The assessment of neuronal plasticity following sciatic nerve injuries in rats using electron microscopy and stereological methods.

The transmission of signals to the cell body from injured axons induces significant alterations in primary sensory neurons located in the ganglion tissue, the site of the perikaryon of the affected nerve fibers. Disruption of the continuity between the proximal and distal ends leads to substantial adaptability in ganglion cells and induces macrophage-like activity in the satellite cells. Research findings have demonstrated the plasticity of satellite cells following injury. Satellite cells work together with sensory neurons to extend the interconnected surface area in order to permit effective communication. The dynamic cellular environment within the ganglion undergoes several alterations that ultimately lead to differentiation, transformation, or cell death. In addition to necrotic and apoptotic cell morphology, phenomena such as histomorphometric alterations, including the development of autophagic vacuoles, chromatolysis, cytosolic degeneration, and other changes, are frequently observed in cells following injury. The use of electron microscopic and stereological techniques for assessing ganglia and nerve fibers is considered a gold standard in terms of investigating neuropathic pain models, regenerative therapies, some treatment methods, and quantifying the outcomes of pharmacological and bioengineering interventions. Stereological techniques provide observer-independent and reliable results, which are particularly useful in the quantitative assessment of three-dimensional structures from two-dimensional images. Employing the fractionator and disector techniques within stereological methodologies yields unbiased data when assessing parameters such as number. The fundamental concept underlying these methodologies involves ensuring that each part of the structure under evaluation has an equal opportunity of being sampled. This review describes the stereological and histomorphometric evaluation of dorsal root ganglion neurons and satellite cells following nerve injury models.

Safety of Special Waveform of Transcranial Electrical Stimulation (TES): In Vivo Assessment.

Intermittent theta burst (iTBS) powered by direct current stimulation (DCS) can safely be applied transcranially to induce neuroplasticity in the human and animal brain cortex. tDCS-iTBS is a special waveform that is used by very few studies, and its safety needs to be confirmed. Therefore, we aimed to evaluate the safety of tDCS-iTBS in an animal model after brain stimulations for 1 h and 4 weeks. Thirty-one Sprague Dawley rats were divided into two groups: (1) short-term stimulation for 1 h/session (sham, low, and high) and (2) long-term for 30 min, 3 sessions/week for 4 weeks (sham and high). The anodal stimulation applied over the primary motor cortex ranged from 2.5 to 4.5 mA/cm2. The brain biomarkers and scalp tissues were assessed using ELISA and histological analysis (H&E staining) after stimulations. The caspase-3 activity, cortical myelin basic protein (MBP) expression, and cortical interleukin (IL-6) levels increased slightly in both groups compared to sham. The serum MBP, cortical neuron-specific enolase (NSE), and serum IL-6 slightly changed from sham after stimulations. There was no obvious edema or cell necrosis seen in cortical histology after the intervention. The short- and long-term stimulations did not induce significant adverse effects on brain and scalp tissues upon assessing biomarkers and conducting histological analysis.

Assessment of astrocytes as a mediator of memory and learning in rodents.

The classical view of astrocytes is that they provide supportive functions for neurons, transporting metabolites and maintaining the homeostasis of the extracellular milieu. This view is gradually changing with the advent of molecular genetics and optical methods allowing interrogation of selected cell types in live experimental animals. An emerging view that astrocytes additionally act as a mediator of synaptic plasticity and contribute to learning processes has gained in vitro and in vivo experimental support. Here we focus on the literature published in the past two decades to review the roles of astrocytes in brain plasticity in rodents, whereby the roles of neurotransmitters and neuromodulators are considered to be comparable to those in humans. We outline established inputs and outputs of astrocytes and discuss how manipulations of astrocytes have impacted the behavior in various learning paradigms. Multiple studies suggest that the contribution of astrocytes has a considerably longer time course than neuronal activation, indicating metabolic roles of astrocytes. We advocate that exploring upstream and downstream mechanisms of astrocytic activation will further provide insight into brain plasticity and memory/learning impairment.

Assessment of Cortical Plasticity in Schizophrenia by Transcranial Magnetic Stimulation.

Neural plasticity refers to the capability of the brain to modify its structure and/or function and organization in response to a changing environment. Evidence shows that disruption of neuronal plasticity and altered functional connectivity between distinct brain networks contribute significantly to the pathophysiological mechanisms of schizophrenia. Transcranial magnetic stimulation has emerged as a noninvasive brain stimulation tool that can be utilized to investigate cortical excitability with the aim of probing neural plasticity mechanisms. In particular, in pathological disorders, such as schizophrenia, cortical dysfunction, such as an aberrant excitatory-inhibitory balance in cortical networks, altered cortical connectivity, and impairment of critical period timing are very important to be studied using different TMS paradigms. Studying such neurophysiological characteristics and plastic changes would help in elucidating different aspects of the pathophysiological mechanisms underlying schizophrenia. This review attempts to summarize the findings of available TMS studies with diagnostic and characterization aims, but not with therapeutic purposes, in schizophrenia. Findings provide further evidence of aberrant excitatory-inhibitory balance in cortical networks, mediated by neurotransmitter pathways such as the glutamate and GABA systems. Future studies with combining techniques, for instance, TMS with brain imaging or molecular genetic typing, would shed light on the characteristics and predictors of schizophrenia.

Assessment of cortical reorganization and preserved function in phantom limb pain: a methodological perspective.

Phantom limb pain (PLP) has been associated with reorganization in primary somatosensory cortex (S1) and preserved S1 function. Here we examined if methodological differences in the assessment of cortical representations might explain these findings. We used functional magnetic resonance imaging during a virtual reality movement task, analogous to the classical mirror box task, in twenty amputees with and without PLP and twenty matched healthy controls. We assessed the relationship between task-related activation maxima and PLP intensity in S1 and motor cortex (M1) in individually-defined or group-conjoint regions of interest (ROI) (overlap of task-related activation between the groups). We also measured cortical distances between both locations and correlated them with PLP intensity. Amputees compared to controls showed significantly increased activation in M1, S1 and S1M1 unrelated to PLP. Neural activity in M1 was positively related to PLP intensity in amputees with PLP when a group-conjoint ROI was chosen. The location of activation maxima differed between groups in S1 and M1. Cortical distance measures were unrelated to PLP. These findings suggest that sensory and motor maps differentially relate to PLP and that methodological differences might explain discrepant findings in the literature.

Assessment of Long-term Depression Induction in Adult Cerebellar Slices.

Synaptic plasticity provides a mechanism for learning and memory. For cerebellar motor learning, long-term depression (LTD) of synaptic transmissions from parallel fibers (PF) to Purkinje cells (PC) is considered the basis for motor learning, and deficiencies of both LTD and motor learning are observed in various gene-manipulated animals. Common motor learning sets, such as adaptation of the optokinetic reflex (OKR), the vestibular-ocular reflex (VOR), and rotarod test were used for evaluation of motor learning ability. However, results obtained from the GluA2-carboxy terminus modified knock-in mice demonstrated normal adaptation of the VOR and the OKR, despite lacking PF-LTD. In that report, induction of LTD was only attempted using one type of stimulation protocol at room temperature. Thus, conditions to induce cerebellar LTD were explored in the same knock-in mutants using various protocols at near physiological temperature. Finally, we found stimulation protocols, by which LTD could be induced in these gene-manipulated mice. In this study, a set of protocols are proposed to evaluate LTD-induction, which will more accurately allow examination of the causal relationship between LTD and motor learning. In conclusion, experimental conditions are crucial when evaluating LTD in gene-manipulated mice.

Medición de reserva cognitiva: estudio en una muestra de adultos chilenos / Cognitive reserve assessment: a study in a sample of chilean adults

Mayor reserva se asocia con resistencia al deterioro en sujetos con enfermedades neurodegenerativas. En personas sanas explica las diferencias interindividuales en el rendimiento de tareas. Medir los factores de reserva cognitiva permite contar con un índice numérico de la ganancia cognitiva acumulada por un sujeto. Este índice puede ser correlacionado con otras funciones cuantificables. El presente trabajo tiene como objetivo presentar los índices de reserva obtenidos por una población chilena en la aplicación del Cognitive Reserve Index Questionnaire (CRIq). Para ello 90 adultos (18-85 años) sin evidencias de trastorno cognitivo, de la región de Valparaíso-Chile, fueron entrevistados sobre actividades de estudio, laborales y de tiempo libre ejecutadas desde los 18 años.Los resultados muestran que los índices de reserva de los sujetos varían en función del tiempo de ejecución de actividades promotoras de reserva y no por su edad. Se encontraron diferencias estadísticamente significativas entre los grupos etarios. Estos resultados permiten concluir que la ejecución de actividades de estudio, laborales, sociales, entre otras aumenta los índices de reserva cognitiva, que es una variable diferenciadora entre individuos. La medición de dichos índices puede ser útil en un amplio campo de disciplinas (medicina, neurología, neuropsicología, educación, psicología, fonoaudiología, neurociencias y en las ciencias cognitivas en general).

A higher cognitive reserve is linked to higher resistance to deterioration among subjects suffering from neurodegenerative disorders. In healthy persons the cognitive reserve explains inter-individual differences in task performance. Measuring the cognitive reserve factors involves obtaining a numerical index of the cumulative cognitive gain accumulated by a subject. This index can be correlated with other measurable functions.This study was conceived to determine the reserve indexes accumulated by a Chilean sample, by means of the administration of the Cognitive Reserve Index Questionnaire (CRIq).In order to do so, 90 adults (18-85 years old) without evidence of cognitive disorder, living in Valparaíso region, Chile, were interviewed about their education, their work environment and their and leisure activities carried out since they were 18 years old.Results showed that reserve indexes of the subjects vary as a function of the time of execution of reserve-promoting activities, not age. Statistically significant differences were found among age-groups. These findings allow us to conclude that studying, working and engaging in social activities, among other things, increase the cognitive reserve indexes, which are a differentiating variable among individuals.The measurement of these indexes can be useful in a wide array of disciplines: medicine, neurology, neuropsychology, education, psychology, phonoaudiology, neurosciences and cognitive sciences in general.

Assessment of Somatosensory Reorganization by Functional Magnetic Resonance Imaging After Hand Replantation.

INTRODUCTION: Amputation of the hand is a rare and extremely intense trauma. Replanting and allografting after this type of injury require a major reorganization of the brain. Brain plasticity, though better known in the context of disorders of the central nervous system, is just as indispensable when the extremities are damaged. MATERIALS AND METHODS: A 17-year-old patient underwent replantation of the nondominant hand after transmetaphyseal amputation after traumatic injury. After 18 days in hospital and subsequent treatment in a physical rehabilitation center, the patient attended clinical and radiology follow-up sessions over the next 2 years. RESULTS: The management of this patient led to an excellent functional outcome in conjunction with successful social and professional reintegration. Electromyography at 18 months confirmed nerve regrowth. Functional magnetic resonance imaging was done at 2 years to evaluate cerebral plasticity. Motor function, largely dependent on the primary motor area, is aided by the addition of secondary and accessory motor areas for both simple and complex movements. A change in sensory information is stimulation in its own right hemisphere and increases solicitation of the contralateral precentral and postcentral gyrus. CONCLUSIONS: There seems to be a real reversible dynamic plasticity under the balance of inhibitory and excitatory influences exerted on the cortical neurons. Any disruption of this balance requires the brain to adapt to the new circumstances to reestablish the hand as a functioning part of the body.

Thoracic Spinal Cord Hemisection Surgery and Open-Field Locomotor Assessment in the Rat.

Spinal cord injury (SCI) causes disturbances in motor, sensory, and autonomic function below the level of the lesion. Experimental animal models are valuable tools to understand the neural mechanisms involved in locomotor recovery after SCI and to design therapies for clinical populations. There are several experimental SCI models including contusion, compression, and transection injuries that are used in a wide variety of species. A hemisection involves the unilateral transection of the spinal cord and disrupts all ascending and descending tracts on one side only. Spinal hemisection produces a highly selective and reproducible injury in comparison to contusion or compression techniques that is useful for investigating neural plasticity in spared and damaged pathways associated with functional recovery. We present a detailed step-by-step protocol for performing a thoracic hemisection at the T8 vertebral level in the rat that results in an initial paralysis of the hindlimb on the side of the lesion with graded spontaneous recovery of locomotor function over several weeks. We also provide a locomotor scoring protocol to assess functional recovery in the open-field. The locomotor assessment provides a linear recovery profile and can be performed both early and repeatedly after injury in order to accurately screen animals for appropriate time points in which to conduct more specialized behavioral testing. The hemisection technique presented can be readily adapted to other transection models and species, and the locomotor assessment can be used in a variety of SCI and other injury models to score locomotor function.

Assessment of genes involved in behavior, learning, memory, and synaptic plasticity following status epilepticus in rats.

OBJECTIVE: In this study, it was aimed to evaluate cognitive and behavioral changes after status epilepticus (SE) induced by pentylenetetrazole in immature rats via Morris water maze and open-field area tests and to assess alterations in expression of 84 key genes involved in synaptic plasticity after SE. METHOD: The study was conducted on 30 immature rats (12-days old). The rats were assigned into groups as control and experiment (SE) groups. The SE was induced by pentylenetetrazole in 12-days old rats. In addition, experiment group was divided into two groups as mature (n = 8) and immature SE (n = 8) subgroups. Again, the control group was divided into two groups as mature (n = 7) and immature control (n = 7) subgroups. Hippocampal tissue samples were prepared, and expression of 84 key genes involved in synaptic plasticity was assessed in Genome and Stem Cell Center of Erciyes University before behavioral tests in immature rats (22-days old) and after open-filed area and Morris water maze tests in mature rats (72-days old) in both experiment and control groups. RESULTS: No significant difference was detected in behavioral tests assessing spatial memory and learning among groups. Significant differences were detected, ARC (activity-regulated cytoskeleton-associated protein), BDNF (brain-derived neurotrophic factor), MAPK1 (mitogen-activated protein kinase 1), NR4A1 (nuclear receptor subfamily 4 group A member 1), PPP3CA (protein phosphatase 3 catalytic subunit alpha), RGS2 (regulator of G protein signaling 2), and TNF (tumor necrosis factor) gene expressions between control and experiment groups in immature rats whereas in ADCY8 (adenylate cyclase 8), BDNF (brain-derived neurotrophic factor), EGR4 (early growth response 4), and KIF17 (kinesin family member 17) gene expressions between control and experiment groups in mature rats. DISCUSSION: In this study, differences detected in gene expressions of synaptic plasticity after SE indicate in which steps of synaptic plasticity may be problematic in epileptogenesis. The gene expressions in this study may be considered as potential biomarkers; however, epileptogenesis is a dynamic process and cannot be explained through a single mechanism. Future studies on epileptogenesis and studies specifically designed to evaluate genes detected in our study will further elucidate synaptic plasticity in epilepsy and epileptogenesis.

Assessment of conditioned pain modulation in healthy participants and patients with chronic pain: manifestations and implications for pain progression.

PURPOSE OF REVIEW: The purpose of this review is to summarize recent findings on conditioned pain modulation (CPM) in humans with a focus on methodology, factors modulating CPM, and the potential for CPM as a clinical marker for pain progression. RECENT FINDINGS: CPM can be evoked by combining different stimulus modalities with good reliability; sequential CPM effects are stable over time with limited carryover effects. Optimism and pain catastrophizing might influence pain inhibition. Further, studies suggest that the CPM effect can be improved by gabapentinoids, transcranial direct current stimulation to cortical structures, and exercise and that long-term opioid use might impair CPM in patients with chronic pain. Clinical evidence suggests that preoperative impaired CPM may predict more severe chronic postoperative pain. The effect of pain duration on CPM impairment has been challenged by recent studies. SUMMARY: As CPM methodology is optimized, studies are revealing factors that can modulate descending pain inhibitory pathways. Understanding underlying mechanisms of CPM will improve the utility of CPM in a clinical setting and potentially lead to personalized treatments for chronic pain patients.

Dreaming neural networks: Forgetting spurious memories and reinforcing pure ones.

The standard Hopfield model for associative neural networks accounts for biological Hebbian learning and acts as the harmonic oscillator for pattern recognition, however its maximal storage capacity is α∼0.14, far from the theoretical bound for symmetric networks, i.e. α=1. Inspired by sleeping and dreaming mechanisms in mammal brains, we propose an extension of this model displaying the standard on-line (awake) learning mechanism (that allows the storage of external information in terms of patterns) and an off-line (sleep) unlearning&consolidating mechanism (that allows spurious-pattern removal and pure-pattern reinforcement): this obtained daily prescription is able to saturate the theoretical bound α=1, remaining also extremely robust against thermal noise. The emergent neural and synaptic features are analyzed both analytically and numerically. In particular, beyond obtaining a phase diagram for neural dynamics, we focus on synaptic plasticity and we give explicit prescriptions on the temporal evolution of the synaptic matrix. We analytically prove that our algorithm makes the Hebbian kernel converge with high probability to the projection matrix built over the pure stored patterns. Furthermore, we obtain a sharp and explicit estimate for the "sleep rate" in order to ensure such a convergence. Finally, we run extensive numerical simulations (mainly Monte Carlo sampling) to check the approximations underlying the analytical investigations (e.g., we developed the whole theory at the so called replica-symmetric level, as standard in the Amit-Gutfreund-Sompolinsky reference framework) and possible finite-size effects, finding overall full agreement with the theory.

Social plasticity in the fish brain: Neuroscientific and ethological aspects.

Social plasticity, defined as the ability to adaptively change the expression of social behavior according to previous experience and to social context, is a key ecological performance trait that should be viewed as crucial for Darwinian fitness. The neural mechanisms for social plasticity are poorly understood, in part due to skewed reliance on rodent models. Fish model organisms are relevant in the field of social plasticity for at least two reasons: first, the diversity of social organization among fish species is staggering, increasing the breadth of evolutionary relevant questions that can be asked. Second, that diversity also suggests translational relevance, since it is more likely that "core" mechanisms of social plasticity are discovered by analyzing a wider variety of social arrangements than relying on a single species. We analyze examples of social plasticity across fish species with different social organizations, concluding that a "core" mechanism is the initiation of behavioral shifts through the modulation of a conserved "social decision-making network", along with other relevant brain regions, by monoamines, neuropeptides, and steroid hormones. The consolidation of these shifts may be mediated via neurogenomic adjustments and regulation of the expression of plasticity-related molecules (transcription factors, cell cycle regulators, and plasticity products).

Depression.

Major depression is a common illness that severely limits psychosocial functioning and diminishes quality of life. In 2008, WHO ranked major depression as the third cause of burden of disease worldwide and projected that the disease will rank first by 2030.1 In practice, its detection, diagnosis, and management often pose challenges for clinicians because of its various presentations, unpredictable course and prognosis, and variable response to treatment.

Emergence of Binocular Disparity Selectivity through Hebbian Learning.

Neural selectivity in the early visual cortex strongly reflects the statistics of our environment (Barlow, 2001; Geisler, 2008). Although this has been described extensively in literature through various encoding hypotheses (Barlow and Földiák, 1989; Atick and Redlich, 1992; Olshausen and Field, 1996), an explanation as to how the cortex might develop the computational architecture to support these encoding schemes remains elusive. Here, using the more realistic example of binocular vision as opposed to monocular luminance-field images, we show how a simple Hebbian coincidence-detector is capable of accounting for the emergence of binocular, disparity selective, receptive fields. We propose a model based on spike timing-dependent plasticity, which not only converges to realistic single-cell and population characteristics, but also demonstrates how known biases in natural statistics may influence population encoding and downstream correlates of behavior. Furthermore, we show that the receptive fields we obtain are closer in structure to electrophysiological data reported in macaques than those predicted by normative encoding schemes (Ringach, 2002). We also demonstrate the robustness of our model to the input dataset, noise at various processing stages, and internal parameter variation. Together, our modeling results suggest that Hebbian coincidence detection is an important computational principle and could provide a biologically plausible mechanism for the emergence of selectivity to natural statistics in the early sensory cortex.SIGNIFICANCE STATEMENT Neural selectivity in the early visual cortex is often explained through encoding schemes that postulate that the computational aim of early sensory processing is to use the least possible resources (neurons, energy) to code the most informative features of the stimulus (information efficiency). In this article, using stereo images of natural scenes, we demonstrate how a simple Hebbian rule can lead to the emergence of a disparity-selective neural population that not only shows realistic single-cell and population tunings, but also demonstrates how known biases in natural statistics may influence population encoding and downstream correlates of behavior. Our approach allows us to view early neural selectivity, not as an optimization problem, but as an emergent property driven by biological rules of plasticity.

Assessment of neuroplasticity in late-life depression with transcranial magnetic stimulation.

BACKGROUND: Studies using Transcranial Magnetic Stimulation (TMS), a non-invasive method of brain stimulation, have implicated impaired neuroplasticity in the pathophysiology of depression in younger adults. The role of neuroplasticity in late-life depression (LLD) has not yet been explored using TMS. OBJECTIVE: This study aimed at evaluating motor cortical neuroplasticity using paired associative stimulation (PAS). Single-pulse TMS was used to induce motor-evoked potentials (MEP) in the contralateral hand muscle before and after PAS. The potentiation of MEP amplitudes after PAS was used as an indirect index of associative plasticity and long-term potentiation (LTP) (i.e. PAS-LTP). RESULTS: 48 older adults with depression and 34 age-matched healthy controls (HC) were compared. PAS- LTP was successfully induced in 68.8% of older adults with depression and 47.1% of HC. At the group level, older adults with depression failed to show statistically significant induction of neuroplasticity, which was observed in HC. However, no significant differences were observed between the two groups for PAS-LTP. CONCLUSION: Our results suggest that associative plasticity does not differ substantially between older adults with depression and age-matched HC. Continued research is needed to more comprehensively understand the role of neuroplasticity in the pathophysiology of LLD.

Is Objectively Assessed Sedentary Behavior, Physical Activity and Cardiorespiratory Fitness Linked to Brain Plasticity Outcomes in Old Age?

The aim of this cross-sectional study was to determine the associations of objectively assessed habitual physical activity and physical performance with brain plasticity outcomes and brain-derived neurotrophic factor (BDNF) levels in cognitively healthy older adults. Physical performance was analyzed based on cardiopulmonary exercise-testing data and accelerometer-based physical activity was analyzed as total activity counts, sedentary time, light physical activity and moderate to vigorous physical activity. Brain plasticity outcomes included magnetic resonance spectroscopy (MRS)-based markers, quantitative imaging-based hippocampal volume and BDNF serum levels. The association between physical performance and hippocampal volume was strongly influenced by participants' education, sex, age and BMI. Confounder-controlled correlation revealed significant associations of brain plasticity outcomes with physical activity but not with performance. MRS-based adenosine triphosphate to phosphocreatine and glycerophosphocholine to phosphocreatine ratios were significantly associated with accelerometer total activity counts. BDNF was detrimentally associated with sedentary time but beneficially related to accelerometer total activity counts and moderate to vigorous physical activity. Exceeding the current moderate to vigorous physical activity recommendations led to significantly higher BDNF levels. Our results indicate that regular physical activity might be beneficial for preserving brain plasticity in higher age. In this study these associations were not mediated significantly by physical performance. Overall physical activity and exceeding current moderate to vigorous physical activity recommendations were positively associated with BDNF. Sedentary behavior, however, seems to be negatively related to neurotrophic factor bioavailability in the elderly.

Language Exposure Relates to Structural Neural Connectivity in Childhood.

Neuroscience research has elucidated broad relationships between socioeconomic status (SES) and young children's brain structure, but there is little mechanistic knowledge about specific environmental factors that are associated with specific variation in brain structure. One environmental factor, early language exposure, predicts children's linguistic and cognitive skills and later academic achievement, but how language exposure relates to neuroanatomy is unknown. By measuring the real-world language exposure of young children (ages 4-6 years, 27 male/13 female), we confirmed the preregistered hypothesis that greater adult-child conversational experience, independent of SES and the sheer amount of adult speech, is related to stronger, more coherent white matter connectivity in the left arcuate and superior longitudinal fasciculi on average, and specifically near their anterior termination at Broca's area in left inferior frontal cortex. Fractional anisotropy of significant tract subregions mediated the relationship between conversational turns and children's language skills and indicated a neuroanatomical mechanism underlying the SES "language gap." Post hoc whole-brain analyses revealed that language exposure was not related to any other white matter tracts, indicating the specificity of this relationship. Results suggest that the development of dorsal language tracts is environmentally influenced, specifically by early, dialogic interaction. Furthermore, these findings raise the possibility that early intervention programs aiming to ameliorate disadvantages in development due to family SES may focus on increasing children's conversational exposure to capitalize on the early neural plasticity underlying cognitive development.SIGNIFICANCE STATEMENT Over the last decade, cognitive neuroscience has highlighted the detrimental impact of disadvantaged backgrounds on young children's brain structure. However, to intervene effectively, we must know which proximal aspects of the environmental aspects are most strongly related to neural development. The present study finds that young children's real-world language exposure, and specifically the amount of adult-child conversation, correlates with the strength of connectivity in the left hemisphere white matter pathway connecting two canonical language regions, independent of socioeconomic status and the sheer volume of adult speech. These findings suggest that early intervention programs aiming to close the achievement gap may focus on increasing children's conversational exposure to capitalize on the early neural plasticity underlying cognitive development.

Concurrence of form and function in developing networks and its role in synaptic pruning.

A fundamental question in neuroscience is how structure and function of neural systems are related. We study this interplay by combining a familiar auto-associative neural network with an evolving mechanism for the birth and death of synapses. A feedback loop then arises leading to two qualitatively different types of behaviour. In one, the network structure becomes heterogeneous and dissasortative, and the system displays good memory performance; furthermore, the structure is optimised for the particular memory patterns stored during the process. In the other, the structure remains homogeneous and incapable of pattern retrieval. These findings provide an inspiring picture of brain structure and dynamics that is compatible with experimental results on early brain development, and may help to explain synaptic pruning. Other evolving networks-such as those of protein interactions-might share the basic ingredients for this feedback loop and other questions, and indeed many of their structural features are as predicted by our model.