Brain Areas Research Articles

A common and specialized neural code for social attention triggered by eye gaze and biological motion

Humans appear to be endowed with the ability to readily share attention with interactive partners through the utilization of social direction cues, such as eye gaze and biological motion (BM). Here, we investigated the specialized brain mechanism underlying this fundamental social attention ability by incorporating different types of social (i.e., BM, gaze) and non-social (arrow) cues and combining functional magnetic resonance imaging (fMRI) with a modified central cueing paradigm. Using multi-voxel pattern analysis (MVPA), we found that although gaze- and BM-mediated attentional orienting could be decoded from neural activity in a wide range of brain areas, only the right anterior and posterior superior temporal sulcus (aSTS and pSTS) could specifically decode attentional orienting triggered by social but not non-social cues. Critically, cross-category MVPA further revealed that social attention could be decoded across BM and gaze cues in the right STS and the right superior temporal gyrus (STG). However, these regions could not decode attentional orienting across social and non-social cues. These findings together provide evidence for the existence of a specialized social attention module in the human brain, with the right STS/STG being the critical neural site dedicated to social attention.

Disturbances of Interoception in Schizophrenia – Focus on Neuroimaging

Abstract: The current paper presents the most recent theoretical understanding of interoception (INTC) in light of the predictive processing framework and the Embodied Predictive Interoceptive Coding model and reviews recent experimental data on different interoceptive disturbances in schizophrenia (SCZ) such as lower interoceptive accuracy, nociceptive dysfunction reflected by reduced pain sensitivity, disturbed thermoregulation, impaired gastrointestinal regulation, cardiovascular and respiratory dysfunction, and immune disturbances. The immense clinical implications of these disturbances are discussed in the context of the high rates of morbidity and mortality in SCZ related to suicide and cardiac death. Next, the potential of INTC-related treatments is reviewed, and conclusions are made on the evidence for the use of vagus nerve stimulation, mindfulness-based interventions, and exercise therapy. The neuroimaging perspective is given in a brief account of the INTC-related findings in healthy individuals suggesting the right anterior insula and anterior cingulate cortex as key brain areas for interoceptive awareness, accuracy, and sensibility, by supporting higher-order representation and integration of visceral, and somatosensory interoception with exteroceptive information. In SCZ, on the other hand, neuroimaging research on specific interoceptive abilities is lacking but indirect evidence points to disrupted activation of major INTC network hubs. There is converging evidence of changes in these hubs in terms of both structure and function (volume reductions, aberrant activation, and connectivity). This narrative review identifies several gaps in contemporary INTC-related research in SCZ that need to be addressed in future experimental and clinical studies to elucidate the exact nature of the disturbances of interoceptive abilities in modalities other than cardioception; the interactions between different interoceptive modalities; the association between interoceptive abilities and other mental functions (such as emotion recognition and regulation, decision making, learning, memory, etc.); the efficacy of nonpharmacological and pharmacological INTC-based interventions; and the relation of disturbed interoceptive abilities with brain structure and function.

Preserved working memory performance along with subcortical modulation during peri-ictal phases in spontaneous migraine attacks.

To analyze cognitive performance and brain activation during a working memory task in patients with migraine during various phases of the migraine cycle and compare to healthy participants. Cognitive difficulties reported during migraine attacks remain poorly understood, despite evidence that the lateral frontoparietal network undergoes reversible disturbances and decreased activation during attacks. Recent findings in resting state functional magnetic resonance imaging suggest that brain areas involved in this network interact with subcortical regions during spontaneous migraine attacks. In this prospective, within-subject study, 10 patients with diagnosed menstrual-related episodic migraine without aura underwent 3T functional magnetic resonance imaging assessments while performing a working memory task across four phases of the natural migraine cycle: peri-ictal (preictal, ictal, postictal) phases and interictally (between attacks). Migraine prophylaxis was an exclusion criterion. Fourteen healthy controls were assessed during the corresponding phases of their menstrual cycles. The protocol was completed by 24 female participants aged 21 to 47 years: 10 with migraine (four sessions each) and 14 healthy controls (two sessions each) yielding a total of 68 analyzed datasets. Patients and controls showed similar performance on the working memory task and displayed increased brain activity in regions linked to this function, namely the middle frontal gyrus, inferior parietal lobe, and anterior cingulate cortex, during all phases of the migraine/menstrual cycle. Patients with migraine (N = 10) exhibited a significant decrease in hypothalamic activity (p = 0.007) as measured by the percent signal change (PSC) during the postictal phase compared to perimenstrual controls (N = 14), with -2 (16) and 31 (35) PSC, respectively. Comparing across the migraine cycle, the change in hypothalamic activity relative to controls in the postictal phase -0.33 (0.2) ΔPSC was significantly different from the ones in the interictal (0.006 [0.5] ΔPSC; p = 0.002) and preictal (-0.08 [0.4] ΔPSC; p = 0.034) phases. During a working memory task, cognition-related brain activation was present across all phases of the migraine cycle similarly to healthy control participants. Patients with migraine, however, displayed lower neural activity at the subcortical level in the postictal phase. Nonetheless, the sample size is a limitation for the generalization of our results. More research is needed to fully understand how the brain copes with cognitive demands during spontaneous migraine attacks.

Early disruption of entorhinal dopamine in a knock-in model of Alzheimer's disease.

The entorhinal cortex (EC) is a critical brain area for memory formation, while also the region exhibiting the earliest histological and functional alterations in Alzheimer's disease (AD). The EC thus has been long hypothesized as one of the originating brain areas of AD pathophysiology, although circuit mechanisms causing its selective vulnerability remain poorly understood. We found that dopamine neurons projecting their axons to the lateral EC (LEC), critical for memory formation in healthy brains, become dysfunctional and cause memory impairments in early AD brains. In amyloid precursor protein knock-in mice with associative memory impairment, LEC dopamine activity and associative memory encoding of LEC layer 2/3 neurons were disrupted in parallel from the early pathological stage. Optogenetic reactivation of LEC dopamine fibers, as well as L- DOPA treatment, rescued associative learning behavior. These results suggest that dysfunction of LEC-projecting dopamine neurons underlies memory impairment in AD from early stages, pointing to a need for clinical investigation of LEC dopamine in AD patients.

Estrogen Receptor Beta Agonist Influences Presynaptic NMDA Receptor Distribution in the Paraventricular Hypothalamic Nucleus Following Hypertension in a Mouse Model of Perimenopause.

Women become susceptible to hypertension as they transition to menopause (i.e., perimenopause); however, the underlying mechanisms are unclear. Animal studies using an accelerated ovarian failure (AOF) model of peri-menopause (peri-AOF) demonstrate that peri-AOF hypertension is associated with increased postsynaptic NMDA receptor plasticity in the paraventricular hypothalamic nucleus (PVN), a brain area critical for blood pressure regulation. However, recent evidence indicates that presynaptic NMDA receptors also play a role in neural plasticity. Here, using immuno-electron microscopy, we examine the influence of peri-AOF hypertension on the subcellular distribution of the essential NMDA GluN1 receptor subunit in PVN axon terminals in peri-AOF and in male mice. Hypertension was produced by 14-day slow-pressor angiotensin II (AngII) infusion. The involvement of estrogen signaling was investigated by co-administering an estrogen receptor beta (ERß) agonist. Although AngII induced hypertension in both peri-AOF and male mice, peri-AOF females showed higher cytoplasmic GluN1 levels. In peri-AOF females, activation of ERß blocked hypertension and increased plasmalemmal GluN1 in axon terminals. In contrast, stimulation of ERß did not inhibit hypertension or influence presynaptic GluN1 localization in males. These results indicate that sex-dependent recruitment of presynaptic NMDA receptors in the PVN is influenced by ERß signaling in mice during early ovarian failure.

A Pilot Randomized Control Trial Testing a Smartphone-Delivered Food Attention Retraining Program in Adolescent Girls with Overweight or Obesity.

Attention bias (AB) toward food is associated with obesity, but it is unclear if programs designed to reduce AB can impact adolescents' eating behavior. We investigated whether a two-week, smartphone-delivered attention retraining (AR) program (vs a control program) altered food AB in adolescent girls with overweight. Participants completed three food-cue visual-probe trainings/day. The AR and control programs directed attention away from food stimuli during 100% and 50% of trainings, respectively. Before and after completion of the programs, girls completed a food-cue visual-probe task while undergoing magnetoencephalography (MEG), and then a laboratory test meal. Sixty-eight adolescents were randomized; 58 completed post-program visits. There was minimal effect of condition on AB scores (β [95%CI] = -1.9 [-20.8, 16.9]; d = -0.06). There was a small effect of condition on energy intake (EMMcontrol = 1017 kcal, EMMAR = 1088 kcal, d = 0.29). Within the AR group, there was slightly blunted initial engagement in brain areas associated with reward response and subsequent increased goal-directed attention and action control. We found preliminary support for efficacy of an intensive smartphone-delivered AR program to alter neural correlates of attention processing in adolescent girls with overweight or obesity. Studies with larger sample sizes are needed to elucidate if AR trainings disrupt the link between food AB and eating behavior.

Vesicular Transport and Amyloids: The Growing Relationship

Protein aggregation may lead to detrimental changes in brain and several other tissues. Amyloids or large protein aggregates are formed in different brain areas under multiple diseases classified as proteinopathies. However, our understanding of the initiation, elongation, and spread of amyloid aggregates is limited. Our current knowledge about these diseases is generic and we lack specific mechanisms for several diseases affecting memory, movement, and behavior. Multiple studies have indicated the involvement of vesicular transport in the spread of aggregates formed inside the brain. For example, the trafficking of amyloid precursor protein (APP) occurs from Golgi to Endosome using an adapter protein complex. Amyloids, once formed, may also affect cholesterol (an important membrane constituent), homeostasis, and overall membranous transport. A disruption of vesicular transport could be deleterious for synaptic neurotransmission. Alterations caused by amyloid proteins in vesicular transport may form a feedback loop and thus contribute further to the pathogenesis of Alzheimer’s disease (AD) and many others. In this review, we are providing recent updates on this crisscross puzzle and exploring an evolving correlation between amyloid formation and vesicular transport.

Cell class-specific long-range axonal projections of neurons in mouse whisker-related somatosensory cortices.

Long-range axonal projections of diverse classes of neocortical excitatory neurons likely contribute to brain-wide interactions processing sensory, cognitive and motor signals. Here, we performed light-sheet imaging of fluorescently labeled axons from genetically defined neurons located in posterior primary somatosensory barrel cortex and supplemental somatosensory cortex. We used convolutional networks to segment axon-containing voxels and quantified their distribution within the Allen Mouse Brain Atlas Common Coordinate Framework. Axonal density was analyzed for different classes of glutamatergic neurons using transgenic mouse lines selectively expressing Cre recombinase in layer 2/3 intratelencephalic projection neurons (Rasgrf2-dCre), layer 4 intratelencephalic projection neurons (Scnn1a-Cre), layer 5 intratelencephalic projection neurons (Tlx3-Cre), layer 5 pyramidal tract projection neurons (Sim1-Cre), layer 5 projection neurons (Rbp4-Cre), and layer 6 corticothalamic neurons (Ntsr1-Cre). We found distinct axonal projections from the different neuronal classes to many downstream brain areas, which were largely similar for primary and supplementary somatosensory cortices. Functional connectivity maps obtained from optogenetic activation of sensory cortex and wide-field imaging revealed topographically organized evoked activity in frontal cortex with neurons located more laterally in somatosensory cortex signaling to more anteriorly located regions in motor cortex, consistent with the anatomical projections. The current methodology therefore appears to quantify brain-wide axonal innervation patterns supporting brain-wide signaling.

ARISE-The Accuracy Evaluation of a Patient-Specific 3D-Printed Biopsy System Based on MRI Data: A Cadaveric Study.

Brain biopsy is required for the accurate specification and further diagnosis of intracranial findings. The conventional stereotactic frames are used clinically for biopsies and offer the highest possible precision. Unfortunately, they come with some insurmountable technical and logistical limitations. The aim of the present work is to determine the clinical precision in the needle biopsy of the human brain using a new patient-specific stereotactic navigation device based on 3D printing. MRI data sets of human cadaver heads were used to plan 32 intracranial virtual biopsy targets located in different brain regions. Based on these data, 16 individualized stereotactic frames were 3D-printed. After the intraoperative application of the stereotactic device to the cadaver's head, the actual needle position was verified by postoperative CT. Thirty-two brain areas were successfully biopsied. The target point accuracy was 1.05 ± 0.63 mm, which represents the difference between the planned and real target points. The largest target point deviation was in the coronal plane at 0.60 mm; the smallest was in the transverse plane (0.45 mm). Three-dimensional-printed, personalized stereotactic frames or platforms are an alternative to the commonly used frame-based and frameless stereotactic systems. They are particularly advantageous in terms of accuracy, reduced medical imaging, and significantly simplified intraoperative handling.

Cell class-specific long-range axonal projections of neurons in mouse whisker-related somatosensory cortices

Long-range axonal projections of diverse classes of neocortical excitatory neurons likely contribute to brain-wide interactions processing sensory, cognitive and motor signals. Here, we performed light-sheet imaging of fluorescently labeled axons from genetically defined neurons located in posterior primary somatosensory barrel cortex and supplemental somatosensory cortex. We used convolutional networks to segment axon-containing voxels and quantified their distribution within the Allen Mouse Brain Atlas Common Coordinate Framework. Axonal density was analyzed for different classes of glutamatergic neurons using transgenic mouse lines selectively expressing Cre recombinase in layer 2/3 intratelencephalic projection neurons (Rasgrf2-dCre), layer 4 intratelencephalic projection neurons (Scnn1a-Cre), layer 5 intratelencephalic projection neurons (Tlx3-Cre), layer 5 pyramidal tract projection neurons (Sim1-Cre), layer 5 projection neurons (Rbp4-Cre), and layer 6 corticothalamic neurons (Ntsr1-Cre). We found distinct axonal projections from the different neuronal classes to many downstream brain areas, which were largely similar for primary and supplementary somatosensory cortices. Functional connectivity maps obtained from optogenetic activation of sensory cortex and wide-field imaging revealed topographically organized evoked activity in frontal cortex with neurons located more laterally in somatosensory cortex signaling to more anteriorly located regions in motor cortex, consistent with the anatomical projections. The current methodology therefore appears to quantify brain-wide axonal innervation patterns supporting brain-wide signaling.

Neural correlates of working memory training: An fMRI meta-analysis

Working memory (WM) can be improved by cognitive training. Numerous studies examined neural mechanisms underlying WM training, although with differing conclusions. Therefore, we conducted a meta-analysis to examine the neural substrates underlying WM training in healthy adults. Findings from global analyses showed substantial neural changes in the frontoparietal and subcortical regions. Results from training dosage analyses of WM training showed that shorter WM training could produce neural changes in the frontoparietal regions, whereas longer WM training could produce changes in the subcortical regions (striatum, anterior cingulate cortex, and insula). WM training-induced neural changes were also moderated by the type of training task, with updating tasks inducing neural changes in more regions than maintenance tasks. Overall, these results indicate that the neural changes associated with WM training occur in the frontoparietal network and dopamine-related brain areas, extending previous meta-analyses on WM training and advancing our understanding of the neural underpinnings of WM training effects.

Hearing Impairment: Reduced Pupil Dilation Response and Frontal Activation During Degraded Speech Perception.

A relevant aspect of listening is the effort required during speech processing, which can be assessed by pupillometry. Here, we assessed the pupil dilation response of normal-hearing (NH) and hard of hearing (HH) individuals during listening to clear sentences and masked or degraded sentences. We combined this assessment with functional magnetic resonance imaging (fMRI) to investigate the neural correlates of the pupil dilation response. Seventeen NH participants (Mage = 46 years) were compared to 17 HH participants (Mage = 45 years) who were individually matched in age and educational level. Participants repeated sentences that were presented clearly, that were distorted, or that were masked. The sentence intelligibility level of masked and distorted sentences was 50% correct. Silent baseline trials were presented as well. Performance measures, pupil dilation responses, and fMRI data were acquired. HH individuals had overall poorer speech reception than the NH participants, but not for noise-vocoded speech. In addition, an interaction effect was observed with smaller pupil dilation responses in HH than in NH listeners for the degraded speech conditions. Hearing impairment was associated with higher activation across conditions in the left superior temporal gyrus, as compared to the silent baseline. However, the region of interest analysis indicated lower activation during degraded speech relative to clear speech in bilateral frontal regions and the insular cortex, for HH compared to NH listeners. Hearing impairment was also associated with a weaker relation between the pupil response and activation in the right inferior frontal gyrus. Overall, degraded speech evoked higher frontal activation than clear speech. Brain areas associated with attentional and cognitive-control processes may be increasingly recruited when speech is degraded and are related to the pupil dilation response, but this relationship is weaker in HH listeners. https://doi.org/10.23641/asha.27162135.

Exosomal therapy mitigates silver nanoparticles-induced neurotoxicity in rats

Introduction Our investigation aims to appraise the neuroprotective impact of Bone Marrow-Mesenchymal Stem Cells (BM-MSCs) derived exosomes against Ag NPs-inducing neurotoxicity in rats. Materials and Methods Twenty-four albino rats were divided into 3 groups. Group I (control negative), Group II (intraperitoneally injected with Ag NPs for 28 days, whereas Group III (intraperitoneally injected with Ag NP and BM-MSCs derived exosomes. Results There was a marked elevation of Malondialdehyde (MDA) along with a reduction of brain antioxidants, Gamma-aminobutyric acid (GABA) and Monoamine Oxidase (MAO) in the Ag NPs receiving group. Ag NPs upregulated c-Jun N-terminal Kinases (JNK) genes and c-Myc and downregulated the tissue inhibitors of metalloproteinases (TIMP-1) and Histone deacetylase 1 (HDAC1) genes. Otherwise, the co-treatment of BM-MSCs derived exosomes with Ag NPs could markedly increase the rat’s body weight, activity and learning while, decreasing anxiety, restoring all the toxicological parameters and improving the microscopic appearance of different brain areas. Conclusion BM-MSCs-derived exosomes downregulated both apoptotic and inflammatory mediators and upregulated the antiapoptotic genes. BM-MSCs-derived exosomes exhibit a great therapeutic effect against the neurotoxic effects of Ag NPs.

Pre-Stimulus Activity of Left and Right TPJ in Linguistic Predictive Processing: A MEG Study.

The left and right temporoparietal junctions (TPJs) are two brain areas involved in several brain networks, largely studied for their diverse roles, from attentional orientation to theory of mind and, recently, predictive processing. In predictive processing, one crucial concept is prior precision, that is, the reliability of the predictions of incoming stimuli. This has been linked with modulations of alpha power as measured with electrophysiological techniques, but TPJs have seldom been studied in this framework. The present article investigates, using magnetoencephalography, whether spontaneous oscillations in pre-stimulus alpha power in the left and right TPJs can modulate brain responses during a linguistic task that requires predictive processing in literal and non-literal sentences. Overall, results show that pre-stimulus alpha power in the rTPJ was associated with post-stimulus responses only in the left superior temporal gyrus, while lTPJ pre-stimulus alpha power was associated with post-stimulus activity in Broca's area, left middle temporal gyrus, and left superior temporal gyrus. We conclude that both the right and left TPJs have a role in linguistic prediction, involving a network of core language regions, with differences across brain areas and linguistic conditions that can be parsimoniously explained in the context of predictive processing.

Imaging the large-scale and cellular response to focal traumatic brain injury in mouse neocortex.

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behavior are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1). Widefield imaging revealed an immediate CCI-induced activation at the injury site, followed by a massive slow wave of calcium signal activation that traveled across the majority of the dorsal cortex within approximately 30 s. Correspondingly, two-photon calcium imaging in primary somatosensory cortex (S1) found strong activation of neuropil and neuronal populations during the CCI-induced traveling wave. A depression of calcium signals followed the wave, during which we observed atypical activity of a sparse population of S1 neurons. Longitudinal imaging in the hours and days after CCI revealed increases in the area of whisker-evoked sensory maps at early time points, in parallel to decreases in cortical functional connectivity and behavioral measures. Neural and behavioral changes mostly recovered over hours to days in our M1-TBI model, with a more lasting decrease in the number of active S1 neurons. Our results in unanesthetized mice describe novel spatial and temporal neural adaptations that occur at cortical sites remote to a focal brain injury.

Cerebellar activity predicts vocalization in fruit bats

Echolocating bats exhibit remarkable auditory behaviors, enabled by adaptations both within and outside their auditory system. Yet research on echolocating bats has focused mostly on brain areas that belong to the classic ascending auditory pathway. This study provides direct evidence linking the cerebellum, an evolutionarily ancient and non-classic auditory structure, to vocalization and hearing. We report that in the fruit-eating bat Carollia perspicillata, external sounds can evoke cerebellar responses with latencies below 20ms. Such fast responses are indicative of early inputs to the bat cerebellum. After establishing fruit-eating bats as a good model to study cerebellar auditory responses, we searched for a neural correlate of vocal production within the cerebellum. We investigated spike trains and field potentials occurring before and after vocalization and found that the type of sound produced (echolocation pulses or communication calls) can be decoded from pre-vocal and post-vocal neural signals, with prediction accuracies that reach above 85%. The latter provides a direct correlate of vocalization in an ancient motor-coordination structure that lies outside of the classic ascending auditory pathway. Taken together, our findings provide evidence of specializations for vocalization and hearing in the cerebellum of an auditory specialist.

Bio-inspired feature selection for early diagnosis of Parkinson's disease through optimization of deep 3D nested learning.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders that affect the quality of human life of millions of people throughout the world. The probability of getting affected by this disease increases with age, and it is common among the elderly population. Early detection can help in initiating medications at an earlier stage. It can significantly slow down the progression of this disease, assisting the patient to maintain a good quality of life for a more extended period. Magnetic resonance imaging (MRI)-based brain imaging is an area of active research that is used to diagnose PD disease early and to understand the key biomarkers. The prior research investigations using MRI data mainly focus on volume, structural, and morphological changes in the basal ganglia (BG) region for diagnosing PD. Recently, researchers have emphasized the significance of studying other areas of the human brain for a more comprehensive understanding of PD and also to analyze changes happening in brain tissue. Thus, to perform accurate diagnosis and treatment planning for early identification of PD, this work focuses on learning the onset of PD from images taken from whole-brain MRI using a novel 3D-convolutional neural network (3D-CNN) deep learning architecture. The conventional 3D-Resent deep learning model, after various hyper-parameter tuning and architectural changes, has achieved an accuracy of 90%. In this work, a novel 3D-CNN architecture was developed, and after several ablation studies, the model yielded results with an improved accuracy of 93.4%. Combining features from the 3D-CNN and 3D ResNet models using Canonical Correlation Analysis (CCA) resulted in 95% accuracy. For further enhancements of the model performance, feature fusion with optimization was employed, utilizing various optimization techniques. Whale optimization based on a biologically inspired approach was selected on the basis of a convergence diagram. The performance of this approach is compared to other methods and has given an accuracy of 97%. This work represents a critical advancement in improving PD diagnosis techniques and emphasizing the importance of deep nested 3D learning and bio-inspired feature selection.

The neural mechanisms of race priming in American politics

Abstract What are the psychological mechanisms of racial “dog whistles” in American politics? Literature on race priming in American politics argues when race is primed implicitly, racial biases influence political evaluations, but when race is made salient, individuals can use controlled processing to inhibit automatic biases and abide by egalitarian norms. However, the neural mechanisms underlying these processes have yet to be examined directly. In a 2 × 2 within-groups experiment using functional magnetic resonance imaging, we examine these neural mechanisms. We find brain areas associated with conflict detection, evaluative processing, and controlled processing are more active when race is primed explicitly rather than implicitly, as expected, although we do not find substantial brain activation associated with automatic responses to be more active during implicit than explicit primes. Results are discussed in terms of understanding how racial cues influence political evaluations while considering America’s ever-changing racial norms.

Liaisons Among Symbols

Biologic processes can be depicted as circular algorithms on a limited number of distinct elements. The concept deviates from the Sumerian tradition of using an unlimited number of identical units in a linear, noncircular fashion. We have uncovered relations between distinguishable elements that are constructed by using two natural numbers a, b (a, b ≤ 16, a ≤ b) that make up together one “Akkadian” unit. We propose to use the etalon collection of 136 units, each of which is a pair of a,b. (The collection consists of numeric values: {(1,1), (1,2), (1,3),…,(2,2), (2,3),…., (15,16), (16,16).}). We order and reorder the etalon collection by sorting and resorting it, paying attention to the cycles that appear during a resort, and to the certitude of coincidences appearing as a consequence of several cycles running parallel (like wheels of a Las Vegas machine). Reader is strongly advised to conduct a simple exercise of self-education, by ordering 12 books on their table, first in a sequence author – title, from which the reorder into the sequence title – author is the source of the self-education. Ordering and sorting are abilities that children learn sooner than at the age of 6 years, before the child learns the Sumerian concepts of what is a unit. The ability to recognize sorting procedures generating circular references has not been educated along with the ability to recognize multitudes made up of identical units. The terms ‘place’, ‘value’, ‘movement’, ‘time’, ‘coincidence’, ‘potential’, ‘information’, etc. are experienced anew, while doing the self-educating experiment with 12 books, based on the insights coming from deictic procedures, as one moves one’s books from their old place to their new place, ejecting other books in the process. We look at the books in transit. Elements that are in transit generate one distinct, their own logical class. There are rules pertaining to order and reorder, and to observe such, the best introduction is to use 12 random objects that are classified in 2 aspects. Because the entry to the thought system of circular order engages brain areas hitherto not trained, and because the basic concepts shift from “limitless, linear, unidentifiable” to “limited size, periodic/cyclic/circular, individuals”, the explanation of the discovery faces didactic difficulties. Reader is invited to overcome traditional eye-blinders and habitual blind spots, and to learn the particular techniques of periodic counting. The algorithms work in tandem with their well-known Sumerian counterparts and allow deep insights into Nature’s organizational principles.

Computation with Sequences of Assemblies in a Model of the Brain.

Even as machine learning exceeds human-level performance on many applications, the generality, robustness, and rapidity of the brain's learning capabilities remain unmatched. How cognition arises from neural activity is the central open question in neuroscience, inextricable from the study of intelligence itself. A simple formal model of neural activity was proposed in Papadimitriou etal. (2020) and has been subsequently shown, through both mathematical proofs and simulations, to be capable of implementing certain simple cognitive operations via the creation and manipulation of assemblies of neurons. However, many intelligent behaviors rely on the ability to recognize, store, and manipulate temporal sequences of stimuli (planning, language, navigation, to list a few). Here we show that in the same model, sequential precedence can be captured naturally through synaptic weights and plasticity, and, as a result, a range of computations on sequences of assemblies can be carried out. In particular, repeated presentation of a sequence of stimuli leads to the memorization of the sequence through corresponding neural assemblies: upon future presentation of any stimulus in the sequence, the corresponding assembly and its subsequent ones will be activated, one after the other, until the end of the sequence. If the stimulus sequence is presented to two brain areas simultaneously, a scaffolded representation is created, resulting in more efficient memorization and recall, in agreement with cognitive experiments. Finally, we show that any finite state machine can be learned in a similar way, through the presentation of appropriate patterns of sequences. Through an extension of this mechanism, the model can be shown to be capable of universal computation. Taken together, these results provide a concrete hypothesis for the basis of the brain's remarkable abilities to compute and learn, with sequences playing a vital role.