A reward effect on memory retention, consolidation, and generalization?

Reward improves memory through both encoding and consolidation processes. In this preregistered study, we tested whether reward effects on memory generalize from high-rewarded items to low-rewarded but episodically related items. Fifty-nine human volunteers incidentally encoded associations between unique objects and repeated scenes. Some scenes typically yielded high reward, whereas others typically yielded low reward. Memory was tested immediately after encoding (n = 29) or the next day (n = 30). Overall, reward had only a limited influence on memory. It did not enhance consolidation and its effect did not generalize to episodically related stimuli. We thus contribute to understanding the boundary conditions of reward effects on memory.

Category-specific memory encoding in the medial temporal lobe and beyond: the role of reward.

The medial temporal lobe (MTL), including the hippocampus (HC), perirhinal cortex (PRC), and parahippocampal cortex (PHC), is central to memory formation. Reward enhances memory through interplay between the HC and substantia nigra/ventral tegmental area (SNVTA). While the SNVTA also innervates the MTL cortex and amygdala (AMY), their role in reward-enhanced memory is unclear. Prior research suggests category specificity in the MTL cortex, with the PRC and PHC processing object and scene memory, respectively. It is unknown, however, whether reward modulates category-specific memory processes. Furthermore, no study has demonstrated clear category specificity in the MTL for encoding processes contributing to subsequent recognition memory. To address these questions, we had 39 healthy volunteers (27 for all memory-based analyses) undergo functional magnetic resonance imaging while performing an incidental encoding task pairing objects or scenes with high or low reward, followed by a next-day recognition test. Behaviorally, high reward preferably enhanced object memory. Neural activity in the PRC and PHC reflected successful encoding of objects and scenes, respectively. Importantly, AMY encoding effects were selective for high-reward objects, with a similar pattern in the PRC. The SNVTA and HC showed no clear evidence of successful encoding. This behavioral and neural asymmetry may be conveyed through an anterior-temporal memory system, including the AMY and PRC, potentially in interplay with the ventromedial prefrontal cortex.

Category-sensitive incidental reinstatement in medial temporal lobe subregions during word recognition.

During associative retrieval, the brain reinstates neural representations that were present during encoding. The human medial temporal lobe (MTL), with its subregions hippocampus (HC), perirhinal cortex (PRC), and parahippocampal cortex (PHC), plays a central role in neural reinstatement. Previous studies have given compelling evidence for reinstatement in the MTL during explicitly instructed associative retrieval. High-confident recognition may be similarly accompanied by recollection of associated information from the encoding context. It is unclear, however, whether high-confident recognition memory elicits reinstatement in the MTL even in the absence of an explicit instruction to retrieve associated information. Here, we addressed this open question using high-resolution fMRI. Twenty-eight male and female human volunteers engaged in a recognition memory task for words that they had previously encoded together with faces and scenes. Using complementary univariate and multivariate approaches, we show that MTL subregions including the PRC, PHC, and HC differentially reinstate category-sensitive representations during high-confident word recognition, even though no explicit instruction to retrieve the associated category was given. This constitutes novel evidence that high-confident recognition memory is accompanied by incidental reinstatement of associated category information in MTL subregions, and supports a functional model of the MTL that emphasizes content-sensitive representations during both encoding and retrieval.

Content Tuning in the Medial Temporal Lobe Cortex: Voxels that Perceive, Retrieve.

How do we recall vivid details from our past based only on sparse cues? Research suggests that the phenomenological reinstatement of past experiences is accompanied by neural reinstatement of the original percept. This process critically depends on the medial temporal lobe (MTL). Within the MTL, perirhinal cortex (PRC) and parahippocampal cortex (PHC) are thought to support encoding and recall of objects and scenes, respectively, with the hippocampus (HC) serving as a content-independent hub. If the fidelity of recall indeed arises from neural reinstatement of perceptual activity, then successful recall should preferentially draw upon those neural populations within content-sensitive MTL cortex that are tuned to the same content during perception. We tested this hypothesis by having eighteen human participants undergo functional MRI (fMRI) while they encoded and recalled objects and scenes paired with words. Critically, recall was cued with the words only. While HC distinguished successful from unsuccessful recall of both objects and scenes, PRC and PHC were preferentially engaged during successful versus unsuccessful object and scene recall, respectively. Importantly, within PRC and PHC, this content-sensitive recall was predicted by content tuning during perception: Across PRC voxels, we observed a positive relationship between object tuning during perception and successful object recall, while across PHC voxels, we observed a positive relationship between scene tuning during perception and successful scene recall. Our results thus highlight content-based roles of MTL cortical regions for episodic memory and reveal a direct mapping between content-specific tuning during perception and successful recall.

Enhanced Neural Reinstatement for Evoked Facial Pain Compared With Evoked Hand Pain.

Memory retrieval is accompanied by a reactivation of cortical and subcortical areas that have been active during encoding. This neural reinstatement is stronger during retrieval of pain-associated material compared with other unpleasant events. In this functional magnetic resonance imaging study, we investigated the differences in neural reinstatement during recognition of visual stimuli that had been paired with face or hand pain during memory encoding. Body site-specific neural reinstatement was tested in 23 healthy young volunteers who performed a visual categorization and a surprise recognition task. Our data shows increased neural reinstatement in task-specific and encoding-related areas, such as the parahippocampus (left: x = -26, y = -30, z = -18, t = 4.11; right: x = 26, y = -38, z = -6, t = 4.36), precuneus (x = 2, y = -56, z = 2, t = 3.77), fusiform gyrus (left: x = -24, y = -26, z = -20, t = 5.41; right: x = 18, y = -58, z = -14, t = 4.52), and amygdala (x = -34, y = -4, z = -20, t = 4.49) for pictures that were previously presented with face compared with hand pain. These results correlated with the individual's recognition confidence, although recognition rates did not differ between the conditions. Functional connectivity was increased between the amygdala and parahippocampus (x = 34, y = -10, z = -28, t = 5.13) for pictures that had previously been paired with face compared with hand pain. Our results were positively correlated with pain-related fear, represented by neural activation in the thalamus (x = -14, y = -35, z = 4, t = 3.54). The reported results can be interpreted as compensatory resource activation and support the notion of a stronger affective component of face compared with hand pain, potentially in line with its greater biological relevance. PERSPECTIVE: This study demonstrates neural reinstatement of face pain-related information, which might be related to the increased biological and affective component of face pain compared with pain on the extremities. Our results might contribute to the understanding of the development and prevalence of head and face pain conditions.

Sleep Deprivation Selectively Upregulates an Amygdala-Hypothalamic Circuit Involved in Food Reward.

Sleep loss is associated with increased obesity risk, as demonstrated by correlations between sleep duration and change in body mass index or body fat percentage. Whereas previous studies linked this weight gain to disturbed endocrine parameters after sleep deprivation or restriction, neuroimaging studies revealed upregulated neural processing of food rewards after sleep loss in reward-processing areas such as the anterior cingulate cortex, ventral striatum, and insula. To address this ongoing debate between hormonal versus hedonic factors underlying sleep-loss-associated weight gain, we rigorously tested the association between sleep deprivation and food cue processing using high-resolution fMRI and assessment of hormones. After taking blood samples from 32 lean, healthy, human male participants, they underwent fMRI while performing a neuroeconomic, value-based decision-making task with snack food and trinket rewards following a full night of habitual sleep and a night of sleep deprivation in a repeated-measures crossover design. We found that des-acyl ghrelin concentrations were increased after sleep deprivation compared with habitual sleep. Despite similar hunger ratings due to fasting in both conditions, participants were willing to spend more money on food items only after sleep deprivation. Furthermore, fMRI data paralleled this behavioral finding, revealing a food-reward-specific upregulation of hypothalamic valuation signals and amygdala-hypothalamic coupling after a single night of sleep deprivation. Behavioral and fMRI results were not significantly correlated with changes in acyl, des-acyl, or total ghrelin concentrations. Our results suggest that increased food valuation after sleep loss might be due to hedonic rather than hormonal mechanisms.SIGNIFICANCE STATEMENT Epidemiological studies suggest an association between overweight and reduced nocturnal sleep, but the relative contributions of hedonic and hormonal factors to overeating after sleep loss are a matter of ongoing controversy. Here, we tested the association between sleep deprivation and food cue processing in a repeated-measures crossover design using fMRI. We found that willingness to pay increased for food items only after sleep deprivation. fMRI data paralleled this behavioral finding, revealing a food-reward-specific upregulation of hypothalamic valuation signals and amygdala-hypothalamic coupling after a single night of sleep deprivation. However, there was no evidence for hormonal modulations of behavioral or fMRI findings. Our results suggest that increased food valuation after sleep loss is due to hedonic rather than hormonal mechanisms.

The Role of the Human Entorhinal Cortex in a Representational Account of Memory.

Connectivity studies in animals form the basis for a representational view of medial temporal lobe (MTL) subregions. In this view, distinct subfields of the entorhinal cortex (EC) relay object-related and spatial information from the perirhinal and parahippocampal cortices (PRC, PHC) to the hippocampus (HC). Relatively recent advances in functional magnetic resonance imaging (fMRI) methodology allow examining properties of human EC subregions directly. Antero-lateral and posterior-medial EC subfields show remarkable consistency to their putative rodent and nonhuman primate homologs with regard to intra- and extra-MTL functional connectivity. Accordingly, there is now evidence for a dissociation of object-related vs. spatial processing in human EC subfields. Here, variance in localization may be integrated in the antero-lateral vs. posterior-medial distinction, but may additionally reflect process differences. Functional results in rodents further suggest material-specific representations may be more integrated in EC compared to PRC/PHC. In humans, however, evidence for such a dissociation between EC and PRC/PHC is lacking. Future research may elucidate on the unique contributions of human EC to memory, especially in light of its high degree of intrinsic and extrinsic connectivity. A thorough characterization of EC subfield function may not only advance our understanding of human memory, but also have important clinical implications.

The effect of estrogen synthesis inhibition on hippocampal memory.

17-Beta-estradiol (E2) facilitates long term-potentiation (LTP) and increases spine synapse density in hippocampal neurons of ovariectomized rodents. Consistent with these beneficial effects on the cellular level, E2 improves hippocampus-dependent memory. A prominent approach to study E2 effects in rodents is the inhibition of its synthesis by letrozole, which reduces LTPs and spine synapse density. In the current longitudinal functional magnetic resonance imaging (fMRI) study, we translated this approach to humans and compared the impact of E2 synthesis inhibition on memory performance and hippocampal activity in post-menopausal women taking letrozole (n = 21) to controls (n = 24). In particular, we employed various behavioral memory paradigms that allow the disentanglement of hippocampus-dependent and -independent memory. Consistent with the literature on rodents, E2 synthesis inhibition specifically impaired hippocampus-dependent memory, however, this did not apply to the same degree to all of the employed paradigms. On the neuronal level, E2 depletion tended to decrease hippocampal activity during encoding, whereas it increased activity in the anterior cingulate and the dorsolateral prefrontal cortex. We thus infer that the inhibition of E2 synthesis specifically impairs hippocampal functioning in humans, whereas the increased prefrontal activity presumably reflects a compensatory mechanism, which is already known from studies on cognitive aging and Alzheimer's disease.

Menstrual-cycle dependent fluctuations in ovarian hormones affect emotional memory.

The hormones progesterone and estradiol modulate neural plasticity in the hippocampus, the amygdala and the prefrontal cortex. These structures are involved in the superior memory for emotionally arousing information (EEM effects). Therefore, fluctuations in hormonal levels across the menstrual cycle are expected to influence activity in these areas as well as behavioral memory performance for emotionally arousing events. To test this hypothesis, naturally cycling women underwent functional magnetic resonance imaging during the encoding of emotional and neutral stimuli in the low-hormone early follicular and the high-hormone luteal phase. Their memory was tested after an interval of 48 h, because emotional arousal primarily enhances the consolidation of new memories. Whereas overall recognition accuracy remained stable across cycle phases, recognition quality varied with menstrual cycle phases. Particularly recollection-based recognition memory for negative items tended to decrease from early follicular to luteal phase. EEM effects for both valences were associated with higher activity in the right anterior hippocampus during early follicular compared to luteal phase. Valence-specific modulations were found in the anterior cingulate, the amygdala and the posterior hippocampus. Current findings connect to anxiolytic actions of estradiol and progesterone as well as to studies on fear conditioning. Moreover, they are in line with differential networks involved in EEM effects for positive and negative items.

Direct evidence for domain-sensitive functional subregions in human entorhinal cortex.

The medial temporal lobes (MTL) are known to play a crucial role in memory processes. Anatomical findings from animal studies suggest partially segregated MTL pathways converge in the hippocampus, with a posterior stream including parahippocampal and medial lateral entorhinal cortex and an anterior stream including perirhinal and lateral entorhinal cortex. These streams may operate on spatial and nonspatial information, respectively. In humans, such a functional dissociation has been suggested between parahippocampal and perirhinal cortex. Data from rodents and nonhuman primates suggest a similar dissociation between medial and lateral entorhinal cortex, which are reciprocally connected to parahippocampal and perirhinal cortex, but evidence for functional subregions within entorhinal cortex in humans is lacking. We addressed this issue using high-resolution fMRI with improved spatial normalization. Volunteers (n = 28) performed a working memory paradigm involving the retrieval of spatial (scenes) and nonspatial (faces) information after distraction. A clear dissociation between MTL subcircuits emerged. A perirhinal-lateral entorhinal pathway was more involved in the retrieval of faces after distraction, whereas a parahippocampal-medial entorhinal pathway was more involved in the retrieval of scenes after distraction. A cluster in posterior hippocampus showed a deactivation for the retrieval of faces after distraction. Our data thus provide direct evidence for a functional specialization within human entorhinal cortex and thereby strongly support MTL models that emphasize the importance of partially segregated parallel processing streams.