Godehard Weniger

Cerebellar lesions in the PICA but not SCA territory impair cognition

The authors sought to clarify whether lesions in different parts of the cerebellum result in differential cognitive and affective impairment. Six subjects with cerebellar lesions due to posterior inferior cerebellar artery (PICA) infarction, five subjects with lesions in the SCA vascular territory, and 11 matched controls were administered a battery of standard neuropsychological tests. PICA lesions but not SCA lesions resulted in cognitive and affective deficits pointing to a dominant role of posterior cerebellar regions in cognitive and affective processing.

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.

Differential impairments of facial affect recognition in schizophrenia subtypes and major depression

The goal of this study was to assess facial affect recognition abilities in subjects with various schizophrenia subtypes and subjects with major depression. A total of six disorganized, 21 paranoid and 18 residual subjects with schizophrenia (DSM-IV criteria) were compared with 21 subjects with major depression (DSM-IV criteria) and 30 matched healthy control subjects. Two experimental tasks requiring the sorting and rating of emotional facial expressions were applied. Disorganized and paranoid subjects showed strong impairments in the sorting of emotional facial expressions. Depressive subjects displayed only minor deficits, and residual subjects were unimpaired. Subjects with disorganized schizophrenia rated emotional facial expressions as more aroused, and depressive subjects rated them as less aroused, than the other study groups. Our study demonstrates strong deficits in facial affect recognition in subjects with schizophrenia and pronounced disorganized or psychotic symptoms. Deficits in facial affect recognition are specific to schizophrenia. They may be considered as a state marker of schizophrenia.

Implicit and explicit memory after focal thalamic lesions

Background: Lesions of the thalamus interfere with cognitive functions mainly in the area of declarative learning and memory. Little is known about the role the thalamus plays in implicit learning. Objective: To study explicit and implicit learning and memory in subjects with thalamic lesions and to analyze the influence of lesion characteristics on cognitive performance. Methods: The authors studied the performance of 15 subjects with focal thalamic infarction or hemorrhage on a comprehensive neuropsychological test battery focusing on tests of explicit memory and learning of a nondeclarative motor skill. Subjects with thalamic lesions were compared to 15 healthy matched control subjects and to a clinical control group of 22 subjects who had sustained basal ganglia lesions. Results: Subjects with thalamic lesions showed well-preserved intellectual and executive functions but demonstrated deficits on measures of attention and psychomotor speed, explicit memory, and implicit visuomotor sequence learning. Lesion size in the thalamus was clearly related to subjects’ long-term explicit memory performance. However, few of the neuropsychological deficits found seemed specific to the long-term neuropsychological outcome of focal thalamic infarctions. Subjects with lesions in the basal ganglia demonstrated similar deficits. Conclusions: Focal subcortical lesions in the thalamus and the basal ganglia lead to a similar profile of neuropsychological deficits. Lesions in the thalamus not only affect declarative memory but also interfere with nondeclarative motor skill learning.

Neuropsychological performance in frontal lobe epilepsy

The search for a special neuropsychological profile of frontal lobe epilepsy subjects (FLE) has so far led to inconclusive results. In this paper we compared the preoperative neuropsychological performance of FLE and temporal lobe epilepsy (TLE) subjects. We further investigated whether frontal lobe lesions of epileptogenic cause produce the same type of cognitive dysfunction as do tumours of the frontal lobe. Sixteen FLE subjects were compared to 16 TLE subjects as well as to a group of 10 subjects after the removal of frontal lobe tumors (TUM) and a healthy control group. A set of neuropsychological test measures routinely used for presurgical evaluation, an emotional conceptualization task and two associative learning tasks were administered. We found that subjects with frontal lobe damage were significantly impaired relative to controls on a wide range of cognitive functions independent of neurological cause. FLE subjects could hardly be discriminated from TLE subjects as both groups showed a similarly reduced level of neuropsychological performance. Our results demonstrate the devastating effect that frontal lobe epilepsy can have on cognitive functioning. Routinely used neuropsychological test measures lack the specificity to distinguish between frontal and temporal lobe epilepsy. Highly specialized measures are necessary to reveal differences.

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.

Impaired emotional learning and reduced amygdala size in schizophrenia: a 3-month follow-up

Individuals with schizophrenia have difficulties in emotional information processing. A relationship between behavioral variables of emotional processing and structural amygdala alterations in schizophrenia has been proposed but not shown, yet. Morphological studies of amygdala size in schizophrenia have yielded inconsistent results. The current study assessed paired associates learning of emotional and neutral faces in 16 subjects with schizophrenia during acute episode and in relative remission after 3 months. Sixteen matched controls were studied for comparison. Subjects also underwent structural magnetic resonance imaging (3D-MRI) at the first time of assessment. Subjects with schizophrenia showed a significant decrease (by 13%) in total size of the amygdala compared to controls, which was more pronounced on the right side. Subjects with schizophrenia improved associative learning of facial identities but not of emotional facial expressions after relative remission of psychotic symptoms. Volume of the right amygdala in subjects with schizophrenia and in controls was significantly related to emotional learning, indicating better learning in subjects with larger amygdala size. Our results indicate that subjects with schizophrenia have a deficit to form associations when emotionally loaded material is used. This deficit seems to be trait-like and independent of disease state. It seems to be linked to size reduction of the right amygdala in schizophrenia.

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.

The Social Phobia Psychotherapy Research Network : The First Multicenter Randomized Controlled Trial of Psychotherapy for Social Phobia: Rationale, Methods and Patient Characteristics

This paper presents the Social Phobia Psychotherapy Research Network. The research program encompasses a coordinated group of studies adopting a standard protocol and an agreed-on set of standardized measures for the assessment and treatment of social phobia (SP). In the central project (study A), a multicenter randomized controlled trial, refined models of manualized cognitive-behavioral therapy and manualized short-term psychodynamic psychotherapy are compared in the treatment of SP. A sample of 512 outpatients will be randomized to either cognitive-behavioral therapy, short-term psychodynamic psychotherapy or waiting list. Assessments will be made at baseline, at the end of treatment and 6 and 12 months after the end of treatment. For quality assurance and treatment integrity, a specific project using highly elaborated measures has been established (project Q). Study A is complemented by 4 interrelated add-on projects focusing on attachment style (study B1), on cost-effectiveness (study B2), on variation in the serotonin transporter gene in SP (study C1) and on structural and functional deviations of the hippocampus and amygdala (study C2). Thus, the Social Phobia Psychotherapy Research Network program enables a highly interdisciplinary research into SP. The unique sample size achieved by the multicenter approach allows for studies of subgroups (e.g. comorbid disorders, isolated vs. generalized SP), of responders and nonresponders of each treatment approach, for generalization of results and for a sufficient power to detect differences between treatments. Psychological and biological parameters will be related to treatment outcome, and variables for differential treatment indication will be gained. Thus, the results provided by the network may have an important impact on the treatment of SP and on the development of treatment guidelines for SP.

Blood‐based neurochemical diagnosis of vascular dementia: a pilot study

Blood‐based tests for the differential diagnosis of Alzheimer’s disease (AD) are under intensive investigation and have shown promising results with regard to Aβ40 and Aβ42 peptide species in incipient AD. Moreover, plasma Aβ40 was suggested as an independent cerebrovascular risk factor candidate. These considerations prompted us to analyse a total of 72 plasma samples in vascular dementias (VAD, n = 15), AD with cerebrovascular disease (AD with CVD, n = 7), AD (n = 15), Parkinson’s disease and Parkinson’s disease dementia (PD/PDD, n = 20) and 15 patients with depression that served as controls (DC) for distinct plasma amyloid‐beta (Aβ) peptide patterns. For the analysis of plasma we used immunoprecipitation followed by the quantitative Aβ‐SDS‐PAGE/immunoblot. For comparison, CSF tau and Aβ1–42 analyses were performed. The major outcome was an increase in Aβ1–40 in plasma of VAD paralleled by a decrease in the ratio of Aβ1–38/Aβ1–40. The ratio Aβ1–38/Aβ1–40 in plasma enabled contrasts of beyond 85% and 80% for discriminating VAD from DC and all other patients, respectively. In CSF, we confirmed the typical CSF biomarker constellation of increased tau and diminished Aβ1–42 levels for AD. The diagnostic accuracy of plasma Aβ1–38/Aβ1–40 for VAD resembled the accuracy of CSF biomarkers for AD. From the presented results, we consider the ratio of plasma Aβ1–38/Aβ1–40 peptides to be a blood‐based biomarker candidate for VAD.