Brain Areas Research Articles

Increased functional connectivity between brain regions involved in social cognition, emotion and affective-value in psychedelic states induced by N,N-Dimethyltryptamine (DMT)

The modulation of social cognition is suggested as a possible mechanism contributing to the potential clinical efficacy of psychedelics in disorders involving socio-emotional and reward processing deficits. Resting-state functional Magnetic Resonance Imaging (rs-fMRI) can be used to detect changes in brain connectivity during psychedelic-induced states. Thus, this pharmacoimaging study investigates the effects of N,N-Dimethyltryptamine (DMT) on functional connectivity in brain areas relevant to social cognition, using a within-subject design in eleven healthy experienced users. The study included both an active and a control condition, conducted at different time points. The active condition involved DMT inhalation, while the control condition did not. Seed-based connectivity was measured for the two core regions involved in theory of mind and emotional processing, respectively, the posterior supramarginal gyrus and the amygdala. DMT increased supramarginal gyrus connectivity with the precuneus, posterior cingulate gyrus, amygdala, and orbitofrontal cortex. Additionally, increased connectivity emerged between the amygdala and orbitofrontal cortex. These results demonstrate that DMT modulates brain connectivity in socio-emotional and affective-value circuits, advancing our understanding of the neural mechanisms underlying the psychedelic experience and its potential therapeutic action.

Integrity of the circadian clock determines regularity of high-frequency and diurnal LFP rhythms within and between brain areas.

Circadian clocks control most physiological processes of many species. We specifically wanted to investigate the influence of environmental and endogenous rhythms and their interplay on electrophysiological dynamics of neuronal populations. Therefore, we measured local field potential (LFP) time series in wild-type and Cryptochrome 1 and 2 deficient (Cry1/2-/-) mice in the suprachiasmatic nucleus and the nucleus accumbens under regular light conditions and constant darkness. Using refined descriptive and statistical analyses, we systematically profiled LFP time series activity. We show that both environmental and endogenous rhythms strongly influence the rhythmicity of LFP signals and their frequency components, but also shape neuronal patterns on much smaller time scales, as neuronal activity in Cry1/2-/- mice is significantly less regular but at each time more synchronous within and between brain areas than in wild-type mice. These results show that functional circadian rhythms are integral for both circadian and non-circadian coordination of neuronal ensemble dynamics.

Awake surgery with mapping-based resection to treat focal epilepsy in eloquent brain areas.

Resective surgery is a potential therapeutic option for select patients with intractable focal epilepsy. However, the presence of ictal onset zones within or surrounding highly functional brain areas presents a surgical challenge, leading to poor seizure and functional outcomes. This report describes our experiences with awake mapping-tailored resection of epileptogenic areas involving eloquent cortices and evaluates their feasibility, tolerance, limitations, and significance. The study included patients who underwent surgery for drug-resistant focal epilepsy at our center under awake conditions. The surgical approach aimed to achieve maximum resection of preoperatively defined epileptogenic zones, considering the boundaries defined by surrounding functional areas. We collected data on preoperative evaluations, intraoperative tests and seizures, postoperative status epilepticus, and neurological functional outcomes. We included 22 patients, 10 of whom had non-lesional epilepsy. Language, motor function, and sensory function were at risk in 19, 9, and 4 patients, respectively. Resection was performed as planned in 14 (63.6%) patients, while modifications were necessary in 8 (36.4%) patients due to functional constraints. The mean follow-up duration was 29.8months. Sixteen (72.7%) patients achieved Engel class Ia outcomes, indicating seizure freedom, while none of the patients experienced clinically significant permanent postoperative neurological deficits. Resective surgery with intraoperative brain mapping under awake conditions was a valid treatment option for achieving a cure in cases of drug-resistant focal epilepsy, even in situations in which the condition is considered inoperable due to the risk of significant postoperative neurological deficits.

Neuronal excitation-inhibition imbalance in the basolateral amygdala is involved in propofol-mediated enhancement of fear memory

Posttraumatic stress disorder (PTSD) is associated with glutamatergic neuron hyperactivation in the basolateral amygdala (BLA) brain area, while GABAergic interneurons in the BLA modulate glutamatergic neuron excitability. Studies have shown that propofol exerts its effects through potentiation of the inhibitory neurotransmitter γ-aminobutyric acid. The neuronal mechanism by which propofol anesthesia modulates fear memory is currently unknown. Here, we used optogenetics and chemogenetics to suppress glutamatergic neurons or activate GABAergic interneurons in the BLA to assess alterations in neuronal excitation-inhibition balance and investigate fear memory. The excitability of glutamatergic neurons in the BLA was significantly reduced by the suppression of glutamatergic neurons or activation of GABAergic interneurons, while propofol-mediated enhancement of fear memory was attenuated. We suggest that propofol anesthesia could reduce the excitability of GABAergic neurons through activation of GABAA receptors, subsequently increasing the excitability of glutamatergic neurons in the mice BLA; the effect of propofol on enhancing mice fear memory might be mediated by strengthening glutamatergic neuronal excitability and decreasing the excitability of GABAergic neurons in the BLA; neuronal excitation-inhibition imbalance in the BLA might be important in mediating the enhancement of fear memory induced by propofol.

PACAP regulates neuroendocrine and behavioral stress responses via CRF-containing neurons of the rat hypothalamic paraventricular nucleus

AbstractPituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide widely distributed in the brain including the hypothalamic paraventricular nucleus (PVN) implying a regulatory role in stress function. Recent evidence indicates that one of the main targets of PACAP within the PVN are corticotropin-releasing factor (CRF) neurons, which are key regulators of the hypothalamic-pituitary-adrenal (HPA) axis. However, the neural correlates that mediate PACAP effects on stress function are not fully understood. In the present study, we characterized the neuronal mechanism by which PACAP regulates neuroendocrine and behavioral stress responses in rats. We found that intracerebroventricular administration of PACAP increased the swim stress-induced c-Fos expression in distinct brain areas of the stress and anxiety circuitry including the parvocellular part of the PVN and changed behavioral stress coping during forced swimming to a more passive coping style (i.e., indicated by increased floating and reduced struggling behavior). Subsequently, PACAP administration directly into the PVN mimicked these behavioral effects and potentiated the plasma ACTH response to forced swim stress suggesting an excitatory role of PACAP on HPA stress axis reactivity. In addition, immunohistochemical analysis revealed a considerable portion of stress-activated CRF neurons in the medial parvocellular part of the PVN that co-localized PAC1 receptors suggesting that PACAP-induced effects on stress function are likely mediated directly by activation of CRF neurons in the PVN. Thus, these findings suggest that the PVN may represent one of the key areas where PACAP regulates the neuroendocrine and behavioral stress response.

Parkinson’s disease models and death signaling: what do we know until now?

Parkinson’s disease (PD) is the second neurodegenerative disorder most prevalent in the world, characterized by the loss of dopaminergic neurons in the Substantia Nigra (SN). It is well known for its motor and non-motor symptoms including bradykinesia, resting tremor, psychiatric, cardiorespiratory, and other dysfunctions. Pathological apoptosis contributes to a wide variety of diseases including PD. Various insults and/or cellular phenotypes have been shown to trigger distinct signaling events leading to cell death in neurons affected by PD. The intrinsic or mitochondrial pathway, inflammatory or oxidative stress-induced extrinsic pathways are the main events associated with apoptosis in PD-related neuronal loss. Although SN is the main brain area studied so far, other brain nuclei are also affected by the disease leading to non-classical motor symptoms as well as non-motor symptoms. Among these, the respiratory symptoms are often overlooked, yet they can cause discomfort and may contribute to patients shortened lifespan after disease diagnosis. While animal and in vitro models are frequently used to investigate the mechanisms involved in the pathogenesis of PD in both the SN and other brain regions, these models provide only a limited understanding of the disease’s actual progression. This review offers a comprehensive overview of some of the most studied forms of cell death, including recent research on potential treatment targets for these pathways. It highlights key findings and milestones in the field, shedding light on the potential role of understanding cell death in the prevention and treatment of the PD. Therefore, unraveling the connection between these pathways and the notable pathological mechanisms observed during PD progression could enhance our comprehension of the disease’s origin and provide valuable insights into potential molecular targets for the developing therapeutic interventions.

The role of surgery in recurrent local cerebral metastases: a multi-institutional retrospective analysis.

Local recurrent brain metastases are defined as lesions that recur in the brain at the same site after a previous local therapy. In patients already submitted to surgery, a second operation may be potentially challenging due to scar formation, infiltration of cerebral vessels or eloquent brain areas and local effect of previous radiotherapy. The aim of this study is to retrospectively review the results and complications of a second surgical treatment in a series of local recurrent lesions and to review the literature on this topic. 37 patients submitted to surgery for a local, histologically confirmed, recurrent brain metastases between 2000 and 2022 were retrospectively analyzed with respect to the following parameters: age, histology, anatomic location, time to recurrence, previous radiotherapy, size of recurrent tumors, preoperative and postoperative Karnofsky Performance Status(KPS) score, recursive partitioning analysis (RPA) class and graded prognostic assessment (GPA) score, surgery-related complications and the presence of further cerebral metastases. Overall survival (OS) was calculated using the Kaplan-Meier method. A multivariate Cox proportional hazard model was developed using stepwise regression (forwards selection) with predictive variables that were significant in the univariate analyses. A significant improvement of post-operative KPS status was obtained after second surgery. At multivariate analysis better results in terms of OS were achieved in patients with a pre-operative KPS ≥ 70 and in patients who had received radiotherapy after the initial surgery. No significant postoperative complications related to previous treatments were observed. Surgical resection of local recurrent brain metastases may improve patients ́ neurologic conditions allowing more time for systemic therapies to act with a low incidence of surgery-related morbidity and mortality. However, careful patient selection with a fair pre-operative clinical status seems mandatory to achieve the best post-operative results, since uniform treatment-paradigms cannot be established yet, due to the highly heterogeneous patient cohort.

Mild cognitive impairment in amyotrophic lateral sclerosis: current view.

Amyotrophic lateral sclerosis (ALS) is a fatal multi-system neurodegenerative disorder with no effective treatment or cure. Although primarily characterized by motor degeneration, cognitive dysfunction is an important non-motor symptom that has a negative impact on patient and caregiver burden. Mild cognitive deficits are present in a subgroup of non-demented patients with ALS, often preceding motor symptoms. Detailed neuropsychological assessments reveal deficits in a variety of cognitive domains, including those of verbal fluency and retrieval, language, executive function, attention and verbal memory. Mild cognitive impairment (MCI), a risk factor for developing dementia, affects between 10% and over 50% of ALS patients. Neuroimaging revealed atrophy of frontal and temporal cortices, disordered white matter Integrity, volume reduction in amygdala and thalamus, hypometabolism in the frontal and superior temporal gyrus and anterior insula. Neuronal loss in non-motor brain areas, associated with TDP-43 deposition, one of the morphological hallmarks of ALS, is linked to functional disruption of frontostriatal and frontotemporo-limbic connectivities as markers for cognitive deficits in ALS, the pathogenesis of which is still poorly understood. Early diagnosis by increased cerebrospinal fluid or serum levels of neurofilament light/heavy chain or glial fibrillary acidic protein awaits confirmation for MCI in ALS. These fluid biomarkers and early detection of brain connectivity signatures before structural changes will be helpful not only in establishing early premature diagnosis but also in clarifying the pathophysiological mechanisms of MCI in ALS, which might serve as novel targets for prohibition/delay and future adequate treatment of this debilitating disorder.

Learning-dependent gating of hippocampal inputs by frontal interneurons

The hippocampus is a brain region that is essential for the initial encoding of episodic memories. However, the consolidation of these memories is thought to occur in the neocortex, under guidance of the hippocampus, over the course of days and weeks. Communication between the hippocampus and the neocortex during hippocampal sharp wave-ripple oscillations is believed to be critical for this memory consolidation process. Yet, the synaptic and circuit basis of this communication between brain areas is largely unclear. To address this problem, we perform in vivo whole-cell patch-clamp recordings in the frontal neocortex and local field potential recordings in CA1 of head-fixed mice exposed to a virtual-reality environment. In mice trained in a goal-directed spatial task, we observe a depolarization in frontal principal neurons during hippocampal ripple oscillations. Both this ripple-associated depolarization and goal-directed task performance can be disrupted by chemogenetic inactivation of somatostatin-positive (SOM+) interneurons. In untrained mice, a ripple-associated depolarization is not observed, but it emerges when frontal parvalbumin-positive (PV+) interneurons are inactivated. These results support a model where SOM+ interneurons inhibit PV+ interneurons during hippocampal activity, thereby acting as a disinhibitory gate for hippocampal inputs to neocortical principal neurons during learning.

Boosting Resilience Attentional Bias in Previously Bullied University Students with Low Post-Traumatic Growth: A Transcranial Direct Current Stimulation Study

Background/Objectives: Post-traumatic growth (PTG) has the potential to draw positive consequences from trauma. Hence, there is interest in finding ways to promote PTG. Research has identified an attentional bias towards positive resilience-related words (e.g., “persistence”, “purpose”) in university students who report high PTG after experiencing adversities. Although people can respond to these experiences by showing low PTG, this bias seems to help with their struggle by making purposeful contents more accessible. Therefore, boosting attentional bias towards positive resilience-related words could help people with low PTG. Methods: In this study, the participants were thirty-six university students who had experienced bullying before entering university. Using a Stroop emotional task, they identified the color of resilience and neutral words, either positive or negative, before and after being submitted to transcranial direct current stimulation. Stimulation was targeted at the right temporal area involved in intentionality processing. Results: In the anodal condition, the results support a stimulation effect on the resilience attentional bias that could benefit participants with low PTG. A significant moderation of approach motivation for this effect was also found. Specifically, only when participants had medium or high approach motivation did stimulation boost the attentional bias in students with low PTG. Conclusions: These results support that tDCS stimulation in this brain area is effective in enhancing resilience attentional bias in low-PTG students. However, for this effect to occur it is necessary to have approach motivation, which is motivation related to goals.

Adolescent social stress alters the role of orexin innervation in the hindbrain in male hamsters.

Juvenile male hamsters exposed to chronic social stress eat more, gain weight, and have larger fat pads. The purpose of the present study was to address possible changes in food hoarding and orexin/hypocretin innervation in response to social stress. Male hamsters in early adolescence were exposed to a resident-intruder social stress paradigm or control condition daily for 2 weeks. Metabolism-related physiological measures and behaviors were tracked, and brains were immunocytochemically labeled for orexin-A. Our data confirm our previous observations on appetite, weight gain, and obesity, and showed a strong trend toward enhanced food hoarding as in prior studies. In addition, there were no statistically significant differences in orexin innervation in any brain area analyzed. However, unique correlation patterns were observed between orexin innervation and appetite or metabolic outcome. In particular, opposite correlations were observed between groups within the dorsal raphe nucleus, lateral parabrachial nucleus, and nucleus of the solitary tract. These opposite patterns of correlations suggest chronic social stress causes site-specific alterations in synaptic activity in relation with these behaviors.

Encoding manifolds constructed from grating responses organize responses to natural scenes in cortical visual areas.

We have created "encoding manifolds" to reveal the overall responses of a brain area to a variety of stimuli. Encoding manifolds organize response properties globally: each point on an encoding manifold is a neuron, and nearby neurons respond similarly to the stimulus ensemble in time. We previously found, using a large stimulus ensemble including optic flows, that encoding manifolds for the retina were highly clustered, with each cluster corresponding to a different ganglion cell type. In contrast, the topology of the V1 manifold was continuous. Now, using responses of individual neurons from the Allen Institute Visual Coding-Neuropixels dataset in the mouse, we infer encoding manifolds for V1 and for five higher cortical visual areas (VISam, VISal, VISpm, VISlm, and VISrl). We show here that the encoding manifold topology computed only from responses to various grating stimuli is also continuous, not only for V1 but also for the higher visual areas, with smooth coordinates spanning it that include, among others, orientation selectivity and firing-rate magnitude. Surprisingly, the encoding manifold for gratings also provides information about natural scene responses. To investigate whether neurons respond more strongly to gratings or natural scenes, we plot the log ratio of natural scene responses to grating responses (mean firing rates) on the encoding manifold. This reveals a global coordinate axis organizing neurons' preferences between these two stimuli. This coordinate is orthogonal (i.e., uncorrelated) to that organizing firing rate magnitudes in VISp. Analyzing layer responses, a preference for gratings is concentrated in layer 6, whereas preference for natural scenes tends to be higher in layers 2/3 and 4. We also find that preference for natural scenes dominates the responses of neurons that prefer low (0.02 cpd) and high (0.32 cpd) spatial frequencies, rather than intermediate ones (0.04 to 0.16 cpd). Conclusion: while gratings seem limited and natural scenes unconstrained, machine learning algorithms can reveal subtle relationships between them beyond linear techniques.

Cerebral hyperactivation across the Alzheimer’s disease pathological cascade

Abstract Neuronal dysfunction in specific brain regions or across distributed brain networks is a known feature of Alzheimer’s disease. An often reported finding in the early stage of the disease is the presence of increased functional MRI (fMRI) BOLD signal under task conditions relative to cognitively normal controls, a phenomenon known as “hyperactivation”. However, research in the past decades yielded complex, sometimes conflicting results. The magnitude and topology of fMRI hyperactivation patterns have been found to vary across the preclinical and clinical spectrum of Alzheimer’s disease, including concomitant “hypoactivation” in some cases. These incongruences are likely due to a range of factors, including the disease stage at which the cohort is examined, the brain areas or networks studied, and the fMRI paradigm utilised to evoke these functional abnormalities. Additionally, a perennial question pertains to the nature of hyperactivation in the context of Alzheimer’s disease. Some propose it reflects compensatory mechanisms to sustain cognitive performance while others suggest it is linked to the pathological disruption of a highly regulated homeostatic cycle that contributes to, or even drives, disease progression. Providing a coherent narrative for these empirical and conceptual discrepancies is paramount to develop disease models, understand the synergy between hyperactivation and the Alzheimer’s disease pathological cascade, and tailor effective interventions. We first provide a comprehensive overview of functional brain changes spanning the course from normal ageing to the clinical spectrum of Alzheimer’s disease. We then highlight evidence supporting a close relationship between fMRI hyperactivation and in vivo markers of Alzheimer’s pathology. We primarily focus on task-based fMRI studies in humans, but also consider studies using different functional imaging techniques and animal models. We then discuss the potential mechanisms underlying hyperactivation in the context of Alzheimer’s disease, and provide a testable framework bridging hyperactivation, ageing, cognition, and the Alzheimer’s disease pathological cascade. We conclude with a discussion of future challenges and opportunities to advance our understanding of the fundamental disease mechanisms of Alzheimer’s disease, and the promising development of therapeutic interventions incorporating or aimed at hyperactivation and large-scale functional systems.

Analysis of nerve excitability in the dentate gyrus of the hippocampus in cerebral ischaemia-reperfusion mice

Ischemic stroke often leads to cognitive dysfunction, which delays the recovery process of patients. However, its pathogenesis is not yet clear. In this study, the cerebral ischemia-reperfusion model was built as the experimental object, and the hippocampal dentate gyrus (DG) was the target brain area. TTC staining was used to evaluate the degree of cerebral infarction, and nerve cell membrane potentials and local field potentials (LFPs) signals were collected to explore the mechanism of cognitive impairment in ischemia-reperfusion mice. The results showed that the infarcted area on the right side of the brain of the mice in the model group was white. The resting membrane potential, the number of action potential discharges, the post-hyperpolarization potential and the maximum ascending slope of the hippocampal DG nerve cells in the model mice were significantly lower than those in the control group ( P < 0.01); the peak time, half-wave width, threshold and maximum descending slope of the action potential were significantly higher than those in the control group ( P < 0.01). The time-frequency energy values of LFPs signals in the θ and γ bands of mice in the ischemia and reperfusion groups were significantly reduced ( P < 0.01), and the time-frequency energy values in the reperfusion group were increased compared with the ischemia group ( P < 0.01). The signal complexity of LFPs in the ischemia and reperfusion group was significantly reduced ( P < 0.05), and the signal complexity in the reperfusion group was increased compared with the ischemia group ( P < 0.05). In summary, cerebral ischemia-reperfusion reduced the excitability of nerve cells in the DG area of the mouse hippocampus; cerebral ischemia reduced the discharge activity and signal complexity of nerve cells, and the electrophysiological indicators recovered after reperfusion, but it failed to reach the healthy state during the experiment period.

Ultrasound Neuromodulation for Sleep and Neurological Disorder Therapy: A Path to Clinical Translation.

Ultrasound neuromodulation is a promising noninvasive technique capable of penetrating the skull and precisely targeting deep brain regions with millimeter accuracy. Recent studies have demonstrated that transcranial ultrasound stimulation (TUS) of sleep-related brain areas can induce sleep in mice and even trigger a reversible, hibernation-like state without causing damage. Beyond its utility in preclinical models of central nervous system diseases, such as epilepsy, tremors, Alzheimer's disease, and depression, TUS holds significant potential for clinical translation. Given that many neurological disorders, including Alzheimer's and Parkinson's disease, are associated with sleep abnormalities, leveraging clinical TUS applications for these diseases also creates a pathway for translating this technology to sleep modulation in human use. These findings highlight the potential for ultrasound neuromodulation to advance neuroscience research and clinical applications in sleep control.

Latent dynamics of primary sensory cortical population activity structured by fluctuations in the local field potential.

As emerging technologies enable measurement of precise details of the activity within microcircuits at ever-increasing scales, there is a growing need to identify the salient features and patterns within the neural populations that represent physiologically and behaviorally relevant aspects of the network. Accumulating evidence from recordings of large neural populations suggests that neural population activity frequently exhibits relatively low-dimensional structure, with a small number of variables explaining a substantial fraction of the structure of the activity. While such structure has been observed across the brain, it is not known how reduced-dimension representations of neural population activity relate to classical metrics of "brain state," typically described in terms of fluctuations in the local field potential (LFP), single-cell activity, and behavioral metrics. Hidden state models were fit to spontaneous spiking activity of populations of neurons, recorded in the whisker area of primary somatosensory cortex of awake mice. Classic measures of cortical state in S1, including the LFP and whisking activity, were compared to the dynamics of states inferred from spiking activity. A hidden Markov model fit the population spiking data well with a relatively small number of states, and putative inhibitory neurons played an outsize role in determining the latent state dynamics. Spiking states inferred from the model were more informative of the cortical state than a direct readout of the spiking activity of single neurons or of the population. Further, the spiking states predicted both the trial-by-trial variability in sensory responses and one aspect of behavior, whisking activity. Our results show how classical measurements of brain state relate to neural population spiking dynamics at the scale of the microcircuit and provide an approach for quantitative mapping of brain state dynamics across brain areas.

Sensory experience steers representational drift in mouse visual cortex

Representational drift—the gradual continuous change of neuronal representations—has been observed across many brain areas. It is unclear whether drift is caused by synaptic plasticity elicited by sensory experience, or by the intrinsic volatility of synapses. Here, using chronic two-photon calcium imaging in primary visual cortex of female mice, we find that the preferred stimulus orientation of individual neurons slowly drifts over the course of weeks. By using cylinder lens goggles to limit visual experience to a narrow range of orientations, we show that the direction of drift, but not its magnitude, is biased by the statistics of visual input. A network model suggests that drift of preferred orientation largely results from synaptic volatility, which under normal visual conditions is counteracted by experience-driven Hebbian mechanisms, stabilizing preferred orientation. Under deprivation conditions these Hebbian mechanisms enable adaptation. Thus, Hebbian synaptic plasticity steers drift to match the statistics of the environment.

Abnormal EEG Effects of Acute Apomorphine Injection in 5xFAD Transgenic Mice Are Partially Normalized in Those Chronically Pretreated with Apomorphine: The Time–Frequency Clustering of EEG Spectra

Background: In experimental and clinical studies of pharmacological treatments for Alzheimer’s disease (AD), the electroencephalogram (EEG) frequency spectrum approach has demonstrated its efficacy in determining the characteristics of pathological changes in the functioning of different cerebral structures, interconnections between them, and disturbances in the brain neurotransmitter systems. The main results have been obtained in frames of traditionally used so-called “classical” EEG frequency bands: delta, theta, alpha, and beta. Objective: This unified approach simplifies comparing data from different studies but loses the dynamic peculiarities of the effects because of their time-dependent transition through the borders of the “classical” bands. Methods: In this study on non-narcotized freely moving 5xFAD transgenic mice, a model of AD, chronically pretreated with a non-selective dopamine (DA) receptor agonist, apomorphine (APO), we analyze the transitory EEG effects of acute APO injection in different brain areas by use of our “time–frequency” clustering program. The acute injection of APO was used to compare DA receptor sensitivity in 5xFAD mice pretreated with either APO or saline vs. wild-type (WT) mice pretreated with saline. Results: After acute APO injection, the clusters of enhanced EEG activity centered in the theta–alpha frequency range observed in WT mice disappeared in 5xFAD mice pretreated with saline and practically recovered in 5xFAD mice pretreated with APO. Conclusions: In 5xFAD mice pretreated with saline, the sensitivity of DA receptors was disturbed; chronic APO pretreatment mainly recovered this characteristic in 5xFAD mice. The “clustering” of pharmacological EEG effects and their time-dependent transition between classical frequency bands is a new effective approach for analyzing cerebral neurotransmission in neurodegenerative pathologies.

Element Changes Occurring in Brain Point at the White Matter Abnormalities in Rats Exposed to the Ketogenic Diet During Prenatal Life.

A large number of clinical studies demonstrate that the ketogenic diet (KD) may be an effective approach to the reduction of epileptic seizures in children and adults. Such dietary therapy could also help pregnant women with epilepsy, especially since most antiseizure drugs have teratogenic action. However, there is a lack of medical data, considering the safety of using KD during gestation for the progeny. Therefore, we examined the influence of KD used prenatally in rats on the elemental composition of the selected brain regions in their offspring. For this purpose, synchrotron radiation-induced X-ray fluorescence (SR-XRF) microscopy was utilized, and elements such as P, S, K, Ca, Fe, and Zn were determined. Moreover, to verify whether the possible effects of KD are temporary or long-term, different stages of animal postnatal development were taken into account in our experiment. The obtained results confirmed the great applicability of SR-XRF microscopy to track the element changes occurring in the brain during postnatal development as well as those induced by prenatal exposure to the high-fat diet. The topographic analysis of the brains taken from offspring of mothers fed with KD during pregnancy and appropriate control individuals showed a potential influence of such dietary treatment on the brain levels of elements such as P and S. In the oldest progeny, a significant reduction of the surface of brain areas characterized by an increased P and S content, which histologically/morphologically correspond to white matter structures, was noticed. In turn, quantitative elemental analysis showed significantly decreased levels of Fe in the striatum and white matter of 30-day-old rats exposed prenatally to KD. This effect was temporary and was not noticed in adult animals. The observed abnormalities may be related to the changes in the accumulation of sphingomyelin and sulfatides and may testify about disturbances in the structure and integrity of the myelin, present in the white matter.

Behavior can be decoded across the cortex when individual differences are considered

Abstract Group-level analyses have typically linked behavioral signatures to a constrained set of brain areas. Here we show that two behavioral metrics — reaction time (RT) and confidence — can be decoded across the cortex when each individual is considered separately. Subjects (N=50) completed a perceptual decision-making task with confidence. We built models decoding trial-level RT and confidence separately for each subject using the activation patterns in one brain area at a time after splitting the entire cortex into 200 regions of interest (ROIs). First, we developed a simple test to determine the robustness of decoding performance, which showed that several hundred trials per subject are required for robust decoding. We then examined the decoding performance at the group and subject levels. At the group level, we replicated previous results by showing that both RT and confidence could be decoded from a small number of ROIs (12.0% and 3.5%, respectively). Critically, at the subject level, both RT and confidence could be decoded from most brain regions even after Bonferroni correction (90.0% and 72.5%, respectively). Surprisingly, we observed that many brain regions exhibited opposite brain-behavior relationships across individuals, such that, for example, higher activations predicted fast RTs in some subjects but slow RTs in others. All results were replicated in a second dataset. These findings show that behavioral signatures can be decoded from a much broader range of cortical areas than previously recognized and suggest the need to study the brain-behavior relationship at both the group and subject levels.