Associative learning shapes the neural code for stimulus magnitude in primary auditory cortex

Since the dawn of experimental psychology, researchers have sought an understanding of the fundamental relationship between the amplitude of sensory stimuli and the magnitudes of their perceptual representations. Contemporary theories support the view that magnitude is encoded by a linear increase in firing rate established in the primary afferent pathways. In the present study, we have investigated sound intensity coding in the rat primary auditory cortex (AI) and describe its plasticity by following paired stimulus reinforcement and instrumental conditioning paradigms. In trained animals, population-response strengths in AI became more strongly nonlinear with increasing stimulus intensity. Individual AI responses became selective to more restricted ranges of sound intensities and, as a population, represented a broader range of preferred sound levels. These experiments demonstrate that the representation of stimulus magnitude can be powerfully reshaped by associative learning processes and suggest that the code for sound intensity within AI can be derived from intensity-tuned neurons that change, rather than simply increase, their firing rates in proportion to increases in sound intensity.     

Correspondence of presaccadic activity in the monkey primary visual cortex with saccadic eye movements

We continuously scan the visual world via rapid or saccadic eye movements. Such eye movements are guided by visual information, and thus the oculomotor structures that determine when and where to look need visual information to control the eye movements. To know whether visual areas contain activity that may contribute to the control of eye movements, we recorded neural responses in the visual cortex of monkeys engaged in a delayed figure-ground detection task and analyzed the activity during the period of oculomotor preparation. We show that approximately 100 ms before the onset of visually and memory-guided saccades neural activity in V1 becomes stronger where the strongest presaccadic responses are found at the location of the saccade target. In addition, in memory-guided saccades the strength of presaccadic activity shows a correlation with the onset of the saccade. These findings indicate that the primary visual cortex contains saccade-related responses and participates in visually guided oculomotor behavior.     

Markers of inflammation are inversely related to physical activity and fitness in sedentary men with treated hypertension

BACKGROUND: Physical inactivity is an important risk factor for atherosclerotic disease. We studied the relationship between physical activity and physical fitness and soluble markers of atherosclerotic activity in men with drug-treated hypertension. METHODS: The participants (n = 177, 40 to 74 years of age), who were randomly recruited from the Hypertension High Risk Management Trial (HYRIM), were overweight and had sedentary lifestyles. The inflammatory markers high-sensitivity C-reactive protein (hs-CRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (SICAM-1) and soluble E-selectin (sE-selectin) and the hemostatic markers soluble thrombomodulin (sTM), von Willebrand factor (vWf), and tissue plasminogen activator antigen (tPAag) were measured. Physical activity was measured by use of a questionnaire. Time to exhaustion in a bicycle test was used as an expression of physical fitness. RESULTS: The hs-CRP showed a significant inverse relationship with physical fitness independent of major cardiovascular risk factors (P = .017) but was not related to physical activity. The sE-selectin was significantly related to physical activity, although only when other factors were taken into account (P = .033), and it had no significant association with physical fitness. In addition there were strong associations between hs-CRP and sICAM-1 and the Framingham Coronary Heart Disease risk score (P < .001). CONCLUSIONS: The observed inverse relations between physical fitness and hs-CRP and between level of physical activity and sE-selectin in drug-treated, hypertensive sedentary men indicates a beneficial effect of good fitness status as well as activity of low intensity on vessel wall inflammation.     

Plasma bilirubin and gamma-glutamyltransferase activity are inversely related in dyslipidemic patients with metabolic syndrome: Relevance to oxidative stress

Background

Subnormal levels of plasma bilirubin levels are associated with premature coronary artery disease and cardiovascular morbidity. Plasma gamma-glutamyltransferase (GGT) activity is linked to bilirubin level in hepatic disease and elevated GGT is equally associated with hepatic steatosis, a frequent feature of metabolic syndrome (MS). In order to assess the potential relationship between GGT activity and bilirubin levels in subjects exhibiting features of the metabolic syndrome, we determined circulating bilirubin levels and GGT activity in a cohort of dyslipidemic patients.

Methods and results

This cross-sectional study involved patients (n = 1433) displaying atherogenic dyslipidemia in primary prevention referred to our Prevention Center. Among these patients, 25% presented with MS as defined by recent NCEP ATP III criteria. Circulating levels of transaminases, as well as GGT activity, were elevated in MS patients; by contrast, bilirubin concentrations were significantly lower in such patients as compared to those lacking this syndrome (p < 10–4 for all comparisons). Comparisons of patient groups on the basis of the number of MS criteria which were concomitantly present revealed a progressive decrease in mean bilirubin levels; this reduction paralleled a progressive increase in mean GGT activity as a function of the number of MS components in the overall population (p value for trend < 10–4).

Conclusion

Elevation in systemic GGT activity, which is characterized by extended generation of ROS, together with potentially deficient bilirubin-mediated antioxidative capacity of plasma, may therefore constitute key components of the systemic oxidative stress typical of metabolic syndrome.     

Dynamics of dendritic spines in the mouse auditory cortex during memory formation and memory recall

Long-lasting changes in synaptic connections induced by relevant experiences are believed to represent the physical correlate of memories. Here, we combined chronic in vivo two-photon imaging of dendritic spines with auditory-cued classical conditioning to test if the formation of a fear memory is associated with structural changes of synapses in the mouse auditory cortex. We find that paired conditioning and unpaired conditioning induce a transient increase in spine formation or spine elimination, respectively. A fraction of spines formed during paired conditioning persists and leaves a long-lasting trace in the network. Memory recall triggered by the reexposure of mice to the sound cue did not lead to changes in spine dynamics. Our findings provide a synaptic mechanism for plasticity in sound responses of auditory cortex neurons induced by auditory-cued fear conditioning; they also show that retrieval of an auditory fear memory does not lead to a recapitulation of structural plasticity in the auditory cortex as observed during initial memory consolidation.Mammalian brains are characterized by a tremendous level of plasticity. This plasticity is believed to underlie the ability to extract and store information about past experiences and is crucial for animals and humans to interact adaptively in a changing environment. Therefore, detection and localization of a physical representation of a memory has been an intriguing aspect for a long time (1). Plastic changes in synapses are believed to be substrates of memory (2). The development of imaging techniques that allow chronic monitoring of dendritic spines, the morphological correlates of excitatory synapses on pyramidal neurons, in the living animal has provided valuable insights in the dynamics of neuronal circuits (3–5). It has recently been shown that not only chronic perturbations of sensory inputs (6, 7), but also temporally restricted learning experiences, impact the turnover of synaptic structures in the motor cortex and frontal association cortex of the mouse (8–10) and the high vocal center in zebra finches (11).Auditory-cued fear conditioning (ACFC) is an associative learning paradigm that has been widely used to analyze mechanisms of learning in the auditory modality (12). During a conditioning session, subjects quickly learn to associate a previously neutral sound cue [the conditional stimulus (CS)] with an aversive stimulus like a mild foot shock [unconditional stimulus (US)]. It is well established that memory traces after initial formation undergo several processes at different time scales that lead to their consolidation and render them to a stable state that is, e.g., resistant to trauma introduced by an electroconvulsive shock (13). Interestingly, similar molecular cascades are triggered not only during memory formation, but also when a memory trace is retrieved (14, 15). Furthermore, memory traces that were recently retrieved become sensitive again to manipulations like electroconvulsive shock (16), blockade of NMDA receptors (17), or blockade of protein synthesis (18). These similarities have been suggested to reflect remodeling of memory traces following recall (14, 19). However, data on the dynamics of synaptic structures during memory recall is lacking up to date.A number of brain structures have been identified mediating the formation of a memory induced by ACFC (12). Whereas inputs via the auditory cortex (ACx) to the amygdala, an essential brain structure for this learning paradigm, appear to be always sufficient to support fear conditioning (20), their necessity can depend on the spectrotemporal properties of the auditory CS (21, 22). The ACx as the primary sensory cortical area for the auditory modality has been extensively analyzed in the past during classical conditioning to sound stimuli (23–25) or pairing of sounds with artificial stimulation of the cholinergic system, which can substitute for aspects of the US (26–28). These paradigms lead to changes in the receptive fields of ACx neurons that are specific to the conditioned sound. There is evidence based on local pharmacological or optogenetic manipulations that plasticity of the ACx itself is necessary for experience-induced alterations in sound responses and does not simply reflect plasticity elsewhere in the auditory pathway (29, 30). Indeed, there is evidence based on electrophysiological recordings that synaptic plasticity at intracortical synapses can be induced by pairing of a sound with stimulation of the cholinergic system in vivo (28). Structural plasticity following ACFC has been observed in the frontal association cortex (10). However, it remains elusive if plasticity in sound responses in the ACx induced by ACFC (23–25) also has a structural correlate at the synaptic level.In this study, we asked two major questions: Does ACFC in behaving mice induce structural plasticity in synaptic circuits of the ACx? To what extent do memory formation and memory recall share similarities at the level of synaptic structures? We addressed these questions by combining sound-cued fear conditioning and memory testing with chronic in vivo imaging of dendritic spines in the ACx.     

Geometry and orientation of neuronal processes in cat primary auditory cortex (AI) related to characteristic-frequency maps.

Microelectrode mapping and horseradish peroxidase oxidase histochemistry were combined to study the relationship between the characteristic-frequency representation and the intrinsic connectivity of the primary auditory cortex in the cat. Small extracellular iontophoretic injections of horseradish peroxidase within the characteristic-frequency map resulted in labeling of neuronal processes that, in the tangential plane, radiated out asymmetrically from the injection site over distances of several millimeters. The heaviest concentration of labeled fibers was along an axis parallel with the orientation of the isofrequency line within which the injection had been made. Thus, primary field neurons that have the same or a similar characteristic frequency have the potential of being preferentially interconnected.     

Autoantibodies to oxidised low density lipoproteins in IDDM are inversely related to metabolic control and microvascular complications

Summary Diabetes mellitus is associated with an increased risk of atherosclerosis. The oxidation of low-density lipoproteins (LDL) is considered a key event in the initiation of atherosclerosis. To investigate LDL oxidation in vivo we measured autoantibodies to oxidised LDL (oxLDL) in 94 patients with insulin-dependent diabetes mellitus (IDDM), compared to 27 age-matched, healthy control subjects. Patients and control subjects were screened for autoantibodies using a solid phase ELISA, comparing the binding to oxLDL with that to native LDL (nLDL). In patients with IDDM the oxLDL/nLDL antibody ratio was significantly higher than in control subjects (means ± SEM: 2.24 ± 0.26 vs 1.17 ± 0.17, p < 0.03). Antibody-negative patients had a longer diabetes duration (13.5 ± 1.3 vs 9.1 ± 1.1 years, p < 0.01) and higher actual and mean HbA_{1 c} levels compared to antibody-positive patients (8.8 ± 0.2 vs 7.9 ± 0.2 %, p < 0.005 and 8.3 ± 0.2 vs 7.7 ± 0.2 %, p < 0.03; respectively). In patients with a high microangiopathy score, the antibody ratio was lower than in patients without complications (1.04 ± 0.10 vs 2.40 ± 0.29, p < 0.01). OxLDL specific immune complexes were found exclusively in antibody-negative as compared to antibody-positive patients (18.3 vs 0 %; p < 0.01). Our data demonstrate an inverse relationship between free oxLDL antibodies and the severity of the disease. This apparent paradox can be explained in part by our demonstration of oxLDL immune complexes, masking free antibodies. [Diabetologia (1998) 41: 350–356] Received: 18 June 1997 and in final revised form: 30 September 1997     

Adiponectin levels are reduced in children born small for gestational age and are inversely related to postnatal catch-up growth

Adiponectin is an adipocytokine with insulin-sensitizing and antiatherogenic properties. Reduced concentrations of adiponectin precede the onset of type 2 diabetes and the development of atherosclerosis. Our aim was to quantify adiponectin concentrations in small for gestational age (SGA) children. Fifty-one SGA children, 24 obese, and 17 short-normal children with birth weight appropriate for gestational age (short-AGA) were studied. The statures of the SGA children were corrected for their midparental height and subdivided into two groups according to their corrected height: catch-up growth group, children with corrected height of 0 z-score or greater (n = 17); and noncatch-up growth group, subjects with corrected height less than 0 z-score (n = 34). SGA children showed adiponectin levels significantly lower than short- normal children (35.2 +/- 3.5 vs. 80.4 +/- 26.6 micro g/ml; P < 0.0001) and obese children (77.5 +/- 39.4 micro g/ml; P < 0.0001). Catch-up growth children showed adiponectin levels significantly lower than noncatch-up growth subjects (29.4 +/- 10.3 vs. 38.1 +/- 11.5 micro g/ml; P = 0.01). Adiponectin concentrations were inversely related to height z-score, corrected stature, weight, and body mass index and were positively related to birth weight. Our results suggest that adiponectin levels are reduced in SGA children and are even lower in those with postnatal catch-up growth. Whether this finding implies a higher risk of developing type 2 diabetes and atherosclerosis remains to be established.     

Pharmacological modulation of subliminal learning in Parkinson's and Tourette's syndromes

Theories of instrumental learning aim to elucidate the mechanisms that integrate success and failure to improve future decisions. One computational solution consists of updating the value of choices in proportion to reward prediction errors, which are potentially encoded in dopamine signals. Accordingly, drugs that modulate dopamine transmission were shown to impact instrumental learning performance. However, whether these drugs act on conscious or subconscious learning processes remains unclear. To address this issue, we examined the effects of dopamine-related medications in a subliminal instrumental learning paradigm. To assess generality of dopamine implication, we tested both dopamine enhancers in Parkinson''s disease (PD) and dopamine blockers in Tourette''s syndrome (TS). During the task, patients had to learn from monetary outcomes the expected value of a risky choice. The different outcomes (rewards and punishments) were announced by visual cues, which were masked such that patients could not consciously perceive them. Boosting dopamine transmission in PD patients improved reward learning but worsened punishment avoidance. Conversely, blocking dopamine transmission in TS patients favored punishment avoidance but impaired reward seeking. These results thus extend previous findings in PD to subliminal situations and to another pathological condition, TS. More generally, they suggest that pharmacological manipulation of dopamine transmission can subconsciously drive us to either get more rewards or avoid more punishments.     

Outcome and costs of laparoscopic pancreaticoduodenectomy during the initial learning curve vs laparotomy

AIM:To compare laparoscopic pancreaticoduodenectomy(TLPD) during the initial learning curve with open pancreaticoduodenectomy in terms of outcome and costs.METHODS:This is a retrospective review of the consecutive patients who underwent TLPD between December 2009 and April 2014 at our institution.The experiences of the initial 15 consecutive TLPD cases,considered as the initial learning curve of each surgeon,were compared with the same number of consecutive laparotomy cases with the same spectrum of diseases in terms of outcome and costs.Laparoscopic patients with conversion to open surgery were excluded.Preoperative demographic and comorbidity data were obtained.Postoperative data on intestinal movement,pain score,mortality,complications,and costs were obtained for analysis.Complications related to surgery included pneumonia, intra-abdominal abscess,postpancreatectomy hemorrhage,biliary leak,pancreatic fistula,delayed gastric emptying,and multiple organ dysfunction syndrome.The total costs consisted of cost of surgery,anesthesia,and admission examination.RESULTS:A total of 60 patients,including 30 consecutive laparoscopic cases and 30 consecutive open cases,were enrolled for review.Demographic and comorbidity characteristics of the two groups were similar.TLPD required a significantly longer operative time(513.17 ± 56.13 min vs 371.67 ± 85.53 min,P 0.001).The TLPD group had significantly fewer mean numbers of days until bowel sounds returned(2.03 ± 0.55 d vs 3.83 ± 0.59 d,P 0.001) and exhaustion(4.17 ± 0.75 d vs 5.37 ± 0.81 d,P 0.001).The mean visual analogue score on postoperative day 4 was less in the TLPD group(3.5 ± 9.7 vs 4.47 ± 1.11,P 0.05).No differences in surgery-related morbidities and mortality were observed between the two groups.Patients in the TLPD group recovered more quickly and required a shorter hospital stay after surgery(9.97 ± 3.74 d vs 11.87 ± 4.72 d,P 0.05).A significant difference in the total cost was found between the two groups(TLPD 81317.43 ± 2027.60 RMB vs laparotomy 78433.23 ± 5788.12 RMB,P 0.05).TLPD had a statistically higher cost for both surgery(24732.13 ± 929.28 RMB vs 19317.53 ± 795.94 RMB,P 0.001)and anesthesia(6192.37 ± 272.77 RMB vs 5184.10 ± 146.93 RMB,P 0.001),but a reduced cost for admission examination(50392.93 ± 1761.22 RMB vs 53931.60 ± 5556.94 RMB,P 0.05).CONCLUSION:TLPD is safe when performed by experienced pancreatobiliary surgeons during the initial learning curve,but has a higher cost than open pancreaticoduodenectomy.     

Antibodies to high-density lipoprotein and beta2-glycoprotein I are inversely correlated with paraoxonase activity in systemic lupus erythematosus and primary antiphospholipid syndrome

OBJECTIVE: To determine the prevalence of anti-high-density lipoprotein (anti-HDL) antibodies and to establish a possible relationship between anti-HDL, anticardiolipin antibodies (aCL), anti-beta(2)-glycoprotein I (anti-beta(2)GPI), and paraoxonase (PON) activity in patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). METHODS: Thirty-two patients with SLE and 36 with primary APS were enrolled in a cross-sectional study. Twenty age- and sex-matched healthy subjects were used as controls. Serum levels of IgG and IgM aCL, anti-beta(2)GPI, and antiprothrombin antibodies and IgG anti-HDL were measured by enzyme-linked immunosorbent assay. Total cholesterol, HDL cholesterol, HDL(2), and HDL(3) were determined by standard enzymatic techniques. PON activity was assessed by quantification of nitrophenol formation, and total antioxidant capacity (TAC) by chemiluminescence. RESULTS: Levels of total HDL, HDL(2), and HDL(3) were reduced in patients with SLE compared with controls (mean +/- SD 0.51 +/- 0.3, 0.37 +/- 0.3, and 0.14 +/- 0.1 mmoles/liter, respectively, versus 1.42 +/- 0.9, 1.01 +/- 0.7, and 0.40 +/- 0.2). Patients with SLE and primary APS had higher titers of anti-HDL antibodies and lower PON activity than controls. In the SLE population, PON activity was inversely correlated with IgG anti-HDL titers (r = -0.48, P = 0.005) whereas in the primary APS population, IgG anti-beta(2)GPI was the only independent predictor of PON activity (r = -0.483, P = 0.003). In the SLE group, anti-HDL was inversely correlated with TAC (r = -0.40, P < 0.02), and PON activity was positively correlated with TAC (r = 0.43, P < 0.02). CONCLUSION: IgG anti-HDL and IgG anti-beta(2)GPI antibodies are associated with reduced PON activity in patients with SLE and primary APS. Since the physiologic role of PON is to prevent low-density lipoprotein oxidation with its attendant atherogenic effects, the reported interactions may be relevant to the development of atherosclerosis in SLE and primary APS.     

Immunoglobulin E and mast cell responses are related to worm biomass but not expulsion of Hymenolepis diminuta during low dose infection in rats

It is well known that the destrobilation and later expulsion are characteristics of multiple Hymenolepis diminuta infections in rats. This process is suggested to be mediated by a variety of host cellular responses. It has also been suggested that immunoglobulin (Ig) E may have a beneficial role for some cestodes including H. diminuta. We examined the intestinal mast cell and serum IgE responses to a 10-H. diminuta infection in three different rat strains. Tapeworm infection induced no increased mast cell and IgE responses in F344 rats in which neither worm biomass nor worm burden decreased during 6 weeks of observation. The number of mast cells and amounts of serum rat mast cell protease (RMCP) II and IgE markedly increased from 3 weeks postinfection (p.i.) in BN rats. The worm biomass in BN rats was significantly lower than that in F344 rats, but worm burden was not different from that in F344 rats at 3 or 6 weeks p.i. In DA rats, the number of mast cells and levels of serum RMCP II and IgE increased at 6 weeks but not at 3 weeks p.i. Although numbers of mast cells and serum RMCP II and IgE levels were lower in DA rats than in BN rats, smaller and fewer worms were recovered in DA rats than in F344 and BN rats at from 3 and 6 weeks p.i. Worms were recovered from all of F344 and BN rats, while only 40% of DA rats harboured worms at 6 weeks p.i. These results suggested that the worm biomass was related to mast cell and IgE responses, but these responses were not required for worm expulsion during low dose H. diminuta infection in rats.     

Bronchoalveolar lavage fluid surfactant protein-A and surfactant protein-D are inversely related to inflammation in early cystic fibrosis

The pulmonary collectins surfactant protein (SP)-A and SP-D play important roles in innate lung defense, enhancing opsonization of microbes and limiting lung inflammatory responses. To quantify relationships among collectins, bacteria, and inflammation in early cystic fibrosis (CF) airway secretions, bronchoalveolar lavage fluids (BALFs) were collected from children undergoing clinically indicated bronchoscopy. Quantitative bacteriology, differential cell counts, and ELISA for SP-A and SP-D were assessed. Significantly increased numbers of neutrophils relative to bacteria were noted in BALF from CF compared with non-CF subjects. Although SP-A levels tended to be lower in CF compared with non-CF, this was only significant in the presence of bacterial infection. Among CF patients, SP-A concentrations in BALF were inversely related to inflammation, bacterial colony-forming units per milliliter, and age. SP-D levels were significantly decreased in CF patients, and SP-D was rarely detectable in the presence of infection. Among CF patients, SP-D correlated inversely with inflammation and bacterial colony-forming units per milliliter, and there was decreased immunostaining of BALF cells for SP-D in CF. Immunohistochemistry of CF autopsy lung sections for SP-A and SP-D confirmed their paucity at sites of infection and inflammation. We conclude that relative collectin deficiency occurs early in CF airways and is inversely related to inflammation in CF airways.     

Learning in deep neural networks and brains with similarity-weighted interleaved learning

Understanding how the brain learns throughout a lifetime remains a long-standing challenge. In artificial neural networks (ANNs), incorporating novel information too rapidly results in catastrophic interference, i.e., abrupt loss of previously acquired knowledge. Complementary Learning Systems Theory (CLST) suggests that new memories can be gradually integrated into the neocortex by interleaving new memories with existing knowledge. This approach, however, has been assumed to require interleaving all existing knowledge every time something new is learned, which is implausible because it is time-consuming and requires a large amount of data. We show that deep, nonlinear ANNs can learn new information by interleaving only a subset of old items that share substantial representational similarity with the new information. By using such similarity-weighted interleaved learning (SWIL), ANNs can learn new information rapidly with a similar accuracy level and minimal interference, while using a much smaller number of old items presented per epoch (fast and data-efficient). SWIL is shown to work with various standard classification datasets (Fashion-MNIST, CIFAR10, and CIFAR100), deep neural network architectures, and in sequential learning frameworks. We show that data efficiency and speedup in learning new items are increased roughly proportionally to the number of nonoverlapping classes stored in the network, which implies an enormous possible speedup in human brains, which encode a high number of separate categories. Finally, we propose a theoretical model of how SWIL might be implemented in the brain.

Artificial neural networks (ANNs) tend to lose previously acquired knowledge abruptly when new information is incorporated too quickly (“catastrophic interference”) (1, 2). Successful lifelong learners (e.g., humans) do not suffer from this problem, potentially by using mechanisms suggested in the Complementary Learning Systems Theory (CLST) (3) (see also ref. 4). CLST states that the brain relies on complementary learning systems: the hippocampus (HC) for rapid acquisition of new memories and the neocortex (NC) for the gradual incorporation of the new data into context-independent structured knowledge. During “offline periods,” such as sleep and quiet awake rest, the HC triggers replay of recent experiences in the NC, while the NC spontaneously retrieves and interleaves representations of existing classes (5–7). The interleaved replay allows gradual adjustment of NC synaptic weights, in a gradient-descent manner, to create context-independent category representations, thereby gracefully integrating new memories and overcoming catastrophic interference. Numerous studies have since successfully used interleaved replay to achieve lifelong learning in neural networks (8, 9).In practice, however, the CLST raises two significant issues. First, how can the brain possibly perform a comprehensive interleaving when it does not have access to all the old data? One potential solution is “Pseudorehearsal” (10), where random inputs can elicit generative replay of internal representations without requiring explicit access to previously learned examples. Attractor-like dynamics may allow the brain to accomplish pseudorehearsal, but it is unclear what to pseudorehearse. Thus, the second problem is that there is not enough time to interleave all of the previously learned information after each new learning event. “Similarity Weighted Interleaved Learning” (SWIL) was proposed as a solution to this second problem, suggesting that it may be sufficient to interleave only old items with substantial representational similarity to new items (11). Empirical behavioral studies showed that highly consistent new items could be rapidly integrated into NC structured knowledge with little or no interference (12, 13). This indicates that the speed of integrating new information depends on its consistency with the prior knowledge (14). Inspired by this behavioral result, and by a reexamination of the distribution of catastrophic interference among previously acquired classes, which is described below, McClelland et al. (11) demonstrated that SWIL allowed learning new information using 2.5x fewer item presentations per epoch in a simple dataset with two superordinate categories and achieved the same performance as training the network on the entire data. However, the authors did not find a similar effect when using more complex datasets, raising concerns about the algorithm’s scalability.The current study has overcome these limitations by modifying the SWIL algorithm to work with Convolutional Neural Networks (CNNs) on traditional classification datasets (Fashion-MNIST, CIFAR10, and CIFAR100). We exploit the hierarchical structure of existing knowledge to selectively interleave only the old items that have higher representational similarity to new items. With this strategy, we can reach performance levels comparable to that achieved by using the entire training dataset, thereby substantially reducing the amount of data required (data-efficient) and learning time (speedup). We then show that SWIL can also be used in a sequential learning framework. Additionally, we show that learning a new class can be extremely data-efficient—i.e., a much smaller number of old items being presented—if it shares similarities with far fewer previously learned classes, which is likely the case in human learning. Finally, we present a theoretical model of how SWIL might be implemented in the brain using previously stored attractors with an excitability bias proportional to their overlap with new items.     

Serum potassium concentrations are inversely related to ventricular, but not to atrial, arrhythmias in acute myocardial infarction

In a study of 1033 consecutive patients with acute myocardialinfarction, serum potassium concentrations were determined onadmission to hospital and studied with respect to the subsequentoccurrence of atrial fibrillation and flutter and of ventriculartachycardia and fibrillation. The study cohort fulfilled theinclusion criteria for the Norwegian timolol trial in whichthey later took part. In multivariate analysis, with serum potassiumconcentrations as a continuous variable, age, the presence ofventricular tachycardia and fibrillation, and maximum levelof aspartate aminotransferase greater than four times the upperlimit of normal were significantly associated with the occurrenceof atrial fibrillation and flutter, while serum potassium concentrationwas not. Serum potassium concentrations and time from onsetof the infarction to hospital admission were significantly negativelyassociated with the occurrence of ventricular tachycardia andfibrillation; while age, cardiomegaly, transient hypotension,pathological Q-waves in the electrocardiogram, atrial fibrillationand flutter, and ventricular premature beats were positivelyrelated to these arrhythmias.     

Leisure-time physical activity is inversely related to risk factors for coronary heart disease in middle-aged Finnish men

Coronary risk factors and levels of physical activity at leisurewere measured in a random sample of 3975 men 25–64 yearsof age residing in four areas of Finland. An index of leisure-timephysical activity (LTPA) as the product of weekly exercise sessionstimes their usual intensity (expressed as metabolic equivalents)was computed. It showed a graded, inverse association with meanarterial blood pressure, smoking and serum thiocyanate, coronaryheart disease risk estimate (combining blood pressure, totalcholesterol and smoking), and a nonlinear favorable associationwith serum lipoproteins. In multiple regression analysis, LTPAcontributed significantly and independently to the variationin mean arterial pressure; the standardized regression coefficientswere –0.06 for LTPA, 0.09 for weekly alcohol consumption,0.25 for body mass index, 0.25 age. In the regression of coronaryrisk estimate, the standardized regression coefficients were–0.19 for LTPA, 0.22 for weekly alcohol consumption, 0.09for body mass index, 0.15 for age. There was no evidence thatLTPA above 2000 kcal of weekly energy expenditure was associatedwith further reduced coronary risk factor levels. These findingsthus support the inverse direction of the association betweenexercise and coronary risk factors but they also point towardsan independent, but modest, role of leisure-time physical activityas determinant of coronary risk estimate and blood pressure     

Leisure-time physical activity is inversely related to risk factors for coronary heart disease in middle-aged Finnish men

Coronary risk factors and levels of physical activity at leisurewere measured in a random sample of 3975 men 25–64 yearsof age residing in four areas of Finland. An index of leisure-timephysical activity (LTPA) as the product of weekly exercise sessionstimes their usual intensity (expressed as metabolic equivalents)was computed. It showed a graded, inverse association with meanarterial blood pressure, smoking and serum thiocyanate, coronaryheart disease risk estimate (combining blood pressure, totalcholesterol and smoking), and a nonlinear favorable associationwith serum lipoproteins. In multiple regression analysis, LTPAcontributed significantly and independently to the variationin mean arterial pressure; the standardized regression coefficientswere –0.06 for LTPA, 0.09 for weekly alcohol consumption,0.25 for body mass index, 0.25 age. In the regression of coronaryrisk estimate, the standardized regression coefficients were–0.19 for LTPA, 0.22 for weekly alcohol consumption, 0.09for body mass index, 0.15 for age. There was no evidence thatLTPA above 2000 kcal of weekly energy expenditure was associatedwith further reduced coronary risk factor levels. These findingsthus support the inverse direction of the association betweenexercise and coronary risk factors but they also point towardsan independent, but modest, role of leisure-time physical activityas determinant of coronary risk estimate and blood pressure     

Frequency preference and attention effects across cortical depths in the human primary auditory cortex

Columnar arrangements of neurons with similar preference have been suggested as the fundamental processing units of the cerebral cortex. Within these columnar arrangements, feed-forward information enters at middle cortical layers whereas feedback information arrives at superficial and deep layers. This interplay of feed-forward and feedback processing is at the core of perception and behavior. Here we provide in vivo evidence consistent with a columnar organization of the processing of sound frequency in the human auditory cortex. We measure submillimeter functional responses to sound frequency sweeps at high magnetic fields (7 tesla) and show that frequency preference is stable through cortical depth in primary auditory cortex. Furthermore, we demonstrate that—in this highly columnar cortex—task demands sharpen the frequency tuning in superficial cortical layers more than in middle or deep layers. These findings are pivotal to understanding mechanisms of neural information processing and flow during the active perception of sounds.Auditory perception starts in our ears, where hair cells at different places in the cochlea respond to different sound frequencies. The spatially ordered arrangement of neural responses to frequencies (tonotopy) that arises from this transduction mechanism is preserved in subcortical (1, 2) and cortical stages of processing, where neuronal populations form multiple tonotopic maps (3, 4). At the cortical level, tonotopic maps describe systematic changes along the surface. In the orthogonal direction (i.e., perpendicular to the cortical surface), aggregates of neurons with parallel axons have been reported (5, 6). These anatomical observations of cortical microcolumns inspired invasive electrophysiological investigations in cats (7), demonstrating that frequency preference is constant across cortical depth (i.e., frequency columns). Since this early study, frequency columns have been observed in a variety of animals (3, 8–10), and a columnar organization has been suggested for other acoustic properties (10, 11). Despite this anatomical and physiological evidence from animal models, the role of cortical columns in auditory perception is not understood (6, 12, 13). To unravel intracolumnar computations, it is of fundamental importance to analyze the transformation of information across cortical depths. Differences in cell types and in patterns of input and output projections suggest a distinct role of cortical layers in neural information processing (5). In particular, behavioral demands and ongoing brain states can modulate the functional properties of layer 2/3 neurons, suggesting that supragranular neuronal populations may be of fundamental relevance for the processing of sensory information in a context-dependent manner (14). Recordings in the primary auditory cortex of animals have shown differences across layers in response latency (15, 16), in frequency selectivity (i.e., tuning width) (8, 16), and in the complexity of neuronal preference to acoustic information (i.e., receptive field) (17). However, the reports are not concordant across species. Moreover, most of the knowledge regarding auditory columnar processing has been obtained in anesthetized animals, making its relation to human behavior unclear.To date, there is no functional evidence for a columnar organization and for the layer-dependent processing of sound frequency in the human auditory cortex from either invasive or noninvasive recordings. In this study, we address this question noninvasively using high magnetic field (7 tesla) functional magnetic resonance imaging (fMRI) at high spatial resolution and specificity (18, 19). We acquired functional images in the primary auditory cortex (PAC) of five healthy volunteers and estimated the best frequency (BF) responses voxel-by-voxel. Then, by analyzing the 3D spatial variations of these responses, we identified the PAC regions with a stable arrangement of BF across cortical depths. The term “column” has been used with multiple meanings in the past (13). Here, we refer to columnar region as the cortical region where the variation of frequency with depth is significantly smaller compared with the frequency variation orthogonal to depth (i.e., across the surface) (SI Text). Further, we examined the functional differences across cortical layers by estimating the cortical depth-dependent changes in frequency tuning during an auditory and a control visual task. We hypothesized that additional top-down processing engaged by the auditory task would modulate the frequency tuning of fMRI responses in the PAC in a cortical depth-dependent manner. Finally, we simulated how the observed changes of frequency tuning across layers and tasks may result in behaviorally relevant changes of neuronal population-based sound representations.