Elsevier

NeuroImage

Volume 35, Issue 2, 1 April 2007, Pages 928-939
NeuroImage

Acute effects of alcohol on neural correlates of episodic memory encoding

https://doi.org/10.1016/j.neuroimage.2006.12.024Get rights and content

Abstract

Although it is well established that alcohol impairs episodic memory encoding, it is unknown how this occurs on a cerebral level. We scanned intoxicated and sober individuals with functional magnetic resonance imaging (fMRI) while they encoded various materials that were recalled the following day. Alcohol impaired memory for object pairs and face–name pairs, but not for words and phrase–word pairs. Impaired performance was associated with reduced bilateral prefrontal activation and non-specific activation of the parahippocampal gyrus. These results suggest that alcohol impairs episodic memory by interfering with activity of regions involved in encoding, and further indicate which regions are critical for human memory.

Introduction

Alcohol is one of the world’s most popular drugs, such that the subjective effects of alcohol on the mind and body are known to almost everyone. Thanks to a considerable amount of behavioral research, it is well established that alcohol impairs episodic memory as assessed through traditional laboratory memory tasks (Hashtroudi et al., 1984, Nilsson et al., 1989, Curran and Hildebrandt, 1999), and encoding more so than retrieval (Soderlund et al., 2005). However, even though this has been demonstrated behaviorally for decades, and in spite of advances in human neuroimaging techniques, no study has yet identified the neural correlates of alcohol-induced memory impairment. Identifying how alcohol interferes with episodic encoding is informative for both alcohol’s effects on the brain, and for the neural correlates of episodic memory. Here we report the first study exploring alcohol’s effects on brain activity during episodic memory encoding of verbal and nonverbal information.

There are many cerebral blood flow (CBF) studies of alcohol’s effects on various processes, although no such study exists on episodic memory. Compared to placebo, alcohol reduces CBF in the task-implicated areas during perceptual processing, simulated driving (Calhoun et al., 2004), divided attention (Haier et al., 1999), and verbal fluency (Wendt and Risberg, 2001). This suggests that reduced CBF may also occur during memory processing. Hints about where such reductions may take place are found in the rodent literature, where mainly the hippocampus has been explored and identified as a target of alcohol’s memory-impairing effects in a number of behavioral, in-vitro, and in-vivo studies (Silvers et al., 2003). Although it is possible that alcohol impairs memory in humans because of its effects on the hippocampus, it is likely that additional structures involved in memory, such as temporal structures surrounding the hippocampus (e.g., the parahippocampal gyrus) and the frontal lobes (Schacter and Wagner, 1999, Cabeza and Nyberg, 2000), also are affected by alcohol. Alcohol effects on both the parahippocampal gyrus and prefrontal cortex have been observed under acute intoxication (Schreckenberger et al., 2004). Our goal here was to determine which encoding-related brain areas have altered activity under the influence of alcohol, and to assess how these changes are related to subsequent memory performance.

Since this is, to our knowledge, the first study to assess the neural correlates of alcohol-induced memory impairment, we included tasks of varying difficulty and stimulus characteristics to cover a wide range of potential alcohol effects. Hence, the intention is not so much to compare alcohol’s effects across tasks, but rather assess its effects within each task. Associative learning frequently activates the hippocampus (Henke et al., 1999, Sperling et al., 2003) and because of this area’s suggested role in alcohol-induced memory impairment, we included associative learning of two types of materials: face–name pairs and pairs of line-drawings of objects, hereafter referred to as object pairs. Face–name pair encoding was used as it is impaired by the central nervous system depressants lorazepam and scopolamine (Sperling et al., 2002), and is relevant for real life situations. Lorazepam also impairs picture recognition (O’Neill et al., 1995), which motivated the inclusion of the object pairs. Unrelated object pairs were chosen, since processing of unrelated pairs is accompanied by more prefrontal activity than related pairs (Iidaka et al., 2001). Two verbal tasks were also included: a task of new semantic learning, consisting of witty word definitions (Tulving and Watkins, 1977), that has previously shown large effects of alcohol (Soderlund et al., 2005), and a word categorization task. These tests were included to examine alcohol’s effect on the neural correlates of semantic processing, which has been associated with a reduction of left prefrontal activity (Wendt and Risberg, 2001).

We hypothesized that alcohol would impair subsequent memory performance in general, and associative memory in particular, because of the hippocampus’ role in successful associative encoding and the previous reports of alcohol’s influence on this region. Reduced performance was expected to be associated with reduced hippocampal activity during associative encoding, and with reduced left prefrontal activity during encoding in general.

Section snippets

Participants

Twenty-seven men were recruited for the study. Only men were chosen to reduce overall variability, given sex differences in the response to alcohol (Mumenthaler et al., 1999). They were screened over the phone prior to participation, and excluded if they had any neurological, psychiatric or medical disorder, were on any medication, were left-handed, had not spoken English regularly since the age of 7, were outside the 20–40 year age range, had problematic drinking habits or were unaccustomed to

Behavioral data (Day 1)

There was no difference between the groups in reaction time or responses in the scanner on Day 1. These data can be viewed in Supplementary Table 1.

Memory performance (Day 2)

Performance in word recognition (F < 1), cued recall (F < 1), and face recognition (F1,23 = 3.0, p > 0.05) was equivalent in the two groups (Table 1). In addition to word recognition, we also assessed the quality of the memory experience using the remember/know paradigm (Tulving, 1985, Gardiner, 1988), where a “remember” response indicates that a

Discussion

This is the first study to identify some of the neural correlates of alcohol-induced memory impairment in humans during episodic encoding of various materials. Three major findings emerged. First, when performance was spared under alcohol, i.e., for verbal materials, the alcohol group activated the same set of left prefrontal regions at encoding, including the inferior frontal gyrus, as the placebo group. The left inferior frontal gyrus was not active in the alcohol group during encoding when

Acknowledgments

The authors wish to thank our subjects that were willing to have a large amount of alcohol and thereafter get into the scanner. We thank Michael Dixon for providing a breathalyzer. We also thank Fergus Craik and Morris Moscovitch for providing testing space for the recall session, and Moeshe Naveh-Benjamin for providing materials for the face–name conditions. Dr. Tulving’s research is supported by the Natural Sciences and Engineering Research Council of Canada and by an endowment by Anne and

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