Changes In Neural Activity Research Articles

Efficient inference of synaptic plasticity rule with Gaussian process regression

Finding the form of synaptic plasticity is critical to understanding its functions underlying learning and memory. We investigated an efficient method to infer synaptic plasticity rules in various experimental settings. We considered biologically plausible models fitting a wide range of in-vitro studies and examined the recovery of their firing-rate dependence from sparse and noisy data. Among the methods assuming low-rankness or smoothness of plasticity rules, Gaussian process regression (GPR), a nonparametric Bayesian approach, performs the best. Under the conditions measuring changes in synaptic weights directly or measuring changes in neural activities as indirect observables of synaptic plasticity, which leads to different inference problems, GPR performs well. Also, GPR could simultaneously recover multiple plasticity rules and robustly perform under various plasticity rules and noise levels. Such flexibility and efficiency, particularly at the low sampling regime, make GPR suitable for recent experimental developments and inferring a broader class of plasticity models.

Age, sex, and apolipoprotein E isoform alter contextual fear learning, neuronal activation, and baseline DNA damage in the hippocampus

Age, female sex, and apolipoprotein E4 (E4) are risk factors to develop Alzheimer’s disease (AD). There are three major human apoE isoforms: E2, E3, and E4. Compared to E3, E4 increases while E2 decreases AD risk. However, E2 is associated with increased risk and severity of post-traumatic stress disorder (PTSD). In cognitively healthy adults, E4 carriers have greater brain activation during learning and memory tasks in the absence of behavioral differences. Human apoE targeted replacement (TR) mice display differences in fear extinction that parallel human data: E2 mice show impaired extinction, mirroring heightened PTSD symptoms in E2 combat veterans. Recently, an adaptive role of DNA double strand breaks (DSBs) in immediate early gene expression (IEG) has been described. Age and disease synergistically increase DNA damage and decrease DNA repair. As the mechanisms underlying the relative risks of apoE, sex, and their interactions in aging are unclear, we used young (3 months) and middle-aged (12 months) male and female TR mice to investigate the influence of these factors on DSBs and IEGs at baseline and following contextual fear conditioning. We assessed brain-wide changes in neural activation following fear conditioning using whole-brain cFos imaging in young female TR mice. E4 mice froze more during fear conditioning and had lower cFos immunoreactivity across regions important for somatosensation and contextual encoding compared to E2 mice. E4 mice also showed altered co-activation compared to E3 mice, corresponding to human MRI and cognitive data, and indicating that there are differences in brain activity and connectivity at young ages independent of fear learning. There were increased DSB markers in middle-aged animals and alterations to cFos levels dependent on sex and isoform, as well. The increase in hippocampal DSB markers in middle-aged animals and female E4 mice may play a role in the risk for developing AD.

Leucine deprivation results in antidepressant effects via GCN2 in AgRP neurons

Abstract Essential amino acids (EAAs) are crucial nutrients, whose levels change in rodents and patients with depression. However, how the levels of a single EAA affects depressive behaviors remains elusive. Here, we demonstrate that although deprivation of the EAA leucine has no effect in unstressed mice, it remarkably reverses the depression-like behaviors induced by chronic restraint stress (CRS). This beneficial effect is independent of feeding and is applicable to the dietary deficiency of other EAAs. Furthermore, the effect of leucine deprivation is suppressed by central injection of leucine or mimicked by central injection of leucinol. Moreover, hypothalamic agouti-related peptide (AgRP) neural activity changes during CRS and leucine deprivation, and chemogenetically inhibiting AgRP neurons eliminates the antidepressant effects of leucine deprivation. Finally, the leucine deprivation-regulated behavioral effects are mediated by amino acid sensor general control non-derepressible 2 (GCN2) in AgRP neurons. Taken together, our results suggest a new drug target and/or dietary intervention for the reduction of depressive symptoms.

Neurophysiology of Vestibular Compensation

Vestibular compensation is the process by which patients achieve functional recovery after vestibular lesions, and can be divided into static compensation and dynamic compensation. The first stage, static static compensation, consists of eliminating static symptoms (i.e., spontaneous nystagmus and skew deviation) by rebalancing the tonic neural activity in the vestibular nuclei. The second stage, dynamic compensation is much more subtle, takes longer, and involves a central recalibration of the response properties of the vestibulo-ocular reflex (VOR) (i.e., timing and gain) in order to restore the compensatory actions of the VOR to pre-impairment levels. This review is to introduce the normal vestibular function in humans to understand the neurophysiology of vestibular compensation after vestibular lesions, and to review the effects of various types of lesions and the clinical findings in various stages of compensation after each type of lesion. Vestibular compensation is most effective for unilateral vestibular dysfunctions in which tonic neural activity of the vestibular nucleus is rebalanced to achieve static compensation. Adaptive changes in tonic neural activity occur in the normal vestibular pathways to achieve dynamic compensation. In other types of vestibular lesions, vestibular compensation is possible, but not as effective.

Temporal pain processing in the primary somatosensory cortex and anterior cingulate cortex

Pain is known to have sensory and affective components. The sensory pain component is encoded by neurons in the primary somatosensory cortex (S1), whereas the emotional or affective pain experience is in large part processed by neural activities in the anterior cingulate cortex (ACC). The timing of how a mechanical or thermal noxious stimulus triggers activation of peripheral pain fibers is well-known. However, the temporal processing of nociceptive inputs in the cortex remains little studied. Here, we took two approaches to examine how nociceptive inputs are processed by the S1 and ACC. We simultaneously recorded local field potentials in both regions, during the application of a brain-computer interface (BCI). First, we compared event related potentials in the S1 and ACC. Next, we used an algorithmic pain decoder enabled by machine-learning to detect the onset of pain which was used during the implementation of the BCI to automatically treat pain. We found that whereas mechanical pain triggered neural activity changes first in the S1, the S1 and ACC processed thermal pain with a reasonably similar time course. These results indicate that the temporal processing of nociceptive information in different regions of the cortex is likely important for the overall pain experience.

Changes in Resting-State Neural Activity and Nerve Fibres in Ischaemic Stroke Patients with Hemiplegia.

Many neuroimaging studies have reported that stroke induces abnormal brain activity. However, little is known about resting-state networks (RSNs) and the corresponding white matter changes in stroke patients with hemiplegia. Here, we utilized functional magnetic resonance imaging (fMRI) to measure neural activity and related fibre tracts in 14 ischaemic stroke patients with hemiplegia and 12 healthy controls. Fractional amplitude of low-frequency fluctuations (fALFF) calculation and correlation analyses were used to assess the relationship between regional neural activity and movement scores. Tractography was performed using diffusion tensor imaging (DTI) data to analyse the fibres passing through the regions of interest. Compared with controls, stroke patients showed abnormal functional connectivity (FC) between some brain regions in the RSNs. The fALFF was increased in the contralesional parietal lobe, with the regional fALFF being correlated with behavioural scores in stroke patients. Additionally, the passage of fibres across regions with reduced FC in the RSNs was increased in stroke patients. This study suggests that structural remodelling of functionally relevant white matter tracts is probably an adaptive response that compensates for injury to the brain.

Mindful attention promotes control of brain network dynamics for self-regulation and discontinues the past from the present

Mindful attention is characterized by acknowledging the present experience as a transient mental event. Early stages of mindfulness practice may require greater neural effort for later efficiency. Early effort may self-regulate behavior and focalize the present, but this understanding lacks a computational explanation. Here we used network control theory as a model of how external control inputs-operationalizing effort-distribute changes in neural activity evoked during mindful attention across the white matter network. We hypothesized that individuals with greater network controllability, thereby efficiently distributing control inputs, effectively self-regulate behavior. We further hypothesized that brain regions that utilize greater control input exhibit shorter intrinsic timescales of neural activity. Shorter timescales characterize quickly discontinuing past processing to focalize the present. We tested these hypotheses in a randomized controlled study that primed participants to either mindfully respond or naturally react to alcohol cues during fMRI and administered text reminders and measurements of alcohol consumption during 4 wk postscan. We found that participants with greater network controllability moderated alcohol consumption. Mindful regulation of alcohol cues, compared to one's own natural reactions, reduced craving, but craving did not differ from the baseline group. Mindful regulation of alcohol cues, compared to the natural reactions of the baseline group, involved more-effortful control of neural dynamics across cognitive control and attention subnetworks. This effort persisted in the natural reactions of the mindful group compared to the baseline group. More-effortful neural states had shorter timescales than less effortful states, offering an explanation for how mindful attention promotes being present.

Modified T2 Statistics for Improved Detection of Aided Cortical Auditory Evoked Potentials in Hearing-Impaired Infants.

The cortical auditory evoked potential (CAEP) is a change in neural activity in response to sound, and is of interest for audiological assessment of infants, especially those who use hearing aids. Within this population, CAEP waveforms are known to vary substantially across individuals, which makes detecting the CAEP through visual inspection a challenging task. It also means that some of the best automated CAEP detection methods used in adults are probably not suitable for this population. This study therefore evaluates and optimizes the performance of new and existing methods for aided (i.e., the stimuli are presented through subjects' hearing aid(s)) CAEP detection in infants with hearing loss. Methods include the conventional Hotellings T2 test, various modified q-sample statistics, and two novel variants of T2 statistics, which were designed to exploit the correlation structure underlying the data. Various additional methods from the literature were also evaluated, including the previously best-performing methods for adult CAEP detection. Data for the assessment consisted of aided CAEPs recorded from 59 infant hearing aid users with mild to profound bilateral hearing loss, and simulated signals. The highest test sensitivities were observed for the modified T2 statistics, followed by the modified q-sample statistics, and lastly by the conventional Hotelling's T2 test, which showed low detection rates for ensemble sizes <80 epochs. The high test sensitivities at small ensemble sizes observed for the modified T2 and q-sample statistics are especially relevant for infant testing, as the time available for data collection tends to be limited in this population.

Supplemental Material for Changes in Neural Activity Following a Randomized Trial of Cognitive Behavioral Therapy for Hoarding Disorder

Supplemental Material for Changes in Neural Activity Following a Randomized Trial of Cognitive Behavioral Therapy for Hoarding Disorder

Effects of emotional changes in brain neural activity in relation to food intake

Effects of emotional changes in brain neural activity in relation to food intake

The alterations of spontaneous neural activities and white matter microstructures in anti-N-methyl-D-aspartate receptor encephalitis: a resting-state fMRI and DTI study.

Limited studies had jointly excavated the structural and functional changes in cognitive deficit in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients. We aimed to explore these changes in anti-NMDAR patients and their effect on cognitive function. Twenty-three patients and 25 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging, diffusion tensor imaging scanning, and neuroethology tests. The significantly differentiated brain regions via the fractional amplitude of low-frequency fluctuation (fALFF) were defined as regions of interest (ROIs). Granger causal, functional connectivity, and tract-based spatial statistical analyses were applied to explore the functional changes in ROIs and assess the structural changes. HCs outperformed patients in Montreal Cognitive Assessment. The fALFF values of right gyrus rectus (RGR) in patients were significantly reduced. The fractional anisotropy (FA) values of WM in the genu of corpus callosum and right superior corona radiata were significantly decreased and positively associated with neuroethology testing scores. The Granger causal connectivity (GCC) from the left inferior parietal lobule to RGR was significantly decreased and positively associated with inherent vigilance. Indicated by the multiple linear regression result, decreased FA value of the right superior corona radiata might be a reliable marker that reflects the cognitive impairment. Significant changes in spontaneous neural activities, GCC, and WM structures in anti-NMDAR encephalitis were reported. These findings promote the understanding of underlying relationships between cerebral function, structural network alterations, and cognitive dysfunction.

Nicotine addiction and overweight affect intrinsic neural activity and neurotransmitter activity: A fMRI study of interaction effects.

Nicotine addiction and overweight often co-exist, but the neurobiological mechanism of their co-morbidity remains to be clarified. In this study, we explore how nicotine addiction and overweight affect intrinsic neural activity and neurotransmitter activity. This study included 54 overweight people and 54 age-, sex-, and handedness-matched normal-weight individuals, who were further divided into four groups based on nicotine addiction. We used a two-way factorial design to compare intrinsic neural activity (calculated by the fALFF method) in four groups based on resting-state functional magnetic resonance images (rs-fMRI). Furthermore, the correlation between fALFF values and PET- and SPECT-derived maps to examine specific neurotransmitter system changes underlying nicotine addiction and overweight. Nicotine addiction and overweight affect intrinsic neural activity by themselves. In combination, they showed antagonistic effects in the interactive brain regions (left insula and right precuneus). Cross-modal correlations displayed that intrinsic neural activity changes in the interactive brain regions were related to the noradrenaline system (NAT). Due to the existence of interaction, nicotine partially restored the changes of spontaneous activity in the interactive brain regions of overweight people. Therefore, when studying one factor alone, the other should be used as a control variable. Besides, this work links the noradrenaline system with intrinsic neural activity in overweight nicotine addicts. By examining the interactions between nicotine addiction and overweight from neuroimaging and molecular perspectives, this study provides some ideas for the treatment of both co-morbidities.

Neuroanatomical predictors of real-time fMRI-based anterior insula regulation. A supervised machine learning study.

Increasing evidence showed that learned control of metabolic activity in selected brain regions can support emotion regulation. Notably, a number of studies demonstrated that neurofeedback-based regulation of fMRI activity in several emotion-related areas leads to modifications of emotional behavior along with changes of neural activity in local and distributed networks, in both healthy individuals and individuals with emotional disorders. However, the current understanding of the neural mechanisms underlying self-regulation of the emotional brain, as well as their relationship with other emotion regulation strategies, is still limited. In this study, we attempted to delineate neuroanatomical regions mediating real-time fMRI-based emotion regulation by exploring whole brain GM and WM features predictive of self-regulation of anterior insula (AI) activity, a neuromodulation procedure that can successfully support emotional brain regulation in healthy individuals and patients. To this aim, we employed a multivariate kernel ridge regression model to assess brain volumetric features, at regional and network level, predictive of real-time fMRI-based AI regulation. Our results showed that several GM regions including fronto-occipital and medial temporal areas and the basal ganglia as well as WM regions including the fronto-occipital fasciculus, tapetum and fornix significantly predicted learned AI regulation. Remarkably, we observed a substantial contribution of the cerebellum in relation to both the most effective regulation run and average neurofeedback performance. Overall, our findings highlighted specific neurostructural features contributing to individual differences of AI-guided emotion regulation. Notably, such neuroanatomical topography partially overlaps with the neurofunctional network associated with cognitive emotion regulation strategies, suggesting common neural mechanisms.

The medial preoptic area and acute cocaine's stimulant effects in rats: Potential influences of estradiol and biological sex

The medial preoptic area (mPOA) in the hypothalamus is an important integrator of neuroendocrine signaling and a key regulator of both natural and drug-induced reward. Although the mPOA modulates sex differences in other behaviors, whether it also modulates sex differences in cocaine response remains unclear. To help us better understand the mPOA's role in sex differences associated with cocaine response, we examined cocaine-induced changes in locomotion and neural activity in the mPOA of male and female rats. In addition, neural activity in the striatum, a brain area known to be involved in cocaine response, was examined for comparison purposes. Fos, the protein product of the immediate early gene c-fos, was used as the marker of neural activity. Locomotion chambers were used to measure behavior, radioimmunoassays and vaginal lavages were used to determine hormonal status, and immunohistochemical assays were used to quantify Fos. To account for the effects of gonadal hormones, rats were left gonadally intact and categorized as either ‘low-estradiol’ or ‘high-estradiol’ based on their hormonal status on test day. Results indicate that high-estradiol females experienced greater cocaine-induced mPOA Fos-immunoreactivity (Fos-ir) and displayed greater cocaine-induced locomotion than low estradiol females. Conversely, high-estradiol males experienced less cocaine-induced mPOA Fos-ir and displayed less cocaine-induced locomotion than low-estradiol males. Cocaine-induced Fos-ir in the mPOA also correlated with cocaine-induced Fos-ir in areas of the striatum already associated with cocaine response. These findings further support the mPOA's role in the endocrine-mediated response to cocaine. It also identifies the mPOA as a contributor to sex differences in cocaine response and potential differences in vulnerability to developing cocaine use disorders.

Dynamic local metrics changes in patients with toothache: A resting-state functional magnetic resonance imaging study.

To study the dynamic changes of local metrics in patients with toothache (TA, Toothache) in the resting state, in order to further understand the changes of central neural mechanism in patients with dental pain and its effect on cognition and emotion. Thirty patients with TA and thirty matched healthy (HC) control volunteers were recruited, and resting-state functional magnetic resonance (rs-MRI) scans were performed on all subjects, and data were analyzed to compare group differences in three dynamic local indices: dynamic regional homogeneity (dReHO), dynamic low-frequency fluctuation amplitude (dALFF) and dynamic fractional low-frequency fluctuation amplitude (dfALFF). In addition, the association between dynamic local metrics in different brain regions of TA patients and scores on the Visual Analog Scale (VAS) and the Hospital Anxiety and Depression Scale (HADS) was investigated by Pearson correlation analysis. In this study, we found that The local metrics of TA patients changed with time Compared with the HC group, TA patients showed increased dReHo values in the left superior temporal gyrus, middle frontal gyrus, precentral gyrus, precuneus, angular gyrus, right superior frontal gyrus, middle temporal gyrus, postcentral gyrus and middle frontal gyrus, increased dALFF values in the right superior frontal gyrus, and increased dfALFF values in the right middle temporal gyrus, middle frontal gyrus and right superior occipital gyrus (p < 0.01, cluster level P < 0.05). Pearson correlation analysis showed that dReHo values of left precuneus and left angular gyrus were positively correlated with VAS scores in TA group. dReHo value of right posterior central gyrus was positively correlated with HADS score (P < 0.05). There are differences in the patterns of neural activity changes in resting-state brain areas of TA patients, and the brain areas that undergo abnormal changes are mainly pain processing brain areas, emotion processing brain areas and pain cognitive modulation brain areas, which help to reveal their underlying neuropathological mechanisms. In the hope of further understanding its effects on cognition and emotion.

Changes in neural activity during the combining affect labeling and reappraisal

Reappraisal, an emotion regulation strategy, is an effective way of controlling negative emotions. Conversely, it is known that affect labeling regulates negative emotions using a different process from reappraisal, and it is possible that the combined use of affect labeling and reappraisal might enhance the control of negative emotion. In this study, we compared the brain activity during combined use of affect labeling and reappraisal to negative emotion with the sole use of reappraisal by using fMRI. The participants performed a reappraisal after affect labeling to negative emotion which induced by negative image. In comparison to the sole use of reappraisal, increased activity was found in the bilateral inferior frontal gyrus and medial frontal gyrus, whereas decreased activity in the right amygdala. Furthermore, based on the results of a functional connectivity analysis using the seed region of the right amygdala, it was determined that coupling with the right amygdala increases due to the combined use of affect labeling and reappraisal. The results reveal that affect labeling of negative emotion potentially effects on reappraisal, which has implications for the more effective use of reappraisal.

Abnormal Regional Spontaneous Neural Activity and Functional Connectivity in Unmedicated Patients with Narcolepsy Type 1: A Resting-State fMRI Study.

Previous Resting-state functional magnetic resonance imaging (fMRI) studies have mainly focused on cerebral functional alteration in processing different emotional stimuli in patients with narcolepsy type 1 (NT1), but were short of exploration of characteristic brain activity and its remote interaction patterns. This study aimed to investigate the spontaneous blood oxygen fluctuations at rest and to elucidate the neural mechanisms underlying neuropsychiatric behavior. A total of 18 unmedicated patients with NT1 and matched healthy individuals were recruited in a resting-state fMRI study. Magnetic resonance imaging (MRI) data were first analyzed using fractional low-frequency amplitude of low-frequency fluctuation (fALFF) to detect changes in local neural activity, and regions with group differences were taken as regions of interest (ROIs). Secondly, functional connectivity (FC) analysis was used to explore altered connectivity between ROIs and other areas. Lastly, the relationship between functional brain activity and neuropsychiatric behaviors was analyzed with correlation analysis. fALFF analysis revealed enhanced neural activity in bilateral fusiform gyrus (FFG), right precentral gyrus, and left postcentral gyrus (PoCG) in the NT1 group. The patients indicated reduced activity in the bilateral temporal pole middle temporal gyrus (TPOmid), left caudate nucleus (CAU), left parahippocampus, left precuneus (PCUN), right amygdala, and right anterior cingulate and paracingulate gyri. ESS score was negatively correlated with fALFF in the right FFG. The NT1 group revealed decreased connectivity between left TPOmid and right PoCG, the bilateral middle frontal gyrus, left superior frontal gyrus, medial, and right supramarginal gyrus. Epworth Sleepiness Scale (ESS) was negatively correlated with FC of the left TPOmid with left putamen (PUT) in NT1. Compared with healthy controls (HCs), enhanced FC of the left CAU with right FFG was positively associated with MSLT-SOREMPs in patients. Furthermore, increased FC of the left PCUN with right PoCG was positively correlated with SDS score. We found that multiple functional activities related to the processing of emotional regulation and sensory information processing were abnormal, and some were related to clinical characteristics. fALFF in the left postcentral or right precentral gyrus may be used as a biomarker of narcolepsy, whereas fALFF in the right fusiform and the FC strength of the left temporal pole middle temporal gyrus with the putamen may be clinical indicators to assess the drowsiness severity of narcolepsy.

Low Intensity Noise Exposure Enhanced Auditory Loudness and Temporal Processing by Increasing Excitability of DCN.

Sound stimulation is generally used for tinnitus and hyperacusis treatment. Recent studies found that long-term noise exposure can change synaptic and firing properties in the central auditory system, which will be detected by the acoustic startle reflex. However, the perceptual consequences of long-term low-intensity sound exposure are indistinct. This study will detect the effects of moderate-level noise exposure (83 dB SPL) on auditory loudness, and temporal processing was evaluated using CBA/CaJ mice. C-Fos staining was used to detect neural activity changes in the central auditory pathway. With two weeks of 83 dB SPL noise exposure (8 hours per day), no persistent threshold shift of the auditory brainstem response (ABR) was identified. On the other hand, noise exposure enhanced the acoustic startle response (ASR) and gap-induced prepulse inhibition significantly (gap-PPI). Low-level noise exposure, according to the findings, can alter temporal acuity. Noise exposure increased the number of c-Fos labeled neurons in the dorsal cochlear nucleus (DCN) and caudal pontine reticular nucleus (PnC) but not at a higher level in the central auditory nuclei. Our results suggested that noise stimulation can change acoustical temporal processing presumably by increasing the excitability of auditory brainstem neurons.

Anomalies in neurovascular coupling during early diabetes: A review.

Diabetic retinopathy is the most feared complication for those with diabetes. Although visible vascular pathology traditionally defines the management of this condition, it is now recognised that a range of cellular changes occur in the retina from an early stage of diabetes. One of the most significant functional changes that occurs in those with diabetes is a loss of vasoregulation in response to changes in neural activity. There are several retinal cell types that are critical for mediating so-called neurovascular coupling, including Müller cells, microglia and pericytes. Although there is a great deal of evidence that suggests that Müller cells are integral to regulating the vasculature, they only modulate part of the vascular tree, highlighting the complexity of vasoregulation within the retina. Recent studies suggest that retinal immune cells, microglia, play an important role in mediating vasoconstriction. Importantly, retinal microglia contact both the vasculature and neural synapses and induce vasoconstriction in response to neurally expressed chemokines such as fractalkine. This microglial-dependent regulation occurs via the vasomediator angiotensinogen. Diabetes alters the way microglia regulate the retinal vasculature, by increasing angiotensinogen expression, causing capillary vasoconstriction and contributing to a loss of vascular reactivity to physiological signals. This article summarises recent studies showing changes in vascular regulation during diabetes, the potential mechanisms by which this occurs and the significance of these early changes to the progression of diabetic retinopathy.

Control-theoretic integration of stimulation and electrophysiology for cognitive enhancement.

Transcranial electrical stimulation (tES) technology and neuroimaging are increasingly coupled in basic and applied science. This synergy has enabled individualized tES therapy and facilitated causal inferences in functional neuroimaging. However, traditional tES paradigms have been stymied by relatively small changes in neural activity and high inter-subject variability in cognitive effects. In this perspective, we propose a tES framework to treat these issues which is grounded in dynamical systems and control theory. The proposed paradigm involves a tight coupling of tES and neuroimaging in which M/EEG is used to parameterize generative brain models as well as control tES delivery in a hybrid closed-loop fashion. We also present a novel quantitative framework for cognitive enhancement driven by a new computational objective: shaping how the brain reacts to potential "inputs" (e.g., task contexts) rather than enforcing a fixed pattern of brain activity.