When memories get complex, sleep comes to their rescue

Here I point to a PNAS article by Lutz et al. and a commentary on the work by Schechtman. Here is the Lutz. et al. abstract:

Significance

Real-life events usually consist of multiple elements such as a location, people, and objects that become associated during the event. Such associations can differ in their strength, and some elements may be associated only indirectly (e.g., via a third element). Here, we show that sleep compared with nocturnal wakefulness selectively strengthens associations between elements of events that were only weakly encoded and of such that were not encoded together, thus fostering new associations. Importantly, these sleep effects were associated with an improved recall of the complete event after presentation of only a single cue. These findings uncover a fundamental role of sleep in the completion of partial information and are critical for understanding how real-life events are processed during sleep.

Abstract

Sleep supports the consolidation of episodic memory. It is, however, a matter of ongoing debate how this effect is established, because, so far, it has been demonstrated almost exclusively for simple associations, which lack the complex associative structure of real-life events, typically comprising multiple elements with different association strengths. Because of this associative structure interlinking the individual elements, a partial cue (e.g., a single element) can recover an entire multielement event. This process, referred to as pattern completion, is a fundamental property of episodic memory. Yet, it is currently unknown how sleep affects the associative structure within multielement events and subsequent processes of pattern completion. Here, we investigated the effects of post-encoding sleep, compared with a period of nocturnal wakefulness (followed by a recovery night), on multielement associative structures in healthy humans using a verbal associative learning task including strongly, weakly, and not directly encoded associations. We demonstrate that sleep selectively benefits memory for weakly associated elements as well as for associations that were not directly encoded but not for strongly associated elements within a multielement event structure. Crucially, these effects were accompanied by a beneficial effect of sleep on the ability to recall multiple elements of an event based on a single common cue. In addition, retrieval performance was predicted by sleep spindle activity during post-encoding sleep. Together, these results indicate that sleep plays a fundamental role in shaping associative structures, thereby supporting pattern completion in complex multielement events.

Brains creating stories of selves: the neural basis of autobiographical reasoning

We all create our experienced selves from autobiographical reasoning based on remembered events in stories from our lives. In the journal Social Cognitive and Affective Neuroscience  D'Argembeau et al.  (open source) do an interesting fMRI study observing brain areas that are active during this process that are not recruited by more simple factual recall of the events.

...A few days before the scanning session, participants selected a set of memories that have been important in developing and sustaining their sense of self and identity (self-defining memories). During scanning, we instructed participants to approach each of their memories in two different ways: in some trials, they had to remember the concrete content of the event in order to mentally re-experience the situation in its original context (autobiographical remembering), whereas in other trials they were asked to reflect on the broader meaning and implications of their memory (autobiographical reasoning). Contrasting the neural activity associated with these two ways of approaching the same self-defining memories allowed us to identify the brain regions specifically involved in the autobiographical reasoning process.

The text of the article notes the functions of the brain areas mentioned in the article abstract (below) and has a nice graphic depiction of areas that were more active during autobiographical remembering compared with autobiographical reasoning versus areas that were more active during autobiographical reasoning compared with autobiographical remembering.  Here is the abstract:

Personal identity critically depends on the creation of stories about the self and one’s life. The present study investigates the neural substrates of autobiographical reasoning, a process central to the construction of such narratives. During functional magnetic resonance imaging scanning, participants approached a set of personally significant memories in two different ways: in some trials, they remembered the concrete content of the events (autobiographical remembering), whereas in other trials they reflected on the broader meaning and implications of their memories (autobiographical reasoning). Relative to remembering, autobiographical reasoning recruited a left-lateralized network involved in conceptual processing [including the dorsal medial prefrontal cortex (MPFC), inferior frontal gyrus, middle temporal gyrus and angular gyrus]. The ventral MPFC—an area that may function to generate personal/affective meaning—was not consistently engaged during autobiographical reasoning across participants but, interestingly, the activity of this region was modulated by individual differences in interest and willingness to engage in self-reflection. These findings support the notion that autobiographical reasoning and the construction of personal narratives go beyond mere remembering in that they require deriving meaning and value from past experiences.

Traumatic Memories Are Processed as Present Experience

Ellen Barry points to work by Perl et al. showing that different patterns of brain activity underlie sad versus traumatic autobiographical memories.  The Perl et al. abstract:

For people with post-traumatic stress disorder (PTSD), recall of traumatic memories often displays as intrusions that differ profoundly from processing of ‘regular’ negative memories. These mnemonic features fueled theories speculating a unique cognitive state linked with traumatic memories. Yet, to date, little empirical evidence supports this view. Here we examined neural activity of patients with PTSD who were listening to narratives depicting their own memories. An intersubject representational similarity analysis of cross-subject semantic content and neural patterns revealed a differentiation in hippocampal representation by narrative type: semantically similar, sad autobiographical memories elicited similar neural representations across participants. By contrast, within the same individuals, semantically similar trauma memories were not represented similarly. Furthermore, we were able to decode memory type from hippocampal multivoxel patterns. Finally, individual symptom severity modulated semantic representation of the traumatic narratives in the posterior cingulate cortex. Taken together, these findings suggest that traumatic memories are an alternative cognitive entity that deviates from memory per se.

The neurophysiology of consciousness - neural correlates of qualia

This is a post for consciousness mavens.Tucker, Luu, and Johnson have offered a neurophyiological model of consciousness, Neurophysiological mechanisms of implicit and explicit memory in the process of consciousness. The open source article has useful summary graphics, and embraces the 'Hard Problem' of consciousness - the nature of 'qualia' (how it feels to see red, eat an apple, etc.) Here I pass on brief, and then more lengthy, paragraphs on what the authors think is new and noteworthy about their ideas.

The process of consciousness, generating the qualia that may appear to be irreducible qualities of experience, can be understood to arise from neurophysiological mechanisms of memory. Implicit memory, organized by the lemnothalamic brain stem projections and dorsal limbic consolidation in REM sleep, supports the unconscious field and the quasi-conscious fringe of current awareness. Explicit memory, organized by the collothalamic midbrain projections and ventral limbic consolidation of NREM sleep, supports the focal objects of consciousness.

Neurophysiological mechanisms are increasingly understood to constitute the foundations of human conscious experience. These include the capacity for ongoing memory, achieved through a hierarchy of reentrant cross-laminar connections across limbic, heteromodal, unimodal, and primary cortices. The neurophysiological mechanisms of consciousness also include the capacity for volitional direction of attention to the ongoing cognitive process, through a reentrant fronto-thalamo-cortical network regulation of the inhibitory thalamic reticular nucleus. More elusive is the way that discrete objects of subjective experience, such as the color of deep blue or the sound of middle C, could be generated by neural mechanisms. Explaining such ineffable qualities of subjective experience is what Chalmers has called “the hard problem of consciousness,” which has divided modern neuroscientists and philosophers alike. We propose that insight into the appearance of the hard problem can be gained through integrating classical phenomenological studies of experience with recent progress in the differential neurophysiology of consolidating explicit versus implicit memory. Although the achievement of consciousness, once it is reflected upon, becomes explicit, the underlying process of generating consciousness, through neurophysiological mechanisms, is largely implicit. Studying the neurophysiological mechanisms of adaptive implicit memory, including brain stem, limbic, and thalamic regulation of neocortical representations, may lead to a more extended phenomenological understanding of both the neurophysiological process and the subjective experience of consciousness.

Widespread ripples synchronize human cortical activity during sleep, waking, and memory recall

I pass on the summaries of work by Dickey et al.:  

Significance

Different elements of a memory, or any mental event, are encoded in locations distributed across the cortex. A prominent hypothesis proposes that widespread networks are integrated with bursts of synchronized high-frequency oscillations called “ripples,” but evidence is limited. Here, using recordings inside the human brain, we show that ripples occur simultaneously in multiple lobes in both cortical hemispheres and the hippocampus, generally during sleep and waking, and especially during memory recall. Ripples phase-lock local cell firing and phase-synchronize with little decay between locations separated by up to 25 cm, enabling long-distance integration. Indeed, corippling sites have increased correlation of very-high-frequency activity which reflects cell firing. Thus, ripples may help bind information across the cortex in memory and other mental events.

Abstract

Declarative memory encoding, consolidation, and retrieval require the integration of elements encoded in widespread cortical locations. The mechanism whereby such “binding” of different components of mental events into unified representations occurs is unknown. The “binding-by-synchrony” theory proposes that distributed encoding areas are bound by synchronous oscillations enabling enhanced communication. However, evidence for such oscillations is sparse. Brief high-frequency oscillations (“ripples”) occur in the hippocampus and cortex and help organize memory recall and consolidation. Here, using intracranial recordings in humans, we report that these ∼70-ms-duration, 90-Hz ripples often couple (within ±500 ms), co-occur (≥ 25-ms overlap), and, crucially, phase-lock (have consistent phase lags) between widely distributed focal cortical locations during both sleep and waking, even between hemispheres. Cortical ripple co-occurrence is facilitated through activation across multiple sites, and phase locking increases with more cortical sites corippling. Ripples in all cortical areas co-occur with hippocampal ripples but do not phase-lock with them, further suggesting that cortico-cortical synchrony is mediated by cortico-cortical connections. Ripple phase lags vary across sleep nights, consistent with participation in different networks. During waking, we show that hippocampo-cortical and cortico-cortical coripples increase preceding successful delayed memory recall, when binding between the cue and response is essential. Ripples increase and phase-modulate unit firing, and coripples increase high-frequency correlations between areas, suggesting synchronized unit spiking facilitating information exchange. co-occurrence, phase synchrony, and high-frequency correlation are maintained with little decrement over very long distances (25 cm). Hippocampo-cortico-cortical coripples appear to possess the essential properties necessary to support binding by synchrony during memory retrieval and perhaps generally in cognition.

How the organization of generalized knowledge promotes memory.

From Wing et al.: Significance

What we remember is shaped by what we already know. For example, remembering the angelfish from a recent aquarium visit is easier for those who already know what angelfish are and know things about them. In addition to facilitating memory retrieval of specific items, prior knowledge also supports memory by providing an overarching organizational structure for new information. Here, we show how expert knowledge leads birdwatchers to organize birds based on conceptual features, in contrast to novices who organize birds based on perceptual features. In turn, experts’ organizational structure supports memory by reducing interference typically caused by high overlap among items, even when to-be-remembered birds were unfamiliar species. These findings demonstrate how the organization of generalized knowledge promotes memory.

Abstract

The influence of prior knowledge on memory is ubiquitous, making the specific mechanisms of this relationship difficult to disentangle. Here, we show that expert knowledge produces a fundamental shift in the way that interitem similarity (i.e., the perceived resemblance between items in a set) biases episodic recognition. Within a group of expert birdwatchers and matched controls, we characterized the psychological similarity space for a set of well-known local species and a set of less familiar, nonlocal species. In experts, interitem similarity was influenced most strongly by taxonomic features, whereas in controls, similarity judgments reflected bird color. In controls, perceived episodic oldness during a recognition memory task increased along with measures of global similarity between items, consistent with classic models of episodic recognition. Surprisingly, for experts, high global similarity did not drive oldness signals. Instead, for local birds memory tracked the availability of species-level name knowledge, whereas for nonlocal birds, it was mediated by the organization of generalized conceptual space. These findings demonstrate that episodic memory in experts can benefit from detailed subcategory knowledge, or, lacking that, from the overall relational structure of concepts. Expertise reshapes psychological similarity space, helping to resolve mnemonic separation challenges arising from high interitem overlap. Thus, even in the absence of knowledge about item-specific details or labels, the presence of generalized knowledge appears to support episodic recognition in domains of expertise by altering the typical relationship between psychological similarity and memory.

Older adults store too much information.

From Amer et al.:  

Highlights

Healthy aging is accompanied by declines in control of attention.

These reductions in the control of attention, result in older adults processing too much information, creating cluttered memory representations.

Cluttered representations can impair memory by interfering with the retrieval of target information, but can also provide an advantage on tasks that benefit from extensive knowledge.

Abstract

Declines in episodic memory in older adults are typically attributed to differences in encoding strategies and/or retrieval processes. These views omit a critical factor in age-related memory differences: the nature of the representations that are formed. Here, we review evidence that older adults create more cluttered (or richer) representations of events than do younger adults. These cluttered representations might include target information along with recently activated but no-longer-relevant information, prior knowledge cued by the ongoing situation, as well as irrelevant information in the current environment. Although these representations can interfere with the retrieval of target information, they can also support other memory-dependent cognitive functions.

Temporal Self-Compression

Brietzke and Meyer (open source) provide behavioral and neural evidence that our past and future selves are compressed as they move away from the present:  

Significance

For centuries, great thinkers have struggled to understand how people represent a personal identity that changes over time. Insight may come from a basic principle of perception: as objects become distant, they also become less discriminable or “compressed.” In Studies 1–3, we demonstrate that people’s ratings of their own personality become increasingly less differentiated as they consider more distant past and future selves. In Study 4, we found neural evidence that the brain compresses self-representations with time as well. When we peer out a window, objects close to us are in clear view, whereas distant objects are hard to tell apart. We provide evidence that self-perception may operate similarly, with the nuance of distant selves increasingly harder to perceive.

Abstract

A basic principle of perception is that as objects increase in distance from an observer, they also become logarithmically compressed in perception (i.e., not differentiated from one another), making them hard to distinguish. Could this basic principle apply to perhaps our most meaningful mental representation: our own sense of self? Here, we report four studies that suggest selves are increasingly non-discriminable with temporal distance from the present as well. In Studies 1 through 3, participants made trait ratings across various time points in the past and future. We found that participants compressed their past and future selves, relative to their present self. This effect was preferential to the self and could not be explained by the alternative possibility that individuals simply perceive arbitrary self-change with time irrespective of temporal distance. In Study 4, we tested for neural evidence of temporal self-compression by having participants complete trait ratings across time points while undergoing functional MRI. Representational similarity analysis was used to determine whether neural self-representations are compressed with temporal distance as well. We found evidence of temporal self-compression in areas of the default network, including medial prefrontal cortex and posterior cingulate cortex. Specifically, neural pattern similarity between self-representations was logarithmically compressed with temporal distance. Taken together, these findings reveal a “temporal self-compression” effect, with temporal selves becoming increasingly non-discriminable with distance from the present.

Two promising post-traumatic stress disorder treatments

I want to pass on references to two new approaches to relieving the symptoms of post-traumatic stress disorder (PTSD). Nuwer describes a new study showing that MDMA (known as the party drug Ecstasy, or Molly) can bring relief to PTSD when used in conjunction with talk therapy. Ressler et al. address the problem that human patients cannot be directly re-exposed to trauma-cues of the sort that have been used in animal studies to induce and then disrupt reconsolidation of traumatic memories. They devise a procedure for covertly capturing and attenuating a hippocampu-dependent fear memory in male rats, a procedure that might prove to be useful in human therapy. Here is their abstract:

Reconsolidation may be a viable therapeutic target to inhibit pathological fear memories. In the clinic, incidental or imaginal reminders are used for safe retrieval of traumatic memories of experiences that occurred elsewhere. However, it is unknown whether indirectly retrieved traumatic memories are sensitive to disruption. Here we used a backward (BW) conditioning procedure to indirectly retrieve and manipulate a hippocampus (HPC)-dependent contextual fear engram in male rats. We show that conditioned freezing to a BW conditioned stimulus (CS) is mediated by fear to the conditioning context, activates HPC ensembles that can be covertly captured and chemogenetically activated to drive fear, and is impaired by post-retrieval protein synthesis inhibition. These results reveal that indirectly retrieved contextual fear memories reactivate HPC ensembles and undergo protein synthesis-dependent reconsolidation. Clinical interventions that rely on indirect retrieval of traumatic memories, such as imaginal exposure, may open a window for editing or erasure of neural representations that drive pathological fear.

Gamma-frequency oscillations link different brain regions during learning.

Fernández-Ruiz et al. demonstrate that specific, projected gamma-frequency oscillation patterns dynamically engage functionally related cell assemblies across brain regions in a task-specific manner. I pass along their entire structured abstract:  

INTRODUCTION

Learning induces a dynamic reorganization of brain circuits but the neuronal mechanisms underlying this process are not well understood. Interregional gamma-frequency oscillations (~30 to 150 Hz) have been postulated as a mechanism to precisely coordinate upstream and downstream neuronal ensembles, for example, in the hippocampal system. The lateral (LEC) and medial (MEC) entorhinal cortex receive inputs from two distinct streams of cortical hierarchy (the “what” and the “where” pathways) and convey these neuronal messages to the hippocampus. However, the mechanisms by which such messages are packaged and integrated or segregated by hippocampal circuits had yet to be explored.

RATIONALE

Neuronal assemblies firing within gamma time frames in an upstream region can most effectively discharge their downstream partners. This gamma-time-scale organization appears essential for physiological functions because manipulations that impair precision timing of spikes in the hippocampus often affect behavior. However, direct support for distinct gamma-frequency communication in appropriate behavioral situations is missing. To bring physiological operations closer to behavior, we designed “spatial” and “object” learning tasks and examined the selective engagement of gamma-frequency communication between the MEC and LEC inputs and their target neuronal assemblies in the hippocampal dentate gyrus. We combined these correlational observations with optogenetic perturbation of gamma oscillations in LEC and MEC, respectively, to test their roles in pathway-specific neuronal communication and learning.

RESULTS

During spatial learning, fast gamma (100 to 150 Hz) oscillations synchronized MEC and dentate gyrus and entrained predominantly granule cells. During object learning, slow gamma (30 to 50 Hz) oscillations synchronized LEC and dentate gyrus and preferentially recruited mossy cells and CA3 pyramidal neurons, suggesting task-specific routing of MEC and LEC messages in the form of gamma-cycle-spike packets of selected cell types. The low- and high-frequency gamma sub-bands were dominant in the outer and middle third of the dentate molecular layer, respectively, and their amplitude maxima were locked to different phases of theta oscillations.

Gamma frequency optogenenetic perturbation of MEC and LEC led to learning impairments in a spatial and object learning task, respectively. In the same animals, the dentate layer–specific low- and high-frequency gamma sub-bands and spike-gamma LFP coupling were selectively reduced, coupled with deterioration of spatial and object-related firing of dentate neurons.

CONCLUSION

These findings demonstrate that distinct gamma-frequency-specific communication between MEC and LEC and hippocampal cell assemblies are critical for routing task-relevant information, and our selective gamma-band perturbation experiments suggest that they support specific aspects of learning. We hypothesize that sending neuronal messages by segregated gamma-frequency carriers allows a target “reader” area to disambiguate convergent inputs. In general, these results demonstrate that specific projected gamma patterns dynamically engage functionally related cell assemblies across brain regions in a task-specific manner.

False memories can be reversed without damage to true memories.

 Oeberst et al.  demonstrate the effectiveness of source sensitization, which involves alerting participants that their memories could come from external sources, and false memory sensitization, which involves informing individuals that repeatedly being asked to recollect events can produce false memories. The two strategies could be widely implemented in real-world settings and do not require interviewers to know any ground truths.:  

Significance

Human memory is fallible and malleable. In forensic settings in particular, this poses a challenge because people may falsely remember events with legal implications that never actually happened. Despite an urgent need for remedies, however, research on whether and how rich false autobiographical memories can be reversed under realistic conditions (i.e., using reversal strategies that can be applied in real-world settings) is virtually nonexistent. The present study therefore not only replicates and extends previous demonstrations of false memories but, crucially, documents their reversibility after the fact: Employing two ecologically valid strategies, we show that rich but false autobiographical memories can mostly be undone. Importantly, reversal was specific to false memories (i.e., did not occur for true memories).

Abstract

False memories of autobiographical events can create enormous problems in forensic settings (e.g., false accusations). While multiple studies succeeded in inducing false memories in interview settings, we present research trying to reverse this effect (and thereby reduce the potential damage) by means of two ecologically valid strategies. We first successfully implanted false memories for two plausible autobiographical events (suggested by the students’ parents, alongside two true events). Over three repeated interviews, participants developed false memories (measured by state-of-the-art coding) of the suggested events under minimally suggestive conditions (27%) and even more so using massive suggestion (56%). We then used two techniques to reduce false memory endorsement, source sensitization (alerting interviewees to possible external sources of the memories, e.g., family narratives) and false memory sensitization (raising the possibility of false memories being inadvertently created in memory interviews, delivered by a new interviewer). This reversed the false memory build-up over the first three interviews, returning false memory rates in both suggestion conditions to the baseline levels of the first interview (i.e., to ∼15% and ∼25%, respectively). By comparison, true event memories were endorsed at a higher level overall and less affected by either the repeated interviews or the sensitization techniques. In a 1-y follow-up (after the original interviews and debriefing), false memory rates further dropped to 5%, and participants overwhelmingly rejected the false events. One strong practical implication is that false memories can be substantially reduced by easy-to-implement techniques without causing collateral damage to true memories.

Cannabis increases susceptibility to false memory.

From Kloft et al.:  

Significance

This unique randomized, double-blind, placebo-controlled trial examined the susceptibility to false memories under the influence of cannabis, using a basic (DRM) and two applied (misinformation) paradigms. We used a highly powered experimental design, allowing us to test acute and residual drug effects. To achieve high reproducibility and ecological validity, the misinformation paradigms included an eyewitness and a perpetrator scenario, presented in a virtual-reality environment. We show across different paradigms that cannabis consistently increases susceptibility to false memories. The results have implications for police, legal professionals, and policymakers with regard to the treatment of cannabis-intoxicated witnesses and suspects and the validity of their statements.

Abstract

With the growing global acceptance of cannabis and its widespread use by eyewitnesses and suspects in legal cases, understanding the popular drug’s ramifications for memory is a pressing need. In a double-blind, randomized, placebo-controlled trial, we examined the acute and delayed effects of Δ9-tetrahydrocannabinol (THC) intoxication on susceptibility to false memory in 64 healthy volunteers. Memory was tested immediately (encoding and retrieval under drug influence) and 1 wk later (retrieval sober). We used three different methods (associative word lists and two misinformation tasks using virtual reality). Across all methods, we found evidence for enhanced false-memory effects in intoxicated participants. Specifically, intoxicated participants showed higher false recognition in the associative word-list task both at immediate and delayed test than controls. This yes bias became increasingly strong with decreasing levels of association between studied and test items. In a misinformation task, intoxicated participants were more susceptible to false-memory creation using a virtual-reality eyewitness scenario and virtual-reality perpetrator scenario. False-memory effects were mostly restricted to the acute-intoxication phase. Cannabis seems to increase false-memory proneness, with decreasing strength of association between an event and a test item, as assessed by different false-memory paradigms. Our findings have implications for how and when the police should interview suspects and eyewitnesses.

The role of memory suppression in resilience after trauma.

Mary et al. report the neural differences that control the retrieval of traumatic memories in 102 individuals who were affected by the Paris terror attacks but who dealt with these memories in different ways: 55 developed posttraumatic stress disorder (PTSD), and 47 did not. The used functional magnetic resonance imaging to measure how the dorsolateral prefrontal cortex (DLPFC), a core hub of the brain control system, regulated and suppressed memory activity during the reexperiencing of these intrusive memories. Their abstract:

In the aftermath of trauma, little is known about why the unwanted and unbidden recollection of traumatic memories persists in some individuals but not others. We implemented neutral and inoffensive intrusive memories in the laboratory in a group of 102 individuals exposed to the 2015 Paris terrorist attacks and 73 nonexposed individuals, who were not in Paris during the attacks. While reexperiencing these intrusive memories, nonexposed individuals and exposed individuals without posttraumatic stress disorder (PTSD) could adaptively suppress memory activity, but exposed individuals with PTSD could not. These findings suggest that the capacity to suppress memory is central to positive posttraumatic adaptation. A generalized disruption of the memory control system could explain the maladaptive and unsuccessful suppression attempts often seen in PTSD, and this disruption should be targeted by specific treatments.

Mechanism of exercise and antioxidant stimulation of memory and new nerve cell growth

On reading this article by Yook et al. I promptly ordered a bottle of 10 mg astaxanthin capsules to add to my normal array of supplements (and exercise).

Significance

Leptin (LEP, a small protein hormone), produced and acting in the hippocampus, mediates enhancement by mild exercise (ME) of hippocampus-related memory and neurogenesis, which are further increased by an antioxidant carotenoid, astaxanthin (AX). Both are facilitated by the administration of ME or AX alone. The up-regulation of the LEP gene and LEP protein expression in the hippocampus by ME is further elevated when combined with AX. Consistently, the combined interventions increased hippocampal LEP protein. In LEP-deficient ob/ob mice, LEP replacement in the brain restored the ability of ME+AX to enhance hippocampal function. Thus, a combined lifestyle intervention based on ME, including yoga and tai chi, and specific dietary supplements that include antioxidants may together improve cognition and possibly retard cognitive decline in humans.

Abstract

Regular exercise and dietary supplements with antioxidants each have the potential to improve cognitive function and attenuate cognitive decline, and, in some cases, they enhance each other. Our current results reveal that low-intensity exercise (mild exercise, ME) and the natural antioxidant carotenoid astaxanthin (AX) each have equivalent beneficial effects on hippocampal neurogenesis and memory function. We found that the enhancement by ME combined with AX in potentiating hippocampus-based plasticity and cognition is mediated by leptin (LEP) made and acting in the hippocampus. In assessing the combined effects upon wild-type (WT) mice undergoing ME with or without an AX diet for four weeks, we found that, when administrated alone, ME and AX separately enhanced neurogenesis and spatial memory, and when combined they were at least additive in their effects. DNA microarray and bioinformatics analyses revealed not only the up-regulation of an antioxidant gene, ABHD3, but also that the up-regulation of LEP gene expression in the hippocampus of WT mice with ME alone is further enhanced by AX. Together, they also increased hippocampal LEP (h-LEP) protein levels and enhanced spatial memory mediated through AKT/STAT3 signaling. AX treatment also has direct action on human neuroblastoma cell lines to increase cell viability associated with increased LEP expression. In LEP-deficient mice (ob/ob), chronic infusion of LEP into the lateral ventricles restored the synergy. Collectively, our findings suggest that not only h-LEP but also exogenous LEP mediates effects of ME on neural functions underlying memory, which is further enhanced by the antioxidant AX.

Synchronizing rhythmic brain circuits improves working memory in older adults.

Our short term memory depends on theta rhythms (~6-10 Hz) and gamma rhythms (~25-100 Hz) in different parts of our brain being coupled and in synchrony with each other. They become increasingly uncoordinated as we age, resulting in observable cognitive decline by the time we reach 60 or 70 years of age. Reinhart and Nguyen compare the working memory of subjects in their 20s with 60-70 year olds, and find that 25 min of noninvasive stimulation, frequency-tuned to individual brain network dynamics, dramatically improves the working memory of the older group, making it similar to the younger group.

Understanding normal brain aging and developing methods to maintain or improve cognition in older adults are major goals of fundamental and translational neuroscience. Here we show a core feature of cognitive decline—working-memory deficits—emerges from disconnected local and long-range circuits instantiated by theta–gamma phase–amplitude coupling in temporal cortex and theta phase synchronization across frontotemporal cortex. We developed a noninvasive stimulation procedure for modulating long-range theta interactions in adults aged 60–76 years. After 25 min of stimulation, frequency-tuned to individual brain network dynamics, we observed a preferential increase in neural synchronization patterns and the return of sender–receiver relationships of information flow within and between frontotemporal regions. The end result was rapid improvement in working-memory performance that outlasted a 50 min post-stimulation period. The results provide insight into the physiological foundations of age-related cognitive impairment and contribute to groundwork for future non-pharmacological interventions targeting aspects of cognitive decline.

The Neuroscience of ‘Rock-a-Bye Baby’

I've always wondered why I sleep like a baby when on a boat being slowly rocked by waves, so was intrigued by Friedman's recent piece pointing to work by Perrault et al. showing that a slow rocking motion not only improves sleep but also can help people consolidate memories overnight. This is because continuous rocking stimulation strengthens deep sleep via the neural entrainment of intrinsic sleep oscillations. The Perrault et al. summary:

Highlights

•Rocking boosts deep sleep, sleep maintenance, and memory in healthy sleepers

•Fast spindles increase during rocking and synchronize with the slow oscillation up-state

• Rocking-induced overnight memory improvement relates to increased sigma activity

• Continuous rocking stimulation actively entrains intrinsic sleep oscillations

Summary

Sensory processing continues during sleep and can influence brain oscillations. We previously showed that a gentle rocking stimulation (0.25 Hz), during an afternoon nap, facilitates wake-sleep transition and boosts endogenous brain oscillations (i.e., EEG spindles and slow oscillations [SOs]). Here, we tested the hypothesis that the rhythmic rocking stimulation synchronizes sleep oscillations, a neurophysiological mechanism referred to as “neural entrainment.” We analyzed EEG brain responses related to the stimulation recorded from 18 participants while they had a full night of sleep on a rocking bed. Moreover, because sleep oscillations are considered of critical relevance for memory processes, we also investigated whether rocking influences overnight declarative memory consolidation. We first show that, compared to a stationary night, continuous rocking shortened the latency to non-REM (NREM) sleep and strengthened sleep maintenance, as indexed by increased NREM stage 3 (N3) duration and fewer arousals. These beneficial effects were paralleled by an increase in SOs and in slow and fast spindles during N3, without affecting the physiological SO-spindle phase coupling. We then confirm that, during the rocking night, overnight memory consolidation was enhanced and also correlated with the increase in fast spindles, whose co-occurrence with the SO up-state is considered to foster cortical synaptic plasticity. Finally, supporting the hypothesis that a rhythmic stimulation entrains sleep oscillations, we report a temporal clustering of spindles and SOs relative to the rocking cycle. Altogether, these findings demonstrate that a continuous rocking stimulation strengthens deep sleep via the neural entrainment of intrinsic sleep oscillations.

Enhanced brain activity associated with highly superior memory.

Santangelo et al. show that people with superior memory have enhanced connectivity of their prefrontal cortex with their hippocampus and temporoparietal junction:

Significance

Recent research has identified human subjects who have highly superior autobiographical memory (HSAM). Here, we investigated, using fMRI, the neural activation induced by retrieval of autobiographical memories (AMs) and semantic memories (SMs) in subjects with HSAM and control subjects. While their brains were being scanned, subjects had to retrieve AMs as well as SMs (e.g., examples of animals). The subjects with HSAM displayed a superior ability to retrieve details of AMs, supported by enhanced activation of several brain regions, including the medial prefrontal cortex and temporoparietal junction, as well as increased connectivity of the prefrontal cortex with the hippocampus, a region well known to be involved in memory representation. These findings suggest that activation of these systems may play a critical role in enabling HSAM.

Abstract

Brain systems underlying human memory function have been classically investigated studying patients with selective memory impairments. The discovery of rare individuals who have highly superior autobiographical memory (HSAM) provides, instead, an opportunity to investigate the brain systems underlying enhanced memory. Here, we carried out an fMRI investigation of a group of subjects identified as having HSAM. During fMRI scanning, eight subjects with HSAM and 21 control subjects were asked to retrieve autobiographical memories (AMs) as well as non-AMs (e.g., examples of animals). Subjects were instructed to signal the “access” to an AM by a key press and to continue “reliving” it immediately after. Compared with controls, individuals with HSAM provided a richer AM recollection and were faster in accessing AMs. The access to AMs was associated with enhanced prefrontal/hippocampal functional connectivity. AM access also induced increased activity in the left temporoparietal junction and enhanced functional coupling with sensory cortices in subjects with HSAM compared with controls. In contrast, subjects with HSAM did not differ from controls in functional activity during the reliving phase. These findings, based on fMRI assessment, provide evidence of interaction of brain systems engaged in memory retrieval and suggest that enhanced activity of these systems is selectively involved in enabling more efficient access to past experiences in HSAM.

An optimistic outlook creates a rosy past.

From Devitt and Schacter in the Harvard Psychology department, a study recruiting the usual gaggle of psychology undergraduate students as subjects:

People frequently engage in future thinking in everyday life, but it is unknown how simulating an event in advance changes how that event is remembered once it takes place. To initiate study of this important topic, we conducted two experiments in which participants simulated emotional events before learning the hypothetical outcome of each event via narratives. Memory was assessed for emotional details contained in those narratives. Positive simulation resulted in a liberal response bias for positive information and a conservative bias for negative information. Events preceded by positive simulation were considered more favorably in retrospect. In contrast, negative simulation had no impact on subsequent memory. Results were similar across an immediate and delayed memory test and for past and future simulation. These results provide novel insights into the cognitive consequences of episodic future simulation and build on the optimism-bias literature by showing that adopting a favorable outlook results in a rosy memory.

Sitting is bad for your brain...

It is well known that sitting for long periods each day correlates with higher risk of heart disease, diabetes, and mortality rate. Siddarth et al. at UCLA now show a correlation of sedentary behavior with reduced thickness of the medial temporal lobe of our brains, which contains the hippocampus and is central to learning and memory. Their abstract:

Atrophy of the medial temporal lobe (MTL) occurs with aging, resulting in impaired episodic memory. Aerobic fitness is positively correlated with total hippocampal volume, a heavily studied memory-critical region within the MTL. However, research on associations between sedentary behavior and MTL subregion integrity is limited. Here we explore associations between thickness of the MTL and its subregions (namely CA1, CA23DG, fusiform gyrus, subiculum, parahippocampal, perirhinal and entorhinal cortex,), physical activity, and sedentary behavior. We assessed 35 non-demented middle-aged and older adults (25 women, 10 men; 45–75 years) using the International Physical Activity Questionnaire for older adults, which quantifies physical activity levels in MET-equivalent units and asks about the average number of hours spent sitting per day. All participants had high resolution MRI scans performed on a Siemens Allegra 3T MRI scanner, which allows for detailed investigation of the MTL. Controlling for age, total MTL thickness correlated inversely with hours of sitting/day (r = -0.37, p = 0.03). In MTL subregion analysis, parahippocampal (r = -0.45, p = 0.007), entorhinal (r = -0.33, p = 0.05) cortical and subiculum (r = -0.36, p = .04) thicknesses correlated inversely with hours of sitting/day. No significant correlations were observed between physical activity levels and MTL thickness. Though preliminary, our results suggest that more sedentary non-demented individuals have less MTL thickness. Future studies should include longitudinal analyses and explore mechanisms, as well as the efficacy of decreasing sedentary behaviors to reverse this association.

Locus Coeruleus integrity and memory in aging adults

The locus coeruleus is a deep brain nucleus whose cells synthesize noradrenaline that is sent via its axonal projections to other parts of the brain. Hämmerer et al. show that its integrity is critical in maintaining memory performance:

Significance

Locus coeruleus (LC) integrity in cognitively normal older adults is a potentially important preclinical marker in dementia. Our study establishes a link between variability in LC integrity and cognitive decline related to noradrenergic modulation in old age. We find that in older adults, reduced LC integrity explains lower memory performance. This effect was more pronounced for memory related to negative events, and accompanied by increased pupil diameter size in response to negative events. The study provides a strong motivation for future research investigating the role of LC integrity in healthy, as well as in pathological, aging.

Abstract

The locus coeruleus (LC) is the principal origin of noradrenaline in the brain. LC integrity varies considerably across healthy older individuals, and is suggested to contribute to altered cognitive functions in aging. Here we test this hypothesis using an incidental memory task that is known to be susceptible to noradrenergic modulation. We used MRI neuromelanin (NM) imaging to assess LC structural integrity and pupillometry as a putative index of LC activation in both younger and older adults. We show that older adults with reduced structural LC integrity show poorer subsequent memory. This effect is more pronounced for emotionally negative events, in accord with a greater role for noradrenergic modulation in encoding salient or aversive events. In addition, we found that salient stimuli led to greater pupil diameters, consistent with increased LC activation during the encoding of such events. Our study presents novel evidence that a decrement in noradrenergic modulation impacts on specific components of cognition in healthy older adults. The findings provide a strong motivation for further investigation of the effects of altered LC integrity in pathological aging.