POSSIBILITIES OF NEUROSCIENCE APPLICATION IN HOUSING DEVELOPMENT

Histochemical methods were used to detect differently directed changes in the metabolic activity of neurons in the anterior hypothalamic nuclei in rats during hyperthermia, fever, and hypothermia. Hyperthermia induced by high temperatures was associated with increases in the activities of enzymes involved in energy metabolism, with increases in RNA contents in neurons in the supraoptic, paraventricular, and median preoptic nuclei of the anterior hypothalamus of the rat, which is evidence for increases in metabolic activity in the neurons of these nuclei. Endotoxin-induced fever was accompanied by decreases in the metabolic activity of neurons in the median preoptic nucleus, while activity in neurons of the supraoptic and paraventricular nuclei showed no significant change. The development of hypothermia induced by low temperatures was characterized by decreases in the metabolic activity of neurons in the supraoptic, paraventricular, and median preoptic nuclei of the anterior hypothalamus. It is suggested that the differently directed changes in metabolic activity in the neurons of the anterior hypothalamus in hyperthermia, fever, and hypothermia are associated with their roles in the central mechanisms of thermoregulation (median preoptic nucleus) and neurosecretory processes (supraoptic and paraventricular nuclei).

Functional magnetic resonance imaging (fMRI) is a unique window to the brain, enabling scientists to follow changes in brain activity in response to hormones, ageing, environment, drugs of abuse and other stimuli. There are two features that make fMRI unique when compared with other imaging modalities used in behavioural neuroscience. First, it can be entirely noninvasive: each animal can serve as its own control over the natural course of its life, vital for following neuroadaptation and other developmental processes critical to understanding behaviour. Second, fMRI has the spatial and temporal resolution to observe patterns of neuronal activity across the entire brain in less than a minute. Although fMRI does not have the cellular spatial resolution of immunostaining, nor the millisecond temporal resolution of electrophysiology, synchronised changes in neuronal activity across multiple brain areas seen with functional MRI can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviours. Thus, fMRI affords a systems approach to the study of the brain, complementing and building from other neurobiological techniques to understand how behaviour is organised across multiple brain regions. In this review, we present a general background to fMRI and the different imaging modalities that can be used in fMRI studies. Included are examples of the application of fMRI in behavioural neuroscience research, along with discussion of the advantages and disadvantages of this technology.

BackgroundThe correlation between regional changes in neuronal activity and changes in hemodynamics is a major issue for noninvasive neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and near-infrared optical imaging (NIOI). A tight coupling of these changes has been assumed to elucidate brain function from data obtained with those techniques. In the present study, we investigated the relationship between neuronal activity and hemodynamic responses in the occipital cortex of humans during visual stimulation and in the somatosensory cortex of rats during peripheral nerve stimulation.MethodsThe temporal frequency dependence of macroscopic hemodynamic responses on visual stimuli was investigated in the occipital cortex of humans by simultaneous measurements made using fMRI and NIOI. The stimulus-intensity dependence of both microscopic hemodynamic changes and changes in neuronal activity in response to peripheral nerve stimulation was investigated in animal models by analyzing membrane potential (fluorescence), hemodynamic parameters (visible spectra and laser-Doppler flowmetry), and vessel diameter (image analyzer).ResultsAbove a certain level of stimulus-intensity, increases in regional cerebral blood flow (rCBF) were accompanied by a decrease in regional cerebral blood volume (rCBV), i.e., dissociation of rCBF and rCBV responses occurred in both the human and animal experiments. Furthermore, the animal experiments revealed that the distribution of increased rCBF and O2 spread well beyond the area of neuronal activation, and that the increases showed saturation in the activated area.ConclusionsThese results suggest that above a certain level of neuronal activity, a regulatory mechanism between regional cerebral blood flow (rCBF) and rCBV acts to prevent excess O2 inflow into the focally activated area.

Revealing Brain Activity and White Matter Structure Using Functional and Diffusion-Weighted Magnetic Resonance Imaging

Functional magnetic resonance imaging (FMRI) detects signal changes in brain that accompany regional changes in neuronal activity. In normal human brain, FMRI shows changes in signal in the postcentral gyrus or superior temporal gyrus that correlate with voluntary motor activity or language processing, respectively. The model used to explain the changes in signal linked temporally with cerebral activity is a reduction in cerebral capillary deoxyhemoglobin concentration due to the increased blood flow that accompanies neuronal activity in the cerebrum. FMRI has been used in normal subjects but not extensively in patients. To determine the feasibility of using FMRI to map cerebral functions in patients with partial epilepsy syndromes, we performed a pilot study, using FMRI to identify signal changes in motor and language areas in response to tasks that activate those areas. Signal changes in epilepsy patients approximated those observed in volunteers. We conclude that FMRI can be developed as a method for functional cerebral mapping in partial epilepsies.

Nicotine is an addictive substance historically consumed through smoking and more recently through the use of electronic vapor devices. The increasing prevalence and popularity of vaping prompts the need for preclinical rodent models of nicotine vapor exposure and an improved understanding of the impact of vaping on specific brain regions, bodily functions, and behaviors. We used a rodent model of electronic nicotine vapor exposure to examine the cellular and behavioral consequences of acute and repeated vapor exposure. Adult male C57BL/6J mice were exposed to a single 3-h session (acute exposure) or five daily sessions (repeated exposure) of intermittent vapes of 120 mg/ml nicotine in propylene glycol:vegetable glycerol (PG/VG) or PG/VG control. Acute and repeated nicotine vapor exposure did not alter body weight, and both exposure paradigms produced pharmacologically significant serum nicotine and cotinine levels in the 120 mg/ml nicotine group compared with PG/VG controls. Acute exposure to electronic nicotine vapor increased central amygdala (CeA) activity in individual neuronal firing and in expression of the molecular activity marker, cFos. The changes in neuronal activity following acute exposure were not observed following repeated exposure. Acute and repeated nicotine vapor exposure decreased core body temperature, however acute exposure decreased locomotion while repeated exposure increased locomotion. Collectively, these studies provide validation of a mouse model of nicotine vapor exposure and important evidence for how exposure to electronic nicotine vapor produces differential effects on CeA neuronal activity and on specific body functions and behaviors like thermoregulation and locomotion.

A new method for relating behavior to neuronal activity in performing monkeys

Homeostatic synaptic plasticity, or synaptic scaling, is a mechanism that tunes neuronal transmission to compensate for prolonged, excessive changes in neuronal activity. Both excitatory and inhibitory neurons undergo homeostatic changes based on synaptic transmission strength, which could effectively contribute to a fine-tuning of circuit activity. However, gene regulation that underlies homeostatic synaptic plasticity in GABAergic (GABA, gamma aminobutyric) neurons is still poorly understood. The present study demonstrated activity-dependent dynamic scaling in which NMDA-R (N-methyl-D-aspartic acid receptor) activity regulated the expression of GABA synthetic enzymes: glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67). Results revealed that activity-regulated BDNF (brain-derived neurotrophic factor) release is necessary, but not sufficient, for activity-dependent up-scaling of these GAD isoforms. Bidirectional forms of activity-dependent GAD expression require both BDNF-dependent and BDNF-independent pathways, both triggered by NMDA-R activity. Additional results indicated that these two GAD genes differ in their responsiveness to chronic changes in neuronal activity, which could be partially caused by differential dependence on BDNF. In parallel to activity-dependent bidirectional scaling in GAD expression, the present study further observed that a chronic change in neuronal activity leads to an alteration in neurotransmitter release from GABAergic neurons in a homeostatic, bidirectional fashion. Therefore, the differential expression of GAD65 and 67 during prolonged changes in neuronal activity may be implicated in some aspects of bidirectional homeostatic plasticity within mature GABAergic presynapses.

Depression is a highly prevalent life-threatening disorder, with its first onset commonly occurring during adolescence. Adolescent depression is increasingly being treated with antidepressants, such as fluoxetine. The use of medication during this sensitive period of physiological and cognitive brain development produces neurobiological changes, some of which may outlast the course of treatment. In this review, we look at how antidepressant treatment in adolescence is likely to alter neurovascular coupling and brain energy use and how these changes, in turn, affect our ability to identify neuronal activity changes between participant groups. BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging), the method most commonly used to record brain activity in humans, is an indirect measure of neuronal activity. This means that between-group comparisons – adolescent versus adult, depressed versus healthy, medicated versus non-medicated – rely upon a stable relationship existing between neuronal activity and the BOLD response across these groups. We use data from animal studies to detail the ways in which fluoxetine may alter this relationship, and explore how these alterations may influence the interpretation of BOLD signal differences between groups that have been treated with fluoxetine and those that have not.

The prefrontal-limbic network in the human brain plays a major role in social cognition, especially cognitive control of emotion. The medial frontopolar cortex (mFP; Brodmann Area 10) and the amygdala are part of this network and display correlated neuronal activity in time, as measured by functional magnetic resonance imaging (fMRI). This functional connectivity is dynamic, sensitive to training, and affected in mental disorders. However, the effects of neurostimulation on functional connectivity within this network have not yet been systematically investigated. Here, we investigate the effects of both low- and high-frequency repetitive transcranial magnetic stimulation (rTMS) to the right mFP on functional connectivity between mFP and amygdala, as measured with resting state fMRI (rsfMRI). Three groups of healthy participants received either low-frequency rTMS (1 Hz; N = 18), sham TMS (1 Hz, subthreshold; N = 18) or high-frequency rTMS (20 Hz; N = 19). rsfMRI was acquired before and after (separate days). We hypothesized a modulation of functional connectivity in opposite directions compared to sham TMS through adjustment of the stimulation frequency. Groups differed in functional connectivity between mFP and amygdala after stimulation compared to before stimulation (low-frequency: decrease, high-frequency: increase). Motion or induced changes in neuronal activity were excluded as confounders. Results show that rTMS is effective for increasing and decreasing functional coherence between prefrontal and limbic regions. This finding is relevant for social and affective neuroscience as well as novel treatment approaches in psychiatry.

The aim of this study was to pinpoint the cerebral regions implicated during swallowing by comparing the brain activation areas associated with two different volitional movements: tongue protrusion and tongue elevation. Twenty-four healthy subjects (11—males 22 ± 2.9 y; 13—females 23 ± 4.1 y; were examined through functional magnetic resonance imaging (fMRI) while performing two different swallowing tasks: with tongue protrusion and with tongue elevation. The study was carried out with the help of fMRI imaging which assesses brain signals caused by changes in neuronal activity in response to sensory, motor or cognitive tasks. The precentral gyrus and the cerebellum were activated during both swallowing tasks while the postcentral gyrus, thalamus, and superior parietal lobule could be identified as large activation foci only during the protrusion task. During protrusion tasks, increased activations were also seen in the left-middle and medial frontal gyrus, right thalamus, inferior parietal lobule, and the superior temporal gyrus (15,592-voxels; Z-score 5.49 ± 0.90). Tongue elevation activated a large volume of cortex portions within the left sub-gyral cortex and minor activations in both right and left inferior parietal lobules, right postcentral gyrus, lentiform nucleus, subcortical structures, the anterior cingulate, and left insular cortex (3601-voxels; Z-score 5.23 ± 0.52). However, the overall activation during swallowing tasks with tongue elevation, was significantly less than swallowing tasks with tongue protrusion. These results suggest that tongue protrusion (on inferior incisors) during swallowing activates a widely distributed network of cortical and subcortical areas than tongue elevation (on incisor papilla), suggesting a less economic and physiologically more complex movement. These neuromuscular patterns of the tongue confirm the different purpose of elevation and protrusion during swallowing and might help professionals manage malocclusions and orofacial myofunctional disorders.

Introduction and problem formulation Elucidating how the human brain is structured and how it functions is a fundamental aim of human neuroscience. To achieve such an aim, the activity of the human brain has been measured using noninvasive neuroimaging techniques, the most popular of which is functional magnetic resonance imaging (fMRI) (Ogawa et al . 1990). The fMRI signals are obtained at a spatial resolution of typically 3mm and measure changes of blood flow and blood oxygen consumption whose temporal dynamics are slower than that of neuronal electrical activities, resulting in a poor temporal resolution of the order of seconds. In contrast, magnetoencephalography (MEG) and electroencephalography (EEG) can detect changes of neuronal activities by the millisecond measurement of magnetic and electric fields, respectively, outside the skull (Hamalainen et al . 1993; Nunez & Srinivasan 2006). The high temporal resolution of MEG (and EEG) is useful, especially for studying the dynamic integration of functionally specialized brain regions, which is a subject of growing interest in human neuroscience (de Pasquale et al . 2012). The major problem of MEG is that spatial brain activity patterns are not easily understandable from sensor measurements. This is because the magnetic fields produced by neuronal current sources are superimposed to form rather uninterpretable spatial patterns of signals on sensors. Estimating the position and intensity of these current sources from the sensor measurements is called source reconstruction, or source localization. Solving the source reconstruction problem allows the mapping of temporally dynamic electrical activities in the human brain (Baillet et al . 2001). Since how brain regions are dynamically integrated to produce a variety of functions is of great interest in human neuroscience research, the mission of MEG source reconstruction is not only to localize position of the current sources, but also to identify directed interactions between these sources. A possible approach to this involves constructing a dynamic model of brain electrical activities, as well as developing an estimation algorithm for the source positions and interactions that are parametrized in this model.

Accurate interpretation of functional MRI (fMRI) signals requires knowledge of the relationship between the hemodynamic response and the neuronal activity that underlies it. Here we address the question of coupling between pre- and postsynaptic neuronal activity and the hemodynamic response in rodent somatosensory (Barrel) cortex in response to single-whisker deflection. Using full-field multiwavelength optical imaging of hemoglobin oxygenation and electrophysiological recordings of spiking activity and local field potentials, we demonstrate that a point hemodynamic measure is influenced by neuronal activity across multiple cortical columns. We demonstrate that the hemodynamic response is a spatiotemporal convolution of the neuronal activation. Therefore, positive hemodynamic response in one cortical column might be explained by neuronal activity not only in that column but also in the neighboring columns. Thus, attempts at characterizing the neurovascular relationship based on point measurements of electrophysiology and hemodynamics may yield inconsistent results, depending on the spatial extent of neuronal activation. The finding that the hemodynamic signal observed at a given location is a function of electrophysiological activity over a broad spatial region helps explain a previously observed increase of local vascular response beyond the saturation of local neuronal activity. We also demonstrate that the oxy- and total-hemoglobin hemodynamic responses can be well approximated by space-time separable functions with an antagonistic center-surround spatial pattern extending over several millimeters. The surround "negative" hemodynamic activity did not correspond to observable changes in neuronal activity. The complex spatial integration of the hemodynamic response should be considered when interpreting fMRI data.

Background: Psychological distress is a common reaction to a cancer diagnosis and its treatment. Distress impacts quality of life, adherence to treatment, decision making and survival. Patients with pancreatic adenocarcinoma (PDAC) experience exceptionally high rates of psychological distress, most commonly depression, anxiety and suicidality. Psilocybin, a serotonergic psychedelic which is the active component in “magic mushrooms,” is a promising treatment for several mental health disorders. Prior studies in patients with cancer have combined a single dose of psilocybin with preparation and integration counseling and have shown significant, rapid and sustained improvement in depression, anxiety and quality of life. These studies have primarily been conducted in psychiatry or neuroscience clinics in heterogenous groups of patients, many of whom had completed cancer treatment. This study will evaluate the feasibility and safety of psilocybin-assisted therapy delivered in the outpatient palliative care clinic in patients with advanced PDAC who are receiving chemotherapy. Methods: This is a single center, open label pilot study of a psilocybin-assisted therapy integrated with palliative care in patients with advanced PDAC. The primary endpoints are the feasibility and safety of this strategy when integrated into routine palliative care. Secondary endpoints include short term changes in depression, anxiety and demoralization and changes in neuronal activity by functional MRI (fMRI). After 2-4 outpatient preparation sessions with a palliative medicine physician (PMP), the subject will take psilocybin (25mg capsule) at an individual session supported by a PMP and a trained mental health professional. Up to 3 integration sessions with a PMP will follow. Patient-reported measures of psychological distress and quality of life will be assessed at baseline, after the psilocybin dose and periodically during follow-up. Neuronal changes will be measured using fMRI before and after the psilocybin dose. Eligible patients are adults (ECOG 0-3) with advanced PDAC with adequate organ function. Patients with psychiatric conditions which preclude safe cessation of psychotropic drugs or requires hospitalization, a personal or family history of schizophrenia, psychotic disorder or bipolar disorder, who have a high risk of suicide or have serious or uncontrolled hypertension or cardiovascular disease are ineligible. Given the exploratory nature of the study, a formal statistical assessment of the sample size was not conducted. Twelve evaluable subjects will provide sufficient power to detect large effect sizes (Cohen’s d1.0) in the secondary endpoints. Wilcoxon signed rank test will determine the reduction in distress scores before and after the psilocybin session. Enrollment began in June 2023; two subjects have enrolled. The study is funded by the Jim Young Pancreatic Cancer Research Memorial Fund. Psilocybin is provided by Usona. ClinicalTrials.gov Identifier: NCT05220046 Citation Format: Kelsey A. Klute, Lou Lukas, Soonjo Hwang, Yeongjin Gwon, Mridula Krishnan, Jean Grem, Sunil Hingorani, Jody Koenig Kellas. A pilot study of palliadelic treatment with psilocybin to reduce psychological distress and improve quality of life in patients with advanced pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C001.

Conventional functional magnetic resonance imaging (FMRI) allows the measurement of functional cerebral blood flow changes occurring with specific tasks using standard clinical MR systems. However, the spatial relationship between neuronal activity and functional cerebral blood flow changes is not yet known. This article reviews studies which compared the center of neuronal activation (measured by magnetoencephalography) with that of the hemodynamic response (measured by FMRI) using motor and visual stimulation.