DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm(3) isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

Imaging bilinguals: When the neurosciences meet the languange sciences

The starting point of our investigation was the longstanding notion that bilingual individuals need effective mechanisms to prevent interference from one language while processing material in the other (e.g. Penfield and Roberts, 1959). To demonstrate how the prevention of interference is implemented in the brain we employed event-related brain potentials (ERPs; see Munte, Urbach, ¨ Duzel and Kutas, 2000, for an introductory review) ¨ and functional magnetic resonance imaging (fMRI) techniques, thus pursuing a combined temporal and spatial imaging approach. In contrast to previous investigations using neuroimaging techniques in bilinguals, which had been mainly concerned with the localization of the primary and secondary languages (e.g. Perani, Paulesu, Galles, Dupoux, Dehaene, Bettinardi, Cappa, Fazio and Mehler, 1998; Chee, Caplan, Soon, Sriram, Tan, Thiel and Weekes, 1999), our study addressed the dynamic aspects of bilingual language processing.

Functional connectivity of reward processing in the brain

Controversial results have been reported concerning the neural mechanisms involved in the processing of rewards and punishments. On the one hand, there is evidence suggesting that monetary gains and losses activate a similar fronto-subcortical network. On the other hand, results of recent studies imply that reward and punishment may engage distinct neural mechanisms. Using functional magnetic resonance imaging (fMRI) we investigated both regional and interregional functional connectivity patterns while participants performed a gambling task featuring unexpectedly high monetary gains and losses. Classical univariate statistical analysis showed that monetary gains and losses activated a similar fronto-striatallimbic network, in which main activation peaks were observed bilaterally in the ventral striatum. Functional connectivity analysis showed similar responses for gain and loss conditions in the insular cortex, the amygdala, and the hippocampus that correlated with the activity observed in the seed region ventral striatum, with the connectivity to the amygdala appearing more pronounced after losses. Larger functional connectivity was found to the medial orbitofrontal cortex for negative outcomes. The fact that different functional patterns were obtained with both analyses suggests that the brain activations observed in the classical univariate approach identifi es the involvement of different functional networks in the current task. These results stress the importance of studying functional connectivity in addition to standard fMRI analysis in reward-related studies.

Reward networks in the brain as captured by connectivity measures

An assortment of human behaviors is thought to be driven by rewards including reinforcement learning, novelty processing, learning, decision making, economic choice, incentive motivation, and addiction. In each case the ventral tegmental area/ventral striatum (nucleus accumbens) (VTAVS) system has been implicated as a key structure by functional imaging studies, mostly on the basis of standard, univariate analyses. Here we propose that standard functional magnetic resonance imaging analysis needs to be complemented by methods that take into account the differential connectivity of the VTAVS system in the different behavioral contexts in order to describe reward based processes more appropriately. We fi rst consider the wider network for reward processing as it emerged from animal experimentation. Subsequently, an example for a method to assess functional connectivity is given. Finally, we illustrate the usefulness of such analyses by examples regarding reward valuation, reward expectation and the role of reward in addiction.