A virtual environment for the assessment and the rehabilitation of the visuo-constructional ability in dementia patients

This study proposes a VE that offers a reliable diagnosis of the stage of cognitive decline in dementia patients and assists the delay of this decline in terms of the visuo-constructional ability. The proposed VE, in the case of the assessment, presents a visuo-constructional completion task, which requires spatial perception, motor memory and the perception of the target object. In the case of the rehabilitation the VE uses sound as audio-feedback that, with the aid of the music perception, tends to develop an enhancement in the visuo-construction ability of the dementia patients that can be generalized even outside of the VE. The study examined 30 subjects that were normal controls (N), 30 patients suffering from memory disorders (Age-Associated Memory Impairment--AAMI) and 30 suffering from Alzheimer's Disease (AD). The results showed that there is a significant correlation between the performance in the visuo-constructional task and the dementia diagnosis. It also seems that the visuo-constructional ability of the (AD) patients can be statistically improved by the audio experience in the VE. The empirical results of this study offer an alternative diagnosis and treatment of dementia patients and could share some light in the brain sub-systems that are responsible for the visuo-constructional ability. Further studies are required in order to investigate the nature of this phenomenon more.

Cerebellar disorders in childhood: cognitive problems

Over the last decade, increasing evidence of cognitive functions of the cerebellum during development and learning processes could be ascertained. Posterior fossa malformations such as cerebellar hypoplasia or Joubert syndrome are known to be related to developmental problems in a marked to moderate extent. More detailed analyses reveal special deficits in attention, processing speed, visuospatial functions, and language. A study about Dandy Walker syndrome states a relationship of abnormalities in vermis lobulation with developmental problems. Further lobulation or volume abnormalities of the cerebellum and/or vermis can be detected in disorders as fragile X syndrome, Downs's syndrome, William's syndrome, and autism. Neuropsychological studies reveal a relation of dyslexia and attention deficit disorder with cerebellar functions. These functional studies are supported by structural abnormalities in neuroimaging in these disorders. Acquired cerebellar or vermis atrophy was found in groups of children with developmental problems such as prenatal alcohol exposure or extreme prematurity. Also, focal lesions during childhood or adolescence such as cerebellar tumor or stroke are related with neuropsychological abnormalities, which are most pronounced in visuospatial, language, and memory functions. In addition, cerebellar atrophy was shown to be a bad prognostic factor considering cognitive outcome in children after brain trauma and leukemia. In ataxia teleangiectasia, a neurodegenerative disorder affecting primarily the cerebellar cortex, a reduced verbal intelligence quotient and problems of judgment of duration are a hint of the importance of the cerebellum in cognition. In conclusion, the cerebellum seems to play an important role in many higher cognitive functions, especially in learning. There is a suggestion that the earlier the incorrect influence, the more pronounced the problems.

Stress effects on working memory, explicit memory, and implicit memory for neutral and emotional stimuli in healthy men

Stress is a strong modulator of memory function. However, memory is not a unitary process and stress seems to exert different effects depending on the memory type under study. Here, we explored the impact of social stress on different aspects of human memory, including tests for explicit memory and working memory (for neutral materials), as well as implicit memory (perceptual priming, contextual priming and classical conditioning for emotional stimuli). A total of 35 young adult male students were randomly assigned to either the stress or the control group, with stress being induced by the Trier Social Stress Test (TSST). Salivary cortisol levels were assessed repeatedly throughout the experiment to validate stress effects. The results support previous evidence indicating complex effects of stress on different types of memory: A pronounced working memory deficit was associated with exposure to stress. No performance differences between groups of stressed and unstressed subjects were observed in verbal explicit memory (but note that learning and recall took place within 1 h and immediately following stress) or in implicit memory for neutral stimuli. Stress enhanced classical conditioning for negative but not positive stimuli. In addition, stress improved spatial explicit memory. These results reinforce the view that acute stress can be highly disruptive for working memory processing. They provide new evidence for the facilitating effects of stress on implicit memory for negative emotional materials. Our findings are discussed with respect to their potential relevance for psychiatric disorders, such as post traumatic stress disorder.

Shifted Coupling of EEG Driving Frequencies and fMRI Resting State Networks in Schizophrenia Spectrum Disorders

INTRODUCTION: The cerebral resting state in schizophrenia is altered, as has been demonstrated separately by electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) resting state networks (RSNs). Previous simultaneous EEG/fMRI findings in healthy controls suggest that a consistent spatiotemporal coupling between neural oscillations (EEG frequency correlates) and RSN activity is necessary to organize cognitive processes optimally. We hypothesized that this coupling is disorganized in schizophrenia and related psychotic disorders, in particular regarding higher cognitive RSNs such as the default-mode (DMN) and left-working-memory network (LWMN). METHODS: Resting state was investigated in eleven patients with a schizophrenia spectrum disorder (n = 11) and matched healthy controls (n = 11) using simultaneous EEG/fMRI. The temporal association of each RSN to topographic spectral changes in the EEG was assessed by creating Covariance Maps. Group differences within, and group similarities across frequencies were estimated for the Covariance Maps. RESULTS: The coupling of EEG frequency bands to the DMN and the LWMN respectively, displayed significant similarities that were shifted towards lower EEG frequencies in patients compared to healthy controls. CONCLUSIONS: By combining EEG and fMRI, each measuring different properties of the same pathophysiology, an aberrant relationship between EEG frequencies and altered RSNs was observed in patients. RSNs of patients were related to lower EEG frequencies, indicating functional alterations of the spatiotemporal coupling. SIGNIFICANCE: The finding of a deviant and shifted coupling between RSNs and related EEG frequencies in patients with a schizophrenia spectrum disorder is significant, as it might indicate how failures in the processing of internal and external stimuli, as commonly seen during this symptomatology (i.e. thought disorders, hallucinations), arise.

When the systems fail to communicate. Cerebral resting state networks in schizophrenia spectrum disorders.

There have been numerous attempts to reveal the neurobiological basis of schizophrenia spectrum disorders. Results however, remain as heterogeneous as the schizophrenia spectrum disorders itself. Therefore, one aim of this thesis was to divide patients affected by this disorder into subgroups in order to homogenize the results of future studies. In a first study it is suggested that psychopathological rating scales should focus on symptoms-clusters that may have a common neurophysiological background. The here presented Bern Psychopathology Scale (BPS) proposes that alterations in three wellknown brain systems (motor, language, and affective) are largely leading to the communication failures observable on a behavioral level, but also - as repeatedly hypothesized - to dysconnectivity within and between brain systems in schizophrenia spectrum disorders. The external validity of the motor domain in the BPS was tested against the objective measure of 24 hours wrist actigraphy, in a second study. The subjective, the quantitative, as well as the global rating of the degree of motor disorders in this patient group showed significant correlations to the acquired motor activity. This result confirmed in a first step the practicability of the motor domain of the BPS, but needs further validation regarding pathological brain alterations. Finally, in a third study (independent from the two other studies), two cerebral Resting State Networks frequently altered in schizophrenia were investigated for the first time using simultaneous EEG/fMRI: The well-known default mode network and the left working memory network. Besides the changes in these fMRI-based networks, there are well-documented findings that patients exhibit alterations in EEG spectra compared to healthy controls. However, only through the multimodal approach it was possible to discover that patients with schizophrenia spectrum disorders have a slower driving frequency of the Resting State Networks compared to the matched healthy controls. Such a dysfunctional coupling between neuronal frequency and functional brain organization could explain in a uni- or multifactorial way (dysfunctional cross-frequency coupling, maturational effects, vigilance fluctuations, task-related suppression), how the typical psychotic symptoms might occur. To conclude, the major contributions presented in this thesis were on one hand the development of a psychopathology rating scale that is based on the assumption of dysfunctional brain networks, as well as the new evidence of a dysfunctional triggering frequency of Resting State Networks from the simultaneous EEG/fMRI study in patients affected by a schizophrenia spectrum disorder.