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PubMed2004

Relating fMRI and PET signals to neural activity by means of large-scale neural models.

This article reviews the four ways by which large-scale, neurobiologically realistic modeling can be used in conjunction with functional neuroimaging data, especially that obtained by functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), to help investigators understand the neural bases for sensorimotor and cognitive functions. The conceptually distinct purposes served are:(1) formulating and implementing specific hypotheses about how neuronal populations mediate a task, which will be illustrated using models of visual and auditory object processing; (2) determining how well an experimental design paradigm or analysis method works, which will be illustrated by examining event-related fMRI; (3) investigating the meaning in neural terms of macro-level concepts, which will be illustrated using functional connectivity; and (4) combining different types of macroscopic data with one another, which will be illustrated using transcranial magnetic stimulation (TMS) and PET.

Brain↗
PubMed2000

A positron emission tomographic study of auditory localization in the congenitally blind.

We have used positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in sighted and congenitally blind subjects performing auditory localization tasks. During scanning, the spectral and binaural cues of localized sound were reproduced by a sound system and delivered via headphones. During tasks that required auditory localization both the sighted and blind subjects strongly activated posterior parietal areas. In addition, the blind subjects activated association areas in the right occipital cortex, the foci of which were similar to areas previously identified in visual location and motion detection experiments in sighted subjects. The blind subjects, therefore, demonstrated visual to auditory cross-modal plasticity with auditory localization activating occipital association areas originally intended for dorsal-stream visual processing. To determine the functional connectivity of pre-selected brain regions in primary and non-primary auditory and posterior parietal cortex in the two cohorts, we performed an inter-regional correlation analysis on the rCBF data set. During auditory localization in the blind subjects, rCBF activity in the right posterior parietal cortex was positively correlated with that in the right occipital region, whereas in sighted subjects correlations were generally negative. There were no significant positive occipital correlations in either cohort when reference regions in temporal or left parietal cortex were chosen. This indicates that in congenitally blind subjects the right occipital cortex participates in a functional network for auditory localization and that occipital activity is more likely to arise from connections with posterior parietal cortex.

Adult↗
PubMed1996

Cortical networks for visual reaching: intrinsic frontal lobe connectivity.

The anatomical substrates of reaching to visual targets were studied in monkeys (Macaca nemestrina) by combining behavioural neurophysiology and neuroanatomy. An instructed-delay reaching task was used to characterize the arm-related regions of the dorsolateral frontal cortex. This task revealed gradients of signal-, set- movement- and position-related activity along the rostrocaudal extent of the frontal lobe. The frontal mesial projections to these physiologically defined gradients were studied through anatomical methods based on the retrograde transport of distinguishable tracers. The tangential distribution of the cells of origin of these projections displayed a gradient-like arrangement similar to that defined physiologically in their terminal territory. These mesial projections to the dorsolateral frontal cortex may therefore be considered part of a cortical network wherein connections make only a limited contribution to the integration of different sources of information for the control of reaching movements. Further combination of such information must occur within each given cortical region by intrinsic local connections.

Animals↗
PubMed1993

Architecture of connectivity within a cingulo-fronto-parietal neurocognitive network for directed attention.

The spatial distribution of directed attention is coordinated by a large-scale neural network. The three principal cortical components of this network are located in the region of the frontal eye fields, posterior parietal cortex, and the cingulate cortex. We injected a retrogradely transported fluorescent dye into the frontal eye fields and another into the posterior parietal cortex of the monkey brain. Large numbers of neurons in the cingulate cortex were retrogradely labeled with each of the two fluorescent dyes. The two types of retrogradely labeled neurons were extensively intermingled, but neurons labeled with both tracers constituted less than 1% of retrogradely labeled cingulate neurons. Other cortical areas that contained retrograde neuronal labeling included the premotor, lateral neuronal labeling included the premotor, lateral prefrontal, orbitofrontal, opercular, posterior parietal, lateral temporal, inferior temporal, parahippocampal, and insular regions. These areas contained neurons labeled with each of the two dyes but virtually no neurons labeled with both. In the thalamus, retrogradely labeled nuclei failed to display evidence of double labeling. The overlap between the two populations of retrogradely labeled neurons was far more extensive at the cortical than at the thalamic level. These observations show that cortical and thalamic projections to the frontal eye fields and posterior parietal cortex do not represent axonal collaterals of single neurons but originate from two distinct and partially overlapping populations of neurons.

Animals↗
PubMed2005

Further characterization of muscarinic agonist-induced epileptiform bursting activity in immature rat piriform cortex, in vitro.

The characteristics of muscarinic acetylcholine receptor agonist-induced epileptiform bursting seen in immature rat piriform cortex slices in vitro were further investigated using intracellular recording, with particular focus on its postnatal age-dependence (P+14-P+30), pharmacology, site(s) of origin and the likely contribution of the muscarinic acetylcholine receptor agonist-induced post-stimulus slow afterdepolarization and gap junction functionality toward its generation. The muscarinic agonist, oxotremorine-M (10 microM), induced rhythmic bursting only in immature piriform cortex slices; however, paroxysmal depolarizing shift amplitude, burst duration and burst incidence were inversely related to postnatal age. No significant age-dependent changes in neuronal membrane properties or postsynaptic muscarinic responsiveness accounted for this decline. Burst incidence was higher when recorded in anterior and posterior regions of the immature piriform cortex. In adult and immature neurones, oxotremorine-M effects were abolished by M1-, but not M2-muscarinic acetylcholine receptor-selective antagonists. Rostrocaudal lesions, between piriform cortex layers I and II, or layer III and endopiriform nucleus in adult or immature slices did not influence oxotremorine-M effects; however, the slow afterdepolarization in adult (but not immature) lesioned slices was abolished. Gap junction blockers (carbenoxolone or octanol) disrupted muscarinic bursting and diminished the slow afterdepolarization in immature slices, suggesting that gap junction connectivity was important for bursting. Our data show that neural networks within layers II-III function as primary oscillatory circuits for burst initiation in immature rat piriform cortex during persistent muscarinic receptor activation. Furthermore, we propose that muscarinic slow afterdepolarization induction and gap junction communication could contribute towards the increased epileptiform susceptibility of this brain area.

Animals↗
PubMed1997

Superior temporal gyrus and planum temporale in schizophrenia: a selective review.

1. The normal structure of the superior temporal gyrus (STG) has been elucidated from human and non-human primate research. This brain region is structurally complex, contains several distinct cellular regions and the area known as the planum temporale. 2. The STG connects with heteromodal neocortical regions and temporolimbic areas. 3. Functional studies of the normal STG in animals and in humans, using electrophysiology and PET/fMRI, emphasize the STG's role as part of a cortical network important in the interpretation, production and self-monitoring of language. 4. There is evidence for structural abnormalities of the STG in schizophrenia including both volume reductions and disturbances of normal asymmetries. 5. Functional studies of this region in schizophrenic patients, including measurements of evoked potentials and of bloodflow, are abnormal, especially when patients perform language tasks or experience hallucinations. 6. This structural and functional pathology in the STG probably represents one example of a more general disruption in schizophrenia of the neocortical network of which this region is an essential part. This disturbance may be closely associated with the symptoms of formal thought disorder and of auditory hallucinations commonly seen in the disorder.

Animals↗
PubMed1999

The cognitive neuroscience of visual attention.

In current conceptualizations of visual attention, selection takes place through integrated competition between recurrently connected visual processing networks. Selection, which facilitates the emergence of a 'winner' from among many potential targets, can be associated with particular spatial locations or object properties, and it can be modulated by both stimulus-driven and goal-driven factors. Recent neurobiological data support this account, revealing the activation of striate and extrastriate brain regions during conditions of competition. In addition, parietal and temporal cortices play a role in selection, biasing the ultimate outcome of the competition.

Attention↗
PubMed2000

Post-lesion lateralisation shifts in a computational model of single-word reading.

The mechanisms underlying lateralisation of language are incompletely understood. Existing data is inconclusive, for example, in determining which underlying asymmetries in hemispheric anatomy/physiology lead to lateralisation, the precise role of interhemispheric connections in this process, and exactly how and why lateralisation can shift following focal brain damage. Although these issues will ultimately be settled by experimentation, it is likely that computational modelling can be used to suggest, focus, and even interpret such empirical work. We have recently studied the emergence of lateralisation in an artificial neural network model having paired cerebral hemispheric regions, as the model learned to generate the correct pronunciation for simple words. In this paper we extend this previous work by examining the immediate and longer-term changes in lateralisation that occur following simulated acute hemispheric lesions. Among other things, the results demonstrate that the extent to which the non-lesioned model hemispheric region contributes to recovery is a function of lesion size, prelesion lateralisation, and assumptions about the excitatory/inhibitory influences of the corpus callosum. The relevance of these results to the currently controversial suggestion that language lateralisation shifts following focal damage to language areas, and that the unlesioned hemisphere contributes to recovery from stroke-induced aphasia in adults, is discussed.

Journal Article↗
PubMed2005

Enhancement of spontaneous synaptic activity in rat Purkinje neurones by ATP during development.

The establishment of functional synaptic connections and activity is a pivotal process in the development of neuronal networks. We have studied the synaptic activity in the developing rat cerebellum, and the contribution mediated by purinergic receptors. The mean frequency of the spontaneous postsynaptic currents (sPSCs) recorded with the whole-cell patch-clamp technique from Purkinje neurones in acute brain slices at room temperature, increased fourfold from 4.4+/-0.8 Hz at postnatal day 9/10 (n=23) to 17.8+/-1.6 Hz at postnatal day 17-20 (p17-p20; n=113; P<0.01). ATP, which increased the frequency of sPSCs by up to 100% (EC50=18 microM) in the third postnatal week, started to modulate the synaptic activity during the second postnatal week, which was determined by three processes: (1) the appearance of functional ATP receptors during p10-p12, (2) the enhancement of the sPSC frequency by endogenous ATP release becoming apparent after inhibition of ecto-ATPases by 6-N,N-diethyl-beta,gamma-dibromomethylene-D-adenosine-5-triphosphate (ARL67156; 50 microM) at p11-p12, and (3) with tonic stimulation of purinoceptors at p14, as revealed by the P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM). ATP had a similar effect at later stages (p24-p27) and at 35 degrees C. Our results suggest that endogenous release of ATP starts to enhance the synaptic activity in Purkinje neurones by the end of the second postnatal week.

Action Potentials↗
PubMed2006

Low-dimensional maps encoding dynamics in entorhinal cortex and hippocampus.

Cells that produce intrinsic theta oscillations often contain the hyperpolarization-activated current I(h). In this article, we use models and dynamic clamp experiments to investigate the synchronization properties of two such cells (stellate cells of the entorhinal cortex and O-LM cells of the hippocampus) in networks with fast-spiking (FS) interneurons. The model we use for stellate cells and O-LM cells is the same, but the stellate cells are excitatory and the O-LM cells are inhibitory, with inhibitory postsynaptic potential considerably longer than those from FS interneurons. We use spike time response curve methods (STRC), expanding that technique to three-cell networks and giving two different ways in which the analysis of the three-cell network reduces to that of a two-cell network. We show that adding FS cells to a network of stellate cells can desynchronize the stellate cells, while adding them to a network of O-LM cells can synchronize the O-LM cells. These synchronization and desynchronization properties critically depend on I(h). The analysis of the deterministic system allows us to understand some effects of noise on the phase relationships in the stellate networks. The dynamic clamp experiments use biophysical stellate cells and in silico FS cells, with connections that mimic excitation or inhibition, the latter with decay times associated with FS cells or O-LM cells. The results obtained in the dynamic clamp experiments are in a good agreement with the analytical framework.

Action Potentials↗
PubMed2003

The elusive concept of brain connectivity.

Neurons and neural populations do not function as islands onto themselves. Rather, they interact with other such elements through their afferent and efferent connections in an orchestrated manner so as to enable different sensorimotor and cognitive tasks to be performed. The concept of functional connectivity and the allied notion of effective connectivity were introduced to designate the functional strengths of such interactions. Functional neuroimaging methods, especially PET and fMRI, have been used extensively to evaluate the functional connectivity between different brain regions. After providing a brief historical review of these notions of brain connectivity, I argue that the conceptual formulations of functional and effective connectivity are far from clear. Specifically, the terms functional and effective connectivity are applied to quantities computed on types of functional imaging data (e.g., PET, fMRI, EEG) that vary in spatial, temporal, and other features, using different definitions (even for data of the same modality) and employing different computational algorithms. Until it is understood what each definition means in terms of an underlying neural substrate, comparisons of functional and/or effective connectivity across studies may appear inconsistent and should be performed with great caution.

Brain↗
PubMed2005

A functional glutamatergic neurone network in the medial septum and diagonal band area.

The medial septum and diagonal band complex (MS/DB) is important for learning and memory and is known to contain cholinergic and GABAergic neurones. Glutamatergic neurones have also been recently described in this area but their function remains unknown. Here we show that local glutamatergic neurones can be activated using 4-aminopyridine (4-AP) and the GABA(A) receptor antagonist bicuculline in regular MS/DB slices, or mini-MS/DB slices. The spontaneous glutamatergic responses were mediated by AMPA receptors and, to a lesser extend, NMDA receptors, and were characterized by large, sometimes repetitive activity that elicited bursts of action potentials postsynaptically. Similar repetitive AMPA receptor-mediated bursts were generated by glutamatergic neurone activation within the MS/DB in disinhibited organotypic MS/DB slices, suggesting that the glutamatergic responses did not originate from extrinsic glutamatergic synapses. It is interesting that glutamatergic neurones were part of a synchronously active network as large repetitive AMPA receptor-mediated bursts were generated concomitantly with extracellular field potentials in intact half-septum preparations in vitro. Glutamatergic neurones appeared important to MS/DB activation as strong glutamatergic responses were present in electrophysiologically identified putative cholinergic, GABAergic and glutamatergic neurones. In agreement with this, we found immunohistochemical evidence that vesicular glutamate-2 (VGLUT2)-positive puncta were in proximity to choline acetyltransferase (ChAT)-, glutamic acid decarboxylase 67 (GAD67)- and VGLUT2-positive neurones. Finally, MS/DB glutamatergic neurones could be activated under more physiological conditions as a cholinergic agonist was found to elicit rhythmic AMPA receptor-mediated EPSPs at a theta relevant frequency of 6-10 Hz. We propose that glutamatergic neurones within the MS/DB can excite cholinergic and GABAergic neurones, and that they are part of a connected excitatory network, which upon appropriate activation, may contribute to rhythm generation.

Action Potentials↗
PubMed2003

Learning the Gestalt rule of collinearity from object motion.

The Gestalt principle of collinearity (and curvilinearity) is widely regarded as being mediated by the long-range connection structure in primary visual cortex. We review the neurophysiological and psychophysical literature to argue that these connections are developed from visual experience after birth, relying on coherent object motion. We then present a neural network model that learns these connections in an unsupervised Hebbian fashion with input from real camera sequences. The model uses spatiotemporal retinal filtering, which is very sensitive to changes in the visual input. We show that it is crucial for successful learning to use the correlation of the transient responses instead of the sustained ones. As a consequence, learning works best with video sequences of moving objects. The model addresses a special case of the fundamental question of what represents the necessary a priori knowledge the brain is equipped with at birth so that the self-organized process of structuring by experience can be successful.

Gestalt Theory↗
PubMed2005

An integrative model of developing tinnitus based on recent neurobiological findings.

Brain imaging studies suggest that the functional connectivity of various limbic, prefrontal, and temporal brain structures can be understood as the basis for particularly intense experiences of impairment and many secondary symptoms of decompensated tinnitus. Results to date suggest cortical plasticity as a likely mechanism to be involved in the chronic progression of tinnitus. Relationships between the processing of auditory signals and neural networks associated with somatosensory, attentional, cognitive and emotional processes are relevant for the genesis of the pathology. However, the neural bases of subjective impairment in tinnitus patients are unknown. An integrative model of developing tinnitus is presented here, based on the most recent neurophysiological data in current discussion. We assume the involvement of altered brain functions in the development and maintenance of perceptions of tinnitus and outline various possibilities which could contribute to decompensation and chronic progression. The discussions surrounding present models of the generation of tinnitus and its reinforcement to the point of decompensation make it clear that a unidimensional approach in clinical interventions is insufficient. Patients with decompensated tinnitus suffer from a complex somatic and psychological disorder. The interactive processes involving emotions, behaviour and symptoms, as well as the high co-morbidity with affective and psychosomatic illnesses and the important influence of psychosocial factors (distress), make the use of stage-appropriate interdisciplinary treatments necessary.

Brain↗
PubMed1998

Functional connectivity of the angular gyrus in normal reading and dyslexia.

The classic neurologic model for reading, based on studies of patients with acquired alexia, hypothesizes functional linkages between the angular gyrus in the left hemisphere and visual association areas in the occipital and temporal lobes. The angular gyrus also is thought to have functional links with posterior language areas (e.g., Wernicke's area), because it is presumed to be involved in mapping visually presented inputs onto linguistic representations. Using positron emission tomography , we demonstrate in normal men that regional cerebral blood flow in the left angular gyrus shows strong within-task, across-subjects correlations (i.e., functional connectivity) with regional cerebral blood flow in extrastriate occipital and temporal lobe regions during single word reading. In contrast, the left angular gyrus is functionally disconnected from these regions in men with persistent developmental dyslexia, suggesting that the anatomical disconnection of the left angular gyrus from other brain regions that are part of the "normal" brain reading network in many cases of acquired alexia is mirrored by its functional disconnection in developmental dyslexia.

Adolescent↗
PubMedDate not supplied

Non-sprouting angiogenesis in neurohypophysis after traumatic injury of the cerebral cortex. Electron-microscopic studies.

OBJECTIVES: Angiogenesis comprises two different mechanisms: endothelial sprouting and intussusceptive microvascular growth. The sprouting process is based on endothelial cell migration, proliferation and tube formation. Intussusceptive microvascular growth divides existing vessel lumens by formation and insertion of endothelial columns into the vessel lumen. The morphological features of microvessels of cerebral cortex and neurohypophysis were evaluated in a model of the cerebral traumatic injury. METHOD: The observations were conducted seven days after induction of cortical trauma. Traumatic injury was induced in the fronto-temporal region of cerebral cortex in general anesthesia with 20mg/kg ketamine hydrochloride. RESULTS: Seven days after traumatic brain injury in sections from cerebral cortex and neurohypophysis we can observe morphological features of angiogenesis. Endothelium of the cerebral cortex possesses high endotheliocytes tightly connected and enveloped by amorphous basement membrane-like material. Transcapillary pillars tightly connected with neighbouring endothelial cells split the newly formed vessels and branching takes place. In neurohypophysis we can observe all stages of non-sprouting angiogenesis: proliferation endothelial cells on the inside mother vessel, splitting newly formed blood vessels by transcapillary pillars directed into the vessel lumen, maturation of endothelium and network formation. CONCLUSION: The mechanical injuries directly induced angiogenesis not only in cerebral cortex, but also in neurohypophysis. Our studies show that mechanism of angiogenesis is not the same as observed previously in neurohypophysis after focal cerebral ischemia (Neuroendocrinology Letters 2001; 22:87 92). This study indicates that mechanism of angiogenesis can depend on kind of induction.

Animals↗
PubMed2001

Nucleus accumbens, entorhinal cortex and latent inhibition: a neural network model.

A neural network model of classical conditioning (Schmajuk, Lam, and Gray, J. Exp. Psychol.: Anim. Behav. Process, 22, 1996, 321-349) is applied to the description of the neural substrates of latent inhibition. Experimental data suggest that latent inhibition might be controlled by a circuit that involves the hippocampus, the entorhinal cortex, the nucleus accumbens, and the mesolimbic dopaminergic projection from the ventral tegmental area to the accumbens. By mapping different nodes and connections in the model onto this brain circuit, computer simulations demonstrate that, in most cases, the model provides a good quantitative description of: (1) the impairment of latent inhibition by lesions of the shell of the nucleus accumbens; (2) the restoration of latent inhibition by haloperidol following lesions of the shell; (3) the preservation of latent inhibition by lesions of the core of the nucleus accumbens; (4) the facilitation of latent inhibition by combined shell core lesions and by core lesions with extended conditioning; (5) the impairment of latent inhibition following lesions of the entorhinal cortex or the hippocampus; and (6) the restoration of latent inhibition by haloperidol following lesions of the entorhinal cortex and ventral subiculum. In addition, the model is able to describe neural activity in the nucleus accumbens.

Animals↗
PubMed2001

A model of the interaction between mood and memory.

This paper investigates a neural network model of the interaction between mood and memory. The model has two attractor networks that represent the inferior temporal cortex (IT), which stores representations of visual stimuli, and the amygdala, the activity of which reflects the mood state. The two attractor networks are coupled by forward and backward projections. The model is however generic, and is relevant to understanding the interaction between different pairs of modules in the brain, particularly, as is the case with moods and memories, when there are fewer states represented in one module than in the other. During learning, a large number of patterns are presented to the IT, each paired with one of two mood states represented in the amygdala. The recurrent connections within each module, the forward connections from the memory module to the amygdala, and the backward connections from the amygdala to the memory module, are associatively modified. It is shown how the mood state in the amygdala can influence which memory patterns are recalled in the memory module. Further, it is shown that if there is an existing mood state in the amygdala, it can be difficult to change it even when a retrieval cue is presented to the memory module that is associated with a different mood state. It is also shown that the backprojections from the amygdala to the memory module must be relatively weak if memory retrieval in the memory module is not to be disrupted. The results are relevant to understanding the interaction between structures important in mood and emotion (such as the amygdala and orbitofrontal cortex) and other brain areas involved in storing objects and faces (such as the inferior temporal visual cortex) and memories (such as the hippocampus).

Affect↗