Network interactions of medial prefrontal cortex, hippocampus and reuniens nucleus of the midline thalamus

Le présent mémoire corrobore l'hypothèse selon laquelle l'hippocampe, le cortex préfrontal et le noyau reuniens du thalamus constituent un réseau fonctionnel dans lequel le noyau reuniens servirait d'interfacé entre l'hippocampe et le cortex pré frontal. Bien que la voie hippocampo-corticale de ce réseau ait été abondamment étudiée, cela n'est pas le cas pour la voie reuniens-préfrontale. Nous décrivons ici, pour la première fois, la réponse de neurones du cortex préfrontal médian aux stimulations du noyau reuniens. Chez des chats sous anesthésie (kétamine-xylazine), nous avons effectué simulatanément 1) des enregistrements intra- et extracellulaires dans le cortex préfrontal médian et 2) des stimulations du noyau reuniens ou de l'hippocampe à l'aide d'électrodes bipolaires. Nous avons ainsi démontré que la réponse de neurones du cortex préfrontal médian aux stimulations du noyau reuniens est distincte des réponses évoquées par des stimulations hippocampiques, que la voie reuniens-préfrontale est sujette à la plasticité à court terme et qu'une région restreinte du cortex préfrontal médian sert de relai à la voie hippocampo-cortico-thalamique

Coupled Oscillations Mediate Directed Interactions between Prefrontal Cortex and Hippocampus of the Neonatal Rat

SummaryThe coactivation of prefrontal and hippocampal networks in oscillatory rhythms is critical for precise information flow in mnemonic and executive tasks, yet the mechanisms governing its development are still unknown. Here, we demonstrate that already in neonatal rats, patterns of discontinuous oscillatory activity precisely entrain the firing of prefrontal neurons and have distinct spatial and temporal organization over cingulate and prelimbic cortices. Moreover, we show that hippocampal theta bursts drive the generation of neonatal prefrontal oscillations by phase-locking the neuronal firing via axonal pathways. Consequently, functional impairment of the hippocampus reduces the prefrontal activity. With ongoing maturation continuous theta-gamma oscillations emerge and mutually entrain the prejuvenile prefrontal-hippocampal networks. Thus, theta-modulated communication within developing prefrontal-hippocampal networks may be relevant for circuitry refinement and maturation of functional units underlying information storage at adulthood

Long-range synchrony between medial prefrontal cortex, thalamus and hippocampus underlies working memory behavior in mice.

Presently, there are no antipsychotic drugs capable of treating the cognitive dysfunctions of schizophrenia. In order to inform the development of better therapies, it is essential to understand the mechanism behind dysfunctional cognition, which requires an understanding of functional cognition. Spatial working memory, a measure of cognitive function, can be assessed in the mouse using a task of delayed alternation: the T-maze. In this thesis, I focus on spatial working memory behavior in the mouse and three brain regions that are implicated in this behavior: the medial prefrontal cortex (mPFC), the hippocampus (HPC) and the medial dorsal thalamus (MD). Lesion and electrophysiological studies in each structure have demonstrated their importance during working memory behavior. Disconnection studies also show that the coordination between the mPFC and either the HPC or MD is important for the behavior, but little is known about the mechanism by which they coordinate. The MD and the ventral region of the hippocampus (vHPC) have robust projections into the mPFC. They are therefore in a good position to influence mPFC activity. Previous reports show that the mPFC and the dorsal region of the hippocampus (dHPC) synchronize activity in the theta range (4-12 Hz) with working memory demand. However, the dHPC does not directly connect with the mPFC so it is unclear how this coordination occurs. We hypothesized that the vHPC may also be involved in spatial working memory behavior and that it may mediate the dHPC-mPFC theta synchrony observed. To test these hypotheses, we recorded neural activity simultaneously from the mPFC, dHPC and vHPC in mice performing the T-maze task. Local field potential oscillations (LFPs), thought to be a measure of synchronized synaptic activity, were obtained from each area. We observed an increase in theta synchrony between the mPFC and both the dHPC and vHPC. Removing the influence of vHPC both analytically and experimentally, we found a decrease in synchrony of the dHPC-mPFC.Aside from the disconnection studies, little is known about the MD-mPFC pathway in rodents. However, due to evidence from schizophrenia patients of altered correlation specifically between the MD and PFC, we hypothesized that an electrophysiological correlate of working memory exists in the MD-mPFC pathway as well and that a decrease in MD activity may lead to prefrontal dysfunction. To test these hypotheses, we recorded LFPs from the mPFC and both single unit activity and LFPs from the MD in mice performing the T-maze task. We observed an increase in phase locking of MD cells to mPFC LFPs in beta (13-30Hz) range during the choice phase of the task. We then utilized a pharmacogenetic technique to decrease firing rate in a small portion of MD cells, which resulted in a deficit in both task acquisition and performance. The increase in MD-mPFC beta phase locking we had observed was not present in MD-inactivated animals. Interestingly, beta coherence between the two structures across learning was highly correlated with choice accuracy on the task. This suggests that MD-PFC coordination is predictive of working memory performance.These findings illustrate how long-range synchrony of the mPFC with HPC in the theta frequency range and with the MD in the beta frequency range may be important markers for normal working memory behavior and if disrupted in humans, could contribute to the cognitive symptoms of schizophrenia

Time course of information processing in visual and haptic object classification

Peer reviewedPublisher PD

Role of Anterior Cingulate Cortex in Saccade Control

Cognitive control is referred to the guidance of behavior based on internal goals rather than external stimuli. It has been postulated that prefrontal cortex is mainly involved in higher order cognitive functions. Specifically, anterior cingulate cortex (ACC), which is part of the prefrontal cortex, is suggested to be involved in performance monitoring and conflict monitoring that are considered to be cognitive control functions. Saccades are the fast eye movements that align the fovea on the objects of interest in the environment. In this thesis, I have explored the role of ACC in control of saccadic eye movements. First, I performed a resting-state fMRI study to identify areas within the ACC that are functionally connected to the frontal eye fields (FEF). It has been shown that FEF is involved in saccade generation. Therefore, the ACC areas that are functionally connected to FEF could be hypothesized to have a role in saccade control. Then, I performed simultaneous electrophysiological recordings in the ACC and FEF. Furthermore, I explored whether ACC exerts control over FEF. My results show that ACC is involved in cognitive control of saccades. Furthermore, the ACC and FEF neurons communicate through synchronized theta and beta band activity in these areas. The results of this thesis shine light on the mechanisms by which these brain areas communicate. Moreover, my findings support the notion that ACC and FEF have a unique oscillatory property, and more specifically ACC has a prominent theta band, and to a lesser extent beta band activity

The oscillatory mechanisms of working memory maintenance

Working memory (WM) is a cognitive process which allows for maintenance of information that is no longer perceived. Although theoretical models have recognized that working memory involves interactions across cell assemblies in multiple brain areas, the exact neural mechanisms which support this process remain unknown. In this thesis I investigate the neural dynamics in the human hippocampus, the ventral, dorsal and frontal cortex as well as the long-range network connectivity across these brain areas to understand how such a distributed network allows for maintenance of various information pieces in WM. The results described here support a model in which working memory relies on dynamic interactions across frequencies (the cross-frequency coupling, CFC) in a distributed network of cortical areas coordinated by the prefrontal cortex. In particular, maintenance of information during a delay period selectively involves the hippocampus, dorsal and ventral visual stream as well as the prefrontal cortex each of which represents different features. The hippocampus contributes to this large network specifically by representing multiple items in working memory. In two independent experiments I observed that the low-frequency activity (a marker of neural inhibition) was linearly reduced across memory loads. Importantly, the hippocampus showed very prominent low-frequency power during maintenance of a single item suggesting that during this condition the neural processing was strongly inhibited. In turn, the broadband gamma activity was linearly increasing as a function of memory load. This pattern of results may be interpreted as reflecting an increased involvement of the hippocampus in representing longer sequences. Importantly, the low-frequency decrease was not static but fluctuated periodically between two different modes. One of the modes was characterized by the load-dependent power decreases and reduced cross-frequency coupling (memory activation mode) whereas the other mode was reflected by the load-independent high levels of power and increased coupling strength (load-independent mode). Crucially, these modes were temporally organized by the phase of an endogenous delta rhythm forming a “hierarchy of oscillations”. This periodicity was essential for the successful performance. Finally, during the memory activation mode the WM capacity limit was inter-individually correlated with the peak frequency change as predicted by the multiplexing model of WM. All these effects were subsequently replicated in an independent dataset. These results suggest that the hippocampus is involved in WM maintenance showing periodic fluctuations between two different oscillatory modes. Parameters of the hippocampal iEEG signal correlate with individual WM capacity, specifically during the memory activation mode. The ventral and dorsal visual stream each contributes to the distributed WM network by representing configuration and spatial information, respectively. Specifically, the alpha power in the ventral visual stream was decreased during maintenance of face identities. In turn, the alpha power was desynchronized in the dorsal visual stream while participants were maintaining face orientations. This shows that the alpha power double dissociates between the feature specific networks in the ventral and dorsal visual stream. These effects are further interpreted as reflecting selective involvement of the dorsal and ventral visual pathway depending on the maintained features. Importantly, each of the visual streams was selectively synchronized with the prefrontal cortex depending on the memory condition and the alpha power. This corroborates a central prediction from the gating by inhibition model which assumes that the increased alpha power serves as the mechanism for gating of information by inhibiting task redundant pathways. Moreover, during maintenance of information the phase of alpha modulated the amplitude of high-frequency activity both in the dorsal and ventral visual stream. Additionally,the low-frequency phase in the prefrontal cortex modulated high-frequency activity both in the dorsal and ventral visual stream. These results suggest that both the dorsal and ventral visual streams are selectively involved during maintenance of distinct features (i.e. face orientation and identity, respectively). They also indicate that the prefrontal cortex selectively gets synchronized with the visual regions depending on the alpha power in that region and the maintained feature. Finally, the activity in the prefrontal cortex influences processing across long distance as evident from changes in the phase synchrony with the visual cortical areas and by modulating gamma power in the visual cortical regions. It is also noted that the ventrolateral prefrontal cortex (vlPFC) contains information regarding abstract rules (i.e. response mapping). In particular, using a multivariate decoding approach I found that the local field potentials recorded from the vlPFC dissociate between different types of responses. At the same time I observed no evidence for the load-dependent or stimulus-specific changes in that brain region. The null effect should be treated with caution. Nevertheless, the current results suggest that the vlPFC may contribute to working memory by processing of abstract rules such as a mapping between the stimulus and the response. Furthermore, I found that the alpha power dependent duty cycle in the vlPFC constrains the duration of the gamma burst which has been suggested as a mechanism for neural inhibition. This finding is important because such a property of the alpha activity has never been observed in a brain region other than the primary sensory cortex. Together, the results presented in this thesis support a model according to which the working memory is a complex and highly dynamic process engaging hierarchies of oscillations across multiple cortical regions. In particular, the hippocampus is important for the multi-item WM. The dorsal and ventral visual streams are relevant for distinct visual features. Finally, the prefrontal cortex represents abstract rules and influences processing in other cortical regions likely providing a top down control over these regions

Non-Verbal Working Memory: A functional near-infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI) comparison

Ulike hjernenettverk virker å bli aktivert for verbal og ikke-verbal visuell og romlig informasjon i arbeidsminnet. Det finnes et bredt spenn av forskning på det visuell-romlige arbeidsminnet. Likevel, har en tilnærming som benytter seg av objekter med flere integrerte egenskaper og en klar spesifikasjon på den verbale dimensjonen blitt mindre anvendt. Det ikke-verbale arbeidsminnet for visuell-romlig informasjon har blitt mer oversett enn det verbale arbeidsminnet. Derfor søker denne studien å adressere de nevrale nettverkene som utnyttes for ikke-verbal arbeidsminneprestasjon. Hjerneaktivitet ble målt fra totalt 12 deltagere mens de utførte en nylig komponert ikke-verbal arbeidsminneoppgave. Både funksjonell nær-infrarød spektroskopi (fNIRS) og funksjonell magnetisk resonans avbildning (fMRI) ble benyttet for formålet. Resultatene indikerte at det ikke-verbale arbeidsminnet involverer høyre-lateraliserte hjerneaktiveringer, hvor frontoparietale nettverk og visuelle traséer ble benyttet for prestasjon. Disse funnene tilbyr viktig tilførsel til den nevrale nettverksmodellen av det ikke-verbale arbeidsminnet. Dermed virker oppgaven å teste konseptet effektivt. fNIRS og fMRI ble også brukt for å måle resting-state fra de samme deltagerne. Resultatene uttrykket forskjeller mellom de to øktene ved både fMRI og fNIRS. Endringene i konnektivitet kan reflektere effekter av oppgaven på resting-state.Masteroppgave i psykologiMAPSYK360INTL-SVINTL-MEDINTL-PSYKINTL-HFINTL-KMDINTL-JUSINTL-MNMAPS-PSY

Aging brain from a network science perspective: Something to be positive about?

To better understand age differences in brain function and behavior, the current study applied network science to model functional interactions between brain regions. We observed a shift in network topology whereby for older adults subcortical and cerebellar structures overlapping with the Salience network had more connectivity to the rest of the brain, coupled with fragmentation of large-scale cortical networks such as the Default and Fronto-Parietal networks. Additionally, greater integration of the dorsal medial thalamus and red nucleus in the Salience network was associated with greater satisfaction with life for older adults, which is consistent with theoretical predictions of age-related increases in emotion regulation that are thought to help maintain well-being and life satisfaction in late adulthood. In regard to cognitive abilities, greater ventral medial prefrontal cortex coherence with its topological neighbors in the Default Network was associated with faster processing speed. Results suggest that large-scale organizing properties of the brain differ with normal aging, and this perspective may offer novel insight into understanding age-related differences in cognitive function and well-being. © 2013 Voss et al