in 21 young women with recent-onset MDD and 23 matched control subjects. All subjects underwent structural magnetic resonance imaging (3D-MRI) and a clinical and neuropsychological assessment. RESULTS: Depressive subjects had significantly enlarged amygdala size and significantly reduced hippocampal size compared with controls. Depressive subjects were significantly impaired in learning emotional facial expressions, with deficits being most pronounced for fearful, surprised and disgusted faces. Depressive subjects with amygdala volumes 1 SD or more above the mean of control subjects showed the strongest impairments. Correlation analyses revealed that larger left amygdala volumes were significantly related to worse memory performance and to higher anxiety scores of depressive subjects. Smaller left hippocampal volumes of depressive subjects were related to higher anxiety scores as well. LIMITATIONS: All MDD subjects were taking antidepressant medication at the time of the study. Longitudinal studies are needed to clarify whether the behavioral and/or volumetric abnormalities of MDD subjects can be attributed to medication or MDD or both. CONCLUSIONS: It might be speculated that amygdala enlargement in young MDD subjects is correlated with amygdalar over-activation and resolves with antidepressant treatment, as was shown for amygdalar over-activation.

Reduced size of the pre-supplementary motor cortex and impaired motor sequence learning in first-episode schizophrenia.

Increasing evidence suggests that schizophrenia is associated with various morphological and functional abnormalities of the frontal cortex. So far research has concentrated on the dorsolateral and orbitofrontal cortex. Behavioral evidence suggests however that regions responsible for higher motor control are compromised in schizophrenia as well. The current study assessed volumes of the anterior supplementary motor area (pre-SMA) and implicit motor sequence learning in 15 subjects with first-episode schizophrenia and 15 healthy matched controls. Pre-SMA volumes were assessed by three-dimensional structural magnetic resonance imaging (3D-MRI) and manual parcellation according to an established protocol. Implicit motor sequence learning was assessed using the Serial Reaction-Time Task (SRTT). Compared with control subjects, schizophrenia subjects had significantly smaller volumes of the left pre-SMA (16%). Subjects with schizophrenia were severely impaired on sequence-specific implicit motor learning. Size of the left pre-SMA of schizophrenia subjects was significantly related to impaired implicit learning. We conclude that subjects with first-episode schizophrenia have a morphological abnormality of the left pre-SMA that might predispose them to develop disturbances of higher motor control during acute episodes of psychosis. These structural and behavioral abnormalities might be conceptualized within a broader model that views schizophrenia as a disorder of disturbed coordination of thought and action.

State-dependent implicit learning deficit in schizophrenia: evidence from 20-month follow-up.

Previous research has confirmed stable explicit memory deficits in schizophrenia across disease states. However, little is known about the implicit learning capabilities of individuals with schizophrenia across the course of illness. The current study assessed procedural learning in 19 schizophrenia subjects (DSM-IV criteria) and 19 matched controls using the Serial Reaction-Time Task (SRTT). The severity of negative, positive and disorganized symptoms was assessed using the Scales for the Assessment of Positive and Negative Symptoms. A sub-sample of 11 schizophrenia subjects and 11 controls was reassessed 20 months later when symptoms in the schizophrenia subjects had largely remitted. Schizophrenia subjects were severely impaired on sequence-specific procedural learning during an acute episode. This deficit could not be explained by a general memory or processing speed impairment. Impaired implicit learning scores were significantly related to higher ratings of disorganized symptoms. However, 20 months later, when acute symptoms had remitted, the performance of the schizophrenia subjects on procedural learning had normalized. Our findings might share a conceptual overlap with previous reports of a reduced ability of schizophrenia subjects during an acute episode to adapt ongoing perceptual and behavioral programs to previously experienced regularities in their environment.