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PubMed2024

Shared differential factors underlying individual spontaneous neural activity abnormalities in major depressive disorder.

BACKGROUND: In contemporary neuroimaging studies, it has been observed that patients with major depressive disorder (MDD) exhibit aberrant spontaneous neural activity, commonly quantified through the amplitude of low-frequency fluctuations (ALFF). However, the substantial individual heterogeneity among patients poses a challenge to reaching a unified conclusion. METHODS: To address this variability, our study adopts a novel framework to parse individualized ALFF abnormalities. We hypothesize that individualized ALFF abnormalities can be portrayed as a unique linear combination of shared differential factors. Our study involved two large multi-center datasets, comprising 2424 patients with MDD and 2183 healthy controls. In patients, individualized ALFF abnormalities were derived through normative modeling and further deconstructed into differential factors using non-negative matrix factorization. RESULTS: Two positive and two negative factors were identified. These factors were closely linked to clinical characteristics and explained group-level ALFF abnormalities in the two datasets. Moreover, these factors exhibited distinct associations with the distribution of neurotransmitter receptors/transporters, transcriptional profiles of inflammation-related genes, and connectome-informed epicenters, underscoring their neurobiological relevance. Additionally, factor compositions facilitated the identification of four distinct depressive subtypes, each characterized by unique abnormal ALFF patterns and clinical features. Importantly, these findings were successfully replicated in another dataset with different acquisition equipment, protocols, preprocessing strategies, and medication statuses, validating their robustness and generalizability. CONCLUSIONS: This research identifies shared differential factors underlying individual spontaneous neural activity abnormalities in MDD and contributes novel insights into the heterogeneity of spontaneous neural activity abnormalities in MDD.

Humans↗
PubMed2005

Tapping in synchrony to auditory rhythms: effect of temporal structure on behavior and neural activity.

This study examines how synchronizing movements to auditory rhythms affects behavioral performance and neural activity as assessed using fMRI. Subjects perform worse as they tap along with increasingly complex musical rhythms, with responses becoming progressively asynchronous. This behavioral change also correlates with increasing neural activity in several motor-related brain regions, such as the cerebellum and premotor cortex (medial and lateral), highlighting the role of these areas in auditory-motor interactions during temporal processing.

Acoustic Stimulation↗
PubMed1993

Optical imaging of the ventral medullary surface of cats: hypoxia-induced differences in neural activation.

Large-array optical recording procedures provide the potential to examine simultaneous activity of large numbers of neurons. We applied this technique to examine regional neuronal activation on the ventral medullary surface (VMS) of cats during hypoxic challenges. VMS was exposed through a ventral surgical approach in eight adult cats under pentobarbital sodium anesthesia. Arterial pressure, end-tidal CO2, costal diaphragmatic electromyograms, and electrocardiograms were continuously monitored. A coherent image conduit with 12-microns-fiber resolution was attached to a charge-coupled device camera and positioned over the VMS. Reflected 700-nm light was digitized continuously at 2- to 3-s intervals during baseline period, hypoxic (6, 9, and 12% O2 in N2) exposure, and recovery. Forty images within each epoch were averaged and subtracted from baseline. Regional differences within the image were determined by analysis of variance procedures (alpha = 0.05). In caudal VMS, hypoxic challenges with 12% O2 consistently induced a regional diminution in reflected light (increased neural activity) that was rapid in onset and persisted for approximately 20 min after termination of exposure, well beyond the duration of discernible ventilatory alterations. In contrast, the same challenge resulted in decreased neural activity of similar duration in rostral VMS areas. Challenges with lower inspired concentrations of O2 reversed the pattern of diminished neural activity in rostral regions and led to a dose-dependent increase in neural activity, a dependency also observed in caudal VMS. We conclude that caudal VMS neurons demonstrate a unidirectional dose-dependent response pattern to hypoxic stimuli, whereas rostral VMS regions exhibit a bidirectional response to increasing hypoxic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Auditory training induces asymmetrical changes in cortical neural activity.

Pre-attentive cortical evoked potentials reflect training-induced changes in neural activity associated with speech-sound training. Seven normal-hearing young adults were trained to identify two synthetic speech variants of the syllable /ba/. As subjects learned to correctly identify the two stimuli, changes in P1, N1, and P2 amplitudes were observed. Of particular interest is that P1, N1, and P2 components of the N1-P2 complex responded differently to listening training. That is, significant changes in P1 and N1 amplitude were recorded over the right but not the left hemisphere. In contrast, increases in P2 were observed bilaterally. These results indicate that training-related changes in neural activity are reflected in far-field aggregate neural responses and that distinct patterns of neural change, perhaps reflecting hemispheric specialization, likely represent different aspects of auditory function.

Acoustic Stimulation↗
PubMed2003

Fluctuations in brain temperature during sexual interaction in male rats: an approach for evaluating neural activity underlying motivated behavior.

Since metabolic activity is accompanied by heat release, measurement of brain temperatures offers a method for assessing behavior-associated changes in neural activity. To explore this possibility, we monitored local brain (nucleus accumbens, medial-preoptic hypothalamus, and hippocampus) and body (temporal muscle) temperature in an experienced male rat during sexual behavior with a sexually receptive female. Placement of the female into a neighboring compartment increased the male's temperature and additional increases occurred when rats were allowed to see and partially interact with the female through a Plexiglas barrier with dime-size holes. The temperature increase was robust (1.5-2.0 degrees C), faster in all brain areas than in muscle, and peaked (38-39 degrees C) when the barrier was removed and full interaction was allowed. As the male repeatedly mounted and achieved intromission with the female, temperature further increased, peaking at ejaculation (+0.2-0.4 degrees C). Following ejaculation, the temperature abruptly dropped, until sexual interest and interaction resumed. These biphasic temperature fluctuations were generally similar in each recording location, but all brain sites (particularly, nucleus accumbens and medial-preoptic hypothalamus) showed more profound changes than the muscle. These data generally match single-unit and other physiological findings, suggesting that male sexual behavior is accompanied by sustained and generalized neural activation. This activation is triggered by sexually relevant stimuli (arousal), maintained during repeated mounts and intromissions, and peaked at ejaculation. These findings suggest brain temperature fluctuations not only as a sensitive index of functional neural activation, but as a powerful factor affecting various neural functions and an important part of brain mechanisms underlying motivated behavior.

Action Potentials↗
PubMed2004

Neural activity protects hypothalamic magnocellular neurons against axotomy-induced programmed cell death.

Axotomy typically leads to retrograde neuronal degeneration in the CNS. Studies in the hypothalamo-neurohypophysial system (HNS) have suggested that neural activity is supportive of magnocellular neuronal (MCN) survival after axotomy. In this study, we directly test this hypothesis by inhibiting neural activity in the HNS, both in vivo and in vitro, by the use of tetrodotoxin (TTX). After median eminence compression to produce axonal injury, unilateral superfusion of 3 microM TTX into the rat supraoptic nucleus (SON), delivered with the use of a miniature osmotic pump for 2 weeks in vivo, produced a decrease in the number of surviving MCNs in the TTX-treated SON, compared with the contralateral untreated side of the SON. In vitro application of 2.5 microM TTX for 2 weeks to the SON in organotypic culture produced a 73% decrease in the surviving MCNs, compared with untreated control cultures. Raising the extracellular KCl in the culture medium to 25 mM rescued the MCNs from the axotomy- and TTX-induced cell death. These data support the proposal that after axotomy, neural activity is neuroprotective in the HNS.

Animals↗
PubMed1995

Expiratory neural activities in gasping induced by pharyngeal stimulation and hypoxia.

The purpose was to characterize expiratory neural activities in gasping elicited during the aspiration reflex (AR) in hyperoxia and during hypoxia-induced gasping. In decerebrate, vagotomized and paralyzed cats, we recorded activities of inspiratory and expiratory cranial and spinal nerves. The AR was elicited by touching the epipharyngeal mucosa. In eupnea, spinal expiratory activities were greatly decreased during AR whereas laryngeal expiratory activities were increased. In hypoxia-induced gasping, both the laryngeal and spinal expiratory activities were reduced. All of the inspiratory activities were increased during both gasping and the AR. In addition, neural activities were below control levels following AR; activities gradually recovered to control levels. We conclude that spinal expiratory activities are inhibited during the AR and gasping. Results are consistent with the concept that medullary mechanisms for gasping are recruited by mechanical stimulation of the epipharynx. In hypoxia-induced gasping, the hypoxia, per se, causes a separate suppression of laryngeal expiratory activities.

Animals↗
PubMed2001

Neural activity in primary motor cortex related to mechanical loads applied to the shoulder and elbow during a postural task.

Whole-arm motor tasks performed by nonhuman primates have become a popular paradigm to examine neural activity during motor action, but such studies have traditionally related cell discharge to hand-based variables. We have developed a new robotic device that allows the mechanics of the shoulder and elbow joints to be manipulated independently. This device was used in the present study to examine neural activity in primary motor cortex (MI) in monkeys (Macaca mulatta) actively maintaining their hand at a central target as they compensated for loads applied to the shoulder and/or elbow. Roughly equal numbers of neurons were sensitive to mechanical loads only at the shoulder, only at the elbow, or loads at both joints. Neurons possessed two important properties. First, cell activity during multi-joint loads could be predicted from its activity during single-joint loads as a vector sum in a space defined by orthogonal axes for the shoulder and elbow. Second, most neurons were related to flexor torque at one joint coupled with extensor torque at the other, a distribution that paralleled the observed activity of forelimb muscles. These results illustrate that while MI activity may be described by independent axes representing each mechanical degree-of-freedom, neural activity is also strongly influenced by the specific motor patterns used to perform a given task.

Action Potentials↗
PubMed2005

Information processing flow and neural activations in the dorsolateral prefrontal cortex in the Stroop task in schizophrenic patients. A spatially filtered MEG analysis with high temporal and spatial resolution.

Using a spatially filtered magnetoencephalography analysis (synthetic aperture magnetometry), we estimated neural activations in the Stroop task in nearly real time for schizophrenic patients with/without auditory hallucinations and for normal control subjects. In addition, auditory hallucinations were examined through the information processing flow of the brain neural network, including the frontal regions. One hundred unaveraged magnetoencephalography signals during the incongruent stimulus responses were analyzed with a time window of 200 ms in steps of 50 ms. In the 25-60-Hz band, cortical regions that showed significant current source density changes were examined for each time window. The three groups showed significantly decreased current source density, corresponding to neural activation, with temporal overlap along the fundamental cognitive information processing flow: sensory input system, executive control system, motor output system. Transient neural activations in the dorsolateral prefrontal cortex were bilateral with left-side dominancy for normal controls, left-lateralized for nonhallucinators and right-lateralized for hallucinators. Our results suggest that the dysfunction in the left dorsolateral prefrontal cortex was related to auditory hallucinations, while the information processing flow was unaffected in the schizophrenic subjects in the Stroop task.

Adolescent↗
PubMed1976

Central vestibular compensation. Effect of the bilateral labyrinthectomy on neural activity in the medial vestibular nucleus.

An attempt was made to reconstruct the central events that occurred in the various stages of vestibular compensation after a bilateral labyrinthectomy in the cat. Bilateral labyrinthectomized cats showed no nystagmus, but had unsteady head movements and wide gaits. Neural activity in both sides of the medial vestibular nuclei (MVN) was depressed during the critical stage of compensation; however, the neural activity was full and normal during the acute and compensated stage. The experimental results suggest that removing crossed inhibitory influence and reducing the cerebellar inhibitory influence by bilateral labyrinthectomy enhances the process of recovering neural activity in the vestibular nuclei during central compensation, and that the contralateral vestibular end organ is not a source of the driving force responsible for regeneration of electrical activity in the deafferented MVN after a unilateral labyrinthectomy.

Animals↗
PubMed2005

Changes in cerebral blood flow and cerebral oxygen metabolism during neural activation measured by positron emission tomography: comparison with blood oxygenation level-dependent contrast measured by functional magnetic resonance imaging.

The discrepancy between the increases in cerebral blood flow (CBF) and CMRO2 during neural activation causes an increase in venous blood oxygenation and, therefore, a decrease in paramagnetic deoxyhemoglobin concentration in venous blood. This can be detected by functional magnetic resonance imaging (fMRI) as blood oxygenation level-dependent (BOLD) contrast. In the present study, changes in the cerebral oxygen extraction fraction (OEF) that corresponds to the ratio of CMRO2 to CBF, and in the BOLD signal during neural activation, were measured by both positron emission tomography (PET) and fMRI in the same human subjects. C15O, 15O2, and H2(15)O PET studies were performed in each subject at rest (baseline) and during performance of a right-hand motor task. Functional magnetic resonance imaging studies were then performed to measure the BOLD signal under the two conditions. During performance of the motor task, a significant increase in CBF and a significant decrease in OEF were observed in the left precentral gyrus, left superior frontal gyrus, right precentral gyrus, right cingulate gyrus, and right cerebellum. A significant positive correlation was observed between changes in the CBF and the BOLD signal, and a significant negative correlation was observed between changes in the OEF and the BOLD signal. This supports the assumption on which BOLD contrast studies during neural activation are based.

Adult↗
PubMed2005

Two-dimensional neural activity mapping of the entire population of hippocampal CA1 pyramidal cells responding to fear conditioning.

The hippocampus is involved in the encoding, storage, and retrieval of memory. Here, we have developed a novel mapping method for detecting the distribution of neural activity of the entire population of pyramidal cells in the hippocampal CA1 and subiculum regions, where expression profiles of Arc mRNA were used as an indicator of neural activity. The spherical pyramidal cell layer of the intact hippocampus was flattened into a two-dimensional plane, which was then serially sectioned in parallel with the plane to make tangential sections. Tangential sections were hybridized with an Arc cRNA probe and Arc signals from serial tangential sections were stacked and displayed on a two-dimensional plane, allowing one to easily visualize the neural activity of all pyramidal cells. We applied this method to the hippocampus of rats that had experienced contextual fear conditioning, which requires hippocampal function. We observed a net shift of Arc signals from dorsal to ventral CA1/subiculum with an interval prolongation to reconditioning after the initial conditioning. The reconditioning-revealed shift may reflect a reorganization process, which takes place during the period between initial conditioning and reconditioning, in the CA1/subiculum neural network that represents the neural storage and/or retrieval of the contextual fear conditioning.

Animals↗
PubMed2006

Operant matching is a generic outcome of synaptic plasticity based on the covariance between reward and neural activity.

The probability of choosing an alternative in a long sequence of repeated choices is proportional to the total reward derived from that alternative, a phenomenon known as Herrnstein's matching law. This behavior is remarkably conserved across species and experimental conditions, but its underlying neural mechanisms still are unknown. Here, we propose a neural explanation of this empirical law of behavior. We hypothesize that there are forms of synaptic plasticity driven by the covariance between reward and neural activity and prove mathematically that matching is a generic outcome of such plasticity. Two hypothetical types of synaptic plasticity, embedded in decision-making neural network models, are shown to yield matching behavior in numerical simulations, in accord with our general theorem. We show how this class of models can be tested experimentally by making reward not only contingent on the choices of the subject but also directly contingent on fluctuations in neural activity. Maximization is shown to be a generic outcome of synaptic plasticity driven by the sum of the covariances between reward and all past neural activities.

Animals↗
PubMed2005

Top-down enhancement and suppression of the magnitude and speed of neural activity.

Top-down modulation underlies our ability to selectively attend to relevant stimuli and to ignore irrelevant stimuli. Theories addressing neural mechanisms of top-down modulation are driven by studies that reveal increased magnitude of neural activity in response to directed attention, but are limited by a lack of data reporting modulation of neural processing speed, as well as comparisons with a perceptual (passive view) baseline necessary to evaluate the presence of enhancement and suppression. Utilizing functional MRI (fMRI) and event-related potential recordings (ERPs), we provide converging evidence that both the magnitude of neural activity and the speed of neural processing are modulated by top-down influences. Furthermore, both enhancement and suppression occur relative to a perceptual baseline depending on task instruction. These findings reveal the fine degree of influence that goal-directed attention exerts upon activity within the visual association cortex. We further document capacity limitations in top-down enhancement corresponding with working memory performance deficits.

Adult↗
PubMedDate not supplied

Real-time analysis of hippocampal neural activity in the intervals between interictal spikes.

Previously the electroencephalogram (EEG) was modeled as consisting of faster, smaller waves superimposed on larger, slower waves. The intent of this study is to modify the program to sample neural activity over specific intervals of time following detection of a distinct wave pattern. The use of conditional sampling is illustrated by considering wave detection following epileptic interictal spikes in the rabbit hippocampus. To create an epileptic focus, small pellets of sodium penicillin suspended in agar were placed on the rabbit hippocampus. This produced regularly recurring, spontaneous, large amplitude discharges, or interictal spikes, at the site of application. Following detection of an interictal spike, the program delayed the onset of a sample period for either 1.0 s or 6.0 s. The neural activity was then sampled for 5.1 s, and fast and slow waves were detected over the sample period. The frequency distribution of waves in four of these 5.1 s intervals was calculated. Comparison of the frequency distributions following the 1.0 s and 6.0 s delays showed no discernible differences. The data illustrate that not all types of neural activity are markedly modified by interictal spikes and suggest that hippocampal cellular populations generate similar waves 1.0 s and 6.0 s after such a spike. Moreover, this experiment illustrates adaptation of the program to sample activity over a limited period of time following detection of a specific cortical waveform.

Animals↗
PubMed2002

Changes of neural activity correlate with the severity of cortical ischemia in patients with unilateral major cerebral artery occlusion.

BACKGROUND AND PURPOSE: In major cerebral arterial steno-occlusive diseases, there can be remarkably decreased hemodynamic reserve without marked neurological impairments. In such settings, it is not known whether the neural activity is well maintained or disturbed according to the severity of cerebral ischemia. The present study was therefore undertaken to examine the neural activity under mild cerebral ischemia resulting from major cerebral arterial occlusion. METHODS: Seven patients with minor neurological impairment as well as either unilateral internal carotid artery or middle cerebral artery occlusion were studied. The severity of the cortical ischemia was assessed by measuring regional cerebral blood flow (rCBF) with positron emission tomography. The change in neural activity in the ischemic brain was then evaluated by means of somatosensory evoked magnetic field with magnetoencephalography. RESULTS: The rCBF in the primary sensory area and the strength of the initial component of somatosensory evoked magnetic field (N20 m) were significantly reduced (P<0.01) and the second component (P30 m) was significantly augmented (P<0.05) in the lesioned cerebral hemisphere as compared with the nonlesioned hemisphere. The asymmetry indexes for N20 m were positively correlated (r=0.78) and those for P30 m were inversely correlated (r=-0.92) with asymmetry indexes for rCBF. CONCLUSIONS: In patients with either unilateral internal carotid artery or middle cerebral artery occlusion and minor neural impairments, there was a reduction of afferent signal and an augmentation of the secondary response of the neurons in the primary sensory area. This showed correlation with the severity of cortical ischemia.

Adolescent↗
PubMedDate not supplied

Using near-infrared spectroscopy to assess neural activation during object processing in infants.

The capacity to represent the world in terms of numerically distinct objects (i.e., object individuation) is a milestone in early cognitive development and forms the foundation for more complex thought and behavior. Over the past 10 to 15 yr, infant researchers have expended a great deal of effort to identify the origins and development of this capacity. In contrast, relatively little is known about the neural mechanisms that underlie the ability to individuate objects, in large part because there are a limited number of noninvasive techniques available to measure brain functioning in human infants. Recent research suggests that near-IR spectroscopy (NIRS), an optical imaging technique that uses relative changes in total hemoglobin concentration and oxygenation as an indicator of neural activation, may be a viable procedure for assessing the relation between object processing and brain function in human infants. We examine the extent to which increased neural activation, as measured by NIRS, could be observed in two neural areas known to be involved in object processing, the primary visual cortex and the inferior temporal cortex, during an object processing task. Infants aged 6.5 months are presented with a visual event in which two featurally distinct objects emerge successively to opposite sides of an occluder and neuroimaging data are collected. As predicted, increased neural activation is observed in both the primary visual and inferior cortex during the visual event, suggesting that these neural areas support object processing in the young infant. The outcome has important implications for research in cognitive development, developmental neuroscience, and optical imaging.

Cerebrovascular Circulation↗
PubMed2005

Neural activity associated with cognitive regulation in heroin users: A fMRI study.

Previous research has found heroin addicts to be impulsive. This study employed functional magnetic resonance imaging technology to investigate the differences between heroin addicts and normal controls in neural activity associated with cognitive regulation of behavior. Twenty-one Chinese men participated in this study, 11 of whom were newly admitted heroin-addicted patients and 10 of whom were healthy volunteers. In the experimental task, the subjects were required to first identify the correct directions of arrowheads and then give the opposite answers. Behaviorally, the heroin-dependent patients took a much shorter time to complete the more demanding second part of the task but committed more errors than the normal controls. This pattern of behavior, characteristic of people who are disinhibited and who tend to be impulsive, was consistent with previous reports of impulsivity observed in people who have abused heroin. The neural activity of the patients that was associated with performing the experimental task of cognitive regulation was different to that of the normal controls in terms of the pattern of prefrontal activation, the attenuation of activity in the anterior cingulate, and the additional recruitment of the right inferior parietal region. This study is the first that seeks to understand the neural activity associated with impulsive behavior in people who abuse heroin. The pattern of imaging data obtained resembled the pattern of data observed in immature brains attempting to exercise cognitive control of behavior. Further theoretical and clinical implications of the findings are discussed.

Adult↗