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PubMed1995

Effects of local connectivity on striatal function: stimulation and analysis of a model.

Neuronal population activity was investigated by computer simulation of a network model based on the neostriatum. Three network topologies were studied, based on different assumptions about the synaptic connectivity among medium spiny neurons. In all networks neurons were interconnected by inhibitory synapses. The connectivity was either symmetric, in which case all connections between cells were reciprocal and equal in strength; or asymmetric. Simulations showed that networks with symmetric connectivity receiving randomly distributed afferent excitation produced stationary spatial activity patterns. In contrast, asymmetric connectivity in homogeneous networks produced slow travelling-wave activity across the network. We suggest that the shape of the medium spiny neurons is an important determinant of synaptic connectivity and that changes in the shape of these neurons caused by Huntington's disease would result in asymmetric connectivity. Slow travelling-wave activity produced by asymmetric connectivity in the neostriatum could explain some aspects of the choreic movement and some electromyographic features seen in Huntington's patients.

Computer Simulation↗
PubMed1994

Rat posterior parietal cortex: topography of corticocortical and thalamic connections.

Anatomical and functional findings support the contention that there is a distinct posterior parietal cortical area (PPC) in the rat, situated between the rostrally adjacent hindlimb sensorimotor area and the caudally adjacent secondary visual areas. The PPC is distinguished from these areas by receiving thalamic afferents from the lateral dorsal (LD), lateral posterior (LP), and posterior (Po) nuclei, in the absence of input from the ventrobasal complex (VB) or dorsal lateral geniculate (DLG) nuclei. Behavioral studies have demonstrated that PPC is involved in spatial orientation and directed attention. In the present study we used fluorescent retrograde axonal tracers primarily to investigate the cortical connections of PPC, in order to determine the organization of the circuitry by which PPC is likely to participate in these functions, and also to determine how the topography of its thalamic connections differs from that of neighboring cortical areas. The cortical connections of PPC involve the ventrolateral (VLO) and medial (MO) orbital areas, medial agranular cortex (area Fr2), portions of somatic sensory areas Par1 and Par2, secondary visual areas Oc2M and Oc2L, auditory area Te1, and retrosplenial cortex. The secondary visual areas Oc2L and Oc2M have cortical connections which are similar to those of PPC, but are restricted within orbital cortex to area VLO, and within area Fr2 to its caudal portion, and do not involve auditory area Te1. The cortical connections of hindlimb cortex are largely restricted to somatic sensory and motor areas. Retrosplenial cortex, which is medially adjacent to PPC, has cortical connections that are prominent with visual cortex, do not involve somatic sensory or auditory cortex, and include the presubiculum. We conclude that PPC is distinguished by its pattern of cortical connections with the somatic sensory, auditory and visual areas, and with areas Fr2, and VLO/MO, in addition to its exclusive thalamic connectivity with LD, LP and Po. Because recent behavioral studies indicate that PPC, Fr2 and VLO are involved in directed attention and spatial learning, we suggest that the interconnections among these three cortical areas represent a major component of the circuitry for these functions in rats.

Animals↗
PubMed1996

Neuronal connections of orbital cortex in rats: topography of cortical and thalamic afferents.

The cortical and thalamic afferent connections of rat orbital cortex were investigated using fluorescent retrograde axonal tracers. Each of the four orbital areas has a distinct pattern of connections. Corticocortical connections involving the ventral and ventrolateral orbital areas are more extensive than those of the medial and lateral orbital areas. The medial orbital area has cortical connections with the cingulate, medial agranular (Fr2) and posterior parietal (PPC) cortices. The ventral orbital area has connections with the cingulate area, area Fr2, secondary somatic sensory area Par2, PPC, and visual areas Oc2M and Oc2L. The ventrolateral orbital area (VLO) receives cortical input from insular cortex, area Fr2, somatic sensory areas Par1 and Par2, PPC and Oc2L. The lateral orbital area has cortical connections limited to the agranular and granular insular areas, and Par2. Thalamic afferents to the four orbital fields are also topographically organized, and are focused in the submedial and mediodorsal nuclei. The ventrolateral orbital area receives input from the entirety of the submedial nucleus, whereas the other orbital areas receive input from its periphery only. Each orbital area is connected with a particular segment of the mediodorsal nucleus. The medial orbital area receives its principal thalamic afferents from the parataenial nucleus, the dorsocentral portion of the mediodorsal nucleus, and the ventromedial portion of the submedial nucleus. The ventral orbital area receives input from the lateral segment of the mediodorsal nucleus, the rostromedial portion of the submedial nucleus, and the central lateral nucleus. Thalamic afferents to the ventrolateral orbital area arise from the entirety of the submedial nucleus and from the lateral segment of the mediodorsal nucleus. The lateral orbital area receives thalamic afferents from the central segment of the mediodorsal nucleus, the ventral portion of the submedial nucleus, and the ventromedial nucleus. The paraventricular, ventromedial, rhomboid and reuniens nuclei also provide additional input to the four orbital areas. The connections of the ventrolateral orbital area are interpreted in the context of its role in directed attention and allocentric spatial localization. The present findings provide anatomical support for the view that areas Fr2, PPC and VLO comprise a cortical network mediating such functions.

Animals↗
PubMed1993

Endothelial cell connecting filaments anchor endothelial cells to the subjacent elastic lamina in the developing aortic intima of the mouse.

The ultrastructural association of endothelial cells with the subjacent elastic lamina was investigated in the developing mouse aorta by electron microscopy. In the 5-day postnatal aorta, extensive filament bundles extend along the subendothelial matrix connecting the endothelial cells to the underlying elastic lamina. The connecting filaments form lateral associations with the abluminal surface of the endothelial cells in regions of membrane occupied by membrane-associated dense plaques. On the intracellular face of each plaque, the termini of stress fibers penetrate and anchor to the cell membrane in alignment with the extracellular connecting filaments. Both the stress fibers and the connecting filaments are oriented parallel to the longitudinal axis of the vessel. High magnification electron micrographs of individual endothelial cell connecting filaments reveal features similar to those of elastin-associated microfibrils. Each connecting filament consists of a 9-10 nm linear core with an electron-lucent center and peripheral spike-like projections. From the filaments, small thread-like extensions span laterally, linking the filaments into a loose bundle and anchoring them to the endothelial cell membrane and the surface of the elastic lamina. The filaments also appear heavily coated with electron-dense material; often with some degree of periodicity along the filament length. During development, the number of endothelial cell connecting filaments decreases as the elastic lamina expands and the subendothelial matrix is reduced. In the aortic intima of mature mice, the elastic lamina is closely apposed to the abluminal surface of the endothelial cell and no connecting filaments are seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗
PubMed1995

Dynamics and bifurcations of two coupled neural oscillators with different connection types.

In this paper we present an oscillatory neural network composed of two coupled neural oscillators of the Wilson-Cowan type. Each of the oscillators describes the dynamics of average activities of excitatory and inhibitory populations of neurons. The network serves as a model for several possible network architectures. We study how the type and the strength of the connections between the oscillators affect the dynamics of the neural network. We investigate, separately from each other, four possible connection types (excitatory-->excitatory, excitatory-->inhibitory, inhibitory-->excitatory, and inhibitory-->inhibitory) and compute the corresponding bifurcation diagrams. In case of weak connections (small strength), the connection of populations of different types lead to periodic in-phase oscillations, while the connection of populations of the same type lead to periodic anti-phase oscillations. For intermediate connection strengths, the networks can enter quasiperiodic or chaotic regimes, and can also exhibit multistability. More generally, our analysis highlights the great diversity of the response of neural networks to a change of the connection strength, for different connection architectures. In the discussion, we address in particular the problem of information coding in the brain using quasiperiodic and chaotic oscillations. In modeling low levels of information processing, we propose that feature binding should be sought as a temporally coherent phase-locking of neural activity. This phase-locking is provided by one or more interacting convergent zones and does not require a central ¿top level¿ subcortical circuit (e.g., the septo-hippocampal system). We build a two layer model to show that although the application of a complex stimulus usually leads to different convergent zones with high frequency oscillations, it is nevertheless possible to synchronize these oscillations at a lower frequency level using envelope oscillations. This is interpreted as a feature binding of a complex stimulus.

Animals↗
PubMed1997

Corticocortical connections between visual areas 17 and 18a of the rat studied in vitro: spatial and temporal organisation of functional synaptic responses.

Much is known about the anatomy of corticocortical connections, yet little is known concerning their physiology. In order to have access to the synaptic and temporal aspects of the activity elicited through corticocortical connections, we developed an in vitro approach on slices of rat visual cortex. We used extracellular recordings of field potentials combined with electrical stimulation to localise regions of areas 17 and 18a that are connected. We found that corticocortical connections between areas 17 and 18a can be preserved in 500 microm thick slices, with a focus of activity separated from the stimulating electrode by 1.5 mm to more than 3 mm. The potentials elicited in one area after stimulation of its neighbour displayed fast events, corresponding to action potentials, and slow events, corresponding to synaptic potentials. Intracellular recordings showed that the earliest synaptic responses consisted of monosynaptic excitatory potentials. Measurement of response latency showed that axons involved in both feedforward and feedback corticocortical connections are slowly conducting (0.3-0.8 m/s). Conduction velocity for antidromically activated cells was not significantly different for the two sets of connections. In an attempt to establish the spatial organisation of functional synaptic inputs, field potential recordings were performed in the different cortical layers and used to establish current source density (CSD) graphs along the depth axis. The CSD maps obtained were found to be somewhat variable from one case to another. It is suggested that this variability results from the use of electrical stimulation, which activates axons that are both afferent and efferent to a given cortical area. The field potentials are therefore likely to contain responses that correspond to the activity mediated by the intrinsic collaterals mixed in variable amount with responses produced by corticocortical synapses. With this restriction in mind, it is suggested that, after stimulation of the supragranular layers, the functional synaptic inputs of feedforward connections are concentrated in layer 4 and the bottom of layer 3, while those of feedback axons involve mainly the upper part of the supragranular layers. The intrinsic collaterals of the neurones participating in corticocortical connections seem also to provide the bulk of their inputs to the upper part of the supragranular layers. The laminar pattern of activity obtained after infragranular layer stimulation was comparable to that obtained after supragranular layer stimulation, except for the addition of a supplementary region of activated synapses in the infragranular layers.

Animals↗
PubMed1979

Laminar origins and terminations of cortical connections of the occipital lobe in the rhesus monkey.

Cortical connections within the occipital lobe (areas 17, 18 and 19) of the rhesus monkey are investigated with the autoradiographic and horseradish peroxidase procedures. Two efferent systems, each with a specific laminar organization, are observed. (1) Rostrally directed connections, from area 17 to 18, area 18 to 19 and area 19 to the inferotemporal region (area TE), originate from neurons in layer IIIc (and, in area 19, from a small complement of neurons in layer Va), and terminate in and around layer IV. (2) In contrast, connections in the reverse direction ('caudally directed' connections), from area TE to 19, area 19 to 18, and area 18 to 17, originate from neurons in layers Vb, VI and, to a lesser extent, IIIa, and terminate mainly in layer I. In addition, the laminar organization of several intrinsic and callosal connections are observed. In trinsic connections within areas 18 and 19 originate from neurons in layers IIIc and, to a lesser extent, Va, and terminate in vertical bands in layers I to IV. Callosal connections from areas 18, 19, and the caudal inferotemporal region originate from neurons mainly in layer IIIc. From areas 18 and 19, these callosal connections terminate in vertical bands in layers I through IV. Thus, different cortical projection systems are characterized by specific laminar distributions of efferent terminations as well as of their neurons of origin.

Animals↗
PubMed1983

Cellular, histochemical and connective organization of the hippocampus and fascia dentata transplanted to different regions of immature and adult rat brains.

The aims of the present study were to examine the survival and the cellular and connective differentiation of intracerebral transplants of fascia dentata and hippocampus. Pieces of immature dentate and hippocampal tissue were taken from late embryonic (E18) and early postnatal (1-9 days old) rats and transplanted into the brains of 1- to 13-day-old and adult rats. After survival times from 4 days to 2 years the cellular and connective organization of the transplants was monitored in parallel series of sections stained with thionin (cell bodies), Timm's sulphide silver method (terminal fields). Nauta and Fink-Heimer methods (normal and degenerating fibers) and a method for AChE activity (cholinergic afferents). The transplants survived well in all combinations of donor and recipient ages used, and they survived and differentiated in all parts of the recipient brains, although relations to pial and ventricular surfaces appeared to be optimal. Cell differentiation continued after transplantation, and a characteristic laminar organization was retained, although least in embryonic donor tissues. The distribution of intrinsic connections was determined by the types of subfields present in the transplants and interaction with ingrown host afferents. All aberrant intrinsic connections observed corresponded to aberrant connections formed in the hippocampus and fascia dentata denervated in situ and included supragranular mossy fibers in the fascia dentata, aberrant infrapyramidal mossy fibers in CA3, spread of CA4-associated afferents beyond the normal commissural-associational zone in the dentate molecular layer together with ingrowth of CA3-associated and CA1-subiculum-associated afferents. Most transplants received a cholinergic input of host origin irrespective of the localization in the host brain, but also non-cholinergic host pathways innervated the transplants, in particular when the transplants were in close contact with host fiber tracts, and when the recipients were immature. At various transplant locations the non-cholinergic host afferents belonged to the commissural hippocampo-dentate system, the commissural hippocampal system and the callosal system. Other cases suggested innervation of dentate transplant by host entorhinal afferents. The formation and distribution of intrinsic transplant connections and connections between transplant and host appeared to be regulated by the same factors that regulate the development and reorganization of fiber connections in the normal and the in situ denervated hippocampus and fascia dentata. As a special variety of this, the distribution of cholinergic afferents adjusted to the distribution of the major intrinsic and extrinsic non-cholinergic pathways.

Acetylcholinesterase↗
PubMed1988

The maturational status of thalamocortical and callosal connections of visual areas V1 and V2 in the newborn monkey.

Cytochrome oxidase (CytOx) is known to preferentially stain those regions of the visual cortex which receive direct projections from the thalamus. The pattern of CytOx stain has been used to investigate the maturation of thalamic input to areas V1 and V2 in the newborn monkey. In both areas, the intensity of CytOx activity was similar in newborns and adults. The distribution of CytOx in area V2 was not found to vary with age. In area V1, the only difference in CytOx activity in newborns was a relative immaturity of staining in layer 4C. The callosal connections of visual areas V1 and V2 were investigated by the axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase and free horseradish peroxidase. In the adult, V1 was found to be reciprocally callosally connected for a distance of 1-2.5 mm from the V1/V2 border, whilst V2 was connected for a distance of 3-8 mm from the border. In both areas, callosal connections showed a certain degree of clustering, particularly in V2 which contained 97-98% of the total number of callosal connections of these two areas. In the newborn, the number, tangential extent and clustered distribution of callosal connections were as in the adult. In the newborn, as in the adult, callosal connections coincided with regions of high CytOx activity in area V2. The results showing a relative maturity of the tangential distribution of callosal projecting neurons on the one hand, and an immaturity of thalamic projections on the other, are discussed in terms of: (1) the maturational status of the newborn monkey compared to other mammals at the moment of birth and (2) the possible role of visual experience in shaping cortical connections.

Aging↗
PubMed1987

The organization of the nucleus basalis-neostriatum complex of the mallard (Anas platyrhynchos L.) and its connections with the archistriatum and the paleostriatum complex.

The pattern of connections between the nucleus basalis, neostriatum, hyperstriatum ventrale, paleostriatum complex and archistriatum in the mallard has been analysed using Nissl material and a combination of neuroanatomical tracing procedures (autoradiography, horseradish peroxidase and horseradish peroxidase-wheat germ agglutinin histochemistry, lesion/degeneration technique). The frontal part of the mallard's telencephalon is characterized by its multilayered organization and the predominantly vertical arrangement of the connecting fiber systems. The nucleus basalis, endstation of the ascending sensory trigeminal system, is a large laminar cell area with a dorsal and a ventral layer. The overlying neostriatum frontale can be subdivided into a medial, a dorsal and a ventral intermediate, and a lateral area. The nucleus basalis has distinct connections with the ventral layer and sparse connections with the dorsal layer of the intermediate neostriatum, and abundant reciprocal connections with the ventral layer of the hyperstriatum ventrale. The ventral intermediate neostriatum also has reciprocal connections with the hyperstriatum ventrale; its projections overlap partly with those from the nucleus basalis. The ventral layer of the intermediate neostriatum frontale has a distinct projection upon the paleostriatum augmentatum. The dorsal layer sends fibers to the lateral neostriatum, to the rostral "sensorimotor" part of the archistriatum and to the lateral zone of the lobus parolfactorius. Another source of archistriatal afferents is the paleostriatum ventrale, an area that may also send fibers to the brainstem. Figure 21 summarizes the connections described in this paper. The functional significance of this organization is discussed in relation to its possible role in the guidance of pecking and other feeding behaviors in the mallard. Differences in the organization of the systems in pigeon and mallard are related to the differing degrees of visual and tactile (trigeminal) contributions to feeding in the two birds. It is suggested that the pattern of reciprocal connections between the hyperstriatum ventrale and the nucleus basalis and ventral intermediate neostriatum frontale forms the neuroanatomical substrate for a "comparator-system".

Animals↗
PubMed1990

Malaligned outlet septum with subpulmonary ventricular septal defect and abnormal ventriculoarterial connection: a morphologic spectrum defined echocardiographically.

A retrospective analysis of 62 echocardiograms from 22 patients with malaligned outlet septum, subpulmonary ventricular septal defect and abnormal ventriculoarterial (VA) connection was performed and the results were confirmed by intraoperative inspection, cardiac catheterization and angiography, or pathologic specimen analysis in 21 of the 22 patients. The purpose of this study was to determine the relative incidence of the primary morphologic features; the correlation between the presence or absence of mitral valve to pulmonary valve fibrous continuity and the type of VA connection; the types and incidence of additional cardiovascular anomalies; and the correlation between the determination of the VA connection by echocardiography versus that ascertained at intraoperative and autopsy inspection. A spectrum of VA connections was found, ranging from double outlet right ventricle (23%) at one extreme, through an intermediate type (64%) in which the pulmonary artery was overriding the ventricular septum, thereby having no consistent and predominant connection to either ventricle, to a discordant VA connection (13%) at the opposite end of the spectrum. All three types of VA connection occurred whether or not there was mitral valve to pulmonary valve fibrous continuity. Additional cardiovascular anomalies were present in 95% of patients, the most common being aortic arch obstructive lesions in 59%, anomalous attachments of the atrioventricular valve tension apparatus in 55% and subaortic stenosis in 50%. A method of echocardiographic determination of the VA connection that correlated with that determined intraoperatively and from pathologic specimen analysis is described.

Abnormalities, Multiple↗
PubMed1996

In vitro flow experiments for determination of optimal geometry of total cavopulmonary connection for surgical repair of children with functional single ventricle.

OBJECTIVES: This study sought to evaluate the effect of offsetting cavopulmonary connections at varying pulmonary flow ratios to determine the optimal geometry of the connection. BACKGROUND: Previous investigators have demonstrated energy conservation within the streamlined contours of the total cavopulmonary connection compared with that of the atriopulmonary connection. However, their surgical design of connecting the two cavae directly opposite each other may result in high energy losses. Others have introduced a unidirectional connection with some advantages but with concerns about the formation of arteriovenous malformation in the lung excluded from hepatic venous return. Thus, an optimal surgical design has not been determined. METHODS: In the present models, the caval connections were offset through a range of 0.0 to 2.0 diameters by 0.5 superior cava diameter increments. Flow ratios were fixed for superior and inferior cavae and varied for right and left pulmonary arteries as 70:30, 60:40, 50:50, 40:60 and 30:70 to stimulate varying lung resistance. Pressure measurements and flow visualization were done at steady flows of 2, 4 and 6 liters/min to stimulate rest and exercise. RESULTS: Our data show that the energy losses at the 0.0-diameter offset were double the losses of the 1.0 and 1.5 diameters, which had minimal energy losses. This result was attributable to chaotic patterns seen on flow visualization in the 0.0-diameters offset. Energy savings were more evident at the 50:50 right/left pulmonary artery ratio. Energy losses increased with increased total flow rates. CONCLUSIONS: The results strongly suggest the incorporation of caval offsets in future total cavopulmonary connections.

Child↗
PubMed1995

Acetylcholinesterase histochemistry in the macaque thalamus reveals territories selectively connected to frontal, parietal and temporal association cortices.

The patterns of histochemical staining for acetylcholinesterase (AChE) activity in the macaque thalamus were analyzed and compared with the distribution of cells and terminals labeled from injections of axonal tracers in the dorsolateral and orbital prefrontal cortex, in area 7a of the posterior parietal cortex and in the polysensory cortex of the superior temporal sulcus. AChE histochemistry is very useful in delineating the thalamic nuclei connected with the association cortex and in uncovering thalamic subdivisions that are barely evident on cytoarchitectonic grounds. Moreover, AChE activity reveals previously unrecognized heterogeneities within several thalamic nuclei, like the ventral anterior (VA), where a new ventromedial subdivision (VAvm) is described, the medial pulvinar (PulM) or the mediodorsal nucleus (MD). In this nucleus three distinct chemical domains are present: the medial, ventral and lateral sectors characterized by low, moderate and high AChE activities, respectively. The staining pattern of the lateral sector is markedly heterogeneous with patches of intense AChE activity surrounded by a moderately stained matrix. The MD medial sector is connected with the orbitofrontal cortex, whereas the AChE-rich patches in the lateral sector are selectively connected with the dorsolateral prefrontal, parietal and temporal association cortices. In the PulM, a dorsomedial AChE-rich patch is selectively connected with the orbitofrontal cortex, whereas the surrounding territory, which shows moderate AChE activity, is preferentially connected with the parietal and temporal cortices. Chemically specific domains in the anterior, ventral anterior, midline, and intralaminar thalamic nuclei are also connected with the examined association cortices. These findings indicate that the topographic patterns of the thalamo-cortical connections of primate association areas conform to the chemical architecture of the thalamus. This implies that because each cortical area is connected to a particular set of thalamic regions, the influence of the thalamus on cortical function is exclusive for each area, highly diverse among the various association areas, and subject to a wide range of modulation at the thalamic level.

Acetylcholinesterase↗
PubMed1995

Direct stereological estimation of three-dimensional connectivity in rat vertebrae: effect of estrogen, etidronate and risedronate following ovariectomy.

Newly developed unbiased stereological methods were employed to investigate the effects of estrogen deficiency on the three-dimensional connectivity of vertebral cancellous bone from ovariectomized (OVX) rats. The effects of two classes of antiresorptive agents, estrogen and bisphosphonates, on changes in connectivity in this animal model were also evaluated. Female rats were either sham-operated (sham-op) or surgically OVX at 90 days of age. OVX rats were administered either vehicle, estrogen (10 micrograms/kg 17-beta estradiol, 5 days/week subcutaneously [SC], etidronate disodium (5 mg/kg SC) or risedronate (5 micrograms/kg SC). The bisphosphonates were administered daily for 1 week followed by 3 weeks with no treatment. Treatment duration was 360 days. Systematic random sections, 30-microns thick, were prepared from methylmethacrylate-embedded decalcified second lumbar vertebrae. Total trabecular number and connectivity density were estimated using the ConnEulor principle. Vertebral cancellous bone volume was estimated on undecalcified sections from the first lumbar vertebrae. Connectivity density and cancellous bone volume were significantly reduced (approximately 25% and 40%, respectively) in the OVX group compared with the sham-op group. Estrogen treatment essentially maintained connectivity and cancellous bone volume at the level of the sham-op rats. Connectivity density and total trabecular number were significantly increased in the etidronate- and risedronate-treated rats compared with both the sham-op and OVX rats. These data demonstrate that reduction in the three-dimensional connectivity of vertebral cancellous bone is a long-term consequence of ovariectomy in the rat. This reduction in connectivity can be effectively prevented by the administration of antiresorptive agents such as estrogen, etidronate and risedronate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2007

Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus.

BACKGROUND: Positron emission tomography (PET) studies of major depression have revealed resting-state abnormalities in the prefrontal and cingulate cortices. Recently, fMRI has been adapted to examine connectivity within a specific resting-state neural network--the default-mode network--that includes medial prefrontal and anterior cingulate cortices. The goal of this study was to examine resting-state, default-mode network functional connectivity in subjects with major depression and in healthy controls. METHODS: Twenty-eight subjects with major depression and 20 healthy controls underwent 5-min fMRI scans while resting quietly. Independent component analysis was used to isolate the default-mode network in each subject. Group maps of the default-mode network were compared. A within-group analysis was performed in the depressed group to explore effects of depression refractoriness on functional connectivity. RESULTS: Resting-state subgenual cingulate and thalamic functional connectivity with the default-mode network were significantly greater in the depressed subjects. Within the depressed group, the length of the current depressive episode correlated positively with functional connectivity in the subgenual cingulate. CONCLUSIONS: This is the first study to explore default-mode functional connectivity in major depression. The findings provide cross-modality confirmation of PET studies demonstrating increased thalamic and subgenual cingulate activity in major depression. Further, the within-subject connectivity analysis employed here brings these previously isolated regions of hypermetabolism into the context of a disordered neural network. The correlation between refractoriness and subgenual cingulate functional connectivity within the network suggests that a quantitative, resting-state fMRI measure could be used to guide therapy in individual subjects.

Adult↗
PubMed2005

Evolution of slow-wave sleep and palliopallial connectivity in mammals and birds: a hypothesis.

Mammals and birds are the only animals that exhibit rapid eye-movement (REM) sleep and slow-wave sleep (SWS). Whereas the electroencephalogram (EEG) during REM sleep resembles the low-amplitude, high-frequency EEG of wakefulness, the EEG during SWS displays high-amplitude, slow-waves (1-4Hz). The absence of similar slow-waves (SWs) in sleeping reptiles suggests that the neuroanatomical and neurophysiological traits necessary for the genesis of SWs evolved independently in the mammalian and avian ancestors. Advances in our understanding of comparative neuroanatomy and the genesis of mammalian SWs suggest that the absence of SWs in reptiles is due to limited connectivity within the pallium, the dorsal portion of the telencephalon that includes the mammalian neocortex, reptilian dorsal cortex and avian Wulst (hyperpallium), as well as the dorsal ventricular ridge in birds and reptiles and the mammalian claustrum and pallial amygdala. In mammals, the slow oscillation (<1Hz) of cortical neurons acts through reciprocal corticothalamic loops and corticocortical connections to synchronize the 1-4Hz activity of thalamocortical neurons in a manner sufficient to generate SWs detectable in the EEG. Given the role that corticocortical (or palliopallial) connections play in the genesis of SWs in mammals, the degree of palliopallial connectivity might explain why birds show SWs and reptiles do not. Indeed, whereas the mammalian neocortex and avian pallium show extensive palliopallial connectivity, the reptilian pallium exhibits limited intrapallial connections. I thus propose that the evolution of SWs is linked to the independent evolution of extensive palliopallial connectivity in mammals and birds. As suggested by experiments functionally linking SWs to performance enhancements, the palliopallial connections that give rise to SWs might also depend on SWs to maintain their efficacy.

Animals↗
PubMed2005

Brain dynamics during natural viewing conditions--a new guide for mapping connectivity in vivo.

We describe here a new way of obtaining maps of connectivity in the human brain based on interregional correlations of blood oxygen level-dependent (BOLD) signal during natural viewing conditions. We propose that anatomical connections are reflected in BOLD signal correlations during natural brain dynamics. This may provide a powerful approach to chart connectivity, more so than that based on the 'resting state' of the human brain, and it may complement diffusion tensor imaging. Our approach relies on natural brain dynamics and is therefore experimentally unbiased and independent of hypothesis-driven, specialized stimuli. It has the advantage that natural viewing leads to considerably stronger cortical activity than rest, thus facilitating detection of weaker connections. To validate our technique, we used functional magnetic resonance imaging (fMRI) to record BOLD signal while volunteers freely viewed a movie that was interrupted by resting periods. We used independent component analysis (ICA) to segregate cortical areas before characterizing the dynamics of their BOLD signal during free viewing and rest. Natural viewing and rest each revealed highly specific correlation maps, which reflected known anatomical connections. Examples are homologous regions in visual and auditory cortices in the two hemispheres and the language network consisting of Wernicke's area, Broca's area, and a premotor region. Correlations between regions known to be directly connected were always substantially higher than between nonconnected regions. Furthermore, compared to rest, natural viewing specifically increased correlations between anatomically connected regions while it decreased correlations between nonconnected regions. Our findings therefore demonstrate that natural viewing conditions lead to particularly specific interregional correlations and thus provide a powerful environment to reveal anatomical connectivity in vivo.

Acoustic Stimulation↗
PubMed2006

Changes in hippocampal connectivity in the early stages of Alzheimer's disease: evidence from resting state fMRI.

A selective distribution of Alzheimer's disease (AD) pathological lesions in specific cortical layers isolates the hippocampus from the rest of the brain. However, functional connectivity between the hippocampus and other brain regions remains unclear in AD. Here, we employ a resting state functional MRI (fMRI) to examine changes in hippocampal connectivity comparing 13 patients with mild AD versus 13 healthy age-matched controls. Hippocampal connectivity was investigated by examination of the correlation between low frequency fMRI signal fluctuations in the hippocampus and those in all other brain regions. We found that functional connectivity between the right hippocampus and a set of regions was disrupted in AD; these regions are: medial prefrontal cortex (MPFC), ventral anterior cingulate cortex (vACC), right inferotemporal cortex, right cuneus extending into precuneus, left cuneus, right superior and middle temporal gyrus and posterior cingulate cortex (PCC). We also found increased functional connectivity between the left hippocampus and the right lateral prefrontal cortex in AD. In addition, rightward asymmetry of hippocampal connectivity observed in elderly controls was diminished in AD patients. The disrupted hippocampal connectivity to the MPFC, vACC and PCC provides further support for decreased activity in "default mode network" previously shown in AD. The decreased connectivity between the hippocampus and the visual cortices might indicate reduced integrity of hippocampus-related cortical networks in AD. Moreover, these findings suggest that resting-state fMRI might be an appropriate approach for studying pathophysiological changes in early AD.

Aged↗