Disrupted parahippocampal and midbrain function underlie slower verbal learning in adolescent-onset regular cannabis use

Grace Blest-Hopley,Sagnik Bhattacharyya,Robin Wilson,Vincent Giampietro,Aisling O'Neill

doi:10.1007/s00213-019-05407-9

Grace Blest-Hopley, Sagnik Bhattacharyya + Show 3 more

Open Access

https://doi.org/10.1007/s00213-019-05407-9

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Abstract

RationaleProlonged use of cannabis, the most widely used illicit drug worldwide, has been consistently associated with impairment in memory and verbal learning. Although the neurophysiological underpinnings of these impairments have been investigated previously using functional magnetic resonance imaging (fMRI), while performing memory tasks, the results of these studies have been inconsistent and no clear picture has emerged yet. Furthermore, no previous studies have investigated trial-by-trial learning.ObjectivesWe aimed to investigate the neural underpinnings of impaired verbal learning in cannabis users as estimated over repeated learning trials.MethodsWe studied 21 adolescent-onset regular cannabis users and 21 non-users using fMRI performed at least 12 h after last cannabis use, while they performed a paired associate verbal learning task that allowed us to examine trial-by-trial learning. Brain activation during repeated verbal encoding and recall conditions of the task was indexed using the blood oxygen level-dependent haemodynamic response fMRI signal.ResultsThere was a significant improvement in recall score over repeated trials indicating learning occurring across the two groups of participants. However, learning was significantly slower in cannabis users compared to non-users (p = 0.032, partial eta-squared = 0.108). While learning verbal stimuli over repeated encoding blocks, non-users displayed progressive increase in recruitment of the midbrain, parahippocampal gyrus and thalamus (p = 0.00939, partial eta-squared = 0.180). In contrast, cannabis users displayed a greater but disrupted activation pattern in these regions, which showed a stronger correlation with new word-pairs learnt over the same blocks in cannabis users than in non-users.ConclusionsThese results suggest that disrupted medial temporal and midbrain function underlie slower learning in adolescent-onset cannabis users.

Highlights

The long-term use of cannabis has long been associated with deficits in cognition (Grant et al 2003; Meier et al 2012; Schreiner and Dunn 2012) including learning and memory function (Meier et al 2018; Schoeler and Bhattacharyya 2013; Solowij and Battisti 2008), verbal learning (Schoeler et al 2016a)
Consistent with this, acute experimental studies have demonstrated that a single dose of delta-9tetrahydrocannabinol (THC), the main psychoactive ingredient of cannabis, or THC-rich cannabis extract, can impair memory (Curran et al 2002; D'Souza et al 2004) in cannabis users (CU) and alter the memory related engagement of medial temporal and prefrontal regions (Bhattacharyya et al 2012; Bhattacharyya et al 2009; Bossong et al 2012) that
NU were required to have a negative result for all substances; CU were required to have a positive result for THC, and a negative urine test result for all other drugs

Summary

Introduction

The long-term use of cannabis has long been associated with deficits in cognition (Grant et al 2003; Meier et al 2012; Schreiner and Dunn 2012) including learning and memory function (Meier et al 2018; Schoeler and Bhattacharyya 2013; Solowij and Battisti 2008), verbal learning (Schoeler et al 2016a). Previous studies have investigated brain functional activation differences between long-term CU and non-users (NU) during the performance of a range of memory tasks using functional magnetic resonance imaging (fMRI) (Carey et al 2015; Jager et al 2010; Jager et al 2006; Jager et al 2007; Nestor et al 2008; Schweinsburg et al 2011).

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