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PubMed1996

Synaptic organizations and dynamical properties of weakly connected neural oscillators. I. Analysis of a canonical model.

We study weakly connected networks of neural oscillators near multiple Andronov-Hopf bifurcation points. We analyze relationships between synaptic organizations (anatomy) of the networks and their dynamical properties (function). Our principal assumptions are: (1) Each neural oscillator comprises two populations of neurons; excitatory and inhibitory ones; (2) activity of each population of neurons is described by a scalar (one-dimensional) variable; (3) each neural oscillator is near a nondegenerate supercritical Andronov-Hopf bifurcation point; (4) the synaptic connections between the neural oscillators are weak. All neural networks satisfying these hypotheses are governed by the same dynamical system, which we call the canonical model. Studying the canonical model shows that: (1) A neural oscillator can communicate only with those oscillators which have roughly the same natural frequency. That is, synaptic connections between a pair of oscillators having different natural frequencies are functionally insignificant. (2) Two neural oscillators having the same natural frequencies might not communicate if the connections between them are from among a class of pathological synaptic configurations. In both cases the anatomical presence of synaptic connections between neural oscillators does not necessarily guarantee that the connections are functionally significant. (3) There can be substantial phase differences (time delays) between the neural oscillators, which result from the synaptic organization of the network, not from the transmission delays. Using the canonical model we can illustrate self-ignition and autonomous quiescence (oscillator death) phenomena. That is, a network of passive elements can exhibit active properties and vice versa. We also study how Dale's principle affects dynamics of the networks, in particular, the phase differences that the network can reproduce. We present a complete classification of all possible synaptic organizations from this point of view. The theory developed here casts some light on relations between synaptic organization and functional properties of oscillatory networks. The major advantage of our approach is that we obtain results about all networks of neural oscillators, including the real brain. The major drawback is that our findings are valid only when the brain operates near a critical regime, viz. for a multiple Andronov-Hopf bifurcation.

Cell Death↗
PubMed1988

Surgical risk factors in total anomalous pulmonary venous connection.

Eighty-three patients underwent surgical correction of total anomalous pulmonary venous connection (TAPVC) between 1973 and 1986. There were 46 boys and 37 girls. Median age at operation was 60 days (1 to 240) and median weight 3.9 kg (1 to 22). The anatomic types encountered included infracardiac connection (16 patients), supracardiac connection (32) and pulmonary venous drainage connected directly to the coronary sinus (27). Mixed anomalous drainage or pulmonary venous return connected directly to the right atrium occurred in 8 patients. Diagnosis was established by cardiac catheterization and angiography (56 patients), clinical examination (3) and cross-sectional echocardiography alone in 24 of the last consecutive 28 patients. Pulmonary hypertension was present in 26 (55%) of those who underwent cardiac catheterization. The median pulmonary vascular resistance was 4.2 units/m2 (body surface area) for all the patients, whereas in those with infracardiac pulmonary venous connection the median value was 10 units/m2. The median interval between admission and operation was 72 hours. Surgical correction was performed using profound hypothermia and circulatory arrest in 68; for the remainder, conventional cardiopulmonary bypass with profound to moderate hypothermia was used. Ten patients developed 1 or more pulmonary hypertensive crises during the early postoperative period. These were diagnosed in 8 by direct pulmonary artery pressure measurement and in 2 by clinical examination. Late reoperation was necessary in 6 patients (10%). Analyses of risk factors for 30-day survival for all patients showed that the risk of early death was associated with the type of anomaly (infradiaphragmatic), occurrence of pulmonary hypertensive crises, year of the operation, set of the patient and pressure of preoperative congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1981

Cortical connections of the occipital lobe in the rhesus monkey: interconnections between areas 17, 18, 19 and the superior temporal sulcus.

Using both anterograde and retrograde tracing techniques, the present report investigates the cortical connections of the lateral, median and ventral portions of areas 17 and 18 in the rhesus monkey. All parts of area 17 are found to send topographically organized connections to a strip of prestriate cortex which closely corresponds to area OB of Bonin and Bailey or area 18 of Vogt and Vogt. Striate-recipient area 18, in turn, is topographically connected with an anterior prestriate zone, whose borders coincide with those of area OA or 19. These efferents are topographically organized, with connections from the medial surface of area 18 directed to lateral parts of area 19. In addition, certain parts of area 18, in the annectent gyrus and the inferior occipital sulcus, send 'crossed', dorsoventral connections to ventral and dorsal parts of area 19, respectively. Both areas 17 and 18 project in a topographic fashion to a distinct region in the caudal part of the superior temporal sulcus. Topographically organized reciprocal connections are also found from area 18 to 17, from area 19 to 18, and from the superior temporal sulcus to both areas 17 and 18.

Animals↗
PubMed1990

The ipsilateral corticocortical connections of area 7 with the frontal lobe in the monkey.

The corticocortical connections between area 7 and the frontal lobe have been studied in the monkey. Injections of HRP were made into area 7 of the parietal lobe or into area 46 in the walls of the principal sulcus. The two subdivisions of area 7, 7a or PG and 7b or PF, are connected with different parts of the frontal lobe, and each subdivision is connected with two distinct areas. Area 7b, PF, is connected in a well organized and somatotopic manner with the lower premotor area and with the lower part of area 46, below the fundus of the principal sulcus. Area 7a, PG, is connected with area 8a and with the upper part of area 46, above the fundus of the principal sulcus; it is suggested that the lower part of area 8a and the posterior part of area 46 are related to the central visual field, while the medial part of area 8a and the anterior part of area 46 are related to the periphery of the visual field. The corticocortical connections between area 7 and the frontal lobe are reciprocal and those passing from area 7 to the frontal lobe are 'feed-forward' and those to area 7 are 'feed-back'.

Animals↗
PubMed1990

Brainstem connections of the rostral ventral respiratory group of the rat.

The pontomedullary connections of the rostral division of the ventral respiratory group (rVRG), the largest medullary population of inspiratory bulbospinal and propriobulbar neurons, were identified in the rat by retrograde and anterograde tracing techniques. These experiments revealed that: (i) the Kölliker-Fuse nucleus, portions of the medial and lateral parabrachial nuclei, and all levels of the ipsilateral and contralateral VRG complex have dense reciprocal connections with the rVRG; (ii) the lateral paragigantocellular nucleus has reciprocal but less dense connections with rVRG; (iii) portions of the nucleus of the solitary tract have prominent projections to, but weaker inputs from rVRG; (iv) the raphe, magnocellular tegmental field and spinal trigeminal nuclei have minor projections to rVRG and receive only sparse inputs from rVRG, and; (v) the retrotrapezoid nucleus, pontine lateral tegmental field and area postrema each have only efferent projections to rVRG. These findings are consistent with previous studies of pontomedullary connections of rVRG in the cat, and further document the extensive reciprocal connections between principal respiratory groups. These connections are likely to be important for generation of the respiratory pattern, for the coordination of effector responses of the cranial and spinal respiratory motor neurons to afferent stimuli, and coordination of the central respiratory and cardiovascular control systems.

Animals↗
PubMed1994

Interhemispheric connections in neonatal owl monkeys (Aotus trivirgatus) and galagos (Galago crassicaudatus).

Interhemispheric connections were studied by injecting a mixture of horseradish peroxidase (HRP) and wheatgerm agglutinin conjugated with horseradish peroxidase (WGA-HRP) into multiple sites in dorsolateral occipital and parietal cortex of one cerebral hemisphere of three galagos (Galago crassicaudatus) and two owl monkeys (Aotus trivirgatus) within seven days of birth. Cortex was either separated from the rest of the brain, flattened and cut parallel to the surface to aid reconstructing surface-view patterns of labeled neurons and processes, or cut in standard coronal or parasagittal planes to better reveal laminar patterns of connections. In both primate species, the surface-view pattern of callosal connections in infants was remarkably adult-like. In infant owl monkeys, callosal connections were concentrated along the margin of area 18 with area 17, and only a few labeled cells were found within area 17. Other visual areas including the second visual area, V-II, and the middle temporal visual area, MT, had patchy distributions of labeled neurons that extended over large parts of the visual field representations. Primary motor, auditory, and somatosensory fields also had patchy distributions of labeled neurons, with regions of areas 3b and adjoining somatosensory fields having few callosal connections in portions that appeared to correspond with representations of the hand and foot. Results were very similar in galagos, except that newborn galagos, as in adults, had a patchy distribution of callosally projecting neurons that extended well within area 17. Furthermore, the labeled neurons were concentrated in patches that aligned with the cytochrome oxidase blobs of area 17. Finally, callosal connections were concentrated in cytochrome oxidase poor regions of area 3b.

Animals↗
PubMed1994

Neonatal frontal cortical lesions in rats alter cortical structure and connectivity.

Rats were given frontal cortical lesions at day 1 or 10 of life. Later, as adults, they were either: (1) processed with Golgi-Cox in order to analyze cortical dendritic arborization; (2) given injections of True Blue into the parietal or visual cortex, or (3) given injections of [3H]leucine into the substantia nigra. An additional group of normal rats were given injections of fluorescent dyes into the cortex on day 4 or 10 of life. The main findings were that (1) adult hemispheres with day 10 lesions had greater dendritic arbor than normal hemispheres, (2) adult hemispheres with day 1 lesions had reduced dendritic branching relative to normal hemispheres, (3) adult rats with day 10 lesions had no obvious abnormalities in cortical connections, (4) adult rats with day 1 lesions had abnormal thalamo-cortical, amygdalo-cortical, and nigro-cortical connections, and (5) many of these abnormal connections were present in the brains of 4-day-old normal rats. Since the 'abnormal' connections in the very early frontal operates were present in day 4 animals, it appears that they result from the failure of exuberant connections to retract after the lesions. The increased dendritic growth in day 10 operates does not appear related to qualitative changes in cortical afferents or efferents and may related to increased intrinsic cortical connectivity. Since rats with day 10 lesions have previously been shown to exhibit significant recovery of function, it is possible that the increased dendritic arborization is supporting the functional restitution.

Aging↗
PubMed1990

Formation of electrical connections between cultured identified neurons and muscle fibers of the snail Helisoma.

We studied the formation of connections between identified neurons removed from the buccal ganglion of the snail Helisoma and muscle fibers dissociated from the buccal mass. Three types of identified neurons--B19, B5, and B4--were placed into cell culture and muscle fibers from the supralateral tensor muscle (SLT), normally innervated by B19, were subsequently plated adjacent to the neuronal cell bodies. Growth cones from the neurons contacted the muscle fibers within 6-12 h after isolation. Simultaneous intracellular recordings from the neuronal cell bodies and muscle fibers after 4 days in culture indicated that the neurons had formed electrical connections with the fibers. All 3 types of neurons coupled to the muscle fibers but displayed differing probabilities and strengths of connections. The role of growth cone contact in the formation of these connections was tested by plating muscle fibers onto fields of neurites after neuronal growth had stopped. Under these conditions, neurons still became electrically coupled to the muscle fibers, but the strength of these connections differed from those formed by neurons and fibers that were plated simultaneously. Thus, quantitative characteristics of electrical connections formed between cultured Helisoma neurons and dissociated muscle fibers are influenced by neuronal identity and the timing of neuronal contacts.

Animals↗
PubMed1993

Development of neural connections between visual cortex and transplanted lateral geniculate nucleus in rats.

The development of neural connections between transplanted lateral geniculate nucleus (LGN) and host visual cortex (VC) was studied in slice preparations obtained from rat brain in which a fetal (embryonic day 15-17) rat LGN was transplanted to the white matter underlying the VC of a neonate rat (postnatal day 0-1). Placing a fluorescent dye (DiI) in the transplant of the fixed slices revealed that retrogradely labeled cortical cells projecting to the transplant were broadly distributed through layers II to VI at 1 week after transplantation. Three weeks after transplantation, these cells were virtually confined to layer VI. Likewise, anterograde labeling showed that cells in the transplant sent axons up to layer I with a few branches at 1 week after transplantation, while the axons were found to terminate at layer IV with many arborizations at 3 weeks after transplantation. These observations were supported by electrophysiological studies. Analysis of the antidromic responses of the cortical cells to stimulation of the transplant showed that the efferent cells projecting to the transplant were broadly distributed in layers II-VI at 1 week after transplantation, while they were virtually restricted to layer VI at 3 weeks after transplantation. Current source-density analysis of the field potentials and intracellular analysis of the synaptic potentials in the cortical cells demonstrated that geniculocortical connections were broadly established in layers II-VI at 1 week after transplantation, and were localized to layer IV and VI at 3 weeks after transplantation. These results suggest that the development of neural connections between transplanted LGN and host VC is characterized by an initial broad distribution of afferent and efferent connections without laminar specificity, and by later selection of appropriate connections to yield lamina-specific connections comparable to those in normal adult VC.

Action Potentials↗
PubMed1985

Afferent and efferent connections of the medial preoptic area in the rat: a WGA-HRP study.

Afferent and efferent connections of the medial preoptic area including medial preoptic nucleus (MP) and periventricular area at the MP level were examined using WGA-HRP as a marker. Injections were performed by insertion of micropipette containing (1) small amount of HRP powder or (2) dryed HRP solution for 24 to 48 hr until the fixation or for 5 min respectively. Dorsal and ventral approaches of injection micropipettes were performed and the results were compared. Previously reported reciprocal connections with lateral septum, bed nucleus of the stria terminalis, medial amygdaloid nucleus, lateral hypothalamic nucleus, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, arcuate nucleus, supramammillary nucleus, central gray at the mesencephalon, raphe dorsalis, raphe medianus, and lateral parabrachial nucleus have been confirmed. In addition, we found reciprocal connections with septo-hypothalamic nucleus, amygdalo-hipocampal nucleus, subiculum, parafascicular thalamic nucleus, posterior thalamic nucleus at the caudo-ventral subdivision, median preoptic nucleus, lateral preoptic nucleus, anterior hypothalamic nucleus, periventricular area at the caudal hypothalamic level, dorsomedial hypothalamic nucleus, posterior hypothalamic nucleus, dorsal and ventral premammillary nucleus, lateral mammillary nucleus, peripeduncular nucleus, periventricular gray, ventral tegmental area, interpeduncular nucleus, nucleus raphe pontis, nucleus raphe magnus, pedunculo-pontine tegmental nucleus, gigantocellular reticular nucleus and solitary tract nucleus. The areas which had only efferent connections from MP were accumbens, caudate putamen, ventral pallidum, substantia innominata, lateral habenular nucleus, paratenial thalamic nucleus, paraventricular thalamic nucleus, mediodorsal thalamic nucleus, reuniens thalamic nucleus, median eminence, medial mammillary nucleus, subthalamic nucleus, pars compacta of substantia nigra, oculomotor nucleus, red nucleus, laterodorsal tegmental nucleus, reticular tegmental nucleus, cuneiform nucleus, nucleus locus coeruleus, and dorsal motor nucleus of vagus among which substantia innominata and median eminence were previously reported. Efferent connections to the nucleus of Darkschewitsch, interstitial nucleus of Cajal, dorsal tegmental nucleus, ventral tegmental nucleus, vestibular nuclei, nucleus raphe obsculus were very weak or abscent in the ventral approach while they were observed in dorsal approach. Previously reported afferent connections from dorsal tegmental nucleus, cuneiform nucleus, and nucleus locus ceruleus were not detected in this study.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

The feasibility of connecting physician offices to a state-level tobacco quit line.

BACKGROUND: Telephone counseling for tobacco cessation is an effective and evidence-based approach to address tobacco use. The wide dissemination of region- and state-level quit lines has been a major goal for public health agencies. However, connecting patients in primary care settings to state-level quit lines has not been evaluated. METHODS: Observational study describing two methods (fax referral and providing a brochure) to connect private physician offices with a state-level quit line in Oregon. This study describes the resources required to create a clinical pathway for the 5A's in primary care (ask, advise, assess, assist, and arrange) using a state-level telephone quit line as an intervention for cessation in primary care clinics sharing a common electronic medical record system, focusing on the costs and generalizability of this approach. RESULTS: Of the 15,662 smokers identified in 19 primary care clinics, 745 patients were referred to the Oregon Tobacco Quit Line during the study period. The program cost in the first year was $15 to $22 per patient connected with the quit line; in subsequent years, the cost decreased to $4 to $6 per quit-line connection. CONCLUSIONS: Connecting private physician offices to a state-level quit line is feasible, can be accomplished at low cost with minimal use of resources, and may be cost effective. Regional, state, and local tobacco quit lines should consider a physician office "quit-line connection" as a practical approach to increase utilization.

Adult↗
PubMedDate not supplied

Incorporating anatomically realistic cellular-level connectivity in neural network models of the rat hippocampus.

The specific connectivity patterns among neuronal classes can play an important role in the regulation of firing dynamics in many brain regions. Yet most neural network models are built based on vastly simplified connectivity schemes that do not accurately reflect the biological complexity. Taking the rat hippocampus as an example, we show here that enough quantitative information is available in the neuroanatomical literature to construct neural networks derived from accurate models of cellular connectivity. Computational simulations based on this approach lend themselves to a direct investigation of the potential relationship between cellular connectivity and network activity. We define a set of fundamental parameters to characterize cellular connectivity, and are collecting the related values for the rat hippocampus from published reports. Preliminary simulations based on these data uncovered a novel putative role for feedforward inhibitory neurons. In particular, "mopp" cells in the dentate gyrus are suitable to help maintain the firing rate of granule cells within physiological levels in response to a plausibly noisy input from the entorhinal cortex. The stabilizing effect of feedforward inhibition is further shown to depend on the particular ratio between the relative threshold values of the principal cells and the interneurons. We are freely distributing the connectivity data on which this study is based through a publicly accessible web archive (http://www.krasnow.gmu.edu/L-Neuron).

Animals↗
PubMed2006

Partially enhanced thalamocortical functional connectivity in autism.

Based on evidence for thalamic abnormalities in autism, impairments of thalamocortical pathways have been suspected. We examined the functional connectivity between thalamus and cerebral cortex in terms of blood oxygen level dependent (BOLD) signal cross-correlation in 8 male participants with high-functioning autism and matched normal controls, using functional MRI during simple visuomotor coordination. Both groups exhibited widespread connectivity, consistent with known extensive thalamocortical connectivity. In a direct group comparison, overall more extensive connectivity was observed in the autism group, especially in the left insula and in right postcentral and middle frontal regions. Our findings are inconsistent with the hypothesis of general underconnectivity in autism and instead suggest that subcortico-cortical connectivity may be hyperfunctional, potentially compensating for reduced cortico-cortical connectivity.

Adolescent↗
PubMed2006

Disturbed functional connectivity in brain tumour patients: evaluation by graph analysis of synchronization matrices.

OBJECTIVE: Cerebral functions are based on the functional interactions between multiple distinct specialized regions of the brain. Functional interactions require anatomical connections as well as the synchronization of brain oscillations. The present work aims at evaluating the impact of brain tumours on spatial patterns of functional connectivity of the brain measured at rest by MEG. METHODS: We analyzed the statistical dependency (by computing the synchronization likelihood (SL, a measure of generalized synchronization)) between MEG signals at rest, in 17 patients with a brain tumour and in 15 healthy controls. Following an approach that derives from graph theory, we also analyzed the architectural properties of the networks by computing two parameters from the SL matrix, the cluster coefficient C and the characteristic path length L. RESULTS: Alterations in synchronization levels were found in the patients and were not focal but involved intra-hemispheric connectivity. Effects were different considering the frequencies sub-bands, predominating in a decrease in high frequencies bands for long-distance connections and an increase in slower bands for local connectivity. In addition, graph analysis reveals changes in the normal "small-world" network architecture in addition to changes in synchronization levels with some differences according to the studied frequency sub-bands. CONCLUSIONS: Brain tumours alter the functional connectivity and the "network" architecture of the brain. These alterations are not focal and effects are different considering the frequencies sub-bands. SIGNIFICANCE: These neurophysiological changes may contribute to the cognitive alterations observed in patients with brain tumours.

Adult↗
PubMed2005

Functional connectivity with anterior cingulate and orbitofrontal cortices during decision-making.

Recent neuroscience research is beginning to discover the brain regions involved in decision-making under uncertainty, but little is known about whether or how these regions functionally interact with each other. Here, we used event-related functional magnetic resonance imaging to examine both changes in overall activity and changes in functional connectivity during risk-taking. Results showed that choosing high-risk over low-risk decisions was associated with increased activity in both anterior cingulate and orbitofrontal cortices. Connectivity analyses revealed that largely distinct, but somewhat overlapping, cortical and subcortical regions exhibited significant functional connectivity with anterior cingulate and orbitofrontal cortices. Additionally, connectivity with the anterior cingulate in some regions, including the orbitofrontal cortex and nucleus accumbens, was modulated by the decision participants chose. These findings (1) elucidate large networks of brain regions that are functionally connected with both anterior cingulate and orbitofrontal cortices during decision-making and (2) demonstrate that the roles of orbitofrontal and anterior cingulate cortices can be functionally differentiated by examining patterns of connectivity.

Adult↗
PubMed2005

Late neurodevelopmental outcome after repair of total anomalous pulmonary venous connection.

Objective We sought to define the neurodevelopmental status of school-aged survivors of total anomalous pulmonary venous connection repaired during infancy. Methods All school-aged survivors of total anomalous pulmonary venous connection repair performed at a single institution were eligible. Thirty children returned for neurologic examination and neurodevelopmental testing. Results The median age at total anomalous pulmonary venous connection repair was 16 days (range, 1-141 days), and age at testing was 11 years (range, 6-19 years). Pulmonary venous return was supracardiac in 14 patients, infracardiac in 12 patients, cardiac in 3 patients, and mixed in 1 patient. Preoperative obstructed total anomalous pulmonary venous connection was present in 6 patients. Circulatory arrest was used in all repairs, with a median duration of 35 minutes (range, 17-55 minutes). At follow-up, microcephaly (head circumference <5%) was present in 28%. Neuromuscular examination was suspect or abnormal in 27%. Mean Full-scale IQ (95.3 +/- 18.5) and Verbal IQ (98.6 +/- 20.2) were not different from population norms, but Performance IQ (92.3 +/- 16.9) was significantly lower than population norms ( P = .02). Fine motor skills and visual-motor coordination were significantly impaired ( P < .01 for Grooved Pegboard and Test of Visual-Motor Integration). Patients with total anomalous pulmonary venous connection also had difficulty with tests of attention (Test of Everyday Attention for Children, P < .01), but results of tests of memory function were not significantly different from population norms. Conclusions School-aged survivors of infant total anomalous pulmonary venous connection repair exhibit a significant incidence of neurodevelopmental difficulties. Fine motor function, visual-motor integration, and attention are the most commonly affected domains. Evaluation of these children is indicated to identify those who are at risk for learning disabilities and who could benefit from early intervention.

Actuarial Analysis↗
PubMed2004

Amygdalar interhemispheric functional connectivity differs between the non-depressed and depressed human brain.

The amygdalae are important, if not critical, brain regions for many affective, attentional and memorial processes, and dysfunction of the amygdalae has been a consistent finding in the study of clinical depression. Theoretical models of the functional neuroanatomy of both normal and psychopathological affective processes which posit cortical hemispheric specialization of functions have been supported by both lesion and functional neuroimaging studies in humans. Results from human neuroimaging studies in support of amygdalar hemispheric specialization are inconsistent. However, recent results from human lesion studies are consistent with hemispheric specialization. An important, yet largely ignored, feature of the amygdalae in the primate brain--derived from both neuroanatomical and electrophysiological data--is that there are virtually no direct interhemispheric connections via the anterior commissure (AC). This feature stands in stark contrast to that of the rodent brain wherein virtually all amygdalar nuclei have direct interhemispheric connections. We propose this feature of the primate brain, in particular the human brain, is a result of influences from frontocortical hemispheric specialization which have developed over the course of primate brain evolution. Results consistent with this notion were obtained by examining the nature of human amygdalar interhemispheric connectivity using both functional magnetic resonance imaging (FMRI) and positron emission tomography (PET). We found modest evidence of amygdalar interhemispheric functional connectivity in the non-depressed brain, whereas there was strong evidence of functional connectivity in the depressed brain. We interpret and discuss the nature of this connectivity in the depressed brain in the context of dysfunctional frontocortical-amygdalar interactions which accompany clinical depression.

Adult↗
PubMed2004

Modulation of effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis.

fMRI and structural equation modeling (SEM) were used to study effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis (MS), while performing paced auditory serial addition test (PASAT), a sensitive task to reveal subtle cognitive impairments related to working memory and information speed processing. The path model used for SEM included bilateral connections between left and right BA 46, left and right BA 40, left and right anterior cingulate cortex (ACC), left BA 44 and left BA 40, right BA 44 and right BA 40, and unidirectional ipsilateral connections from BA 46 to BA 44, from ACC to BA 46, and from ACC to BA 44. Experimental data from the two groups fit accurately the working memory model, in patients [chi20(2) = 13, P = 0.877] as well as in controls [chi20(2) = 13.54, P = 0.853]. The omnibus test indicated a significant difference of model fits in patients and in controls [chi40(2) = 160.07, P < 0.0001]. Connectivity strengths from right BA 46 to left BA 46, from left ACC to left BA 46 were lower in patients than in controls, and higher from right ACC to right BA 46, from left to right and from right to left ACC (stacked model). Effective connectivity inside the working memory network appears altered in patients at the earliest stage of MS. Modulation of effective connectivity is present in patients inside the executive subsystems of working memory, and could be related to adaptive cognitive control processes that may limit the clinical manifestation of MS.

Acoustic Stimulation↗