Misjudging criteria

Most people think of memory as the ‘past’ and judge it by how well it preserves the past. But that is not its function. Memory is material to be used in the ‘present’ and the ‘future’. What happened in the past is not important except to help understand the present and predict/plan the future. Bits of memory out of historical context are the ingredients of imagination. With more context they are the tools we use to identify things in the present and understand their dangers and opportunities. We need to know if we are encountering the old or the new. We need to remember whether someone is trustworthy when we deal with them. When we look at what we remember, how and how long we remember it, and how closely we keep it to the original memory, we should think of what is the point of all of it.

What seems a fault with memory – that memories are not fixed but can change or be lost altogether – is only a side effect of their being modified to stay relevant and useful. We need memories that help us perceive the present and model the future and that is the real criteria, not absolute accuracy. The criteria for a well constructed memory system are biological evolutionary survival ones.

Colour vision is not about accurately perceiving the frequencies of light coming into the eye. It is not about the light; it is about the surface that reflected the light and how it can be identified. There is no use in saying that our vision is not giving us accurate colour, because accurate colour would interfere with accurate characterization of surfaces and identification of objects. The many optical illusions are not faults in the system – they are due to the ways that the visual system protects the stability of our vision so that things do not appear to change colour or size.

Language is not about meaning or logic; it is about communication. People worry about changes in the meaning of words and the use of grammatical forms. Well, here is what happens generation after generation: if people have difficulty communicating, they will change their language. If their way of life changes, if they move to a different region, if the people they are talking to change, then they will change their language. Our language is not the result of biological evolution so much as cultural evolution. But the same idea applies and the criteria have to do with communication. Is language logical? It may seem so from within that language but talk to anyone learning it as a new language and see the illogical, arbitrary quirks in it. There are languages that count negatives and there must be an odd number to be negative. There are languages that have to have all or no words carry a negative marking. Both types of negation seem logical to the speakers. Is language a good communication tool? Without doubt it is better than anything else we have ever tried to invent. No artificial language has ever made a dent on a natural language no matter how clear was the meaning or logical the grammar of the new language.

When we look at biological and even social systems it is important to consider what is their real, primary reason for existence. We have a tendency to misjudge the criteria and need to watch out for this trap.




How is it that people keep their superstitions even after they do not believe they are possible? It is because it is actually difficult to lose a superstition. We learn them as children and they stick at a deep emotional level.

Once long ago in the ’60s, my husband bought my soul. It started somehow in a conversation at a table of people in a cafe. I offered to sell my soul and we did some haggling over price and then he handed over the money and I declared that my soul belonged to him. It was an entertaining little drama but it caused a lot of discomfort in the group. There were people at the table that believed I had a soul and people who did not believe in souls – all were not happy. No one actually thought that my husband now actually had my soul in his possession or under his control but it was still disturbing. The most common phrase was that we were tempting fate, even though few would have agreed that our lives were ruled by fate. Why the disconnect?

ScienceDaily has an item, (here), “The power of magical thinking: Why superstitions are hard to shake”. The article points out that we all have superstitions that we do not rationally defend but that affect our behaviour. We knock on wood, walk around ladders and such things because we feel uncomfortable if we don’t. It feels like we are tempting fate. But we would not seriously defend these actions, instead we laugh apologetically and shrug and says its just a little habit with no harm. We allow an irrational thought to remain an influence on our emotions and behaviour.

The author of an upcoming article, Risen, “contends that detecting an irrational thought and correcting that error are two separate processes, not one as most dual-system cognitive models assume. This insight explains how people can detect irrational thought and choose not to correct it, a process she describes as “acquiescence”Understanding how acquiescence unfolds in magical thinking can help provide insight into how it is that people knowingly behave irrationally in many other areas of life.

In order to reverse these habits and rid thought of magic intuitions it is necessary to recognize that knowing that the intuition is not possible is not enough. Separate effort has to go into loosening the grip of the magic intuitions. And, I think was goes further than magic intuitions and superstitions, named by Risen, but applies also to many habits and thought patterns that we do not believe are rational but are comforting and therefore never corrected. It takes effort.



Cooperation of sight and sound

As a child you were probably taught to tell how far away lightening was. When there is a flash, you count with a particular rhythm until you hear the thunder and that is how many miles the lightening is away from you. Parents are not going to stop teaching this because it is something for a nervous child to do in a thunder storm and it convinces them that they are usually a safe distance from danger. But it only works for distant events.

Events that are close by are synchronized by the brain and consciously we collapse the vision and hearing clues both for time and space to make a single event. We are not conscious of a difference in the timing or of any slight difference in the placing of the event. A particular region of the brain does this aligning – “the superior colliculus, a midbrain region that functions imperatively for integrating auditory and visual signals for attending to and localizing audiovisual stimuli”. But if the difference is too large between the vision and hearing, the collapse into a single event does not happen.

However, we know that, even though it is not consciously experienced, the information about small differences in sound arrival can be used by blind humans to echo-locate by making continuous little clicking noises. Could it be that the discrepancy between sound and sight could be used in other ways? A recent paper (Jaekl P, Seidlitz J, Harris LR, Tadin D (2015) Audiovisual Delay as a Novel Cue to Visual Distance. PLoS ONE 10(10): e0141125. doi:10.1371/journal.pone.0141125) studies the effect of sound delays on the perception of distance. Like the lightening calculation, but it is done unconsciously.

Here is the abstract:

For audiovisual sensory events, sound arrives with a delay relative to light that increases with event distance. It is unknown, however, whether humans can use these ubiquitous sound delays as an information source for distance computation. Here, we tested the hypothesis that audiovisual delays can both bias and improve human perceptual distance discrimination, such that visual stimuli paired with auditory delays are perceived as more distant and are thereby an ordinal distance cue. In two experiments, participants judged the relative distance of two repetitively displayed three-dimensional dot clusters, both presented with sounds of varying delays. In the first experiment, dot clusters presented with a sound delay were judged to be more distant than dot clusters paired with equivalent sound leads. In the second experiment, we confirmed that the presence of a sound delay was sufficient to cause stimuli to appear as more distant. Additionally, we found that ecologically congruent pairing of more distant events with a sound delay resulted in an increase in the precision of distance judgments. A control experiment determined that the sound delay duration influencing these distance judgments was not detectable, thereby eliminating decision-level influence. In sum, we present evidence that audiovisual delays can be an ordinal cue to visual distance.

The brain’s gateway

There have been a few papers lately on the function of the thalamic reticular nucleus (TRN) that characterize it as a filter, a sieve, and a switchboard. The citations and abstracts of 4 of these papers are below. Francis Crick suggested this function for the TRN many years ago but it was not possible until recently to demonstrate it because of the anatomy of the TRN.

The thalamus sits at the center of the brain and is connected to the brain stem and spinal cord below, the cerebral hemispheres above and the basal ganglia to the sides. The thalamus is part of almost all the functional processing loops in the brain. In particular, almost all sensory information enters the cortex from the thalamus, and every corner of the cortex sends signals back to the thalamus. When this traffic, the thalamo-cerebral loops, shut down, so does consciousness.

The TRN is a thin layer of neurons that almost entirely covers the thalamus. Because it is so thin and so deep in the brain, it has been difficult to study. New methods have overcome some of these problems.

In effect all the traffic between the cortex and the thalamus is carried by axons that pass through the TRN and the axons have little branches that make contact with TRN neurons. In other words the TRN gets a smell of all the passing signals – it does not interfere with the axons but just spies on them. The TRN neurons are inhibitory, so when a passing signals activates one of them, it will suppress the neuron in the thalamus that is sending or receiving the signal. This action keeps most activity at a low level. During sleep the thalamo-cerebral loops are effectively turned off and sensory information does not reach the cortex. During attention (and multitasking) the TRN reduces distracting signals but not the attended ones. It also seems to control the type of sleep by controlling types of brain waves in the cortex during sleep. The executive functions of the prefrontal cortex seems to act through the TRN rather than directly on areas of the cortex, to control attention (steer the spotlight of attention).

Here are the abstracts and citations:

Sandra Ahrens, Santiago Jaramillo, Kai Yu, Sanchari Ghosh, Ga-Ram Hwang, Raehum Paik, Cary Lai, Miao He, Z Josh Huang, Bo Li. ErbB4 regulation of a thalamic reticular nucleus circuit for sensory selection. Nature Neuroscience, 2014; DOI: 10.1038/nn.3897

Selective processing of behaviorally relevant sensory inputs against irrelevant ones is a fundamental cognitive function whose impairment has been implicated in major psychiatric disorders. It is known that the thalamic reticular nucleus (TRN) gates sensory information en route to the cortex, but the underlying mechanisms remain unclear. Here we show in mice that deficiency of the Erbb4 gene in somatostatin-expressing TRN neurons markedly alters behaviors that are dependent on sensory selection. Whereas the performance of the Erbb4-deficient mice in identifying targets from distractors was improved, their ability to switch attention between conflicting sensory cues was impaired. These behavioral changes were mediated by an enhanced cortical drive onto the TRN that promotes the TRN-mediated cortical feedback inhibition of thalamic neurons. Our results uncover a previously unknown role of ErbB4 in regulating cortico-TRN-thalamic circuit function. We propose that ErbB4 sets the sensitivity of the TRN to cortical inputs at levels that can support sensory selection while allowing behavioral flexibility.

Ralf D. Wimmer, L. Ian Schmitt, Thomas J. Davidson, Miho Nakajima, Karl Deisseroth, Michael M. Halassa. Thalamic control of sensory selection in divided attention. Nature, 2015; DOI: 10.1038/nature15398

How the brain selects appropriate sensory inputs and suppresses distractors is unknown. Given the well-established role of the prefrontal cortex (PFC) in executive function, its interactions with sensory cortical areas during attention have been hypothesized to control sensory selection. To test this idea and, more generally, dissect the circuits underlying sensory selection, we developed a cross-modal divided-attention task in mice that allowed genetic access to this cognitive process. By optogenetically perturbing PFC function in a temporally precise window, the ability of mice to select appropriately between conflicting visual and auditory stimuli was diminished. Equivalent sensory thalamocortical manipulations showed that behaviour was causally dependent on PFC interactions with the sensory thalamus, not sensory cortex. Consistent with this notion, we found neurons of the visual thalamic reticular nucleus (visTRN) to exhibit PFC-dependent changes in firing rate predictive of the modality selected. visTRN activity was causal to performance as confirmed by bidirectional optogenetic manipulations of this subnetwork. Using a combination of electrophysiology and intracellular chloride photometry, we demonstrated that visTRN dynamically controls visual thalamic gain through feedforward inhibition. Our experiments introduce a new subcortical model of sensory selection, in which the PFC biases thalamic reticular subnetworks to control thalamic sensory gain, selecting appropriate inputs for further processing.

Laura D Lewis, Jakob Voigts, Francisco J Flores, Lukas I Schmitt, Matthew A Wilson, Michael M Halassa, Emery N Brown. Thalamic reticular nucleus induces fast and local modulation of arousal state. eLife, October 2015 DOI: 10.7554/eLife.08760

During low arousal states such as drowsiness and sleep, cortical neurons exhibit rhythmic slow wave activity associated with periods of neuronal silence. Slow waves are locally regulated, and local slow wave dynamics are important for memory, cognition, and behaviour. While several brainstem structures for controlling global sleep states have now been well characterized, a mechanism underlying fast and local modulation of cortical slow waves has not been identified. Here, using optogenetics and whole cortex electrophysiology, we show that local tonic activation of thalamic reticular nucleus (TRN) rapidly induces slow wave activity in a spatially restricted region of cortex. These slow waves resemble those seen in sleep, as cortical units undergo periods of silence phase-locked to the slow wave. Furthermore, animals exhibit behavioural changes consistent with a decrease in arousal state during TRN stimulation. We conclude that TRN can induce rapid modulation of local cortical state.

Michael M. Halassa, Zhe Chen, Ralf D. Wimmer, Philip M. Brunetti, Shengli Zhao, Basilis Zikopoulos, Fan Wang, Emery N. Brown, Matthew A. Wilson. State-Dependent Architecture of Thalamic Reticular Subnetworks. Cell, 2014; 158 (4): 808 DOI: 10.1016/j.cell.2014.06.025

Behavioral state is known to influence interactions between thalamus and cortex, which are important for sensation, action, and cognition. The thalamic reticular nucleus (TRN) is hypothesized to regulate thalamo-cortical interactions, but the underlying functional architecture of this process and its state dependence are unknown. By combining the first TRN ensemble recording with psychophysics and connectivity-based optogenetic tagging, we found reticular circuits to be composed of distinct subnetworks. While activity of limbic-projecting TRN neurons positively correlates with arousal, sensory-projecting neurons participate in spindles and show elevated synchrony by slow waves during sleep. Sensory-projecting neurons are suppressed by attentional states, demonstrating that their gating of thalamo-cortical interactions is matched to behavioral state. Bidirectional manipulation of attentional performance was achieved through subnetwork-specific optogenetic stimulation. Together, our findings provide evidence for differential inhibition of thalamic nuclei across brain states, where the TRN separately controls external sensory and internal limbic processing facilitating normal cognitive function.

Attention on attention

A recent paper does a magnificent job of marshaling many sources of information on attention and developing a theory to fit those pieces of research. (Timothy J. Buschman, Sabine Kastner. From Behavior to Neural Dynamics: An Integrated Theory of Attention. Neuron, 2015; 88 (1): 127 DOI: 10.1016/j.neuron.2015.09.017). “The brain has a limited capacity and therefore needs mechanisms to selectively enhance the information most relevant to one’s current behavior. We refer to these mechanisms as ‘‘attention.’’ Attention acts by increasing the strength of selected neural representations and preferentially routing them through the brain’s large-scale network. This is a critical component of cognition and therefore has been a central topic in cognitive neuroscience. Here we review a diverse literature that has studied attention at the level of behavior, networks, circuits, and neurons. We then integrate these disparate results into a unified theory of attention.

They concentrate on visual attention because there has been most research in that area. Recent work has pointed to the visual cortex creating a ‘dictionary’ of objects and object features through learning. The learning process captures the regularities of the world and visual representations are coded in this ‘dictionary’. “Importantly, embedding object-based representations will ensure that the system is tolerant to noise as any input will be transformed by the learned object dictionary: signals that match an expected pattern will be boosted, while signals that are orthogonal to representations in the dictionary will be ignored. As the dictionary has been trained to optimally represent the world, this means the system will, in effect, perform pattern completion, settling on nearby ‘‘known’’ representations, even when provided with a noisy input.” These representations are what top-down and bottom-up attention controls act on.

Their theory proposes a cascade and its regular reset.

(1) Attention can either be (a) automatically grabbed by salient stimuli or (b) guided by task representations in frontal and parietal regions to specific spatial locations or features.

(2) The pattern-completion nature of sensory cortex sharpens the broad top-down attentional bias, restricting it to perceptually relevant representations. Interactions with bottom-up sensory drive will emphasize specific objects.

(3) Interneuron-mediated lateral inhibition normalizes activity and, thus, suppresses competing stimuli. This results in increased sensitivity and decreased noise correlations.

(4) Lateral inhibition also leads to the generation of high-frequency synchronous oscillations within a cortical region. Inter-areal synchronization follows as these local oscillations synchronize along with the propagation of a bottom-up sensory drive. Both forms of synchrony act to further boost selected representations.

(5) Further buildup of inhibition acts to ‘‘reset’’ the network, thereby restarting the process. This reset allows the network to avoid being captured by a single stimulus and allows a positive-only selection mechanism to move over time.

qttention pic

Two things on language

There are a couple of interesting reports about language.

First, it has been shown that repeating something aloud helps us remember it. But a recent study goes further – we remember even better if we repeat it aloud to someone. The act of communication helps the memory. The paper is: Alexis Lafleur, Victor J. Boucher. The ecology of self-monitoring effects on memory of verbal productions: Does speaking to someone make a difference? Consciousness and Cognition, 2015; 36: 139 DOI:10.1016/j.concog.2015.06.015.

From ScienceDaily (here) Previous studies conducted at Professor Boucher’s Phonetic Sciences Laboratory have shown that when we articulate a sound, we create a sensory and motor reference in our brain, by moving our mouth and feeling our vocal chords vibrate. “The production of one or more sensory aspects allows for more efficient recall of the verbal element. But the added effect of talking to someone shows that in addition to the sensorimotor aspects related to verbal expression, the brain refers to the multisensory information associated with the communication episode,” Boucher explained. “The result is that the information is better retained in memory.

No one can tell me that language is not about and for communication.

The second item is reported in ScienceDaily (here) Infants cannot perceive the difference between certain sounds when their tongue is restricted with a teether. They have to be able to mimic the sounds in order to distinguish them. The paper is: Alison G. Bruderer, D. Kyle Danielson, Padmapriya Kandhadai, and Janet F. Werker. Sensorimotor influences on speech perception in infancy. PNAS, October 12, 2015 DOI: 10.1073/pnas.1508631112.

From ScienceDaily: …teething toys were placed in the mouths of six-month-old English-learning babies while they listened to speech sounds–two different Hindi “d” sounds that infants at this age can readily distinguish. When the teethers restricted movements of the tip of the tongue, the infants were unable to distinguish between the two “d” sounds. But when their tongues were free to move, the babies were able to make the distinction. Lead author Alison Bruderer, a postdoctoral fellow in the School of Audiology and Speech Sciences at UBC, said the findings call into question previous assumptions about speech and language development. “Until now, research in speech perception development and language acquisition has primarily used the auditory experience as the driving factor,” she said. “Researchers should actually be looking at babies’ oral-motor movements as well.”

hey say that parents do not need to worry about using teething toys but a child should also have time to freely use their tongue for good development.


Memory switch

A new tool has been used for the first time to look at brain activity – ribosomal profiling. The method identifies the proteins that are being made at any time. Ribosomes make proteins using messenger RNA that was copied from the DNA of genes. The method is to destroy all the messenger RNA that is not actually within a ribosome, or in other words, being actively used to make protein. The protected RNA can be used to identify the genes that were being translated into proteins at the moment that the cell was broken and the free RNA destroyed.

ScienceDaily reports on a press release from the Institute for Basic Science describing the use of this technique to study memory formation. (here) The research was done in the IBS Center for RNA Research and Department of Biological Sciences at Seoul National University. There is a on-off switch for formation of memories that is based on changes in protein production.

When an animal experiences no stimulus in an environment the hippocampus undergoes gene repression which prevents the formation of new memories. Upon the introduction of a stimulus, the hippocampus’ repressive gene regulation is turned off allowing for new memory creation, and as Jun Cho puts it, “Our study illustrates the potential importance of negative gene regulation in learning and memory”.

I assume this research will appear in a journal paper and that the technique will be used in other studies of the brain. It is always good to hear of new methods being available.

Islands and ocean of memory

Episodic memories are tagged with information about time and place. If we remember an event then it is almost certain we will remember where it happened and where it lies in the temporal sequence of events. Research has shown that an activity pattern in a part of the brain involved in memory, the entorhinal cortex, feeds where and when information to the hippocampus which forms the new memory.

The research is reported in a recent paper: Takashi Kitamura, Chen Sun, Jared Martin, Lacey J. Kitch, Mark J. Schnitzer, Susumu Tonegawa. Entorhinal Cortical Ocean Cells Encode Specific Contexts and Drive Context-Specific Fear Memory. Neuron, 2015; DOI: 10.1016/j.neuron.2015.08.036.

The entorhinal area involved has been likened to an ocean of context specific ‘where’ cells with islands of ‘when’ cells. The ocean cells signal the CA3 cells of the hippocampus and the island cells signal the CA1 cells. If ocean cells are blocked, animals cannot learn to connect fear with a particular environment. Island cells seem to react to the speed an animal is moving at and manipulating their signals changed the gap between events being linked in an animals memory. This is probably one of many ingredients in the processing of time-and-space.

Absract: “Forming distinct representations and memories of multiple contexts and episodes is thought to be a crucial function of the hippocampal-entorhinal cortical network. The hippocampal dentate gyrus (DG) and CA3 are known to contribute to these functions, but the role of the entorhinal cortex (EC) is poorly understood. Here, we show that Ocean cells, excitatory stellate neurons in the medial EC layer II projecting into DG and CA3, rapidly form a distinct representation of a novel context and drive context-specific activation of downstream CA3 cells as well as context-specific fear memory. In contrast, Island cells, excitatory pyramidal neurons in the medial EC layer II projecting into CA1, are indifferent to context-specific encoding or memory. On the other hand, Ocean cells are dispensable for temporal association learning, for which Island cells are crucial. Together, the two excitatory medial EC layer II inputs to the hippocampus have complementary roles in episodic memory.

The thalamus revisited

For a few decades, I have had the opinion that to understand how the brain works it is important to look at more than the neocortex, but also look to the other areas of the brain that may modify, control or even drive the activity of the cortex. Because of my special interest in consciousness, the thalamus was always interesting in this respect. Metaphorically the cortex seemed to be the big on-line computer run by the thalamus.

A recent paper makes another connection between the cortex and the thalamus, to add to many others – (F. Alcaraz, A. R. Marchand, E. Vidal, A. Guillou, A. Faugere, E. Coutureau, M. Wolff. Flexible Use of Predictive Cues beyond the Orbitofrontal Cortex: Role of the Submedius Thalamic Nucleus. Journal of Neuroscience, 2015; 35 (38): 13183 DOI: 10.1523/JNEUROSCI.1237-15.2015).

The various parts of the thalamus are connected to incoming sensory signals, all parts of the cortex, the hippocampus, the mid-brain areas, the spinal cord and the brain stem. It is one of the ‘hubs’ of the brain and its activity is essential for consciousness. However, the particular bit of the thalamus that is implicated in this particular function (adaptive decision making flexibility) appears to have been mainly studied in relationship to pain and control of pain. There is a lot to learn about the thalamus!

Here is the abstract: “The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of specific events. However, the contribution of OFC thalamic inputs to these processes is largely unknown. Using a tract-tracing approach, we first demonstrated that the submedius nucleus (Sub) shares extensive reciprocal connections with the OFC. We then compared the effects of excitotoxic lesions of the Sub or the OFC on the ability of rats to use outcome identity to direct responding. We found that neither OFC nor Sub lesions interfered with the basic differential outcomes effect. However, more specific tests revealed that OFC rats, but not Sub rats, were disproportionally relying on the outcome, rather than on the discriminative stimulus, to guide behavior, which is consistent with the view that the OFC integrates information about predictive cues. In subsequent experiments using a Pavlovian contingency degradation procedure, we found that both OFC and Sub lesions produced a severe deficit in the ability to update Pavlovian associations. Altogether, the submedius therefore appears as a functionally relevant thalamic component in a circuit dedicated to the integration of predictive cues to guide behavior, previously conceived as essentially dependent on orbitofrontal functions.

SIGNIFICANCE STATEMENT: In the present study, we identify a largely unknown thalamic region, the submedius nucleus, as a new functionally relevant component in a circuit supporting the flexible use of predictive cues. Such abilities were previously conceived as largely dependent on the orbitofrontal cortex. Interestingly, this echoes recent findings in the field showing, in research involving an instrumental setup, an additional involvement of another thalamic nuclei, the parafascicular nucleus, when correct responding requires an element of flexibility (Bradfield et al., 2013a). Therefore, the present contribution supports the emerging view that limbic thalamic nuclei may contribute critically to adaptive responding when an element of flexibility is required after the establishment of initial learning.

Forming memories

The contents of episodic memory (but not other types of memory) are formed in the medial temporal lobe (the hippocampus and neocortical areas adjacent to it, including the entrorhinal area). This part of the brain seems to pick out moments of our conscious experience and commit them to memory. A recent paper looks at individual neurons involved in this memory formation. (Matias J. Ison, Rodrigo Quian Quiroga, Itzhak Fried. Rapid Encoding of New Memories by Individual Neurons in the Human Brain. Neuron, 2015; 87 (1): 220 DOI: 10.1016/j.neuron.2015.06.016)

The researchers used the method of asking cooperation from patients who are awaiting surgery for epilepsy and have been fitted with electrodes in a particular area of the brain to locate the exact focus of the epilepsy. This is probably the only ethical way in which studies can be done involving the recording from individual neurons in humans.

It is thought that memories are established by associations. But it is a puzzle how associations can be made by single exposures to unique natural events. The researchers showed patients many images of people, animals and places. Images that activated a single neuron from those that were being recorded were set aside for use. The images were made into composites where one person or animal image was put into one place image to appear to be the person/animal in that setting. The neurons that had responded to one of the images but not the other began responding to both original images after being exposed to the composite. A neuron was forming an association of the two parts of the composite. Associations formed rapidly in an all-or-nothing manner.

After rapid capture, these associations are probably manipulated and consolidated (or destroyed) in the production of more permanent and complex memories.

Abstract: “The creation of memories about real-life episodes requires rapid neuronal changes that may appear after a single occurrence of an event. How is such demand met by neurons in the medial temporal lobe (MTL), which plays a fundamental role in episodic memory formation? We recorded the activity of MTL neurons in neurosurgical patients while they learned new associations. Pairs of unrelated pictures, one of a person and another of a place, were used to construct a meaningful association modeling the episodic memory of meeting a person in a particular place. We found that a large proportion of responsive MTL neurons expanded their selectivity to encode these specific associations within a few trials: cells initially responsive to one picture started firing to the associated one but not to others. Our results provide a plausible neural substrate for the inception of associations, which are crucial for the formation of episodic memories.