RESUMEN
Teleological reasoning is the tendency for humans to see purpose and intentionality in natural phenomena when there is none. In this study, we assess three competing theories on how bias in reasoning arises by examining performance on a teleological reasoning task while measuring pupil size and response times. We replicate that humans (N = 45) are prone to accept false teleological explanations. Further, we show that errors on the teleological reasoning task are associated with slower response times, smaller baseline pupil size, and larger pupil dilations. The results are in line with the single-process extensive integration account and directly oppose predictions from dual-processing accounts. Lastly, by modeling responses with a drift-diffusion model, we find that larger baseline pupil size is associated with lower decision threshold and higher drift rate, whereas larger pupil dilations are associated with higher decision threshold and lower drift rate. The results highlight the role of neural gain and the Locus Coeruleus-Norepinephrine system in modulating evidence integration and bias in reasoning. Thus, teleological reasoning and susceptibility to bias likely arise due to extensive processing rather than through fast and effortless processing.
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Pupila , Tiempo de Reacción , Pensamiento , Humanos , Pupila/fisiología , Masculino , Adulto , Femenino , Adulto Joven , Pensamiento/fisiología , Tiempo de Reacción/fisiología , Toma de Decisiones/fisiologíaRESUMEN
BACKGROUND AND HYPOTHESIS: Impairments in the expression, experience, and recognition of emotion are common in early psychosis (EP). Computational accounts of psychosis suggest disrupted top-down modulation by the cognitive control system (CCS) on perceptual circuits underlies psychotic experiences, but their role in emotional deficits in EP is unknown. STUDY DESIGN: The affective go/no-go task was used to probe inhibitory control during the presentation of calm or fearful faces in young persons with EP and matched controls. Computational modeling of functional magnetic resonance imaging (fMRI) data were performed using dynamic causal modeling (DCM). The influence of the CCS on perceptual and emotional systems was examined using parametric empirical bayes. STUDY RESULTS: When inhibiting motor response to fearful faces, EP participants showed higher brain activity in the right posterior insula (PI). To explain this, we used DCM to model effective connectivity between the PI, regions from the CCS activated during inhibition (dorsolateral prefrontal cortex [DLPFC] and anterior insula [AI]), and a visual input region, the lateral occipital cortex (LOC). EP participants exerted a stronger top-down inhibition from the DLPFC to the LOC than controls. Within the EP cohort, increased top-down connectivity between the LOC and AI was associated with a higher burden of negative symptoms. CONCLUSIONS: Young persons with a recent onset of psychosis show a disturbance in the cognitive control of emotionally salient stimuli and the suppression of irrelevant distractors. These changes are associated with negative symptoms, suggesting new targets for the remediation of emotional deficits in young persons with EP.
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Corteza Prefrontal , Trastornos Psicóticos , Humanos , Teorema de Bayes , Mapeo Encefálico , Emociones/fisiología , Trastornos Psicóticos/diagnóstico por imagen , Cognición/fisiología , Imagen por Resonancia MagnéticaRESUMEN
Dendrites are essential determinants of the input-output relationship of single neurons, but their role in network computations is not well understood. Here, we use a combination of dendritic patch-clamp recordings and in silico modeling to determine how dendrites of parvalbumin (PV)-expressing basket cells contribute to network oscillations in the gamma frequency band. Simultaneous soma-dendrite recordings from PV basket cells in the dentate gyrus reveal that the slope, or gain, of the dendritic input-output relationship is exceptionally low, thereby reducing the cell's sensitivity to changes in its input. By simulating gamma oscillations in detailed network models, we demonstrate that the low gain is key to increase spike synchrony in PV basket cell assemblies when cells are driven by spatially and temporally heterogeneous synaptic inputs. These results highlight the role of inhibitory neuron dendrites in synchronized network oscillations.
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Interneuronas , Parvalbúminas , Potenciales de Acción/fisiología , Dendritas/fisiología , Interneuronas/fisiología , NeuronasRESUMEN
When listening to music, pitch deviations are more salient and elicit stronger prediction error responses when the melodic context is predictable and when the listener is a musician. Yet, the neuronal dynamics and changes in connectivity underlying such effects remain unclear. Here, we employed dynamic causal modeling (DCM) to investigate whether the magnetic mismatch negativity response (MMNm)-and its modulation by context predictability and musical expertise-are associated with enhanced neural gain of auditory areas, as a plausible mechanism for encoding precision-weighted prediction errors. Using Bayesian model comparison, we asked whether models with intrinsic connections within primary auditory cortex (A1) and superior temporal gyrus (STG)-typically related to gain control-or extrinsic connections between A1 and STG-typically related to propagation of prediction and error signals-better explained magnetoencephalography responses. We found that, compared to regular sounds, out-of-tune pitch deviations were associated with lower intrinsic (inhibitory) connectivity in A1 and STG, and lower backward (inhibitory) connectivity from STG to A1, consistent with disinhibition and enhanced neural gain in these auditory areas. More predictable melodies were associated with disinhibition in right A1, while musicianship was associated with disinhibition in left A1 and reduced connectivity from STG to left A1. These results indicate that musicianship and melodic predictability, as well as pitch deviations themselves, enhance neural gain in auditory cortex during deviance detection. Our findings are consistent with predictive processing theories suggesting that precise and informative error signals are selected by the brain for subsequent hierarchical processing.
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Corteza Auditiva/fisiología , Neuroimagen Funcional , Magnetoencefalografía , Música , Percepción de la Altura Tonal/fisiología , Adulto , Teorema de Bayes , Femenino , Humanos , Masculino , Modelos Teóricos , Adulto JovenRESUMEN
Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, reflected in exaggerated and variable responses to sensory stimuli. Attentional engagement is known to be regulated by the locus ceruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether, under different attentional task demands, individuals with ASD exhibit a different profile of LC activity compared with typically developing controls. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses, an established correlate for LC activity, were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared with controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed specifically in response to task-relevant events, providing confirmation that the group differences most likely were specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD.SIGNIFICANCE STATEMENT Individuals with autism spectrum disorder (ASD) exhibit atypical attentional behaviors, including altered sensory responses and atypical fixedness, but the neural mechanism underlying these behaviors remains elusive. One candidate mechanism is atypical locus ceruleus (LC) activity, as the LC plays a critical role in attentional modulation. Specifically, LC activity is involved in regulating the trade-off between environmental exploration and focused attention. This study shows that, under tightly controlled conditions, task-evoked pupil responses, an LC activity proxy, are lower in individuals with ASD than in controls, but only in the presence of task-irrelevant stimuli. This suggests that individuals with ASD evince atypical modulation of LC activity in accordance with changes in attentional demands, offering a mechanistic account for attentional atypicalities in ASD.
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Atención/fisiología , Trastorno del Espectro Autista/fisiopatología , Locus Coeruleus/fisiopatología , Adulto , Femenino , Humanos , Masculino , Reflejo Pupilar/fisiologíaRESUMEN
Selective attention is a fundamental cognitive function that guides behavior by selecting and prioritizing salient or relevant sensory information of our environment. Despite early evidence and theoretical proposal pointing to an implication of thalamic control in attention, most studies in the past two decades focused on cortical substrates, largely ignoring the contribution of subcortical regions as well as cortico-subcortical interactions. Here, we suggest a key role of the pulvinar in the selection of salient and relevant information via its involvement in priority maps. Prioritization may be achieved through a pulvinar-mediated generation of alpha oscillations, which may then modulate neuronal gain in thalamo-cortical circuits. Such mechanism might orchestrate the synchrony of cortico-cortical interaction, by rendering neural communication more effective, precise and selective. We propose that this theoretical framework will support a timely shift from the prevailing cortico-centric view of cognition to a more integrative perspective of thalamic contributions to attention and executive control processes.
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Ritmo alfa/fisiología , Atención/fisiología , Corteza Cerebral/fisiología , Función Ejecutiva/fisiología , Red Nerviosa/fisiología , Pulvinar/fisiología , HumanosRESUMEN
Cognitive function relies on the dynamic cooperation of specialized regions of the brain; however, the elements of the system responsible for coordinating this interaction remain poorly understood. In this Opinion article I argue that this capacity is mediated in part by competitive and cooperative dynamic interactions between two prominent metabotropic neuromodulatory systems - the cholinergic basal forebrain and the noradrenergic locus coeruleus (LC). I assert that activity in these projection nuclei regulates the amount of segregation and integration within the whole brain network by modulating the activity of a diverse set of specialized regions of the brain on a timescale relevant for cognition and attention.
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Encéfalo/fisiología , Neuronas Adrenérgicas/fisiología , Prosencéfalo Basal/fisiología , Neuronas Colinérgicas/fisiología , Cognición/fisiología , Humanos , Locus Coeruleus/fisiología , Red Nerviosa/fisiologíaRESUMEN
For successful future therapeutic strategies for tinnitus and hyperacusis, a subcategorization of both conditions on the basis of differentiated neural correlates would be of invaluable advantage. In the present study, we used our refined operant conditioning animal model to divide equally noise-exposed rats into groups with either tinnitus or hyperacusis, with neither condition, or with both conditions co-occurring simultaneously. Using click stimulus and noise burst-evoked Auditory Brainstem Responses (ABR) and Distortion Product Otoacoustic Emissions, no hearing threshold difference was observed between any of the groups. However, animals with neither tinnitus nor hyperacusis responded to noise trauma with shortened ABR wave I and IV latencies and elevated central neuronal gain (increased ABR wave IV/I amplitude ratio), which was previously assumed in most of the literature to be a neural correlate for tinnitus. In contrast, animals with tinnitus had reduced neural response gain and delayed ABR wave I and IV latencies, while animals with hyperacusis showed none of these changes. Preliminary studies, aimed at establishing comparable non-invasive objective tools for identifying tinnitus in humans and animals, confirmed reduced central gain and delayed response latency in human and animals. Moreover, the first ever resting state functional Magnetic Resonance Imaging (rs-fMRI) analyses comparing humans and rats with and without tinnitus showed reduced rs-fMRI activities in the auditory cortex in both patients and animals with tinnitus. These findings encourage further efforts to establish non-invasive diagnostic tools that can be used in humans and animals alike and give hope for differentiated classification of tinnitus and hyperacusis.
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Cóclea/fisiopatología , Pérdida Auditiva Provocada por Ruido/fisiopatología , Hiperacusia/fisiopatología , Acúfeno/fisiopatología , Estimulación Acústica/métodos , Animales , Corteza Auditiva/fisiopatología , Umbral Auditivo/fisiología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Femenino , Ruido , Ratas WistarRESUMEN
The human brain can be conceptualized as an inference machine that actively predicts and explains its sensations and perceptions: it makes predictions through a probabilistic model. Such a model is continuously and implicitly updated by the computation and minimization of weighted prediction errors, as shown by numerous studies and experimental results. Nevertheless, such an algorithmic functioning of the brain has not been exploited in the neuropharmacological practice. In this manuscript, we show by theoretical analysis and model fitting of previously published data in two different contexts, how it is possible to increase the effectiveness of neuropharmacological and immunosuppressive drugs, through the modulation of the weighted prediction errors. Moreover, on the basis of the proposed model, we derive an optimized drug administration schedule able to increase the drug effectiveness of one order of magnitude, in psoriasis treatment. We make important testable predictions, evidencing the impact and the potential benefit of prediction errors modulation within the brain, in the pharmacotherapeutic practice. Finally, our results lead to a novel formal theory of implicit learning, and shed lights on the actual roles of classical conditioning and UCS revaluation in behavioral and pharmacological conditioning experiments. The potential practical implications of our results are many: the reduction of drugs side effects; the maximization of the therapeutic outcome; a more effective treatment for chronic pain, certain neuropsychiatric diseases, autoimmune diseases and allergic diseases.
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Encéfalo/efectos de los fármacos , Aprendizaje/efectos de los fármacos , Modelos Neurológicos , Fármacos del Sistema Nervioso Central/administración & dosificación , Humanos , Inmunosupresores/administración & dosificación , Psoriasis/tratamiento farmacológicoRESUMEN
BACKGROUND/AIMS: From invertebrates to mammals, Gαi proteins act together with their common binding partner Gpsm2 to govern cell polarization and planar organization in virtually any polarized cell. Recently, we demonstrated that Gαi3-deficiency in pre-hearing murine cochleae pointed to a role of Gαi3 for asymmetric migration of the kinocilium as well as the orientation and shape of the stereociliary ("hair") bundle, a requirement for the progression of mature hearing. We found that the lack of Gαi3 impairs stereociliary elongation and hair bundle shape in high-frequency cochlear regions, linked to elevated hearing thresholds for high-frequency sound. How these morphological defects translate into hearing phenotypes is not clear. METHODS: Here, we studied global and conditional Gnai3 and Gnai2 mouse mutants deficient for either one or both Gαi proteins. Comparative analyses of global versus Foxg1-driven conditional mutants that mainly delete in the inner ear and telencephalon in combination with functional tests were applied to dissect essential and redundant functions of different Gαi isoforms and to assign specific defects to outer or inner hair cells, the auditory nerve, satellite cells or central auditory neurons. RESULTS: Here we report that lack of Gαi3 but not of the ubiquitously expressed Gαi2 elevates hearing threshold, accompanied by impaired hair bundle elongation and shape in high-frequency cochlear regions. During the crucial reprogramming of the immature inner hair cell (IHC) synapse into a functional sensory synapse of the mature IHC deficiency for Gαi2 or Gαi3 had no impact. In contrast, double-deficiency for Gαi2 and Gαi3 isoforms results in abnormalities along the entire tonotopic axis including profound deafness associated with stereocilia defects. In these mice, postnatal IHC synapse maturation is also impaired. In addition, the analysis of conditional versus global Gαi3-deficient mice revealed that the amplitude of ABR wave IV was disproportionally elevated in comparison to ABR wave I indicating that Gαi3 is selectively involved in generation of neural gain during auditory processing. CONCLUSION: We propose a so far unrecognized complexity of isoform-specific and overlapping Gαi protein functions particular during final differentiation processes.
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Proteínas Portadoras/metabolismo , Factores de Transcripción Forkhead/metabolismo , Subunidad alfa de la Proteína de Unión al GTP Gi2/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Células Ciliadas Auditivas Internas/metabolismo , Audición/fisiología , Proteínas del Tejido Nervioso/metabolismo , Animales , Proteínas Portadoras/genética , Proteínas de Ciclo Celular , Factores de Transcripción Forkhead/genética , Subunidad alfa de la Proteína de Unión al GTP Gi2/genética , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/genética , Células Ciliadas Auditivas Internas/citología , Ratones , Ratones Transgénicos , Proteínas del Tejido Nervioso/genéticaRESUMEN
Cognitive function relies on a dynamic, context-sensitive balance between functional integration and segregation in the brain. Previous work has proposed that this balance is mediated by global fluctuations in neural gain by projections from ascending neuromodulatory nuclei. To test this hypothesis in silico, we studied the effects of neural gain on network dynamics in a model of large-scale neuronal dynamics. We found that increases in neural gain directed the network through an abrupt dynamical transition, leading to an integrated network topology that was maximal in frontoparietal 'rich club' regions. This gain-mediated transition was also associated with increased topological complexity, as well as increased variability in time-resolved topological structure, further highlighting the potential computational benefits of the gain-mediated network transition. These results support the hypothesis that neural gain modulation has the computational capacity to mediate the balance between integration and segregation in the brain.
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Encéfalo/fisiología , Cognición , Red Nerviosa/fisiología , Redes Neurales de la Computación , Neuronas/fisiología , Simulación por ComputadorRESUMEN
Unilateral auditory deprivation induces a reduction in the acoustic reflex threshold (ART) and an increase in loudness. These findings have been interpreted as a compensatory change in neural gain, governed by changes in excitatory and inhibitory neural inputs. There is also evidence to suggest that changes in neural gain can be measured using the auditory brainstem response (ABR). The present study extended Munro et al. (2014) [J. Acoust. Soc. Am. 135, 315-322] by investigating changes after 4 days of unilateral earplug use to: (i) ART, (ii) ABR and (iii) loudness. Because changes may occur during the post-deprivation test session (day 4), ART measurements were taken 1 h and 2 h post-earplug removal. There was a significant reduction in ART in the treatment ear immediately after the removal of the earplug, which is consistent with a compensatory increase in neural gain. A novel finding was the significant return of ARTs to baseline within 2 h of earplug removal. A second novel finding was a significant decrease in the mean amplitude of ABR wave V in the treatment ear, but a significant increase in the control ear, both after 4 days of deprivation. These changes in the ABR are in the opposite direction to those predicted. We were unable to replicate the change in loudness reported in previous deprivation studies; however, the short period of earplug use may have contributed to this null finding.
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Vías Auditivas/fisiología , Umbral Auditivo , Potenciales Evocados Auditivos del Tronco Encefálico , Audición , Juicio , Percepción Sonora , Plasticidad Neuronal , Reflejo Acústico , Privación Sensorial , Estimulación Acústica , Adaptación Fisiológica , Adaptación Psicológica , Adulto , Dispositivos de Protección de los Oídos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Factores de Tiempo , Adulto JovenRESUMEN
Auditory deprivation and stimulation can change the threshold of the acoustic reflex, but the mechanisms underlying these changes remain largely unknown. In order to elucidate the mechanism, we sought to characterize the time-course as well as the frequency specificity of changes in acoustic reflex thresholds (ARTs). In addition, we compared ipsilateral and contralateral measurements because the pattern of findings may shed light on the anatomical location of the change in neural gain. Twenty-four normal-hearing adults wore an earplug continuously in one ear for six days. We measured ipsilateral and contralateral ARTs in both ears on six occasions (baseline, after 2, 4 and 6 days of earplug use, and 4 and 24 h after earplug removal), using pure tones at 0.5, 1, 2 and 4 kHz and a broadband noise stimulus, and an experimenter-blinded design. We found that ipsi- as well as contralateral ARTs were obtained at a lower sound pressure level after earplug use, but only when the reflex was elicited by stimulating the treatment ear. Changes in contralateral ARTs were not the same as changes in ipsilateral ARTs when the stimulus was presented to the control ear. Changes in ARTs were present after 2 days of earplug use, and reached statistical significance after 4 days, when the ipsilateral and contralateral ARTs were measured in the treatment ear. The greatest changes in ARTs occurred at 2 and 4 kHz, the frequencies most attenuated by the earplug. After removal of the earplug, ARTs started to return to baseline relatively quickly, and were not significantly different from baseline by 4-24 h. There was a trend for the recovery to occur quicker than the onset. The changes in ARTs are consistent with a frequency-specific gain control mechanism operating around the level of the ventral cochlear nucleus in the treatment ear, on a time scale of hours to days. These findings, specifically the time course of change, could be applicable to other sensory systems, which have also shown evidence of a neural gain control mechanism.
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Estimulación Acústica , Umbral Auditivo , Plasticidad Neuronal , Reflejo Acústico , Adolescente , Adulto , Núcleo Coclear/fisiología , Femenino , Pruebas Auditivas , Humanos , Masculino , Persona de Mediana Edad , Reflejo , Sensibilidad y Especificidad , Factores de Tiempo , Adulto JovenRESUMEN
Attention-deficit hyperactivity disorder (ADHD), one of the most common psychiatric disorders, is characterised by unstable response patterns across multiple cognitive domains. However, the neural mechanisms that explain these characteristic features remain unclear. Using a computational multilevel approach, we propose that ADHD is caused by impaired gain modulation in systems that generate this phenotypic increased behavioural variability. Using Marr's three levels of analysis as a heuristic framework, we focus on this variable behaviour, detail how it can be explained algorithmically, and how it might be implemented at a neural level through catecholamine influences on corticostriatal loops. This computational, multilevel, approach to ADHD provides a framework for bridging gaps between descriptions of neuronal activity and behaviour, and provides testable predictions about impaired mechanisms.
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Trastorno por Déficit de Atención con Hiperactividad/metabolismo , Trastorno por Déficit de Atención con Hiperactividad/psicología , Encéfalo/metabolismo , Biología Computacional/métodos , Red Nerviosa/metabolismo , Psiquiatría/métodos , Animales , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Humanos , Vías Nerviosas/metabolismoRESUMEN
When perceiving rich sensory information, some people may integrate its various aspects, whereas other people may selectively focus on its most salient aspects. We propose that neural gain modulates the trade-off between breadth and selectivity, such that high gain focuses perception on those aspects of the information that have the strongest, most immediate influence, whereas low gain allows broader integration of different aspects. We illustrate our hypothesis using a neural-network model of ambiguous-letter perception. We then report an experiment demonstrating that, as predicted by the model, pupil-diameter indices of higher gain are associated with letter perception that is more selectively focused on the letter's shape or, if primed, its semantic content. Finally, we report a recognition-memory experiment showing that the relationship between gain and selective processing also applies when the influence of different stimulus features is voluntarily modulated by task demands.
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Atención/fisiología , Fijación Ocular/fisiología , Red Nerviosa/fisiología , Percepción/fisiología , Tiempo de Reacción/fisiología , Adolescente , Adulto , Femenino , Humanos , Masculino , Memoria/fisiología , Procesos Mentales/fisiología , Persona de Mediana Edad , Pupila/fisiología , Semántica , Adulto JovenRESUMEN
Errors in short-term memory increase with the quantity of information stored, limiting the complexity of cognition and behavior. In visual memory, attempts to account for errors in terms of allocation of a limited pool of working memory resources have met with some success, but the biological basis for this cognitive architecture is unclear. An alternative perspective attributes recall errors to noise in tuned populations of neurons that encode stimulus features in spiking activity. I show that errors associated with decreasing signal strength in probabilistically spiking neurons reproduce the pattern of failures in human recall under increasing memory load. In particular, deviations from the normal distribution that are characteristic of working memory errors and have been attributed previously to guesses or variability in precision are shown to arise as a natural consequence of decoding populations of tuned neurons. Observers possess fine control over memory representations and prioritize accurate storage of behaviorally relevant information, at a cost to lower priority stimuli. I show that changing the input drive to neurons encoding a prioritized stimulus biases population activity in a manner that reproduces this empirical tradeoff in memory precision. In a task in which predictive cues indicate stimuli most probable for test, human observers use the cues in an optimal manner to maximize performance, within the constraints imposed by neural noise.