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Matthias Kirschner

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RLDM Conference 2019 Conference Abstract

Reward system connectivity during self-regulation with non-drug reward im- agery in cocaine users

  • Matthias Kirschner
  • Amelie Haugg
  • Philipp Stämpflie
  • Etna Engeli
  • Lea Hulka
  • James Sulzer
  • Erich Seifritz
  • Alain Dagher

Introduction: Humans can voluntary up-regulate brain activity with reward imagery and improve this ability with real-time fMRI (rt-fMRI) Neurofeedback (NFB). Using internal non-drug-related reward imagery cocaine users (CU) were able to activate the ventral tegmental area (VTA) and other regions includ- ing the ventral and dorsal striatum (VS, DS), Hippocampus (Hipp), and medial prefrontal cortex (mPFC). However, it is unknown how interactions among these regions modulate self-regulation and whether connec- tivity is disrupted in CU. Here, we used DCM to investigate whether VTA self-regulation is achieved via the mPFC, VS or VTA, directly and tested whether cocaine craving influences effective connectivity. Methods: Dynamic causal modeling (DCM) was applied on our previous published pre- and post rt-fMRI NFB data from 28 HC and 22 CU. DCM Bayesian Model Selection (BMS) and Averaging (BMA) using a model space of (3 families×1024 models) were performed. In CU, correlation analyses were performed on the posterior DCM parameters to investigate the effects of acute and chronic craving on connectivity. Results: BMS revealed that the mPFC was the exclusive entry point for successful self-regulation with non-drug reward imagery, while reward imagery caused VTA and striatal activation only indirectly via mPFC. In CU, Hipp to mPFC connectivity was reduced before rt-fMRI NFB and restored after rt-fMRI NFB. Severity of chronic craving was associated with reduced intrinsic VTA connectivity, while severity of acute craving was associ- ated with reduced task-dependent DS connectivity. Conclusion: This study showed that the mPFC integrates and transmits representations of non-drug reward imagery to the mesolimbic reward system, thereby initiat- ing successful self-regulation. Disrupted DS connectivity and VTA connectivity was differentially related to acute and chronic craving suggesting separate neural mechanisms contributing to impaired non-drug reward processing in CU.

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