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PubMed2025

The Relationship Among Range Adaptation, Social Anhedonia, and Social Functioning: A Combined Magnetic Resonance Spectroscopy and Resting-State fMRI Study.

BACKGROUND AND HYPOTHESIS: Social anhedonia is a core feature of schizotypy and correlates significantly with social functioning and range adaptation. Range adaptation refers to representing a stimulus value based on its relative position in the range of pre-experienced values. This study aimed to examine the resting-state neural correlates of range adaptation and its associations with social anhedonia and social functioning. STUDY DESIGN: In study 1, 60 participants completed resting-state magnetic resonance spectroscopy and fMRI scans. Range adaptation was assessed by a valid effort-based decision-making paradigm. Self-reported questionnaires was used to measure social anhedonia and social functioning. Study 2 utilized 26 pairs of participants with high (HSoA) and low levels of social anhedonia (LSoA) to examine the group difference in range adaptation's neural correlates and its relationship with social anhedonia and social functioning. An independent sample of 40 pairs of HSoA and LSoA was used to verify the findings. STUDY RESULTS: Study 1 showed that range adaptation correlated with excitation-inhibition balance (EIB) and ventral prefrontal cortex (vPFC) functional connectivity, which in turn correlating positively with social functioning. Range adaptation was specifically determined by the EIB via mediation of ventral-medial prefrontal cortex functional connectivities. Study 2 found HSoA and LSoA participants exhibiting comparable EIB and vPFC connectivities. However, EIB and vPFC connectivities were negatively correlated with social anhedonia and social functioning in HSoA participants. CONCLUSIONS: EIB and vPFC functional connectivity is putative neural correlates for range adaptation. Such neural correlates are associated with social anhedonia and social functioning.

Humans↗
PubMed1994

Reduction of functional neuronal connectivity in long-term treated hypertension.

BACKGROUND AND PURPOSE: Anatomic imaging of patients with chronic well-treated hypertension has demonstrated dilatation of the lateral cerebral ventricles and left brain atrophy, whereas positron emission tomography has shown only subtle reductions in regional cerebral metabolic rates for glucose in some subcortical nuclei. To further explore the implications of the imaging changes, an analytic technique designed to determine functional neuronal connectivity between regions of interest (ROIs) was applied to the data on regional cerebral metabolic rates for glucose to determine if and where in the brain reduction of functional neuronal connectivity occurred. METHODS: Glucose metabolism was measured by positron emission tomography in 17 older men (age, 68 +/- 8 years) with well-controlled, noncomplicated hypertension of at least 10 years' duration and in 25 age- and sex-matched healthy control subjects. A significant correlation difference analysis was performed to determine which ROI pairs had reduced correlation coefficients (reduced functional neuronal connectivity). The vascular pattern of the reduction was determined after allocating the ROIs to their appropriate vascular territories. RESULTS: Compared with the control subjects, hypertensive patients had reduced correlation coefficients in cortical territories of the internal carotid arteries but not of the vertebrobasilar arteries. The border zone supplied by the middle and anterior cerebral arteries was most affected. CONCLUSIONS: The border zone between the anterior and middle cerebral arteries is vulnerable to ischemia from carotid pathology, systemic hypotension, or both. We hypothesize that although these hypertensive patients were "well controlled" and had normal neuropsychological tests, they may have experienced ischemia severe enough to cause border zone reduction of functional neuronal connectivity as a result of carotid pathology, antihypertensive medications, hypotensive episodes with a right-shifted autoregulation curve, or other factors in isolation or combination.

Aged↗
PubMed1990

Functional reciprocal connections of the rat entorhinal cortex and subicular complex with the medial frontal cortex: an in vivo intracellular study.

We used in vivo intracellular recording techniques in the rat in order to determine the properties of projections from the medial frontal cortex to the entorhinal cortex and subicular complex. Three main results were obtained. (1) A high proportion (65%) of neurons within the medial frontal cortex were antidromically activated at short latency (0.4-1.9 ms) by electrical stimulation of the entorhinal cortex or subicular complex. This provided physiological evidence for fast direct projections from the medial frontal cortex to the entorhinal cortex and subicular complex. (2) Clear excitatory postsynaptic potentials (EPSPs) were evoked in 8% of the cells within the entorhinal cortex, subicular complex, or adjacent cortices after electrical stimulation of the medial frontal cortex. (3) The most salient synaptic response was inhibition, as shown by the presence of inhibitory postsynaptic potentials (IPSPs) in 50% of the cells sampled. Similar results were obtained for the reciprocal pathway: 56% of the sampled cells in the entorhinal cortex or subicular complex responded with antidromic spikes to stimulation of the medial cortex; 4% of medial frontal neurons responded to stimulation of the entorhinal cortex or subicular complex with clear EPSPs, and 48% with IPSPs. The latencies of most synaptic responses, 15-25 ms, were inconsistent with monosynaptic activation. This suggests that oligosynaptic relays amplified the signal within or en route to their targets, and/or that cells with more slowly propagating axons were also present but not sampled by the intracellular electrodes. Finally, responsive fast-spiking cells (candidate inhibitory neurons) were encountered within target structures. The results provide evidence that these distant cortical regions are functionally connected in a reciprocal manner, and that both principal and inhibitory neurons are excited by this projection system.

Animals↗
PubMed1997

Abnormal access of axial vibrotactile input to deafferented somatosensory cortex in human upper limb amputees.

We studied two human subjects with total deafferentation of one upper limb secondary to traumatic multiple cervical root avulsions. Both subjects developed a phantom limb and underwent elective amputation of the paralyzed, deafferentated limb. Psychophysical study revealed in each subject an area of skin in the pectoral region ipsilateral to the amputation where vibrotactile stimulation (VS) elicited referred sensations (RS) in the phantom limb. Positron emission tomography was then used to measure regional cerebral blood flow changes during VS of the pectoral region ipsilateral to the amputation with RS and during VS of a homologous part of the pectoral region adjacent to the intact arm without RS. A voxel-based correlation analysis was subsequently used to study functional connectivity. VS of the pectoral region adjacent to the intact arm was associated with activation of the dorsal part of the contralateral primary somatosensory cortex (S1) in a position consistent with the S1 trunk area. In contrast, VS of the pectoral region ipsilateral to the amputation with RS was associated with activation of the contralateral S1 that extended from the level of the trunk representation ventrally over distances of 20 and 12 mm, respectively, in the two subjects. The area of S1 activated during VS of the digits in a normal control subject was coextensive with the ventral S1 region abnormally activated during VS of the ectopic phantom representation in the two amputees, suggesting that the deafferented digit or hand/arm area had been activated by sensory input from the pectoral region. Correlation analysis showed an abnormal pattern of intrinsic connectivity within the deafferented S1 hand/arm area of both amputees. In one subject, the deafferented S1 was functionally connected with 3 times as many S1 voxels as the normally afferented S1. This abnormal functional connectivity extended in both the rostrocaudal and ventrodorsal dimensions. The results demonstrate that sensory input delivered to the axial body surface may gain access to the S1 hand/arm area in some humans who have suffered extensive deafferentation of this area. The findings are consistent with the hypothesis that deafferentation of an area of S1 may result in activation of previously dormant inputs from body surfaces represented in immediately adjacent parts of S1. The results also provide evidence that changes in functional connectivity between these adjacent areas of the cortex play a role in the somatotopic reorganization.

Adult↗
PubMed1990

Alteration of the humoral immune response against muscle acetylcholine receptor by timed administration of alpha(1----3)dextran.

Previously, we discovered a profound idiotypic connectivity among antibodies involved in the immune responses to alpha(1----3)dextran (Dex) and the acetylcholine receptor (AChR). The present studies were undertaken to assess whether these connections represent functional pathways for regulation. It was found that immunization of mice with Dex prior to challenge with AChR reduced the subsequent response to receptor. The timing of the Dex administration was crucial for this effect with a 6-day delay between Dex and AChR being optimal whereas 0- or 12-day delays proved ineffective. The suppressive effect was specific for Dex, as treatment with the closely related, but idiotypically distinct, alpha(1----6)dextran did not diminish the anti-AChR response. Consistent with functional connections in the AChR-Dex network, an inverse relationship between anti-AChR and anti-Dex antibodies was observed in these studies. Thus, high levels of anti-AChR antibodies were associated with low levels of anti-Dex antibodies and vice versa. A similar relationship was observed for serum antibodies from patients with myasthenia gravis. To investigate the mechanism for the antigen-induced cross-regulation, hybridomas were constructed from spleen cells of mice treated 6 days earlier with Dex. A variety of idiotypes (Id), anti-Id and anti-anti-Id were obtained from this fusion. In addition, sera from day-6 mice were examined for the expression of key anti-Id which might provide regulation in the anti-AChR response. The main feature of these sera was the presence of EB3-7-reactive antibodies which did not bind Dex, and hence were not identical to J558. A monoclonal antibody with similar properties was obtained from the day-6 fusion (DX6) which had additional binding specificity for anti-AChR antibodies. Antibodies induced by Dex immunization appear to participate in the cross-regulation observed here. Understanding the mechanisms involved in this phenomenon will have important implications for network theory and for prediction of immune responsiveness.

Animals↗
PubMed2005

Fast orientation mapping from HARDI.

This paper introduces a new, accurate and fast method for fiber orientation mapping using high angular resolution diffusion imaging (HARDI) data. The approach utilizes the Fourier relationship between the water displacement probabilities and diffusion attenuated magnetic resonance (MR) signal expressed in spherical coordinates. The Laplace series coefficients of the water displacement probabilities are evaluated at a fixed distance away from the origin. The computations take under one minute for most three-dimensional datasets. We present orientation maps computed from excised rat optic chiasm, brain and spinal cord images. The developed method will improve the reliability of tractography schemes and make it possible to correctly identify the neural connections between functionally connected regions of the nervous system.

Algorithms↗
PubMed2003

Age-dependent appearance of an insulo-parietal cortical signal propagation that elicits a synchronized population oscillation in the parietal cortex in rats.

We investigated postnatal development of a functional connectivity from the gustatory insular cortex to the parietal cortex, which is known to contain many more neurons responding to oral somesthetic stimulation than the insular cortex, in slices obtained from 9-35-day-old rats. Field potentials were evoked by stimulation to the insular cortex. In the mature cortex, insular stimulation elicited a solitary field potential in both the insular and parietal cortices and, as the simulation continued, the initial solitary potential came to be followed by a population oscillation of field potential in the parietal cortex, but not in the insular cortex. In the immature cortex, by contrast, insular stimulation failed to evoke both the initial solitary potential and the subsequent population oscillation in the parietal cortex. In the mature cortex, application of neither thapsigargin nor AP5 prevented elicitation of the initial solitary potential in the parietal cortex, but either of them abolished the parietal oscillation. In immature cortex bathed with low Mg(2+) medium, insular stimulation elicited both the initial solitary potential and the subsequent parietal oscillation, which were both prevented by thapsigargin or AP5. Theses results suggest that the insular and parietal cortices are anatomically connected but functionally unlinked at an early postnatal stage, and that a functional linkage, dependent both on NMDA and ryanodine receptors, is formed during the first postnatal month.

2-Amino-5-phosphonovalerate↗
PubMed2005

Plasticity and reorganization of the uninjured brain.

Brain capacity is dependent not so much on the number of neurons but on the number of synaptic connections with functional connections that develop over a lifetime of genetic programming and life experiences. In the uninjured human brain, cortical reorganization that occurs in response to learning and experience is referred to as brain plasticity. Motor learning and complex environments result in a greater number of synapses and an increase in dendritic branching, whereas repetitive movements alone, in the absence of motor learning, do not. Learning and experience lead to an expansion of cortical representation, while failure to maintain training results in a contraction of cortical representation. In animals, loss of sensory peripheral afferent input results in an expansion of the forelimb representation of the intact adjacent cortex. Prolonged periods of peripheral nerve stimulation in both animals and humans can lead to reorganization of related sensorimotor cortical maps.

Animals↗
PubMed1987

[Structure of the functional transcallosal connections of the projection and association regions of the cat neocortex].

Homotopic responses of cortical projection areas were found to have smaller amplitude-temporal parameters and a greater stability as compared to the associative fields responses. These responses occur in local portions of the projection areas and the space of their recording enhances in the associative fields. Heterotopic responses in the projection fields occur in stimulation of a relatively lesser space of the symmetrical cortex, and the relative space of their recording is also smaller as compared to associative areas. The revealed regularities seem to reflect augmentation of interhemisphere interaction and complication of the structure of transcallosal connections of cortical associative areas. The structure of functional transcallosal connections of the projection areas seem to correspond to the principle of homotopy while the role of heterotopic transcallosal interactions enhances in the associative areas of the cortex.

Animals↗
PubMed2006

Optical mapping of spatiotemporal emergence of functional synaptic connections in the embryonic chick olfactory pathway.

In order to understand the functional maturation of the CNS, it is essential to first describe the functional maturation of sensory processing. We have approached this topic by following the ontogenetic patterning of neural circuit formation related to cranial and spinal sensory input using voltage-sensitive dye imaging. In previous studies, we have described the functional maturation of synapses in brainstem/midbrain neural circuits. Here, we elucidate the functional maturation of forebrain circuits by investigating neural networks related to the olfactory nerve (N. I) of chicken embryo. In the isolated N. I-olfactory bulb-forebrain preparation, application of electrical stimulation to N. I elicited excitatory postsynaptic potential (EPSP)-related slow optical signals in the olfactory bulb. The slow signal was mainly mediated by glutamate, and was easily fatigued with repetitive stimuli because of the immaturity of synapses in the embryonic CNS. Ontogenetically, the slow signal was detected from the 6-day embryonic stage, suggesting that functional synaptic connections between N. I and olfactory bulb emerge around this stage. In addition, from the 8-day embryonic stage, another response area was discriminated within the forebrain, which corresponded to the higher-ordered nucleus of the olfactory pathway. In comparison with our previous studies concerning the functional development of other cranial nerve-related sensory nuclei in the embryonic brainstem and midbrain, these results suggest that the olfactory pathway is functionally generated in the early stages of development when neural networks related to other visceral and somatic sensory inputs are also in the process of developing.

Aging↗
PubMed1988

[Function of connectives in text-understanding].

This experiment was conducted to investigate the function of connectives in text comprehension. Twenty six subjects were instructed to read six texts, each containing several target sentences. Eighteen target sentences were provided, and each of the subjects was presented half of the target sentences in their original form, i.e., with a connective (Connective condition, C), and the other half, without a connective (No-connective condition, NC). After reading, subjects were asked to recall all the target sentences. In recall, all the sentences preceding the target sentence were presented as a cue. Recall rate was higher for the C condition than for the NC condition. The result indicated that connectives facilitate text comprehension. This effect was seen most clearly in three connective categories called jyunsetsu (e.g., causality), gyakusetsu (i.e., adversity), hosoku (i.e., supplement) in Japanese.

Adult↗
PubMed2026

Dynamic Fusion of Genomics and Functional Network Connectivity in UK Biobank Reveals Schizophrenia-Related SNP Manifolds.

Many mental disorders show strong genetic influence. In parallel, dynamic functional network connectivity (dFNC) has shown high sensitivity to brain changes related to mental disorders. However, previous studies linking dFNC to genetics largely follow a paradigm to identify associations between one set of genetic factors and multiple sets of connectivity features from different dFNC states, ignoring the potential variability in genetic correlates across states. We propose a novel joint ICA (jICA)-based "dynamic fusion" framework to identify dynamically tuned genetic manifolds. A sliding window approach was utilized to estimate four dFNC states and compute subject-level state-average dFNC (sa-dFNC) features. The sa-dFNC features of each state were combined with schizophrenia risk single nucleotide polymorphisms (SNPs) within a jICA fusion framework, resulting in four parallel fusions in 32,861 individuals of the UK Biobank cohort. The extracted four sets of joint SNP-dFNC components were further validated for clinical relevance in a combined schizophrenia cohort of 820 individuals (348 patients). The similarity of SNP-dFNC components across four parallel fusions was evaluated as a measure of state variability. We observed a mixture of "state-invariant" and "state-variant" components for SNP and dFNC modalities. Particularly, the schizophrenia-related state-variant SNP components, or manifolds, complemented each other by capturing different SNPs involved in the same biological functions, revealing a partition of genomic risk particularly elicited by the dynamics of brain function. By augmenting the SNP factors to state-variant manifolds, this dynamic fusion framework promises additional insights into the underlying genetic risk of disease-related alterations in dynamic brain function.

Humans↗
PubMed2003

Developmental hemispheric asymmetry of interregional metabolic correlation of the auditory cortex in deaf subjects.

The functional connectivity of the auditory cortex might be altered in deaf subjects due to the loss of auditory input. We studied the developmental changes of functional connectivity of the primary auditory cortex (A1) in deaf children, deaf adults, and normal hearing adults by examining interregional metabolic correlation with (18)F-FDG PET. The mean activity of FDG uptake in the cytoarchitectonically defined A1 region served as a covariate in the interregional and interhemispheric correlation analysis. A1 metabolic rate was correlated with that of the ipsilateral superior temporal lobe in both normal and deaf subjects. This correlated area was larger in deaf children than in deaf or normal hearing adults. Concerning the functional connectivity of A1, a hemispheric asymmetry was found in that the extent of interregional correlation was clearly larger in the right than in the left hemisphere. This asymmetry was particularly pronounced in the younger deaf children. Both extent and asymmetry of the functional connectivity of A1 subsided with age. Contrary to this, a correlation between the left and the right primary auditory cortices was absent in younger deaf children but became apparent as they grew older.

Adolescent↗
PubMed2003

The Functional Brain Connectivity Workshop: report and commentary.

This report summarizes the presentations and discussions at a recent workshop entitled 'Functional Brain Connectivity', held in Düsseldorf, Germany. The aims of the workshop were to bring together researchers using different approaches to study connectivity in the brain, to enable them to share conceptual, mathematical and experimental ideas and to develop strategies for future work on functional integration. The main themes that emerged included: (1) the importance of anatomical knowledge in understanding functional interactions the brain; (2) the need to establish common definitions for terms used across disciplines; (3) the need to develop a satisfactory framework for inferring causality from functional imaging and electroencephalographic/magneto-encephalographic data; (4) the importance of analytic tools that capture the dynamics of neural interactions; and (5) the role of experimental paradigms that exploit the functional imaging of perturbations to cortical interactions.

Animals↗
PubMed2002

Hierarchical clustering to measure connectivity in fMRI resting-state data.

Low frequency oscillations, which are temporally correlated in functionally related brain regions, characterize the mammalian brain, even when no explicit cognitive tasks are performed. Functional connectivity MR imaging is used to map regions of the resting brain showing synchronous, regional and slow fluctuations in cerebral blood flow and oxygenation. In this study, we use a hierarchical clustering method to detect similarities of low-frequency fluctuations. We describe one measure of correlations in the low frequency range for classification of resting-state fMRI data. Furthermore, we investigate the contribution of motion and hardware instabilities to resting-state correlations and provide a method to reduce artifacts. For all cortical regions studied and clusters obtained, we quantify the degree of contamination of functional connectivity maps by the respiratory and cardiac cycle. Results indicate that patterns of functional connectivity can be obtained with hierarchical clustering that resemble known neuronal connections. The corresponding voxel time series do not show significant correlations in the respiratory or cardiac frequency band.

Adult↗
PubMed2005

A new approach to spatial covariance modeling of functional brain imaging data: ordinal trend analysis.

In neuroimaging studies of human cognitive abilities, brain activation patterns that include regions that are strongly interactive in response to experimental task demands are of particular interest. Among the existing network analyses, partial least squares (PLS; McIntosh, 1999; McIntosh, Bookstein, Haxby, & Grady, 1996) has been highly successful, particularly in identifying group differences in regional functional connectivity, including differences as diverse as those associated with states of awareness and normal aging. However, we address the need for a within-group model that identifies patterns of regional functional connectivity that exhibit sustained activity across graduated changes in task parameters. For example, predictions of sustained connectivity are commonplace in studies of cognition that involve a series of tasks over which task difficulty increases (Baddeley, 2003). We designed ordinal trend analysis (OrT) to identify activation patterns that increase monotonically in their expression as the experimental task parameter increases, while the correlative relationships between brain regions remain constant. Of specific interest are patterns that express positive ordinal trends on a subject-by-subject basis. A unique feature of OrT is that it recovers information about functional connectivity based solely on experimental design variables. In particular, there is no requirement by OrT to provide either a quantitative model of the uncertain relationship between functional brain circuitry and subject variables (e.g., task performance and IQ) or partial information about the regions that are functionally connected. In this letter, we provide a step-by-step recipe of the computations performed in the new OrT analysis, including a description of the inferential statistical methods applied. Second, we describe applications of OrT to an event-related fMRI study of verbal working memory and H(2)15O-PET study of visuo-motor learning. In sum, OrT has potential applications to not only studies of young adults and their cognitive abilities, but also studies of normal aging and neurological and psychiatric disease.

Adult↗
PubMed2006

Brain connectivity related to working memory performance.

Several brain areas show signal decreases during many different cognitive tasks in functional imaging studies, including the posterior cingulate cortex (PCC) and a medial frontal region incorporating portions of the medial frontal gyrus and ventral anterior cingulate cortex (MFG/vACC). It has been suggested that these areas are components in a default mode network that is engaged during rest and disengaged during cognitive tasks. This study investigated the functional connectivity between the PCC and MFG/vACC during a working memory task and at rest by examining temporal correlations in magnetic resonance signal levels between the regions. The two regions were functionally connected in both conditions. In addition, performance on the working memory task was positively correlated with the strength of this functional connection not only during the working memory task, but also at rest. Thus, it appears these regions are components of a network that may facilitate or monitor cognitive performance, rather than becoming disengaged during cognitive tasks. In addition, these data raise the possibility that the individual differences in coupling strength between these two regions at rest predict differences in cognitive abilities important for this working memory task.

Adult↗
PubMed2005

Long-term functional consequences of quinolinic acid striatal lesions and their alteration following an addition of a globus pallidus lesion assessed using pharmacological magnetic resonance imaging.

The present study tested the hypothesis that lesion to the rat globus pallidus (GP) can "normalize" the functioning of the basal ganglia-thalamocortical circuits in striatal-lesioned rats by assessing the functional connectivity of these regions using functional magnetic resonance imaging (fMRI). Changes in brain activation following systemic administration of amphetamine were assessed in (1) rats sustaining a unilateral lesion to the striatum, (2) rats sustaining a combined striatal and pallidal lesion, and (3) control rats. Striatal-lesioned rats showed attenuated cortical activation following amphetamine administration and lower correlations between the responses to amphetamine in different brain regions compared to control rats. Although the addition of an excitotoxic GP lesion failed to prevent striatal lesion-induced attenuation of cortical activation by amphetamine, it was effective in "normalizing" the correlations between the responses to amphetamine in the different areas. These results suggest that, although the GP lesion is ineffective in correcting the global changes in activity caused by the striatal lesion, it may have the capacity to partially restore alterations in functional connectivity resulting from the striatal lesion. These results are further discussed in view of our previous demonstration that lesions to the GP can reverse several behavioral deficits produced by a striatal lesion.

Amphetamine↗