S-68-01

Dynamic causal modelling of evoked brain responses

K. Friston, K. E. Stephan. Functional Imaging Laboratory Institute of Neurology, London, United Kingdom

Objective: We present an approach (DCM) to identifying dynamic input-state-output systems. Identification of the parameters proceeds in a Bayesian framework given the known, deterministic inputs and the observed responses of the [neuronal] system.

Methods: We develop this approach for the analysis of effective connectivity using experimentally designed inputs and fMRI and EEG responses. In this context, the parameters correspond to effective connectivity and, in particular, bilinear parameters reflect the changes in connectivity induced by inputs. The ensuing framework allows one to characterise experiments, conceptually, as an experimental manipulation of integration among brain regions (by contextual or trial-free inputs, like time or attentional set) that is perturbed or probed using evoked responses (to trial-bound inputs like stimuli).

Results: We show that changes in attentional set, adaptation of evoked responses in fMRI and specific ERP components such as the P300 can all be explained by changes in the coupling among brain regions. Furthermore, inferences about these changes can be made, in a connection-specific fashion using DCM.

Conclusion: As with previous analyses of effective connectivity, the focus is on experimentally induced changes in coupling. However, unlike previous approaches to connectivity in neuroimaging, the causal model ascribes responses to designed deterministic inputs, as opposed to treating inputs as unknown and stochastic.

S-68-02

Exploring the human declarative memory system by functional neuroimaging

F. Fernandez. Radboud University F.C. Donders Center, Nijmegen, Netherlands

Objective: The kind of memory one ordinarily means when using the term “memory” is declarative memory, which enables us to retrieve consciously past events and facts. After an era when lesion studies have identified the declarative memory system and its essential anatomical structures, functional imaging techniques like functional MRI and electrophysiology have begun to delineate the neural underpinnings of mnemonic operations like the formation of new memories and the retrieval of old ones. Here, I will initially characterize the neural correlates of these transient and short-lasting operations occurring during memory encoding and retrieval. Thereafter, 1 will present new data shading some light on declarative memory consolidation, a presumably long lasting (set of) operation(s) transforming initial, labile memory traces into stable forms of long-term memory. Our functional MRI data seem to provide initial confirmation for the time limited role of the hippocampus in human declarative memory. With time, memory retrieval is associated with less and less hippocampal activity but in turn with more and more activity in neocortical brain areas related to the specific cortical representation of the stimuli. Moreover, our data is in line with the notion that slow-wave- and rapid-eye- movement sleep plays a crucial role in this operation. In conclusion, functional imaging provides a useful tool for assessing the neural correlates of fundamental mnemonic operations. Thus, we might use these techniques in the near future to probe the genetic and biochemical basis of the normal and the impaired declarative memory system.

S-68-03

E-motion: The importance of optimised fMRI strategies to study emotions

E. Moser, S. Robinson, C. Windischberger, U. Habel, B. Hoheisel. Department of Medical Physics, Wien, Austria

Objective: After a short introduction on fMRI data sampling using BOLD-EPI and spiral imaging, strategies to avoid or reduce artifacts due to physiological and stimulus-correlated motion (SCM), and susceptibility related artifacts in the human brain, will be discussed. Detailed examples illustrate the potential for erroneous results as a consequence of using standard, low- resolution EPI and analyses (e.g. SPM) only and underline the value of methodological improvements in fMRI.

Methods: Advanced measurement and data processing strategies to avoid or ameliorate these problems and an optimised protocol used in Vienna will be presented. In addition, biological factors potentially contributing to gender or cultural differences will be discussed. Visual stimuli - colour images of facial expressions of five emotions (happy, sad, disgust, fear, anger) and neutral expressions - were presented on a screen within the scanner bore. Tasks were presented in an event-related design and EPI- measurements performed on a 3T-scanner (Medspec, BRUKER-

Biospin). Pre- and postprocessing was performed using in-house software and SPM2.

Results: Differences in BOLD-based activation were

established in response to the five emotions, and between male and female viewers, and posers of different ethnic origin. This was made possible via an optimised (high-resolution) EPI measurement protocol and high field strength (3T). Maximum t-values were increased by approximately 20% via the correction of physiological artefacts. Strategies for reducing SCM allow these results to be attributed with unprecedented confidence to genuine activation in the amygdala.

Conclusion: Advanced measurement and data processing strategies help reduce artifacts and improve data quality, which may allow more subtle details in brain function to be studied. This is particularly important in single subject and patient studies.

S-68-04

Learning to play pong with fMRI neurofeedback: Implications for clinicial applications

R. Goebel. Department of Cognitive Neuros, Maastricht, Netherlands

Objective: We report about a novel type of experiment during which fMRI signals of two subjects are measured simultaneously, analyzed in real-time, and used to control actions in a simple video game. The two simultaneously scanned subjects look at a screen depicting the same video game, a simple version of the classical computer game “Pong”. The task of the subjects is to move their racket up and down to hit the approaching ball and to gain as many hit points as possible by regulating the amplitude of the BOLD signal within a selected region-of-interest (ROI).

Methods: The fMRI measurements were performed on two MRI scanners (Siemens 1.5 T Sonata and 3 T Trio, TR=2000ms, 25 slices, matrix: 64x64). In individual neurofeedback sessions, subjects first learned to modulate regional brain activity to 3 or 4 different target levels as well as to adapt to the hemodynamic response delay. The brain area which responded best to imagery episodes was then selected for controlling the vertical position of the subject's racket in the subsequent video game.

Results: During neurofeedback pretraining, all subjects (N = 8) were able to learn to activate spatially localized brain regions to different target levels. In six conducted Pong experiments, subjects succeeded in controlling the up and down movement of the racket by regulating voluntarily the activity in the selected ROIs achieving a hit rate of 50% to 80% (chance hit rate: 20%).

Conclusion: The observed ability of graded control over regional brain activity offers interesting research and clinical applications. Furthermore, the Pong experiment demonstrates that it is now possible to not only simultaneously measure two subjects during social interactions but also to use subjects brain activity in real-time during these interactions.

S-68-05

Neural correlates of emotion and cognition as key components in the understanding of the pathophysiology of psychiatric disorders

F. Schneider. Universitdtssklinik Psychiatrie und Psychotherapie, Aachen, Germany

Objective: Most psychiatric disorders are characterized by impairments in cognitive and emotional processes. FMRI studies on different samples of schizophrenia patients revealed characteristic dysfunctions in the cerebral network underlying emotional experience, emotion recognition, working memory as well as interactional processes between emotion and cognition. Most prominent are amygdala hypoactivations and prefrontal dysfunctions. In a further advance for a more detailed characterization of such dysfunctions, a differentiation between state and trait components has been attempted by investigating . early-onset psychoses, unmedicated and first-episode schizophrenia patients as well as patients with prodromal symptoms and unaffected relatives. Trait components have been revealed in subcortical as well as cortical regions during different cognitive and emotional tasks. However, fMRI in psychiatry reveals its potency last but not least in the evaluation of different therapeutic approaches on cerebral dysfunctions. Pharmacological as well as behavioral interventions have been examined with respect to effects on the activation pattern and have been proven to be effective in reducing abnormal brain activity in schizophrenia during cognitive and emotional processes. Such therapeutic effects could also be demonstrated in alcoholic patients. The neural correlates of craving, elicited by visual and olfactory cues in alcoholic patients, have been examined by fMRI and differential intervention strategies demonstrated modality specific therapeutic effects. Hence, the application of fMRI still offers an exceptional and exciting tool for augmenting the understanding of the pathophysiology of psychiatry disorders.