Effects of non-invasive brain stimulation on associative memory

Highlights

• Participants studied face-name pairs while receiving active (2 mA) or sham (0.1 mA) tDCS.

• Active tDCS significantly improved participants׳ recall of the face-name associations.

• tDCS did not impact participants׳ recognition memory performance.

• tDCS can improve associative memory, particularly for the most difficult memory conditions.

Abstract

Associative memory refers to remembering the association between two items, such as a face and a name. It is a crucial part of daily life, but it is also one of the first aspects of memory performance that is impacted by aging and by Alzheimer׳s disease. Evidence suggests that transcranial direct current stimulation (tDCS) can improve memory performance, but few tDCS studies have investigated its impact on associative memory. In addition, no prior study of the effects of tDCS on memory performance has systematically evaluated the impact of tDCS on different types of memory assessments, such as recognition and recall tests. In this study, we measured the effects of tDCS on associative memory performance in healthy adults, using both recognition and recall tests. Participants studied face-name pairs while receiving either active (30 min, 2 mA) or sham (30 min, 0.1 mA) stimulation with the anode placed at F9 and the cathode placed on the contralateral upper arm. Participants in the active stimulation group performed significantly better on the recall test than participants in the sham group, recalling 50% more names, on average, and making fewer recall errors. However, the two groups did not differ significantly in terms of their performance on the recognition memory test. This investigation provides evidence that stimulation at the time of study improves associative memory encoding, but that this memory benefit is evident only under certain retrieval conditions.

Introduction

Associative memory refers to memory for the association or relationship between two items. Everyday examples include remembering a person׳s name or remembering where you left your car keys. In a typical associative memory experiment, participants study pairs of items, such as face-name pairs, and are tested on their memory for the pairings via recognition or recall tests. In recognition tests, the participants are shown studied pairs as well as lures in which studied pairs are recombined to form novel pairings. Accurate performance requires that participants successfully identify studied pairs while rejecting the novel pairs. In recall tests, participants are shown a cue (e.g., a face) and are asked to generate the other member of the pair (e.g., the name). In both the recognition and recall tasks, successful performance requires the participant to accurately recollect the association between the members of the studied pairs; that is, participants must remember that this face was paired with that name. In this investigation, we seek to improve this type of memory using a noninvasive brain stimulation technique.

Transcranial direct current stimulation (tDCS) is a brain stimulation technique that can modulate neuronal activity at the site of stimulation (Nitsche and Paulus, 2000). Stimulation is thought to produce a two-fold effect – an acute modulation of cortical excitability (Nitsche and Paulus, 2000) followed by lasting effects that are NMDA-receptor dependent (Liebetanz et al., 2002) and therefore similar to long-term potentiation (LTP) and long-term depression (LTD) processes posited to underlie learning and memory (Rioult-Pedotti et al., 1998). Recent studies have shown that tDCS can improve cognitive performance in both clinical populations and healthy adults on tasks ranging from motor learning to decision making (Coffman et al., 2014, Dayan et al., 2013, Manenti et al., 2012). Many of these studies have focused on working memory (Fregni et al., 2005; Ohn et al., 2008) or episodic memory (e.g., Chi et al., 2010, Javadi and Walsh, 2012), and the majority of this work suggests that tDCS can improve performance. However, other studies find little or no benefit from tDCS (e.g., Elmer et al., 2009), suggesting that conditions under which memory might improve are not yet fully understood.

Although associative memory is critically important for learning and for navigating everyday life, few studies have explored whether or not tDCS can enhance associative memory performance. Some prior studies have incorporated associative learning paradigms into investigations of the effects of tDCS on language learning (Fiori et al., 2011, Flöel et al., 2008). In those paradigms, participants were asked to learn novel, nonword names for common objects. These studies have shown that tDCS with the anode placed on the scalp over left Wernicke׳s area improved reaction times in a recall task (Fiori et al., 2011) and performance on an incidental language learning task (Flöel et al., 2008). However, stimulation applied to the same location has been shown to improve reaction times in a picture naming task (Sparing et al., 2008), making it unclear whether the improved performance seen in these studies was due to enhancement of associative memory or to facilitation of lexical access.

There is one study that suggests that tDCS may improve associative memory as measured by recall, but not recognition (Flöel et al., 2012). In this study, older adults learned object-location associations in an incidental learning paradigm while active or sham tDCS was applied with the anode positioned over the right temporoparietal cortex. Participants performed better on a delayed recall test (one week after learning) following active stimulation. Interestingly, although tDCS improved recall performance, it had no effect on learning rates at the time of study. The incidental learning task, in which participants were presented with correct pairs (frequently) and incorrect pairs (infrequently), was functionally similar to a recognition memory task, particularly in the later blocks of the task when the participants had become familiar with the correct object-location pairings. Since active tDCS enhanced the encoding of the associations as measured by delayed recall, we might also expect it to enhance recognition performance during the learning task. The fact that it did not hints at the possibility that tDCS has differential effects on recognition and recall tests of associative memory. However, this prior research was not explicitly designed to test recognition memory performance, so the reasons for this difference are unclear.

Studies of other types of memory (i.e. item memory) have found tDCS-induced improvements as measured by both recognition and recall tests. Studies of recognition memory have found that tDCS with the anode positioned over the left superior parietal cortex improved recognition memory for studied words (Jacobson et al., 2012), while tDCS with the anode located above the right anterior temporal lobe (ATL) reduced false alarms in a shape recognition task (Chi et al., 2010). Studies investigating the timing of stimulation with respect to encoding and retrieval suggest that tDCS has a bigger impact on memory if it is applied at the time of study. For instance, Javadi and Walsh (2012) showed that recognition memory improved when tDCS was applied during encoding, but that memory improvements were only marginal when tDCS was applied during retrieval. Similarly, Javadi et al. (2012) applied stimulation with the anode above the left dorsolateral prefrontal cortex (dlPFC) either during stimulus presentation or immediately after. Results showed that both recognition performance and reaction times were improved when stimulation was applied in a short burst at the beginning, but not at the end, of study trials. Overall, these findings show that tDCS applied during study improves recognition memory performance in healthy adults.

Only a few studies have investigated the effects of tDCS on recall, but these studies have also found improvements in memory performance. In one experiment (Penolazzi et al., 2010), participants studied positively and negatively valanced images while receiving stimulation with the anode placed over the right or left frontotemporal cortex. Right hemisphere stimulation improved participants׳ recall for the positive images while left hemisphere stimulation improved recall for the negative images. Another study found that recall of category exemplars was improved when stimulation was applied to both the left and right dlPFC during a consolidation interval (while the participant slept; Marshall et al., 2004). TDCS has also been shown to reduce rates of false recall (i.e., producing an item not previously studied; Boggio et al., 2009). As was the case with recognition, these results suggest that stimulation improves recall both by increasing the number of items a participant can recall and by reducing the number of memory errors.

In summary, studies investigating memory indicate that tDCS can improve performance as measured by both recognition and recall tasks. However, few studies have tested the effects of tDCS on associative memory performance, and no studies to date have systematically examined the effects of tDCS on both recognition and recall performance in a single experiment. It is not currently known whether tDCS has different effects on these two common measures of memory performance.

In this experiment, we assessed the effects of tDCS on associative memory, as measured by both recognition and recall tests. To test the effects of tDCS on associative memory, we chose to position the anode above the left inferior frontal gyrus (LIFG). Past functional magnetic resonance imaging (fMRI) experiments on face-name associative memory have found that activity in the LIFG at the time of study is associated with successful memory (Sperling et al., 2003b) and fMRI guidance has been used effectively in prior tDCS accelerated-learning paradigms (e.g., Clark et al., 2012). Participants in this experiment received either active or sham tDCS while studying face-name pairs and then completed both recognition and cued recall tests (Fig. 1). We predicted that stimulation would lead to improved memory performance relative to sham stimulation on both recognition and recall tests, consistent with prior reports (e.g., Chi et al., 2010, Jacobson et al., 2012, Marshall et al., 2004, Penolazzi et al., 2010). Finding that tDCS improves associative memory performance on both measures would suggest that stimulation effects are robust, and affect memory regardless of how one attempts to retrieve the stored information.

We also considered the possibility that tDCS would improve associative memory performance as measured by recall tests, but not recognition tests. The prior work using associative learning paradigms have found mixed results in which tDCS improved recall performance, but not performance on the recognition-based learning task (Flöel et al., 2012). In addition, prior work that has examined interventions to improve memory has found memory improvements when performance is measured by recall but not when measured by recognition (Payne and Roediger, 1987), suggesting that the nature of the memory test one employs may affect the ability to detect memory improvements.

Finally, because we used face-name pairs as to-be-encoded stimuli in this investigation, we examined differences in associative memory performance that were related to characteristics of the faces. Prior research suggests that memory is superior for faces of one׳s own age group (own-age bias; Rhodes and Anastasi, 2012), gender (own-gender bias; Wright and Sladden, 2003), and ethnicity (own-ethnicity bias; Gross, 2009). While all of the face stimuli used in the current study were of the same ethnicity, the age and gender of the faces varied. Each participant viewed equal numbers of faces from each age group (young, middle aged, and elderly) and each gender, allowing us to test the effects of stimulation on own-age and own-gender bais.