ABSTRACT
The present fMRI study aimed to investigate effective connectivity within a cortical-subcortical-cerebellar information processing network in drug free schizophrenic patients while performing a 2-back working memory task. The finding of enhanced thalamo-cortical and cortico-cortical intrahemispheric connectivity could be interpreted as a compensatory increase of neuronal connection strength consistent with a model of cortical inefficiency in schizophrenic patients. Additionally, the result could be integrated into a model of deficient thalamo-cortical filter functions. Conversely, lower interhemispheric connectivity of the frontal and parietal association cortex appears to be the functional correlate of reduced cognitive performance in schizophrenic patients. The study demonstrated the feasibility to model information processing within cognitive networks and provided additional evidence for the concept of cognitive dysmetria in schizophrenia.
Subject(s)
Nerve Net/physiology , Schizophrenia/physiopathology , Adult , Analysis of Variance , Cerebellum/physiology , Chi-Square Distribution , Female , Humans , Magnetic Resonance Imaging/methods , Male , Parietal Lobe/physiology , Prefrontal Cortex/physiologyABSTRACT
The present study aimed to explore altered effective connectivity in schizophrenic patients while performing a 2-back working memory task. Twelve right-handed, schizophrenic patients treated with typical or atypical antipsychotics and 6 healthy control subjects were studied with fMRI while performing a "2-back" working memory task. Effective connectivity within a cortical-subcortical-cerebellar network for mnemonic information processing was assessed and compared between both groups. The path model included cortico-cortical connections comprising the parietal association cortex, ventrolateral prefrontal cortex (VLPFC), and the dorsolateral prefrontal cortex (DLPFC) as well as a cortico-cerebellar feedback loop comprising prefrontal cortex, contralateral cerebellum, and thalamus. Group differences were analyzed with a stacked models approach. Relative to normal controls, both patient groups revealed a pattern of reduced connectivity within the prefrontal-cerebellar and the cerebellar-thalamic limbs but enhanced connectivity in the thalamo-cortical limb of the cortical-cerebellar circuit. Moreover, a direct comparison of both treatment groups revealed enhanced connectivity in the interhemispheric connections between the cortical association areas in patients treated with atypical antipsychotics. However, right prefrontal and left parieto-frontal path coefficients were lower in the patient group receiving atypical antispychotic drugs. The findings suggest that the relationship between pathology in cortical-subcortical cerebellar networks and associated functional connectivity is complex and may include aspects of increased and decreased levels of connectivity consistent with the notion of "cognitive dysmetria" in schizophrenia. The observed pronounced connectivity within thalamo-cortical projections could be attributed to a compensatory increase of thalamic input in the presence of disrupted effective connectivity within the preceding limb of the cortical-cerebellar circuitry. The study demonstrated the feasibility of structural equation modeling for the investigation of group and treatment-related differences in effective connectivity and provides a promising approach to further disentangle the relationship between altered functional capacity and associated fMRI signal changes.
Subject(s)
Memory, Short-Term/physiology , Schizophrenia/physiopathology , Schizophrenic Psychology , Adult , Algorithms , Cerebellum/physiopathology , Cerebral Cortex/physiopathology , Female , Humans , Magnetic Resonance Imaging , Male , Models, Neurological , Models, Statistical , Neural Pathways/physiopathology , Psychomotor Performance/physiologyABSTRACT
Previous studies have indicated that the BOLD-fMRI signal can be modified by tumor processes in close vicinity to functional brain areas. This effect has been investigated primarily for the perirolandic area but there is only a limited number of studies concerning frontal cortical regions. Therefore, the aim of the current study was to characterize BOLD-fMRI signal and activation patterns in patients with frontal brain tumors while performing a verbal fluency task. Six patients (ages 31-56 years) suffering from frontal (5 left sided and 1 right sided) intracerebral tumors were examined with fMRI while performing a verbal fluency task in a blocked paradigm design. Eight healthy volunteers served as the control group. The patients (5 right and 1 left handed) demonstrated left frontal activation which could be clearly located outside the tumor area and adjacent edema with varying degrees of additional right frontal activation. In the predominant left frontal activation cluster, the mean voxel based z-score and cluster size were not statistically different between patients and controls. The present fMRI study is indicating that language related BOLD signal changes in the frontal cortex of patients with tumors close to functional areas were comparable to the signal in normal controls. Additionally, the temporal hemodynamic response characteristic was comparable in both groups. This is an important finding consistent with PET results and corroborates the feasibility of functional mapping approaches in patients with tumors affecting the frontal lobe. Additional studies investigating alterations of the hemodynamic response depending on tumor location and histology are required in order to further elucidate the association between pathophysiology and BOLD fMRI signal.
