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Misconfigured striatal connectivity profiles in smokers.

Cole Korponay1, Elliot A Stein2, Thomas J Ross2

  • 1Basic Neuroscience Division, McLean Hospital, Belmont, MA, USA. ckorponay@mclean.harvard.edu.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
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Summary

Substance use disorder (SUD) involves altered brain connectivity. This study reveals distinct frontal-striatal connectivity profile misconfigurations in smokers, differentiating between stable trait adaptations and state-dependent changes during withdrawal.

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Area of Science:

  • Neuroscience
  • Addiction Research
  • Brain Imaging

Background:

  • Dysregulation of frontal cortical inputs to the striatum is central to substance use disorder (SUD).
  • Striatal function is shaped by complex "connectivity profiles" from multiple cortical areas.
  • The specific role of aberrant connectivity profiles in SUD remains unclear.

Purpose of the Study:

  • To investigate how abnormal striatal connectivity profiles contribute to SUD.
  • To introduce a novel "connectivity profile analysis" (CPA) to detect misconfigurations in SUD.
  • To differentiate between trait and state-dependent circuit adaptations in SUD.

Main Methods:

  • Utilized resting-state functional connectivity data.
  • Implemented a novel connectivity profile analysis (CPA) approach.
  • Examined 46 nicotine-dependent smokers and 33 non-smokers.

Main Results:

  • Smokers exhibited distinct dorsal striatum (DS) and ventral striatum (VS) connectivity profile misconfigurations.
  • DS misconfigurations were stable (trait), while VS misconfigurations emerged during abstinence (state).
  • DS involved altered connection strength rank order; VS involved altered aggregate strength. Caudal ventral putamen showed multiple misconfigurations linked to dependence severity.

Conclusions:

  • Findings highlight distinct trait and state circuit adaptations in SUD.
  • CPA approach offers deeper insights into corticostriatal circuit neurobiology in SUD.
  • Abnormal connectivity profiles are crucial in the neural basis of SUD.