When shared concept cells support associations: Theory of overlapping memory engrams.

Assemblies of neurons, called concepts cells, encode acquired concepts in human Medial Temporal Lobe. Those concept cells that are shared between two assemblies have been hypothesized to encode associations between concepts. Here we test this hypothesis in a computational model of attractor neural networks. We find that for concepts encoded in sparse neural assemblies there is a minimal fraction cmin of neurons shared between assemblies below which associations cannot be reliably implemented; and a maximal fraction cmax of shared neurons above which single concepts can no longer be retrieved. In the presence of a periodically modulated background signal, such as hippocampal oscillations, recall takes the form of association chains reminiscent of those postulated by theories of free recall of words. Predictions of an iterative overlap-generating model match experimental data on the number of concepts to which a neuron responds.

Searching for the neural correlates of human intelligence.

In this My Word, Rodrigo Quian Quiroga discusses neural mechanisms underlying human memory and uniquely human cognitive abilities.

Compact standalone platform for neural recording with real-time spike sorting and data logging.

OBJECTIVE: Longitudinal observation of single unit neural activity from large numbers of cortical neurons in awake and mobile animals is often a vital step in studying neural network behaviour and towards the prospect of building effective brain-machine interfaces (BMIs). These recordings generate enormous amounts of data for transmission and storage, and typically require offline processing to tease out the behaviour of individual neurons. Our aim was to create a compact system capable of: (1) reducing the data bandwidth by circa 2 to 3 orders of magnitude (greatly improving battery lifetime and enabling low power wireless transmission in future versions); (2) producing real-time, low-latency, spike sorted data; and (3) long term untethered operation. APPROACH: We have developed a headstage that operates in two phases. In the short training phase a computer is attached and classic spike sorting is performed to generate templates. In the second phase the system is untethered and performs template matching to create an event driven spike output that is logged to a micro-SD card. To enable validation the system is capable of logging the high bandwidth raw neural signal data as well as the spike sorted data. MAIN RESULTS: The system can successfully record 32 channels of raw neural signal data and/or spike sorted events for well over 24 h at a time and is robust to power dropouts during battery changes as well as SD card replacement. A 24 h initial recording in a non-human primate M1 showed consistent spike shapes with the expected changes in neural activity during awake behaviour and sleep cycles. SIGNIFICANCE: The presented platform allows neural activity to be unobtrusively monitored and processed in real-time in freely behaving untethered animals-revealing insights that are not attainable through scheduled recording sessions. This system achieves the lowest power per channel to date and provides a robust, low-latency, low-bandwidth and verifiable output suitable for BMIs, closed loop neuromodulation, wireless transmission and long term data logging.

Improving data quality in neuronal population recordings.

Understanding how the brain operates requires understanding how large sets of neurons function together. Modern recording technology makes it possible to simultaneously record the activity of hundreds of neurons, and technological developments will soon allow recording of thousands or tens of thousands. As with all experimental techniques, these methods are subject to confounds that complicate the interpretation of such recordings, and could lead to erroneous scientific conclusions. Here we discuss methods for assessing and improving the quality of data from these techniques and outline likely future directions in this field.

Magic and cognitive neuroscience.

In recent years, neuroscientists have shown an increasing interest in magic. One reason for this is the parallels that can be drawn between concepts that have long been discussed in magic theory, particularly misdirection, and those that are routinely studied in cognitive neuroscience, such as attention and, as argued in this essay, different forms of memory. A second and perhaps more attractive justification for this growing interest is that magic tricks offer novel experimental approaches to cognitive neuroscience. In fact, magicians continuously demonstrate in very engaging ways one of the most basic principles of brain function - how the brain constructs a subjective reality using assumptions based on relatively little and ambiguous information.

Looking for a face in the crowd: fixation-related potentials in an eye-movement visual search task.

Despite the compelling contribution of the study of event related potentials (ERPs) and eye movements to cognitive neuroscience, these two approaches have largely evolved independently. We designed an eye-movement visual search paradigm that allowed us to concurrently record EEG and eye movements while subjects were asked to find a hidden target face in a crowded scene with distractor faces. Fixation event-related potentials (fERPs) to target and distractor stimuli showed the emergence of robust sensory components associated with the perception of stimuli and cognitive components associated with the detection of target faces. We compared those components with the ones obtained in a control task at fixation: qualitative similarities as well as differences in terms of scalp topography and latency emerged between the two. By using single trial analyses, fixations to target and distractors could be decoded from the EEG signals above chance level in 11 out of 12 subjects. Our results show that EEG signatures related to cognitive behavior develop across spatially unconstrained exploration of natural scenes and provide a first step towards understanding the mechanisms of target detection during natural search.

A detailed and fast model of extracellular recordings.

We present a novel method to generate realistic simulations of extracellular recordings. The simulations were obtained by superimposing the activity of neurons placed randomly in a cube of brain tissue. Detailed models of individual neurons were used to reproduce the extracellular action potentials of close-by neurons. To reduce the computational load, the contributions of neurons further away were simulated using previously recorded spikes with their amplitude normalized by the distance to the recording electrode. For making the simulations more realistic, we also considered a model of a finite-size electrode by averaging the potential along the electrode surface and modeling the electrode-tissue interface with a capacitive filter. This model allowed studying the effect of the electrode diameter on the quality of the recordings and how it affects the number of identified neurons after spike sorting. Given that not all neurons are active at a time, we also generated simulations with different ratios of active neurons and estimated the ratio that matches the signal-to-noise values observed in real data. Finally, we used the model to simulate tetrode recordings.

Gnostic cells in the 21st century.

In this short review, I revise the notion of gnostic cells posited by Konorski, together with similar arguments by James, Lettvin and Barlow--namely, the idea of pontifical, grandmother and cardinal cells, respectively. I then discuss whether the characteristics of the recently discovered concept cells, i.e. neurons in the human medial temporal lobe with a very high degree of specificity and invariance, fit the conjecture of gnostic or grandmother cells and then discuss the key role of concept cells in memory formation.

Concept cells: the building blocks of declarative memory functions.

Intracranial recordings in subjects suffering from intractable epilepsy - made during their evaluation for an eventual surgical removal of the epileptic focus - have allowed the extraordinary opportunity to study the firing of multiple single neurons in awake and behaving human subjects. These studies have shown that neurons in the human medial temporal lobe respond in a remarkably selective and abstract manner to particular persons or objects, such as Jennifer Aniston, Luke Skywalker or the Tower of Pisa. These neurons have been named 'Jennifer Aniston neurons' or, more recently, 'concept cells'. I argue that the sparse, explicit and abstract representation of these neurons is crucial for memory functions, such as the creation of associations and the transition between related concepts that leads to episodic memories and the flow of consciousness.

Fixation-related potentials in visual search: a combined EEG and eye tracking study.

We report a study of concurrent eye movements and electroencephalographic (EEG) recordings while subjects freely explored a search array looking for hidden targets. We describe a sequence of fixation-event related potentials (fERPs) that unfolds during ∼ 400 ms following each fixation. This sequence highly resembles the event-related responses in a replay experiment, in which subjects kept fixation while a sequence of images occurred around the fovea simulating the spatial and temporal patterns during the free viewing experiment. Similar responses were also observed in a second control experiment where the appearance of stimuli was controlled by the experimenters and presented at the center of the screen. We also observed a relatively early component (∼150 ms) that distinguished between targets and distractors only in the freeviewing condition. We present a novel approach to match the critical properties of two conditions (targets/distractors), which can be readily adapted to other paradigms to investigate EEG components during free eye-movements.

In vivo neuronal firing patterns during human epileptiform discharges replicated by electrical stimulation.

OBJECTIVE: To describe neuronal firing patterns observed during human spontaneous interictal epileptiform discharges (IEDs) and responses to single pulse electrical stimulation (SPES). METHODS: Activity of single neurons was recorded during IEDs and after SPES in 11 consecutive patients assessed with depth EEG electrodes and attached microelectrodes. RESULTS: A total of 66 neurons were recorded during IEDs and 151 during SPES. We have found essentially similar patterns of neuronal firing during IEDs and after SPES, namely: (a) a burst of high frequency firing lasting less than 100 ms (in 39% and 25% of local neurons, respectively for IED and SPES); (b) a period of suppression in firing lasting around 100-1300 ms (in 19% and 14%, respectively); (c) a burst followed by suppression (in 10% and 12%, respectively); (d) no-change (in 32% and 50%, respectively). CONCLUSIONS: The similarities in neuronal firing patterns associated with IEDs and SPES suggest that, although both phenomena are initiated differently, they result in the activation of a common cortical mechanism, probably initiated by brief synchronised burst firing in some cells followed by long inhibition. SIGNIFICANCE: The findings provide direct in vivo human evidence to further comprehend the pathophysiology of human focal epilepsy.

Event related potentials to digit learning: tracking neurophysiologic changes accompanying recall performance.

The aim of this study was to track recall performance and event-related potentials (ERPs) across multiple trials in a digit-learning task. When a sequence is practiced by repetition, the number of errors typically decreases and a learning curve emerges. Until now, almost all ERP learning and memory research has focused on effects after a single presentation and, therefore, fails to capture the dynamic changes that characterize a learning process. However, the current study used a free-recall task in which a sequence of ten auditory digits was presented repeatedly. Auditory sequences of ten digits were presented in a logical order (control sequences) or in a random order (experimental sequences). Each sequence was presented six times. Participants had to reproduce the sequence after each presentation. EEG recordings were made at the time of the digit presentations. Recall performance for the control sequences was close to asymptote right after the first learning trial, whereas performance for the experimental sequences initially displayed primacy and recency effects. However, these latter effects gradually disappeared over the six repetitions, resulting in near-asymptotic recall performance for all digits. The performance improvement for the middle items of the list was accompanied by an increase in P300 amplitude, implying a close correspondence between this ERP component and the behavioral data. These results, which were discussed in the framework of theories on the functional significance of the P300 amplitude, add to the scarce empirical data on the dynamics of ERP responses in the process of intentional learning.

How do we see art: an eye-tracker study.

We describe the pattern of fixations of subjects looking at figurative and abstract paintings from different artists (Molina, Mondrian, Rembrandt, della Francesca) and at modified versions in which different aspects of these art pieces were altered with simple digital manipulations. We show that the fixations of the subjects followed some general common principles (e.g., being attracted to saliency regions) but with a large variability for the figurative paintings, according to the subject's personal appreciation and knowledge. In particular, we found different gazing patterns depending on whether the subject saw the original or the modified version of the painting first. We conclude that the study of gazing patterns obtained by using the eye-tracker technology gives a useful approach to quantify how subjects observe art.

A category-specific response to animals in the right human amygdala.

The amygdala is important in emotion, but it remains unknown whether it is specialized for certain stimulus categories. We analyzed responses recorded from 489 single neurons in the amygdalae of 41 neurosurgical patients and found a categorical selectivity for pictures of animals in the right amygdala. This selectivity appeared to be independent of emotional valence or arousal and may reflect the importance that animals held throughout our evolutionary past.

Selectivity of pyramidal cells and interneurons in the human medial temporal lobe.

Neurons in the medial temporal lobe (MTL) respond selectively to pictures of specific individuals, objects, and places. However, the underlying mechanisms leading to such degree of stimulus selectivity are largely unknown. A necessary step to move forward in this direction involves the identification and characterization of the different neuron types present in MTL circuitry. We show that putative principal cells recorded in vivo from the human MTL are more selective than putative interneurons. Furthermore, we report that putative hippocampal pyramidal cells exhibit the highest degree of selectivity within the MTL, reflecting the hierarchical processing of visual information. We interpret these differences in selectivity as a plausible mechanism for generating sparse responses.

On-line, voluntary control of human temporal lobe neurons.

Daily life continually confronts us with an exuberance of external, sensory stimuli competing with a rich stream of internal deliberations, plans and ruminations. The brain must select one or more of these for further processing. How this competition is resolved across multiple sensory and cognitive regions is not known; nor is it clear how internal thoughts and attention regulate this competition. Recording from single neurons in patients implanted with intracranial electrodes for clinical reasons, here we demonstrate that humans can regulate the activity of their neurons in the medial temporal lobe (MTL) to alter the outcome of the contest between external images and their internal representation. Subjects looked at a hybrid superposition of two images representing familiar individuals, landmarks, objects or animals and had to enhance one image at the expense of the other, competing one. Simultaneously, the spiking activity of their MTL neurons in different subregions and hemispheres was decoded in real time to control the content of the hybrid. Subjects reliably regulated, often on the first trial, the firing rate of their neurons, increasing the rate of some while simultaneously decreasing the rate of others. They did so by focusing onto one image, which gradually became clearer on the computer screen in front of their eyes, and thereby overriding sensory input. On the basis of the firing of these MTL neurons, the dynamics of the competition between visual images in the subject's mind was visualized on an external display.

Responses of human medial temporal lobe neurons are modulated by stimulus repetition.

Recent studies have reported the presence of single neurons with strong responses to visual inputs in the human medial temporal lobe. Here we show how repeated stimulus presentation--photos of celebrities and familiar individuals, landmark buildings, animals, and objects--modulates the firing rate of these cells: a consistent decrease in the neural activity was registered as images were repeatedly shown during experimental sessions. The effect of repeated stimulus presentation was not the same for all medial temporal lobe areas. These findings are consistent with the view that medial temporal lobe neurons link visual percepts to declarative memory.