Restore Brain Function Research Articles

Overnight changes in performance fatigability and their relationship to modulated deep sleep oscillations via auditory stimulation.

Deep sleep oscillations are proposed to be central in restoring brain function and to affect different aspects of motor performance such as facilitating the consolidation of motor sequences resulting in faster and more accurate sequence tapping. Yet, whether deep sleep modulates performance fatigability during fatiguing tasks remains unexplored. We investigated overnight changes in tapping speed and resistance against performance fatigability via a finger tapping task. During fast tapping, fatigability manifests as a reduction in speed (or "motor slowing") which affects all tapping tasks, including motor sequences used to study motor memory formation. We further tested whether overnight changes in performance fatigability are influenced by enhancing deep sleep oscillations using auditory stimulation. We found an overnight increase in tapping speed alongside a reduction in performance fatigability and perceived workload. Auditory stimulation led to a global enhancement of slow waves and both slow and fast spindles during the stimulation window and a local increase in slow spindles in motor areas across the night. However, overnight performance improvements were not significantly modulated by auditory stimulation and changes in tapping speed or performance fatigability were not predicted by individual changes in deep sleep oscillations. Our findings demonstrate overnight changes in fatigability but revealed no evidence suggesting that this effect is causally linked to temporary augmentation of slow waves or sleep spindles. Our results are important for future studies using tapping tasks to test the relationship between sleep and motor memory consolidation, as overnight changes in objectively measured and subjectively perceived fatigue likely impact behavioural outcomes.

Interference of default mode on attention networks in adults with attention-deficit/hyperactivity disorder and its association with genetic variants and treatment outcomes.

Altered brain functional connectivity has been proposed as the neurobiological underpinnings of attention-deficit/hyperactivity disorder (ADHD), and the default mode interference hypothesis is one of the most popular neuropsychological models. Here, we explored whether this hypothesis is supported in adults with ADHD and the association with high-risk genetic variants and treatment outcomes. Voxel-based whole-brain connectome analysis was conducted on resting-state functional MRI data from 84 adults with ADHD and 89 healthy controls to identify functional connectivity substrates corresponding to ADHD-related alterations. The candidate genetic variants and 12-week cognitive behavioral therapy data were leveraged from the same population to assess these associations. We detected breakdowns of functional connectivity in the precuneus and left middle temporal gyrus in adults with ADHD, with exact contributions from decreased connectivity within the default mode, dorsal and ventral attention networks, as well as increased connectivity among them with the middle temporal gyrus serving as a crucial 'bridge'. Additionally, significant associations between the altered functional connectivity and genetic variants in both MAOA and MAOB were detected. Treatment restored brain function, with the amelioration of connectivity of the middle temporal gyrus, accompanied by improvements in ADHD core symptoms. These findings support the interference of default mode on attention in adults with ADHD and its association with genetic risk variants and clinical management, providing insights into the underlying pathogenesis of ADHD and potential biomarkers for treatment evaluation.

Sustained insulin treatment restoring metabolic status, body weight, and cognition in an anorexia nervosa-like animal model in mice

IntroductionAnorexia Nervosa (AN) is a psycho-socio-biological disease characterized by severe weight loss as result of dieting and hyperactivity. Effective treatments are scarce, despite its significant prevalence and mortality. AN patients show lower basal insulin levels and increased metabolic clearance, leading to weight loss, cognitive deficits, and hormonal imbalances. Low-dose polymer insulin could potentially reverse these effects by restoring brain function, reducing fear of weight gain, encouraging food intake, and restoring fat depots. This study evaluates an insulin delivery system designed for sustained release and AN treatment. MethodsAN-like model was established through dietary restriction (DR). On days 1–25, mice were on DR, and on days 26–31 they were on ad libitum regimen. An insulin-loaded delivery system was administered subcutaneously (1% w/w insulin). The impact of insulin treatment on gene expression in the hippocampus (cognition, regulation of stress, neurogenesis) and hypothalamus (eating behavior, mood) was assessed. Behavioral assays were conducted to evaluate motor activity and cognitive function. ResultsThe delivery system demonstrated sustained insulin release, maintaining therapeutic plasma levels. Diet restriction mice treated with the insulin delivery system showed body weight restoration. Gene expression analysis revealed enhanced expression of CB1 and CB2 genes associated with improved eating behavior and cognition, while POMC expression was reduced. Insulin-polymer treatment restored cognitive function and decreased hyperactivity in the AN-like model. ConclusionThe PSA-RA-based insulin delivery system effectively restores metabolic balance, body weight, and cognitive function in the AN model. Its ability to steadily release insulin makes it a promising candidate for AN treatment."

Neurolinguistic Features of Digital Autism

The way of thinking and consciousness of a person is not only a problem of an individual, but also a general socio-social problem. In the modern era of “digitalization”, the phenomenon of “digital autism” is rapidly gaining momentum among the younger generation, especially among children and adolescents. Screeners, buzzers or Generation “Z” are modern children who cannot imagine their lives without electronic devices. This makes it difficult not only for the child to develop language abilities and speech activity, but also to adapt to the social environment, get an education, and the path to professional success. The article examines the impact of digital autism, which is the impact of autism on people's daily and personal lives. Currently, social networking or excessive spending time in a virtual environment can give people an advantage over direct communication and give them emotional freedom and confidence that are not always present in ordinary communication. However, excessive isolation from society, the distinction between virtual and real life situations, their correct assessment and the development of specific solutions create certain difficulties. The complexity of the issue of digital autism lies in the fact that digital autism occurs not only in children, but also in adults. Unfortunately, there are few neurolinguistic studies on the prevention of digital autism, treatment of autism, rehabilitation, and restoration of brain function. Digital autism is one of the most difficult problems that requires studying at the junction of several sciences, such as neurolinguistics, sociology, medicine, defectology, from the point of view of the anthropolinguistic paradigm.

Glial cells as a promising therapeutic target of glaucoma: beyond the IOP.

Glial cells, a type of non-neuronal cell found in the central nervous system (CNS), play a critical role in maintaining homeostasis and regulating CNS functions. Recent advancements in technology have paved the way for new therapeutic strategies in the fight against glaucoma. While intraocular pressure (IOP) is the most well-known modifiable risk factor, a significant number of glaucoma patients have normal IOP levels. Because glaucoma is a complex, multifactorial disease influenced by various factors that contribute to its onset and progression, it is imperative that we consider factors beyond IOP to effectively prevent or slow down the disease's advancement. In the realm of CNS neurodegenerative diseases, glial cells have emerged as key players due to their pivotal roles in initiating and hastening disease progression. The inhibition of dysregulated glial function holds the potential to protect neurons and restore brain function. Consequently, glial cells represent an enticing therapeutic candidate for glaucoma, even though the majority of glaucoma research has historically concentrated solely on retinal ganglion cells (RGCs). In addition to the neuroprotection of RGCs, the proper regulation of glial cell function can also facilitate structural and functional recovery in the retina. In this review, we offer an overview of recent advancements in understanding the non-cell-autonomous mechanisms underlying the pathogenesis of glaucoma. Furthermore, state-of-the-art technologies have opened up possibilities for regenerating the optic nerve, which was previously believed to be incapable of regeneration. We will also delve into the potential roles of glial cells in the regeneration of the optic nerve and the restoration of visual function.

Common Data Element for Disorders of Consciousness: Recommendations from the Working Group on Therapeutic Interventions.

Over the past 30years, there have been significant advances in the understanding of the mechanisms associated with loss and recovery of consciousness following severe brain injury. This work has provided a strong grounding for the development of novel restorative therapeutic interventions. Although all interventions are aimed at modulating and thereby restoring brain function, the landscape of existing interventions encompasses a very wide scope of techniques and protocols. Despite vigorous research efforts, few approaches have been assessed with rigorous, high-quality randomized controlled trials. As a growing number of exploratory interventions emerge, it is paramount to develop standardized approaches to reporting results. The successful evaluation of novel interventions depends on implementation of shared nomenclature and infrastructure. To address this gap, the Neurocritical Care Society's Curing Coma Campaign convened nine working groups and charged them with developing common data elements (CDEs). Here, we report the work of the Therapeutic Interventions Working Group. The working group reviewed existing CDEs relevant to therapeutic interventions within the National Institutes of Health National Institute of Neurological Disorders and Stroke database and reviewed the literature for assessing key areas of research in the intervention space. CDEs were then proposed, iteratively discussed and reviewed, classified, and organized in a case report form (CRF). We developed a unified CRF, including CDEs and key design elements (i.e., methodological or protocol parameters), divided into five sections: (1) patient information, (2) general study information, (3) behavioral interventions, (4) pharmacological interventions, and (5) device interventions. The newly created CRF enhances systematization of future work by proposing a portfolio of measures that should be collected in the development and implementation of studies assessing novel interventions intended to increase the level of consciousness or rate of recovery of consciousness in patients with disorders of consciousness.

Youth-associated platelet-derived chemokine reverses brain aging through neuroimmune mechanisms

Age-related loss of brain function has been seen as inevitable, yet recent work leveraging the systemic environment challenges this notion. Schroer et al. demonstrate that youth-associated platelet factor 4 (PF4) partially restores brain function in aged mice while reducing peripheral immune dysfunction, supporting periphery-based approaches to treat age-associated brain disorders.

Evaluation of obesity prevention effect of black ginseng on serum, liver, and hypothalamus of mice on a high-fat diet using a metabolomics approach

Black ginseng is being studied to prevent obesity caused by a high-fat diet (HFD). The aim of this study was to evaluate the obesity-preventing effect of black ginseng extract (BGE) in the serum, liver, and hypothalamus of mice on an HFD using metabolomic techniques. Mice were divided into four groups which were respectively fed a normal diet (CTL), an HFD, an HFD with a low concentration of BGE (BGEL), and an HFD with a high concentration of BGE (BGEH) for 8 weeks. Metabolite profiling revealed a clear separation between the BGE diet and HFD groups. Lipid metabolism, including saturated fatty acids and cholesterol, was decreased in the BGEH mice. Specifically, neurotransmitters and intermediates of the tricarboxylic acid cycle were increased in the hypothalamus of BGEH mice. The results suggest the obesity prevention effect of black ginseng in that BGEH inhibits body fat accumulation and restores brain function damaged by HFD.

In Situ Forming of Nitric Oxide and Electric Stimulus for Nerve Therapy by Wireless Chargeable Gold Yarn-Dynamos.

Endogenous signals, namely nitric oxide (NO) and electrons, play a crucial role in regulating cell fate as well as the vascular and neuronal systems. Unfortunately, utilizing NO and electrical stimulation in clinical settings can be challenging due to NO's short half-life and the invasive electrodes required for electrical stimulation. Additionally, there is a lack of tools to spatiotemporally control gas release and electrical stimulation. To address these issues, an "electromagnetic messenger" approach that employs on-demand high-frequency magnetic field (HFMF) to trigger NO release and electrical stimulation for restoring brain function in cases of traumatic brain injury is introduced. The system comprises a NO donor (poly(S-nitrosoglutathione), pGSNO)-conjugated on a gold yarn-dynamos (GY) and embedded in an implantable silk in a microneedle. When subjected to HFMF, conductive GY induces eddy currents that stimulate the release of NO from pGSNO. This process significantly enhances neural stem cell (NSC) synapses' differentiation and growth. The combined strategy of using NO and electrical stimulation to inhibit inflammation, angiogenesis, and neuronal interrogation in traumatic brain injury is demonstrated in vivo.

Transcriptomic analyses of rats exposed to chronic mild stress: Modulation by chronic treatment with the antipsychotic drug lurasidone

Exposure to stressful experiences accounts for almost half of the risk for mental disorders. Hence, stress-induced alterations represent a key target for pharmacological interventions aimed at restoring brain function in affected individuals. We have previously demonstrated that lurasidone, a multi-receptor antipsychotic drug approved for the treatment of schizophrenia and bipolar depression, can normalize the functional and molecular impairments induced by stress exposure, representing a valuable tool for the treatment of stress-induced mental illnesses. However, the mechanisms that may contribute to the therapeutic effects of lurasidone are still poorly understood. Here, we performed a transcriptomic analysis on the prefrontal cortex (PFC) of adult male rats exposed to the chronic mild stress (CMS) paradigm and we investigated the impact of chronic lurasidone treatment on such changes. We found that CMS exposure leads to an anhedonic phenotype associated with a down-regulation of different pathways associated to neuronal guidance and synaptic plasticity within the PFC. Interestingly, a significant part of these alterations (around 25%) were counteracted by lurasidone treatment. In summary, we provided new insights on the transcriptional changes relevant for the therapeutic intervention with lurasidone, which may ultimately promote resilience.

Neuroprotective properties of xenon. Literature review

A systematic analysis of scientific research devoted to the study of neuroprotective properties of xenon was carried out to determine the possibility of its use for the protection of neuronal tissues in various pathological conditions and neurodegenerative disorders. The search was carried out in freely available scientometric databases, such as PubMed, Google Scholar, Web of Science, Scopus, etc. The criteria for inclusion in the analysis were publications that discussed the role of xenon in the protection of neuronal tissues, studies of the neuroprotective properties of xenon in animal and cellular models, clinical studies demonstrating the neuroprotective potential of xenon in available English-language sources. The literature was analyzed to identify key findings, research methodology, and outcomes related to the neuroprotective properties of xenon. This included an analysis of research methods, models used to assess the impact of xenon on neuronal structures, and the volume and quality of the data obtained. In addition, the pharmacological properties of xenon are considered, in particular, its physicochemical characteristics, mechanisms of action at the molecular level, and pharmacokinetics. The results of studies of the influence of xenon on the state of vascularization of the brain after after traumatic brain injury and the potential of xenon to prevent further injuries are presented. Studies evaluating the effects of xenon on neurological deficits after ischemic stroke and its potential efficacy as an anti-inflammatory and neuroprotective agent are discussed. The effect of xenon on the white matter of the brain in patients with aneurysmal subarachnoid hemorrhage and its potential to reduce damage are highlighted. Research data on the use of the liposomal form of xenon to improve the condition after a stroke, mental health, and the effect of xenon on the intestinal microbiota were analyzed. The results of studies on the effectiveness of repeated injections of xenon to improve sensorimotor and neuropsychic functions in patients after a stroke, as well as the use of xenon as one of the components of intensive therapy for alcohol poisoning and the potential advantages of such an approach are presented. Based on the analysis of literary sources, it was concluded that xenon is a promising tool for protecting brain structures in traumatic injuries and ischemic lesions, which improves rehabilitation. It reduces inflammation and increases the integrity of the blood-brain barrier, which helps restore brain function.

Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity.

Stroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischaemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections. The type-5 metabotropic glutamate receptor (mGluR5) has been shown to modulate brain plasticity and function and is a therapeutic target in neurological diseases outside of stroke. We investigated whether mGluR5 influences functional recovery and network reorganization rodent models of focal ischaemia. Using multiple behavioural tests, we observed that treatment with negative allosteric modulators (NAMs) of mGluR5 (MTEP, fenobam and AFQ056) for 12 days, starting 2 or 10 days after stroke, restored lost sensorimotor functions, without diminishing infarct size. Recovery was evident within hours after initiation of treatment and progressed over the subsequent 12 days. Recovery was prevented by activation of mGluR5 with the positive allosteric modulator VU0360172 and accelerated in mGluR5 knock-out mice compared with wild-type mice. After stroke, multisensory stimulation by enriched environments enhanced recovery, a result prevented by VU0360172, implying a role of mGluR5 in enriched environment-mediated recovery. Additionally, MTEP treatment in conjunction with enriched environment housing provided an additive recovery enhancement compared to either MTEP or enriched environment alone. Using optical intrinsic signal imaging, we observed brain-wide disruptions in resting-state functional connectivity after stroke that were prevented by mGluR5 inhibition in distinct areas of contralesional sensorimotor and bilateral visual cortices. The levels of mGluR5 protein in mice and in tissue samples of stroke patients were unchanged after stroke. We conclude that neuronal circuitry subserving sensorimotor function after stroke is depressed by a mGluR5-dependent maladaptive plasticity mechanism that can be restored by mGluR5 inhibition. Post-acute stroke treatment with mGluR5 NAMs combined with rehabilitative training may represent a novel post-acute stroke therapy.

The restoration ability of a short nap after sleep deprivation on the brain cognitive function: A dynamic functional connectivity analysis.

The brain function impairment induced by sleep deprivation (SD) is temporary and can be fully reversed with sufficient sleep. However, in many cases, long-duration recovery sleep is not feasible. Thus, this study aimed to investigate whether a short nap after SD is sufficient to restore brain function. The data of 38 subjects, including resting state functional magnetic resonance imaging data collected at three timepoints (before SD, after 30 h of SD, and after a short nap following SD) and psychomotor vigilance task (PVT) data, were collected. Dynamic functional connectivity (DFC) analysis was used to evaluate changes in brain states among three timepoints, and four DFC states were distinguished across the three timepoints. Before SD, state 2 (a resting-like FC matrix) was dominant (48.26%). However, after 30 h SD, the proportion of state 2 dramatically decreased, and state 3 (still resting-like, but FCs were weakened) became dominant (40.92%). The increased proportion of state 3 positively correlated with a larger PVT "lapse" time. After a nap, the proportions of states 2 and 3 significantly increased and decreased, respectively, and the change in proportion of state 2 negatively correlated with the change in PVT "lapse" time. Taken together, the results indicated that, after a nap, the cognitive function impairment caused by SD may be reversed to some extent. Additionally, DFC differed among timepoints, which was also associated with the extent of cognitive function impairment after SD (state 3) and the extent of recovery therefrom after a nap (state 2).

In situ magnetoelectric generation of nitric oxide and electric stimulus for nerve therapy by wireless chargeable molybdenum carbide octahedrons

Endogenous signals, such as nitric oxide (NO) and electrons, induce multifaceted physiological functions in the regulation of cell fate as well as vascular and neuronal systems. However, clinical difficulties exist due to the short half-life of NO and the lack of tools to spatiotemporally drive gas release and electrical stimulation. Here, we propose a "magnetoelectric massager" strategy based on alternating magnetic field (AMF)-triggered on-demand NO release and electrical stimulation to restore brain function in traumatic brain injury. The NO and electron transport system was constructed as a metal-organic framework (MOF)-derived molybdenum carbide octahedron (MoCx-Cu) and an NO donor (S-nitrosoglutathione, GSNO), which was embedded in an implantable silk in a microneedle. Under AMF irradiation, eddy currents on conductive MoCx-Cu induced NO release from GSNO through electrical stimulation, thereby significantly promoting the differentiation and growth of neural stem cell (NSC) synapses. A combined strategy of in vivo traumatic brain injury allows NO and electrical stimulation-mediated inhibition of inflammation, angiogenesis, and neuronal interrogation.

Enriched environment-induced neuroplasticity in ischemic stroke and its underlying mechanisms.

Stroke is a common cerebrovascular disease that can interrupt local blood flow in the brain, causing neuronal damage or even death, resulting in varying degrees of neurological dysfunction. Neuroplasticity is an important neurological function that helps neurons reorganize and regain function after injury. After cerebral ischemia, neuroplasticity changes are critical factors for restoring brain function. An enriched environment promotes increased neuroplasticity, thereby aiding stroke recovery. In this review, we discuss the positive effects of the enriched environment on neuroplasticity after cerebral ischemia, including synaptic plasticity, neurogenesis, and angiogenesis. In addition, we also introduce some studies on the clinical application of enriched environments in the rehabilitation of post-stroke patients, hoping that they can provide some inspiration for doctors and therapists looking for new approaches to stroke rehabilitation.

Toward a New Generation of Bio-Scaffolds for Neural Tissue Engineering: Challenges and Perspectives.

Neural tissue engineering presents a compelling technological breakthrough in restoring brain function, holding immense promise. However, the quest to develop implantable scaffolds for neural culture that fulfill all necessary criteria poses a remarkable challenge for material science. These materials must possess a host of desirable characteristics, including support for cellular survival, proliferation, and neuronal migration and the minimization of inflammatory responses. Moreover, they should facilitate electrochemical cell communication, display mechanical properties akin to the brain, emulate the intricate architecture of the extracellular matrix, and ideally allow the controlled release of substances. This comprehensive review delves into the primary requisites, limitations, and prospective avenues for scaffold design in brain tissue engineering. By offering a panoramic overview, our work aims to serve as an essential resource, guiding the creation of materials endowed with bio-mimetic properties, ultimately revolutionizing the treatment of neurological disorders by developing brain-implantable scaffolds.

Activation of Gq-Coupled Receptors in Astrocytes Restores Cognitive Function in Alzheimer's Disease Mice Model.

Alzheimer's disease (AD) is one of the most widespread neurodegenerative diseases. Most of the current AD therapeutic developments are directed towards improving neuronal cell function or facilitating Aβ amyloid clearance from the brain. However, some recent evidence suggests that astrocytes may play a significant role in the pathogenesis of AD. In this paper, we evaluated the effects of the optogenetic activation of Gq-coupled exogenous receptors expressed in astrocytes as a possible way of restoring brain function in the AD mouse model. We evaluated the effects of the optogenetic activation of astrocytes on long-term potentiation, spinal morphology and behavioral readouts in 5xFAD mouse model of AD. We determined that in vivo chronic activation of astrocytes resulted in the preservation of spine density, increased mushroom spine survival, and improved performance in cognitive behavioral tests. Furthermore, chronic optogenetic stimulation of astrocytes resulted in the elevation of EAAT-2 glutamate uptake transporter expression, which could be a possible explanation for the observed in vivo neuroprotective effects. The obtained results suggest that the persistent activation of astrocytes may be considered a potential therapeutic approach for the treatment of AD and possibly other neurodegenerative disorders.

Neural co-processors for restoring brain function: results from a cortical model of grasping

Objective. A major challenge in designing closed-loop brain-computer interfaces is finding optimal stimulation patterns as a function of ongoing neural activity for different subjects and different objectives. Traditional approaches, such as those currently used for deep brain stimulation, have largely followed a manual trial-and-error strategy to search for effective open-loop stimulation parameters, a strategy that is inefficient and does not generalize to closed-loop activity-dependent stimulation. Approach. To achieve goal-directed closed-loop neurostimulation, we propose the use of brain co-processors, devices which exploit artificial intelligence to shape neural activity and bridge injured neural circuits for targeted repair and restoration of function. Here we investigate a specific type of co-processor called a ‘neural co-processor’ which uses artificial neural networks and deep learning to learn optimal closed-loop stimulation policies. The co-processor adapts the stimulation policy as the biological circuit itself adapts to the stimulation, achieving a form of brain-device co-adaptation. Here we use simulations to lay the groundwork for future in vivo tests of neural co-processors. We leverage a previously published cortical model of grasping, to which we applied various forms of simulated lesions. We used our simulations to develop the critical learning algorithms and study adaptations to non-stationarity in preparation for future in vivo tests. Main results. Our simulations show the ability of a neural co-processor to learn a stimulation policy using a supervised learning approach, and to adapt that policy as the underlying brain and sensors change. Our co-processor successfully co-adapted with the simulated brain to accomplish the reach-and-grasp task after a variety of lesions were applied, achieving recovery towards healthy function in the range 75%–90%. Significance. Our results provide the first proof-of-concept demonstration, using computer simulations, of a neural co-processor for adaptive activity-dependent closed-loop neurostimulation for optimizing a rehabilitation goal after injury. While a significant gap remains between simulations and in vivo applications, our results provide insights on how such co-processors may eventually be developed for learning complex adaptive stimulation policies for a variety of neural rehabilitation and neuroprosthetic applications.

Case Report: Zolpidem's paradoxical restorative action: A case report of functional brain imaging.

Zolpidem is a sedative drug that has been shown to induce a paradoxical effect, restoring brain function in wide range of neurological disorders. The underlying functional mechanism of the effect of zolpidem in the brain in clinical improvement is still poorly understood. Thus, we aimed to investigate rest brain function to study zolpidem-induced symptom improvement in a patient who developed postoperative pediatric cerebellar mutism syndrome, a postoperative complication characterized by delayed onset transient mutism/reduced speech that can occur after medulloblastoma resection. The patient experienced clinical recovery after a single dose of zolpidem. Brain function was investigated using arterial spin labeling MRI and resting-state functional MRI. Imaging was performed at three time-points: preoperative, postoperative during symptoms, and after zolpidem intake when the symptoms regressed. Whole brain rest cerebral blood flow (CBF) and resting state functional connectivity using Pearson coefficient correlations between pairs of regions of interest were investigated two-by-two at the different time points. A comparison between postoperative and preoperative images showed a significant decrease in rest CBF in the left supplementary motor area, Broca's area, and the left striatum and a decrease in functional connectivity within the dentato-thalamo-cortical and cortico-striato-pallido-thalamo-cortical loops. Post-zolpidem images showed increased CBF in the left striatum and increased functional connectivity within the disrupted loops relative to postoperative images. Thus, we observed functional changes within the broader speech network and thalamo-subcortical interactions associated with the paradoxical effect of zolpidem in promoting clinical recovery. This should encourage further functional investigations in the brain to better understand the mechanism of zolpidem in neurological recovery.

Mapping human adult hippocampal neurogenesis with single-cell transcriptomics: Reconciling controversy or fueling the debate?

The notion of exploiting the regenerative potential of the human brain in physiological aging or neurological diseases represents a particularly attractive alternative to conventional strategies for enhancing or restoring brain function. However, a major first question to address is whether the human brain does possess the ability to regenerate. The existence of human adult hippocampal neurogenesis (AHN) has been at the center of a fierce scientific debate for many years. The advent of single-cell transcriptomic technologies was initially viewed as a panacea to resolving this controversy. However, recent single-cell RNA sequencing studies in the human hippocampus yielded conflicting results. Here, we critically discuss and re-analyze previously published AHN-related single-cell transcriptomic datasets. We argue that, although promising, the single-cell transcriptomic profiling of AHN in the human brain can be confounded by methodological, conceptual, and biological factors that need to be consistently addressed across studies and openly discussed within the scientific community.