Excerpt From: William James (1887) What is an Instinct? Content Summary: 240 words, 1 min read
Richard Dawkins writes:
There is an anesthetic of familiarity, a sedative of ordinariness which dulls the senses and hides the wonder of existence. For those of us not gifted in poetry, it is at least worth while from time to time making an effort to shake off the anesthetic. What is the best way of countering the sluggish habituation brought about by our gradual crawl from babyhood? We can’t actually fly to another planet. But we can recapture that sense of having just tumbled out to life on a new world by looking at our own world in unfamiliar ways.
To illustrate, the excerpt from William James:
It takes a mind debauched by learning to carry the process of making the natural seem strange, so far as to ask for the why of any instinctive human act.
To the learned man alone can such questions occur as: Why do we smile, when pleased, and not scowl? Why are we unable to talk to a crowd as we talk to a single friend? Why does a particular maiden turn our wits so upside-down?
The common man can only say, of course we smile, of course our heart palpitates at the sight of the crowd, of course we love the maiden, that beautiful soul clad in that perfect form, so palpably and flagrantly made for all eternity to be loved!
And so, probably, does each animal feel about the particular things it tends to do in the presence of particular objects. … To the lion it is the lioness which is made to be loved; to the bear, the she-bear. To the broody hen the notion would probably seem monstrous that there should be a creature in the world to whom a nestful of eggs was not the utterly fascinating and precious and never-to-be-too-much-sat-upon object which it is to her.
Thus we may be sure that, however mysterious some animals’ instincts may appear to us, our instincts will appear no less mysterious to them.
Part Of: Politics sequence Excerpt From: de Waal (1982). Chimpanzee Politics Content Summary: 1400 words, 7 min read
On a hot day two mothers, Jimmie and Tepel, are sitting in the shadow of an oak tree while their two children play in the sand at their feet (playfaces, wrestling, throwing sand). Between the two mothers the oldest female, Mama, lies asleep. Suddenly the children start screaming, hitting, and pulling each other’s hair. Jimmie admonishes them with a soft, threatening grunt, and Tepel anxiously shifts her position. The children go on quarreling, and eventually Tepel wakes Mama by poking her in the ribs several times. As Mama gets up Tepel points to the two quarreling children. As soon as Mama takes one threatening step forward, waves her arm in the air, and barks loudly the children stop quarreling. Mama then lies down again and continues her siesta.
INTERPRETATION. In order to understand this interpretation fully, it is important to know two things: first, that Mama is the highest-ranking female and is greatly respected; and second, that conflicts between children regularly engender such tension between their mothers that they too come to blows. This tension is probably caused by the fact that each mother wishes to help her own child and to prevent the other from interfering in the quarrel. In the case of the example above, when the children’s game turned to fighting, both mothers found themselves in a painful situation. Tepel solved the problem by activating a dominant third party, Mama, and pointing out the problem. Mama obviously realized at a glance that she was expected to act as arbitrator.
Yeroen hurts his hand during a fight with Nikkie. Although it is not a deep wound, we originally think that it is troubling him quite a bit, because he is limping. The next day a student, Dirk Fokkema, reports that in his opinion Yeroen limps only when Nikkie is in the vicinity. I know Dirk as a keen observer, but this time I find it hard to believe him. We go to watch, and it turns out that he is indeed right: Yeroen walks past the sitting Nikkie from a point in front of him to a point behind him and the whole time Yeroen is in Nikkie’s field of vision he hobbles pitifully, but once he has passed Nikkie his behavior changes and he walks normally again. For nearly a week Yeroen’s movement is affected in this way whenever he knows Nikkie can see him.
INTERPRETATION. Yeroen was playacting. He wanted to make Nikkie believe that he had been badly hurt in their fight. The fact that Yeroen acted in an exaggeratedly pitiful way only when he was in Nikkie’s field of vision suggests that he knew that his signals would only have an effect if they were seen; Yeroen kept an eye on Nikkie to see whether he was being watched. He may have learned from incidents in the past in which he had been seriously wounded that his rival was less hard on him during periods when he was (of necessity) limping.
Wouter, a young male chimpanzee of almost three, gets into a quarrel with Amber and screams at the top of his voice. At the same time he advances aggressively towards Amber. His mother, Tepel, goes over to him and quickly places her hand over her son’s mouth, smothering his screams. Wouter calms down and the quarrel is over.
INTERPRETATION. Noisy conflicts attract attention. If they last too long, one of the adult males will come over and put an end to them. When a bluffing male approaches, Wouter will automatically seek refuge near his mother. This means that she runs the risk of receiving the punishment meant for her son. Tepel wanted to avoid this risk by shutting up Wouter before things went too far.
This is not the only known instance of enforced silence. I have also seen a mother place a finger over the small mouth of her baby when the latter started barking aggressively at a dominant group member from the safety of her lap. Once again this was probably due to the mother’s reluctance to get drawn into difficulties because of a social faux pas committed by her child.
Dandy is the youngest and lowest ranking of the four grown males. The other three, and in particular the alpha male, do not tolerate any sexual intercourse between Dandy and the adult females. Nevertheless every now and again he does succeed in mating with them, after having made a “date.” When this happens the female and Dandy pretend to be walking in the same direction by chance, and if all goes well they meet behind a few tree trunks. These “dates” take place after the exchange of a few glances and in some cases a brief nudge.
This kind of furtive mating is frequently associated with signal suppression and concealment… On one occasion Luit was making advances to a female while Nikkie, the alpha male, was lying in the grass about 50 meters away. When Nikkie looked up and got to his feet, Luit slowly shifted a few paces away from the female and sat down, once again with his back to Nikkie. Nikkie slowly moved towards Luit, picking up a heavy stone on his way. His hair was standing slightly on end. Now and then Luit looked round to watch Nikkie’s progress and then he looked back at his own penis, which was gradually losing its erection. Only when his penis was no longer visible did Luit turn around and walk towards Nikkie. He briefly sniffed at the stone Nikkie was holding, then he wandered off leaving Nikkie with the female…
INTERPRETATION. In all these examples sexual signals are either concealed or suppressed… The males are faced with the problem that the evidence of their sexual arousal cannot disappear on command, but they too have their solutions. The audacity of Luit actually sniffing at the weapon Nikkie held in his hand only goes to show how sure he was that the alpha male would find no cause to proceed against him.
This behavior is in marked contrast to an incident I once witnessed between two male macaques. The alpha male met another male several minutes after the latter had secretly mated, Alpha could not possibly have known anything about this, but the other male acted unnecessarily timidly and submissively. His behavior was so exaggerated that, If the alpha male had had a chimpanzee’s social awareness, he would certainly have realized what the matter was. Luit’s behavior after his abortive adventure was very different. There was no trace of a “guilty conscience.” Chimpanzees are masters of pretense and will seldom put an idea into the head of the unsuspecting.
Social Intelligence Hypothesis
Once we have witnessed a number of striking instances of social manipulation and recognized that chimpanzees are more than highly Intelligent, we are forced to consider the nature of the extra faculty they have which most other species appear to lack: the ability to think purposefully. Some goal-directed behavior occurs among chimpanzees, however, without there being any past proof of the effectiveness of the result. They seem to be able to devise effective, on-the-spot solutions, such as in example 1, when Tepel woke Mama and pointed to the two quarreling children, or in example 3, where she effectively silenced her son.
The ability to combine past experiences in order to achieve a goal is best described as reasoning and thought; no better words exist. Instead of testing a particular course of action through actual trial and error, chimpanzees are able to weigh the consequences of a choice in their heads. The result is rational behavior. Primates take such a mass of social information into account, and are so finely attuned to the moods and intentions of others, that it has been speculated that their high intelligence evolved in order to deal with an increasingly complex group life. This idea, known as the social intelligence hypothesis, may also apply to the enormous brain expansion in our own lineage.
These examples, and dozens of others from other primate species, were collated in Whiten & Bryne (1988). They distinguish between forms of deception, including concealment, distraction, image projection etc.
Whiten & Byrne (1988). Tactical deception in primates
When plasma collected from mice that run a lot is transfused into sedentary rodents, the recipients show enhanced learning & memory, and dampened inflammation in the brain. This appears to be mediated by clusterin, a protein boosted by physical activity.
“Long Mono” found to cause most if not all cases of multiple sclerosis. “When the original studies were done with cigarette smoking and lung cancer, they found a 25-fold risk factor for people who smoked more than 25 cigarettes a day. This is even higher.”Here’s hoping an EBV/MS vaccine will arrive soon.
EBV doesn’t only cause multiple sclerosis. It also causes rheumatoid arthritis, and an astonishing 1.5% of all cancer deaths. Germ Theory 2.0 advocates claim that most so-called chronic diseases (incl cancer and heart disease) are not “environment-gene interactions” nor “evolutionary mismatch” but are in fact long-term repercussions from viral infection.
Germ Theory 2.0 attributes most cancer ailments to sexually transmitted pathogens. Consider a virus under strong selective pressure to persist in the body. The immune system operates outside the cell. If a virus can figure out how to spread under the cloak of the cell wall, it can persist. Imagine a virus hacking the cell a) to make more infected cells, b) to prevent cellular suicide, c) to move to other parts of the body… sounds a lot like cancer, right?
Germ Theory 2.0 approach of cardiovascular disease (CVD): Chlamydia pneumonia (Cpn) kills 600,000 Americans every year via CVD. The deadliest germ known to the human race. Most people catch it in grade school, and their immune systems never get rid of it. People with CVD are much more likely to have Cpn than controls, Cpn pathogens are preferentially located in atherosclerotic plaques, Cpn explains why traditional risk factors matter, and infecting animals with Cpn has been shown to accelerate the development of CVD.
When humans were hunting whales, the whales were sharing tips about avoiding hunters. “Our analysis provides substantial support for rapid (less than 20% generation time, so much too fast for genetic evolution) social learning over large spatial scales.”
Synchronization of 32 metronomes. If you put dozens of out-of-phase metronomes on a movable surface, they will synchronize themselves according to what is called a Kuramoto model of synchronization. Relevant to how the brain entrains its resident oscillators.
Last time, we learned that the brain represents behavior on two different timescales.
During locomotion, place cells fire in behavioral sequences that change approximately every 1-2s.
The same trajectories are simultaneously played out in theta sequences every 100-200ms.
But neuroscientists noticed bursts of activity that tend to bracket these sequences. When you zoom in on these short-lived events, you find that they contain the exact same trajectory as the canonical theta sequence. These sharp wave ripples (SWRs) are a brief high-frequency oscillation (~100 ms duration, 80-140 Hz):
You’ll notice two different ripple sequences in the above, which bracket the behavioral sequence in a palindrome:
Forward preplays, which compress the forthcoming sequence.
Reverse replays, which recapitulate past behavior in reverse order.
Why do some occur in reverse order? I personally suspect the answer may be related to orthogonalization. Libby & Bushchman (2021) found that the brain rotates memories to save them from interference from new percepts.
SWRs occur in other contexts besides exploration. In fact, they occur most frequently during sleep, and rest.
SWR rate intensifies in novel environments, and during consumption of reward:
During sleep, ripples are phase locked to two other electrophysiological phenomena: slow oscillations and spindles.
Before sleep ripples, there is activity in sensory areas; afterwards, there is activity in the prefrontal cortex. This temporal structure suggests a cortico-hippocampal-cortical loop of information transmission (Rothschild 2017).
SWRs are anticorrelated with theta. SWRs primarily occur during slow wave sleep (SWS) and restful waking, theta primarily occurs during REM and exploration. A walking rat expresses theta; a stationary rat expresses SWRs. Just before a rat expresses exploratory SWRs (i.e., forward replays), it slows down for a couple seconds (O’Neill et al 2006).
Ripples are brief, they are immersed in a resting oscillatory pattern called N waves (Kay & Frank 2018). N-Waves are not continuously oscillatory, expressed at 1-4 Hz (delta range), and anatomically correlate with a sleep pattern known as microarousal.
The anti-correlation between SWRs and theta is partially mediated by acetylcholine (Ach). Theta is promoted, and SWRs are suppressed, by selective optogenetic activation of Ach neurons in the medial septum (Vandecasteele et al 2014).
Memory Consolidation and Self-Projection
Hippocampal lesions create graded retrograde amnesia, where very old memories are preserved but recent memories are lost. The complementary learning systems model holds this to be evidence of consolidation: a small capacity, highly plastic cache slowly copying memories into a large capacity, less plastic storage in neocortex.
Most models of hippocampal memory are based on autoassociative neural networks (Hopfield 1982). But memory consolidation in such networks requires repeated exposures to the same episode to tune the synaptic matrix. Memories are initially encoded during online experience, but consolidated through offline retrieval. On this two stage model (Marr 1971), these retrieval events should ideally occur during periods of rest, so consolidation does not interfere with online behavior.
But hippocampal lesions don’t just produce amnesia. Patients like H.M also struggled with the imagination of novel and future events (Buckner & Carroll 2006), confabulating or just remaining silent when asked to do so. In fact, the hippocampal system activates during four distinct cognitive abilities: episodic memory, prospection (planning for the future), theory of mind, and navigation. These four abilities are collectively described as self-projection: the ability to shift perspective from the immediate present.
On this view, memory is not simply optimized for retrospective accuracy. Rather, these systems are used to guide prospective decision making. Counterfactual scenarios are simulated, and different episodes are creatively merged to forge novel predictions. This may explain results from Tolman & Gleitman (1949), with rats combining their spatial knowledge of a T-maze with a later, separate event conditioning them to fear one of its two arms:
More generally, we expect the hippocampus to behave something like Alpha-Go, which taught itself chess not through expensive supervision, but rather through self-play. If it did not improve your decision-making, we would experience amnesia.
The real importance of mental time travel applies to travel into the future rather than the past; that is, we predominantly stand in the present facing the future rather than looking back to the past.. The constructive element in episodic recall is adaptive in that it underlies our ability to imagine possible scenarios rather than the actual ones Since the future is not an exact replica of the past, simulations of future episodes may require a system that can draw on the past in a manner that flexibly extracts and recombines elements of previous experiences – a constructive rather than a reproductive system.
In the next section, we identify SWRs with memory consolidation. Later we will also discuss the constructive role of the SWR system.
SWRs as Consolidation Device
Sharp-wave ripples are natural candidates for retrieval-based consolidation. They preferentially occur during rest, and they engage vast swathes of neocortex. Most ripples preferentially activate the default mode network (DMN) (Norman et al 2021) which is associated with daydreaming and recollection.
Wilson & McNaughton (1994) were among the first to demonstrate that sleep SWRs replay past experiences. The correlations between place cells that manifest during running are preferentially reproduced in subsequent sleep. Skaggs & McNaughton (1996) demonstrated that these recapitulations occurred in the same temporal order.
When SWRs are disrupted in sleep after learning, but not after a random foraging task, there is a subsequent increase in their rate (Girardeau et al 2014). This suggests homeostatic control of SWRs that is consistent with their role in the facilitation of learning.
Girardeau et al (2009) provides loss of function evidence that suppression of sleep SWRs dramatically impairs subsequent memory recall for spatial tasks. This finding is nicely complemented by several gain of function experiments. Fernandez-Ruiz et al (2019) were able to prolong ripple duration, and showed that prolongation improved performance, and conversely that shortening impaired performance. This may explain why novel situations naturally evince longer duration ripples.
Gillespie et al (2021) found one category that SWRs tend to prefer: the most recent rewarded location. This relationship held regardless of whether the rat was actively searching for its next reward, or exploiting a reward that it had just found.
You may have noticed a very slight enrichment of current goal arms in the above. This enrichment was accentuated as the rat continued being rewarded during the repeat phase. From a chronological perspective, replays began to prioritize rewarded locations near the end of the repeat phase, and continued to represent that reward location for hours afterward.
SWRs did represent arms not recently associated with reward. In fact, these non-enriched ripples were found to prioritize the arm that was retrieved furthest in the past (Gillespie et al 2021). This suggests a role for consolidation, and is consistent with spaced repetition solutions to the well-known forgetting curve (Murre & Dros 2015).
Most SWR retrieval events are not conscious. But retrieval appears to be a prerequisite of conscious recollection. When Malach Norman asked neurosurgery, electrode-implanted patients to recall pictures presented several minutes ago, he found that SWRs reliably fired immediately before producing the verbal report.
Norman et al (2019) also found that pictures that were recalled featured more frequent ripples while the brain:
Not all ripples correspond to conscious recollection. Buzsaki (2015) proposes that they are the vehicle of subconscious priming, a subset of which are selected for global broadcast to the conscious workspace. To my knowledge, this hypothesis has not yet been tested.
Forward replays preferentially fire before a run; reverse replays fire afterward. Why?
Recall the distinction betweenmodel-based vs. model-free learners. Model-based learners build explicit maps of their environment. When they discover reward prediction error, this information must be propagated backwards (via Bellman backups) to the rest of its cognitive map. This suggests
So how does the hippocampus decide which locations to replay? Mattar & Daw (2018) answer that it should refresh memories with the highest action relevance. We can model this utility as the product of two terms:
Gain: update the locations which reduce uncertainty the most.
Need: update the locations the animal is likely to use soon.
Such a model is consistent with much of our data.
We should expect replay to be biased towards relevant locations, such as the agent’s position (high need) and recent reward sites (high gain).
We should expect replay to be biased forward at the beginning of a trial (high need) and backwards at the end of a trial (high gain).
This model also predicts that reverse replay (driven by gain) should be uniquely sensitive to the magnitude of the reward prediction error. And Ambrose et al (2016) found precisely this: unexpectedly large rewards increased the rate of reverse replay (red bars, top row), and vice versa (blue bars, bottom row).
The hippocampus supports a bewildering number of functions. Ranganath & Ritchey (2012) present evidence for two distinct subsystems:
Posterior-Medial PM System (pHC, MEC, PHC/RSC) as the substrate of episodic memory and egocentric navigation.
Anterior-Temporal AT System (aHC, LEC, PRC) as the substrate of semantic memory, allocentric navigation, and stress/anxiety.
Grid cell spacing and place field size both increase as one travels from posterior to anterior hippocampus (dorsal to ventral in rodents). This observation is consistent with aHC abstracting over specific details in the pHC (Stranger et al 2014). From an ICN perspective, the PM system has been linked to parietal memory and FPCN, and the AT system has been linked to contextual association and DMN (Zheng et al 2021). For a consistent, yet more detailed hypothesis about anatomical function, see Ritchey & Cooper (2020).
The longitudinal axis is immediately relevant to ripples. Posterior SWRs have been found to propagate to the prefrontal cortex. But posterior and anterior SWRs are uncorrelated in time, suggesting their independence. Further, Sosa et al (2020) found they engage different nucleus accumbens (nAC) subpopulations, and inhibit each other’s effects. This suggests ripples may consolidate episodic and semantic memories separately. It also explains how Tingley et al (2021) discovered that SWRs are involved in homeostatic regulation of glucose. All of this underscores our impoverished view of subtypes.
Location isn’t everything, however. Besides longitudinal subtypes, four other distinctions have been identified:
Directionality subtypes. As discussed above, forward and reverse ripples respond differently to reward and novelty.
Consciousness subtypes. Unit recording evidence suggests that PFC neurons respond differently to sleep vs awake SWRs.
Frequency subtypes. Ramirez-Villegas et al (2015) found four subtypes of ripple frequency signatures, each with a different coupling between sharp waves and ripples. Ripples that occurred during the peak of the sharp wave strongly activate neocortical regions; ripples synchronized at the trough communicated more with subcortical regions.
Content subtypes. Denovellis et al (2021) found roughly three categories of ripple. Stationaryripples occur 20% of the time, are overwhelmingly local, with no speed. Continuousripples occur 15% of the time, are usually remote (50cm away) and very high speed (10 m/s). Finally, continuous-stationary ripples occur 50% of the time, are usually remote (60cm away) and real-world speeds (17 cm/s). Jai et al (2017) found that stationary and continuous ripples exert different effects on the prefrontal cortex.
Identifying homologies across these categories would improve our ability to understand ripple function. To this question we turn next.
Homologies across Subtypes
SWRs are brief. Extended experiences are represented by joint replays, with multiple SWRs each representing one area of the maze (Davidson et al 2009). Longer maze segments require more ripples to represent, and these ripples are of longer duration. Wu & Foster (2014) noticed that joint replays tend to cleave at choice points:
Joint replays tended to begin on the current arm and proceed in the reverse order, before switching at the choice point to proceed along either of the two other arms in forward order. This organization suggests that reverse and forward replays may have different functions, with reverse replay representing a rewind of the immediate past, and forward replay representing the exploration of alternative futures, perhaps for the purposes of planning future behavioral trajectories.
Joint replays seem awfully reminiscent of theta sequences. Per the Separate Phases for Encoding and Retrieval (SPEAR) model, we might associate forward replays with retrieval theta, and reverse replays with encoding theta. The SPEAR model associates slow gamma with memory retrieval. Carr et al (2012) note that, when SWRs are synchronized to slow gamma, memory replay is of higher quality.
So which is it? Do forward ripples read values to simulate future behavior (as predicted by SPEAR), or do they update values to calibrate behavior (as predicted by Mattar & Daw 2018)?
Perhaps there is a way to reconcile these accounts. But that still leaves open the question of substrate. There seems to be two competing hypotheses:
Laminar Hypothesis. Wang et al (2020) and de la Prida (2020) present evidence that deep CA1 pyramidal cells not only drive reverse theta sequences (i.e., past encoding), but these same anatomical circuits also contribute to reverse ripples. Similarly, superficial CA1 is held to drive forward theta and forward ripples. The analogy might be strengthened by noting that 70% of SWRs are forward ripples, and theta sequences are asymmetric, devoting more time to forward sweeps.
Longitudinal Hypothesis. Novel and rewarding experiences strongly enhance the rate of posterior SWRs, but have no effect on anterior SWRs (Strange et al 1999; Sosa et al 2019). Reverse ripples bear a similar relationship to forward ripples.
I favor the laminar hypothesis. This synthesis binds together three distinctions in the literature.
There are hints at relationships amongst the unsolved pieces.
SWRs in slow wave sleep are predominantly forward, and not backward, replays (Wikenheiser & Reddish 2013).
Slower mixture ripples may be driven by CA3, while the faster moving ripples are more externally driven by MEC (Denovellis et al 2021).
But a synthesis has not yet been forged. A puzzle for another decade.
The Constructivity of Ripples
So far, we’ve mostly discussed how ripples participate in memory consolidation. But lesion data, neuroimaging, and functional considerations all suggest that the hippocampus underlies self-projection, counterfactual simulations, and creativity. Is the literature consistent with ripples playing a constructive role?
Most SWRs occur during slow-wave sleep, and sleep seems to preferentially sustain creative insight. Ellenbogen et al (2007) found that sleep facilitates the discovery of latent relations in a hierarchical stimulus. Likewise, in a mathematical quiz with a hidden yet elegant transformation rule, Wagner et al (2004) found that subjects allowed to sleep on the problem more than doubled their chances of gaining insight into the shortcut.
Karlsson & Frank (2009) found that sleep replays tend to be lower fidelity than awake replay, which has prompted speculation that this difference may enact a form of generalization.
Constructivity data need not be confined to sleep. Experimental suppression of awake SWRs during a spatial alternation task, for example, failed to impair memory consolidation, but instead degraded decision making (Jadhav et al 2012). This is causal evidence for constructivity.
Some studies report that ripple content can predict future choice. But in a recent study, Gillespie et al (2021) found that the content of remote ripples don’t predict the rat’s future decisions! Even if you compare correct vs incorrect trials, there is no change in ripples associated with the prospective behavioral choice.
Tellingly, awake replay can link familiar paths into novel trajectories never experienced before (Gupta et al 2010). While this line of enquiry is still young, ripples do seem to play a role for constructive, creative exploration of memory.
Ripples and theta are expressed during rest and activity, respectively. It seems likely that theta sequences may also participate in constructive functions, perhaps in joint sequences, just as theta does. However, interplay and potential handoffs between theta and ripples have not yet been fully explored.
Until next time.
Ambrose et al (2016). Reverse Replay of Hippocampal Place Cells Is Uniquely Modulated by Changing Reward
Buckner & Carroll (2006). Self-projection and the brain
Buckner (2010). The Role of the Hippocampus in prediction and imagination
Buzsaki (2015). Two-stage model of memory trace formation: a role for “noisy” brain states.
Carr et al (2012). Transient slow gamma synchrony underlies hippocampal memory replay
Davidson et al (2009). Hippocampal replay of extended experience
de la Prida (2020). Potential factors influencing replay across CA1 during sharp-wave ripples
De la Prida (2019). Potential factors influencing replay across CA1 during sharp-wave ripples
Denovellis et al (2021). Hippocampal replay of experience at real world speeds
Diba & Buzsaki (2007). Forward and reverse hippocampal place-cell sequences during ripples
Ellenbogen et al (2007) Human relational memory requires time and sleep.
Fernandez-Ruiz et al (2019). Long-duration hippocampal sharp wave ripples improve memory.
Gillespie et al (2021). Hippocampal replay reflects specific past experiences rather than a plan for subsequent choice
Girardeau et al (2009). Selective suppression of hippocampal ripples impairs spatial memory.
Girardeau et al (2014). Learning induced plasticity regulates hippocampal sharp wave ripple drive.
Gupta et al (2010). Hippocampal replay is not a simple function of experience
Hopfield (1982). Neural networks and physical systems with emergent collective computational abilities
Jadhav et al (2012). Awake Hippocampal Sharp-Wave Ripples Support Spatial Memory
Jai et al (2017). Distinct hippocampal-cortical memory representations for experiences associated with movement versus immobility
Joo & Frank (2018). The hippocampal sharp wave-ripple in memory retrieval for immediate use and consolidation
Karlsson & Frank (2009). Awake replay of remote experiences in the hippocampus
Kay & Frank (2018). Three brain states in the hippocampus and cortex
Libby & Buschman (2021). Rotational dynamics reduce interference between sensory and memory representations
Marr (1971). Simple memory: a theory for archicortex
Psychotherapy and counseling are becoming increasingly popular in urban China, especially among those feeling marginalized and excluded from kinship networks. This raises the notion that religion and psychotherapy may be fulfilling similar roles in Chinese society… Findings [about political unfairness index] are consistent with the hypothesis that faith in religion and faith in government are substitutes in times of crisis, disorder, and lack of control.
Introducing shardware. “Traditionally software people looked upon hardware people with extraordinary disdain. Now, there’s no longer a crisp boundary between hardware and software, but rather just another translation layer in the stack.”
The placebo effect in the United States has been growing much stronger over time. Drugs that once would have been approved may not be now – because their performance relative to that of placebo is less convincing. May explain why the truth wears off.
Biological age can be measured independently of chronological age. Tests for the latter are becoming more economically feasible, from $200 to $2 per test. This should accelerate progress in gerontology.
Persistent organic pollutants (POPs) can infiltrate the blood-brain barrier.
Aging can be accelerated in real life, not just M Night Shyamalan movies. Cancer survivors who underwent radiation therapy, compared to survivors who didn’t, literally live 21 years less. “Approximately one-third of childhood cancer survivors aged 35 years have a disease phenotype of a person aged 65 years.”
You can only hope to lose 5-10% of your body weight with diet & exercise. Even then, there’s an 85% chance your weight loss attempt will fail. Why? Your hypothalamus has decided that your heaviest weight is your correct weight. And so, for every pound lost, your metabolism decreases 11 calories, and appetite increases 45 calories above baseline. The millstone just gets too heavy. (From here, orange is weight loss maintainer, blue is weight loss regressor)
T-Cell vaccines may provide longer immunity. “The Emergex shot will not be available until 2025 at the earliest, the usual timeframe for vaccine development. Last year Covid vaccines were developed within months as the regulatory process was speeded up, but the emergency has passed…”
The gender-equality paradox is the (disputed) idea that countries with more gender equality have fewer women in STEM careers. This analysis suggests the paradox is robust to different operationalizations of gender equality, but mysteriously evaporates on different operationalizations of STEM participation.
The hippocampus is centrally important for spatial navigation. Neuroscientists have discovered specialized cell types in the medial entorhinal cortex (MEC), including border cells, head-direction cells, and grid cells.
Grids are actually organized hierarchically, with grids growing in size along the dorsal-ventral axis within MEC. But grid size does not increase continuously, rather there are precisely four interlocked grids (Stensola et al 2012). The ratio between grid distances is consistently 1.42, which may be optimally efficient (Mathis et al 2012).
MEC navigational cells allow for the complex behavior of path integration. An ant leaving its nest will search for food by exploring the environment; once it decides to return, it integrates all of its various exploratory movements (each vector is reconstructed from direction, speed, and duration cells) into a single, precise return trajectory. If you abruptly move the ant a couple meters before it returns, it will follow the same return vector, and exhibit confused-search behavior when it cannot find the nest.
But the hippocampus also supports another, more objective approach: allocentric navigation. Essentially, landmarks are used to orient one’s environment.
Place cells also exhibit a reward gradient, perhaps stemming from interactions with the basal ganglia. This reward gradient is significant in reinforcement learning (RL) models.
These independent navigational systems rely on two different representations of the body: egocentric (me-centered) and allocentric (world-centered) perspectives. These representations can come apart in clinical out-of-body experiences. For example, clever uses of VR to disrupt egocentric processing leads to a reduction in activity in egocentric parts of the hippocampus (Bergouignan et al 2015)
Overview of Oscillation
Neural oscillations are a central organizational principle by which the brain coordinates different neural ensembles (Buzsaki 2010). In the following image (a), each row is a different neuron. With these multi-unit recordings, you’ll find that certain groups of neurons consistently fire together (gray ovals) in the trough of the theta cycle.
There are at least ten different oscillators with unique cognitive functions.
Relevant to today’s post, we have,
Gamma oscillations (30-100 Hz, 10-30ms window) are ubiquitous across cortex and associated with perceptual binding (Engel & Singer 2001).
Theta oscillations (4-10 Hz, 100-250ms window) are not as global, but have been detected in hippocampus, MEC, medial prefrontal cortex and ventral striatum (Drieu & Zugaro 2019).
Gamma oscillators can be phase locked with theta, with ~7 gamma cycles nested within theta. Theta and gamma exhibit phase-amplitude coupling (PAC), an example of the more general mechanism of cross-frequency coupling (CPC). This theta-gamma neural code is important for learning and memory (Lisman & Jensen 2013).
Theta Sequences and Phase Precession
In the brain, behavior is represented with at least two different timescales.
During locomotion, place cells fire in behavioral sequences that change approximately every 1-2s (T).
The same trajectories are simultaneously played out in theta sequences every 100-200ms (tau).
As the rat moves, place cells fire at progressively earlier phases within theta cycle. This phase precession was first noticed by O’Keefe & Recce (1993).
The ~7 gamma bursts within each theta rhythm seems to encode a planning trajectory, or sweep, of its upcoming behaviors. In Wikenheiser & Redish (2015), rats could either stop at a feeder (upper left location) or continue moving through the track. Their theta sequences predicted their behavioral choice, well ahead of time. A similar result was found by Gupta et al (2012).
What happens when the rat is still making up its mind? Theta sweeps examine both trajectories within a single trial (Johnson & Redish 2007; Kay et al 2020).
Jezek et al (2011) used flickering to induce confusion whether a rat was located in one of two environments. They found that theta sequences switched between either environment, but within-sequence representations were consistent. This suggests that theta sequences may represent cognitive primitives.
The SPEAR model
We have detected sub-processes within theta sequences. Hasselmo et al (2002) noticed several physiological differences that occur at the peak versus the trough of the theta cycle. They proposed that peak of the theta phase is involved with the encoding of information, while the trough features a retrieval of information. These phases correspond to the pattern separation versus pattern completion, respectively. Notably, long term potentiation (LTP) was much stronger at theta peak. This is largely driven by acetylcholine, which is expressed more strongly during encoding than retrieval (Hasselmo 2006).
Belluscio et al (2012) found that slow gamma (30-50 Hz) and medium gamma (50-90 Hz) exclusively occur in the trough and peak of theta, respectively. Schomberg et al (2014) replicated this result. Wang et al (2020) note that beta oscillations occur only during theta trough.
Navas-Olive et al (2020) associated activity in superficial and deep CA1 pyramidal neurons with trough and peak of theta, respectively. Their lab has posited four sub-circuits which fire at distinctive locations in theta phase.
Phase precession often reveals prospective choices. But neuroscientists have long noted the existence of retrospective sweeps, theta sequences of locations behind the animal. Bieri et al (2014) have linked slow and slow gamma to prospective and retrospective sweeps, respectively. As we saw in the image above, prospective sweeps simulate possible futures, while retrospective sweeps encode the past (Kay et al 2020).
Here are the properties of the Separate Phases of Encoding And Retrieval (SPEAR) model.
The SPEAR Model explains several behavioral results.
Takahashi et al (2014) found that during a fixation cue, where a rat is forced to rely on spatial memory to make a movement decision, there is an abrupt shift to slow gamma emerging from CA3. This is consistent with its hypothesized function of retrieval.
In novel environments, rats tend to move quickly and non-linearly. As an environment becomes familiar, speed slows down but becomes more linear. Kemere et al (2013) show that fast gamma is expressed at higher speeds, and vice versa. This may reflect the process by which as an animal familiarizes itself with an environment, its cognitive operations increasingly rely on memory retrieval. This result was replicated in Zheng et al (2016).
Relation to Working Memory
Long ago, Sternberg (1966) reported a linear relationship between recall latency and the number of memorized items, which suggested that the list was serially scanned at a rate of 20-30ms per memory item. Similarly, Miller (1955) also collated many different experiments showing a ceiling of recall of about 7 items (but the limit becomes 4 items when rehearsal is removed; Cowan 2000).
These constraints on working memory are suggestive: the 20-30ms scan time aligns with the gamma cycle, and there are about 7 gamma cycles within a theta sequence (Lisman & Idiart 1995). The ratio of theta to gamma may even correlate with WM span (Kaminski et al 2011), although this data is fairly uncertain.
Theta power increases systematically with working memory load (Jensen & Tesche 2002). Theta does not occur uniformly across cortex during WM tasks, but is localized to specific sites (Raghavachari et al 2001). Theta frequency decreases during periods of high load, consistent with more representations requiring longer theta sequences (Axmacher et al 2010; but see Moran et al 2010).
Heusser et al (2016) found that maximum gamma power for the memory items occured at distinct locations in theta phase, but only when the subject was able to remember the sequence correctly. Theta also appears conducive to binding together sequences across different modalities. This was replicated in Reddy et al (2021). Clouter et al (2017) found that when audio and video clips were synchronized to theta oscillations (but not other frequency bands), recall accuracy substantially improved.
Roux & Uhlhaas (2014) review studies that explore neural oscillations during WM maintenance. They found that theta activity occurs preferentially in tasks that involve the sequential items, whereas alpha oscillations tend to occur during tasks that require simultaneous maintenance of visuospatial information. They propose to identify theta-gamma binding with one of the subcomponents of working memory: the phonological loop.
Griffiths et al (2021) found that theta-gamma PAC (memory consolidation) arose after reductions in alpha/beta power (sequence perception), indicative of a two-stage retention process.
Until next time.
Axmacher et al (2010). Cross-frequency coupling supports multi-item working memory in the human hippocampus
Bieri et al (2014). Slow and fast gamma rhythms coordinate different spatial coding modes in hippocampal place cells
Bullicino et al (2012). Cross-Frequency Phase–Phase Coupling between Theta and Gamma Oscillations in the Hippocampus
Buzsaki (2010). Neural syntax: cell assemblies, synapsemblies, and readers
Canolty et al (2006). High gamma power is phase-locked to theta oscillations in human neocortex
Clouter et al (2017). Theta Phase Synchronization Is the Glue that Binds Human Associative Memory
Colgin et al (2009). Frequency of gamma oscillations routes flow of information in the hippocampus
Cowan (2000). The magical number 4 in short-term memory: A reconsideration of mental storage capacity
de Almeida (2009). The Input-Output Transformation of the Hippocampal Granule Cells: From Grid Cells to Place Fields
Drieu & Zugaro (2019). Hippocampal Sequences During Exploration: Mechanisms and Functions
Engel & Singer (2001). Temporal binding and the neural correlates of sensory awareness.
Griffiths et al (2021). Disentangling neocortical alpha/beta and hippocampal theta/gamma oscillations in human episodic memory formation
Gupta et al (2012). Segmentation of spatial experience by hippocampal theta sequences
Hasselmo et al (2002). A proposed function for hippocampal theta rhythm: separate phases of encoding and retrieval enhance reversal of prior learning
Hasselmo (2006). The Role of Acetylcholine in Learning and Memory
Hasselmo & Stern (2013). Theta rhythm and the encoding and retrieval of space and time.
Heusser et al (2016). Episodic sequence memory is supported by a theta–gamma phase code
Jensen & Tesche (2002). Frontal theta activity in humans increases with working memory load in a working memory task.
Jezek et al (2011). Theta-paced flickering between place-cell maps in the hippocampus
Johnson & Reddish (2007). Neural ensembles in CA3 transiently encode paths forward of the animal at a decision point
Kaminski et al (2011) Short term memory capacity predicted by theta to gamma cycle length ratio.
Kemere et al (2013). Rapid and continuous modulation of hippocampal network state during exploration of new places
Lisman & Idiart (1995). Storage of 7+/-2 short-term memories in oscillatory subcycles
Lisman & Jensen (2013). The theta-gamma neural code
Mathis et al (2012). Optimal Population Codes for Space: Grid Cells Outperform Place Cells
Miller (1955). The Magical Number Seven, Plus or Minus Two: Some Limits on Our Capacity for Processing Information
Moran et al (2010). Peak frequency in the theta and alpha bands correlates with human working memory capacity.
Navas-Olive et al (2020). Multimodal determinants of phase-locked dynamics across deep-superficial hippocampal sublayers during theta oscillations
O’Keefe & Recce (1993). Phase relationship between hippocampal place units and the EEG theta rhythm
Penttonen & Buzsaki (2003). Natural logarithmic relationship between brain oscillators
Raghavachari et al (2001). Gating of human theta oscillations by a working memory task
Reddy et al (2021). Theta-phase dependent neuronal coding during sequence learning in human single neurons
Roux & Uhlhaas (2014). Working memory and neural oscillations: alpha–gamma versus theta–gamma codes for distinct WM information?
Schonberg et al (2014). Theta phase segregation of input-specific gamma patterns in entorhinal-hippocampal networks
Shrivalkar et al (2010). Bidirectional changes to hippocampal theta-gamma comodulation predict memory for recent spatial episodes
Srinivasan (2015). Where paths meet and cross: navigation by path integration in the desert ant and the honeybee
Stensola et al (2012). The entorhinal grid map is discretized
Sternberg (1966). High-Speed Scanning in Human Memory
Takahashi et al (2014). Theta phase shift in spike timing and modulation of gamma oscillation: a dynamic code for spatial alternation during fixation in rat hippocampal area CA1
Valero & de la Prida (2018). The hippocampus in depth: a sublayer-specific perspective of entorhinal-hippocampal function.
Wang et al (2020). Alternating sequences of future and past behavior encoded within hippocampal theta oscillations.
Wikenheiser & Redish (2015). Hippocampal theta sequences reflect current goals
Zheng et al (2015). The relationship between gamma frequency and running speed differs for slow and fast gamma rhythms in freely behaving rats
Zheng et al (2016). Spatial Sequence Coding Differs during Slow and Fast Gamma Rhythms in the Hippocampus
What’s causing the sex recession? New data suggests a change in religious norms.
Intramuscular injections can accidentally hit a vein, causing injection into the bloodstream. This could explain some of the rare adverse reactions to Covid-19 vaccine. Study shows solid link between intravenous mRNA vaccine and myocarditis (in mice). Needle aspiration is one way to prevent this from happening.
Paxlovid, a bespoke protease inhibitor from Pfizer shows 89% protection from hospitalization. It may be possible to combine with molnupiravir, the new 50% protective transcriptase inhibitor from Merck.
After you exclude the fraudulent and statistically illegitimate studies, several meta-analyses still show that Ivermectin can provide a small amount of protection. The effect is small compared to Paxlovid 89% or mRNA vaccines 95%, but non-zero. What’s going on? The strongyloid hypothesis.
Energy & Climate
High-temperature superconductors are accelerating fusion R&D. The MIT startup is forecasting an energy-positive proof of concept as soon as 2025.
Vox: geothermal energy is poised for a big breakout. One issue with renewables (solar, wind, etc) is they have a low capacity factor: until large-scale energy storage becomes economical they need to be supplemented by high capacity energy sources. Nuclear and geothermal might qualify; main blockers are regulation and R&D, respectively.
What is France’s secret? Nuclear power.
Interesting, bullish take on SpaceX. Its starship program will likely reduce the transport cost-per-kilogram by two orders of magnitude.
Inspired by recent neutrino results, a new dark sector theory attempts to jointly explain dark matter, Hubble tension, baryon asymmetry, and cosmic thinness.
Leading candidate axion theory (explanans: CP parity, dark matter) finds preliminary support
For decades, people have considered computational error to be the most likely source of error when a predicted structure and an experimental one don’t match, and quite rightly so. But now, if you have a big mismatch between the two, it is frankly more likely to be an experimental error, because the folding predictions are getting so solid. This is disorienting, to say the least.
19. Remnants from Theia (the collision that created the moon) forever interred in the deep Earth. Tree-like plumes emanating from these LLSVPs are likely responsible for Deccan Trap volcanism and the K-Pg extinction event.
The team estimates that, in tens of millions of years, a blob of nightmarishly gargantuan proportions will pinch off from the central cusp and rise to meet what is now South Africa’s foundations. This, said Sigloch, would produce cataclysmic eruptions. The Deccan Traps were caused by what we would think of as a solitary mantle plume. This future mega-blob, though, would be capable of producing volcanism so prolific and extensive that the Deccan Traps would be a firecracker in comparison.”
“If mirror cells acquired the ability to photosynthesize, we’d be screwed. “I suspect that all hell would break loose,” says Jim Kasting, a climate scientist at Penn State University and an expert on the global carbon cycle. All it would take would be a droplet of mirror cyanobacteria squirted into the ocean. After doing some rough calculations on the effects of a mirror cyanobacteria invasion, Jim Kasting isn’t sure which would kill us first—the global famine or the ice age.