New TP Straube/Eggert/Dieterich "Brain activity in encoding and retrieval of explicit spatial memory"
Current status of research and general objective
In previous studies (Drever et al. 2011b; Drever et al. 2011a; Eggert et al. 2014) we developed a memory task for deferred imitation of long spatial sequences (DILSS) which allows to test the formation of explicit (declarative) memory.
In this task, subjects view during the training trials a visual target which steps on a video screen through a pseudo-random sequence of 20 different 2D-positions with an inter-target interval of 1 s. Alternating with these training trials, subjects have the task to reproduce (without timing constraints) as many of these positions as possible by pointing to the blank screen. Thereby, the subjects are instructed to point only to target locations that are remembered, to preserve the order of the sequence elements, and to avoid guessing. The reproduction is performed at arbitrary timing without external trigger or time pressure. After the subjects terminate this reproduction trial by pressing a button indicating that they do not remember further targets, the training trial with the very same training sequence is repeated. On average, with each pair of alternating training and reproduction trial, subjects learned to extend the memorized sequence by about 1 to 2 target locations and were able to complete the sequence within a learning session lasting for only about 30 min.
The relevance of DILSS in a wider context is that serial reproduction of long spatial memory sequences may be considered as a basic requirement for task imitations in which success and failure depend on the reproduction of longer action sequences without intermediate feedback. For example, learning to operate an unknown coffee machine by imitation requires to memorize the sequence of the locations of the involved operating controls (power switch, filler openings for water and coffee, start and stop buttons). Another example is homing in a navigation task which requires reproducing a long sequence of spatial actions (choosing the correct junctions). Therefore, performance in the DILSS task may be a critical indicator for performance in imitation learning in everyday behavior. It is important to note that DILSS differs in many aspects from free recall or speeded serial recall.
We showed that with DILSS, the learned sequence was independent of the motor effector (pointing with eye or hand) and was retained for several days to weeks (Drever et al. 2011a). Moreover, compared to the widely used serial reaction time task (SRT) with speeded responses, e.g. Ghilardi et al. (2009), our learning task showed the general lack of proactive and retroactive memory interference of a second sequence learned by deferred imitation before or after the acquisition of the first sequence (Eggert et al. 2014). Since sequence learning in the SRT is believed to comprise both implicit and explicit memory components (Robertson 2007), and because our previous studies (Drever et al. 2011a; Eggert et al. 2014) showed that DILSS did not show features of implicit motor learning such as chunking (Sakai et al. 2003) or error propagation between subsequent elements (Bock and Arnold 1993), we hypothesize that DILSS is a suitable paradigm to investigate the acquisition of explicit spatial long-term memory.
Proposed experiments and methods
To further test this hypothesis, we propose to investigate brain activity during DILSS with functional magnetic resonance imaging (fMRI). In the imaging experiments, pointing during reproduction trials will be performed with eye movements. Subjects will perform 6 different experimental condition: I) Encoding control: visual tracking of random (non-repeated) target sequences; II) Retrieval control: spontaneous generation of pointing movements to arbitrary locations on a blank screen; III) Encoding of novel sequence: repeated visual tracking of an unknown pseudo-target sequence; IV) Retrieval of novel sequence: Reproduction of a partially known sequence; V) Encoding of well-known sequence; and VI) Retrieval of a well-known sequence. The experimental conditions will be alternated within one scanning run, an instruction screen at the beginning of each condition will inform the subject about the task at hand. Brain activity of the encoding [retrieval] conditions during the two stages of the training (III, V [IV, VI]) will be compared with the encoding [retrieval] control condition (I [II]).
Subjects will be scanned in a 3T MRI scanner (Siemens PRISMA) located on the campus Großhadern. Scanning will include functional imaging with an echoplanar imaging sequence covering the whole cortex and cerebellum. An additional structural T1 scan will be acquired to enable spatial normalization of all data sets to a common atlas space (MNI). The equipment for visual presentation of stimuli onto a backprojection screen and video-oculographic eyetracking is already installed at the MRI scanner (PROPixx projector, VPixx Technologies, Canada; EyeLink 1000 Plus, SR Research, Canada). Button responses will be collected using an MRI compatible response device (NordicNeuro Lab, Norway).
Previous studies showed that the dorsolateral prefrontal cortex and the pre-SMA are activated during the acquisition of new spatial sequences, whereas the basal ganglia, especially the middle putamen and the cerebellum are activated during the reproduction of highly automated sequences (Hikosaka et al. 1998; Hikosaka et al. 1999). Many studies show that performance in explicit memory tasks is associated with activity of the medial temporal lobe (Ofen et al. 2007) and the hippocampus (Eichenbaum 2001). Thus, our hypothesis that DILSS elicits explicit spatial learning would be supported if we could demonstrate that encoding and retrieval in our paradigm leads to activation in the hippocampus and the medial temporal lobe rather than the basal ganglia and the cerebellum.
The proposed fMRI study can also reveal whether the DILSS paradigm addresses episodic memory rather than semantic memory. This is suggested by the fact that the reproduction mode in our memory task is not verbal such as in typical learning tasks with wordlists. However, memory performance alone is not sufficient to determine the actual mode of the explicit memory is episodic or semantic (Tulving 2002). The hemispheric retrieval asymmetry (HERA) predicts that the left prefrontal cortex is more involved in the encoding, and the right prefrontal cortex is more involved retrieval of episodic memory(Tulving et al. 1994). Therefore, we plan to compare the activity of right and left prefrontal cortex during DILSS.
A further question that can be addressed by the proposed study is how explicit memory is impaired due to resection in temporal lobe epilepsy. Previous studies demonstrated that these lesions do not only impair the acquisition and short term retention of explicitly learned wordlists, but also the retention across a period of one week(Visser et al. 2018). Testing DILSS (conditions III – VI) in this patient group would reveal whether these impairments occur not only in explicit learning of wordlists, but also in explicit spatial learning.
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