How do memory systems detect and respond to novelty?

Abstract

The efficiency of the memory system lies not only in its readiness to detect and retrieve old stimuli but also in its ability to detect and integrate novel information. In this review, we discuss recent evidence suggesting that the neural substrates sensitive to detecting familiarity and novelty are not entirely overlapping. Instead, these partially distinct familiarity and novelty signals are integrated to support recognition memory decisions. We propose here that the mediodorsal thalamus is critical for familiarity detection, and for combining novelty signals from the medial temporal lobe cortex with the relative familiarity outputs of computations performed in other cortical structures, especially the prefrontal cortex. Importantly, we argue that the anterior hippocampus has a prominent role in detecting novelty and in communicating this with midbrain and striatal structures. We argue that different types of novelty (absolute or contextual) engage different neurotransmitter systems that converge in the hippocampus. We suggest that contextual or unexpected novelty triggers dopaminergic hippocampal-midbrain coupling and noradrenergic-mediated pupil dilation. In contrast, absolute novelty triggers cholinergic-mediated hippocampal encoding accompanied by diminished pupil dilation. These two, distinct hippocampal encoding mechanisms both lead to later recollection but are sensitive to different types of novelty. We conclude that this neurotransmitter-mediated hippocampal encoding establishes the hippocampus in an encoding mode that briefly prevents the engagement of retrieval.

Keywords: Acetylcholine; Dopamine; Familiarity; Hippocampus; Norepinephrine; Novelty.

Fig. 1

Relationship between familiarity and novelty according to the standard view. A) Familiarity and novelty as “mirror images” explain the behavioural output, i.e., something that is more familiar is less novel and vice versa. B) The familiarity – novelty continuum that describes the hypothetical neural response to familiarity and novelty if the two rely on the same neural substrates (consistent with the “mirror image” view). If the full continuum explanation is correct, assuming three levels to familiarity (F) and novelty (N) strength, a graded brain response should be expected honouring the whole scale: F3 (strong F) – F2 (moderate F) – F1 (weak F) – N1 (weak N) – N2 (moderate N) – N3 (strong N). Increased activity with increased familiarity strength is illustrated, but the opposite (i.e., increased activity with increased novelty strength) is also possible.

Fig. 2

Exploring familiarity and novelty detection: Eye tracking and brain responses. A) Participants encoded single objects using a perceptual matching-to-sample task. At retrieval, inside the MRI scanner [5] or while undergoing eye tracking recording [24], participants engaged in two alternating tasks emphasising either familiarity detection (FT) or novelty detection (NT). A rating scale was provided in both tasks to evaluate strength of familiarity or novelty and to indicate instances of spontaneous recollection and correctly rejected stimuli (new items in FT; old items in NT). B) The duration of the first fixation and the pupil response discriminated between familiar and novel stimuli. C) Familiarity-selective and novelty-selective activation patterns were identified in non-overlapping brain regions. Familiarity-selective regions included the mediodorsal thalamus, the dorsolateral and superior medial prefrontal cortex, the anterior cingulate and the left angular gyrus. Regions along the ventral visual stream and critically the anterior hippocampus belong to the novelty-specific network. F1 = weak; F2 = moderate; F3 = strong familiarity; N1 = weak; N2 = moderate; N3 = strong novelty. Figure adapted from [5,24].

Fig. 3

Integration of familiarity and novelty signals in the brain. Computations from novelty-selective and familiarity-selective regions converge to provide a relative familiarity output. The mediodorsal thalamus (MDt) plays a central role in detecting familiarity and in orchestrating convergence of novelty from the medial temporal cortical areas to middle prefrontal regions (Middle Frontal Gyrus, MFG). MFG interacts with the inferior parietal gyrus (IPG), where familiarity- and novelty-sensitive regions also converge to provide a relative familiarity output. The anterior hippocampus detects novelty and conveys novelty-related information to midbrain and striatal structures for salience evaluation.

Fig. 4

Anterior hippocampal novelty detection and associated neurotransmitter-mediated encoding mechanisms for absolute and contextual novelty. A) Detection of contextual novelty engages the dopaminergic SN/VTA [65,68] and affects the sympathetically innervated pupillary response via increased engagement of the noradrenergic system and especially the locus coeruleus (LC). This results in dopamine and norepinephrine release in the hippocampus and ensures effective learning and integration of new information with pre-existing knowledge. Detection of absolute novelty [80] engages the anterior hippocampus but in this case the cholinergic parasympathetic system facilitates learning. The novelty signal triggers the release of acetylcholine into the hippocampus from the pendunculopontine nucleus (PPN) of the midbrain, possibly via the basal forebrain (not shown in the Figure). Both encoding mechanisms enable efficient associative encoding resulting subsequently in recollection of information but are triggered by different types of novelty detected in the anterior hippocampus. B) Contextual and absolute novelty at encoding are accompanied by distinct pupil response patterns although in both cases later memory is supported by recollection. Contextual novelty results in increased phasic pupil dilation [left panel; 68], while absolute novelty is accompanied by a tonic pupil response, characterised by diminished dilation for subsequently recollected stimuli [right panel; 80]. *p < .05. Panel B of the Figure adapted from [68,80].