European Journal of Neuroscience最新文献

Research into the function of deep brain structures has benefited greatly from microelectrode recordings in animals. This has helped to unravel physiological processes in the healthy and malfunctioning brain. Translation to the human is necessary for improving basic understanding of subcortical structures and their implications in diseases. The use of microelectrode recordings as a standard component of deep brain stimulation surgery offers the most viable route for studying the electrophysiology of single cells and local neuronal populations in important deep structures of the human brain. Most of the studies in the basal ganglia have targeted the motor loop and movement disorder pathophysiology. In recent years, however, research has diversified to include limbic and cognitive processes. This review aims to provide an overview of advances in neuroscience made using intraoperative and post-operative recordings with a focus on non-motor activity in the basal ganglia.

Patients with Duchenne muscular dystrophy (DMD) commonly show specific cognitive deficits in addition to a severe muscle impairment caused by the absence of dystrophin expression in skeletal muscle. These cognitive deficits have been related to the absence of dystrophin in specific regions of the central nervous system, notably cerebellar Purkinje cells (PCs). Dystrophin has recently been involved in GABA_A receptors clustering at postsynaptic densities, and its absence, by disrupting this clustering, leads to decreased inhibitory input to PC. We performed an in vivo electrophysiological study of the dystrophin-deficient muscular dystrophy X-linked (mdx) mouse model of DMD to compare PC firing and local field potential (LFP) in alert mdx and control C57Bl/10 mice. We found that the absence of dystrophin is associated with altered PC firing and the emergence of fast (~160–200 Hz) LFP oscillations in the cerebellar cortex of alert mdx mice. These abnormalities were not related to the disrupted expression of calcium-binding proteins in cerebellar PC. We also demonstrate that cerebellar long-term depression is altered in alert mdx mice. Finally, mdx mice displayed a force weakness, mild impairment of motor coordination and balance during behavioural tests. These findings demonstrate the existence of cerebellar dysfunction in mdx mice. A similar cerebellar dysfunction may contribute to the cognitive deficits observed in patients with DMD.

Major depressive disorder (MDD) has been associated with deficits in working memory as well as underlying gamma oscillation power. Consistent with this, overall reductions in cortical excitation have also been described with MDD. In previous work, we have demonstrated that the monoamine reuptake inhibitor venlafaxine increases gamma oscillation power in ex vivo hippocampal slices and that this is associated with concomitant increases in pyramidal arbour and reduced levels of plasticity-restricting perineuronal nets (PNNs). In the present study, we have examined the effects of chronic treatment with pramipexole (PPX), a D3 dopamine receptor agonist, for its effects on gamma oscillation power as measured by in vivo electroencephalography (EEG) recordings in female BALB/c and C57Bl6 mice. We observe a modest but significant increase in 20–50 Hz gamma power with PPX in both strains. Additionally, biochemical analysis of prefrontal cortex lysates from PPX-treated BALB/c mice shows a number of changes that could contribute to, or follow from, increased pyramidal excitability and/or gamma power. PPX-associated changes include reduced levels of specific PNN components as well as tissue inhibitor of matrix metalloproteases-1 (TIMP-1), which inhibits long-term potentiation of synaptic transmission. Consistent with its effects on gamma power, PNN proteins and TIMP-1, chronic PPX treatment also improves working memory and reduces anhedonia. Together these results add to an emerging literature linking extracellular matrix and/or gamma oscillation power to both mood and cognition.

The reproducibility crisis highlights several unresolved issues in science, including the need to develop measures that gauge both the consistency and convergence of data sets. While existing meta-analytic methods quantify the consistency of evidence, they do not quantify its convergence: the extent to which different types of empirical methods have provided evidence to support a hypothesis. To address this gap in meta-analysis, we and colleagues developed a summary metric—the cumulative evidence index (CEI)—which uses Bayesian statistics to quantify the degree of both consistency and convergence of evidence regarding causal hypotheses between two phenomena. Here, we outline the CEI's underlying model, which quantifies the extent to which studies of four types—positive intervention, negative intervention, positive non-intervention and negative non-intervention—lend credence to any of three types of causal relations: excitatory, inhibitory or no-connection. Along with p-values and other measures, the CEI can provide a more holistic perspective on a set of evidence by quantitatively expressing epistemic principles that scientists regularly employ qualitatively. The CEI can thus address the reproducibility crisis by formally demonstrating how convergent evidence across multiple study types can yield progress toward scientific consensus, even when an individual type of study fails to yield reproducible results.

Depression is a heterogeneous syndrome that impacts an individual's emotional, social, cognitive and bodily functioning. Depression is associated with biases in emotional processing, but alterations in basic sensory processing have received less attention in depression research. Here, we measured event-related potentials (ERPs) in response to changes in the intensity of auditory stimuli and the location of somatosensory stimuli in participants with depression and in non-depressed control participants. We tested whether auditory mismatch negativity, P3a or N1 intensity dependence response or somatosensory mismatch response, P3a, P50 or N80 can dissociate depressed participants and non-depressed controls, and we also analysed the effects of depression medication and age in this sample. N1 intensity dependence response was increased in unmedicated depressed participants relative to non-depressed controls. When age was controlled for in the analysis, the effect of depression was only at a trend level. N1 intensity dependence response correlated with depression severity at the whole sample level. We did not observe any depression-related alterations in auditory mismatch negativity or P3a or somatosensory ERPs. Our results may reflect an association between the N1 intensity dependence response and altered neurotransmitter activity in depression, but this should be confirmed in future studies.

Flash sequences appear as steady emission of light if the frequency is above the flicker-fusion threshold. One can display flicker-fused letters against a background, and using the Talbot-Plateau law, vary the average luminance of the letters to control degree of match to background luminance. We have previously reported that the visual system can identify letters that have an average luminance that equals background luminance, which can be described as an anomalous contrast discrimination. The present work confirms the earlier report, and provides additional evidence that the phenomenon is not based on a shift in luminance balance. We discuss the possible role of ON and OFF retinal channels in registering the anomalous contrast.

Despite predictions that neuroscientific discoveries would revolutionize psychiatry, decades of research have not yet led to clinically significant advances in psychiatric care. For this reason, an increasing number of researchers are recognizing the limitations of a purely biomedical approach in psychiatric research. These researchers call for reevaluating the conceptualization of mental disorders and argue for a non-reductionist approach to mental health. The aim of this paper is to discuss philosophical assumptions that underly neuroscientific research in psychiatry and offer practical tools to researchers for overcoming potential conceptual problems that are derived from those assumptions. Specifically, we will discuss: the analogy problem, questioning whether mental health problems are equivalent to brain disorders, the normativity problem, addressing the value-laden nature of psychiatric categories and the priority problem, which describes the level of analysis (e.g., biological, psychological, social, etc.) that should be prioritized when studying psychiatric conditions. In addition, we will explore potential strategies to mitigate practical problems that might arise due to these implicit assumptions. Overall, the aim of this paper is to suggest philosophical tools of practical use for neuroscientists, demonstrating the benefits of a closer collaboration between neuroscience and philosophy.

Gilles de la Tourette syndrome (GTS) and dystonia (DYS) are both hyperkinetic movement disorders effectively treated by deep brain stimulation (DBS) of the internal part of the globus pallidus (GPi). In this study, we compared single-neuron activity in the GPi between 18 GTS patients (with an average of 41 cells per patient) and 17 DYS patients (with an average of 54 cells per patient), all of whom underwent bilateral pallidal stimulation surgery, under general anesthesia or while awake at rest. We found no significant differences in GPi neuronal activity characteristics between patients operated on under general anesthesia versus those who were awake, irrespective of their diagnosis (GTS or DYS). We found higher firing rates, firing rate in bursts, pause duration and interspike interval coefficient of variation in GTS patients compared to DYS patients. On the opposite, we found higher number of pauses and bursts frequency in DYS patients. Lastly, we found a higher proportion of GPi oscillatory activities in DYS compared to GTS patients, with predominant activity within the low-frequency band (theta/alpha) in both patient groups. These findings underscore the complex relationship between the different neuronal discharge characteristic such as oscillatory or bursting activity within the GPi in shaping the clinical phenotypes of hyperkinetic disorders. Further research is warranted to deepen our understanding of how neuronal patterns are transmitted within deep brain structures and to develop strategies aimed at normalizing these pathological activities, by refining DBS techniques to enhance treatment efficacy and individual outcomes.

Ohgomori, T., Yamasaki, R., Takeuchi, H., Kadomatsu, K., Kira, J.-i. and Jinno, S. Differential activation of neuronal and glial STAT3 in the spinal cord of the SOD1^G93A mouse model of amyotrophic lateral sclerosis. European Journal of Neuroscience 2024; 46(4): 2001–2014. https://doi.org/10.1111/ejn.13650

In Figure 2, the magenta image of Figure 2E₂ (STAT3 immunofluorescence) was incorrect. We mistakenly used the magenta image of Figure 2C₃ for 2E₂. In the revised Figure 2, we have replaced the magenta image of 2E₂ with the correct image.

We apologize for this error.

The sleep homeostatic process in adults is moderately stable over time and unique to an individual. Work in transgenic mice has suggested a role of genes in sleep homeostasis. The current study quantified the genetic contribution to sleep homeostasis in adolescence. We use slow wave energy (SWE) as a metric for sleep pressure dissipation during sleep. This measure reflects both sleep intensity and duration. High-density (58 derivations) sleep electroencephalogram (EEG) was recorded in 14 monozygotic and 12 dizygotic adolescent twin pairs (mean age = 13.2 years; standard deviation [SD] = 1.1; 20 females). SWE at the end of sleep was quantified as the cumulative delta power (1–4.6 Hz) over the night. We also examined the time constant of the decay and the level of slow wave activity (SWA) at the beginning of the sleep episode. Structural equation modelling was used to quantify the amount of variance in SWE and the dissipation of sleep pressure due to genes. We found that most (mean = 76% across EEG derivations) of the variance in SWE was due to genes. In contrast, genes had a small (mean = 33%) influence on the rate of dissipation of sleep pressure, and this measure was largely (mean = 67%) driven by environmental factors unique to each twin. Our results show that the amount of dissipated sleep pressure is largely under genetic control; however, the rate of sleep pressure dissipation is largely due to unique environmental factors. Our findings are in line with research in animals and suggest that the heritability of the rate of sleep pressure dissipation is limited.