Assessing Alpha Band Event-related Synchronisation/Desynchronisation Using a Bio-Inspired Computational Model

This paper describes a study of the effects of variation of synaptic connectivity in a thalamo-cortical circuitry using a neural mass model. The oscillatory behaviour of the model output is assessed within the alpha frequency band. The model presented here is a modification of an existing model involving the introduction of biologically plausible synaptic connectivities as well as synaptic structure. Our goal is to study altered event related desynchronisation/synchronisation (ERD/ERS) patterns within the alpha band in Alzheimers disease as observed in experimental studies. ERD is an amplitude attenuation of certain EEG rhythms when an event is initiated or while a certain event is taking place in the brain. ERS is an amplitude enhancement of a certain EEG rhythm when cortical areas are not specifically engaged in a given mode of activity at a certain instant of time. EEG desynchronisation normally blocks alpha rhythms in the EEG due to sensory processing or behaviour. The results show that a decrease in synaptic connectivity induces a time lag in both ERD and ERS peaks in the model output. Furthermore, a deficiency induced in the inhibitory cholinergic pathway results in a distinct effect on time to peak in the ERD/ERS response. These observations are consistent with experimental findings in AD. Variation of the level of interconnectivity has a pronounced effect on the ERS behaviour of the model while the excitatory connectivity in the retino-geniculate pathway during the resting state is more influential on the ERD behaviour

Cognitive Consilience: Primate Non-Primary Neuroanatomical Circuits Underlying Cognition

Interactions between the cerebral cortex, thalamus, and basal ganglia form the basis of cognitive information processing in the mammalian brain. Understanding the principles of neuroanatomical organization in these structures is critical to understanding the functions they perform and ultimately how the human brain works. We have manually distilled and synthesized hundreds of primate neuroanatomy facts into a single interactive visualization. The resulting picture represents the fundamental neuroanatomical blueprint upon which cognitive functions must be implemented. Within this framework we hypothesize and detail 7 functional circuits corresponding to psychological perspectives on the brain: consolidated long-term declarative memory, short-term declarative memory, working memory/information processing, behavioral memory selection, behavioral memory output, cognitive control, and cortical information flow regulation. Each circuit is described in terms of distinguishable neuronal groups including the cerebral isocortex (9 pyramidal neuronal groups), parahippocampal gyrus and hippocampus, thalamus (4 neuronal groups), basal ganglia (7 neuronal groups), metencephalon, basal forebrain, and other subcortical nuclei. We focus on neuroanatomy related to primate non-primary cortical systems to elucidate the basis underlying the distinct homotypical cognitive architecture. To display the breadth of this review, we introduce a novel method of integrating and presenting data in multiple independent visualizations: an interactive website (http://www.frontiersin.org/files/cognitiveconsilience/index.html) and standalone iPhone and iPad applications. With these tools we present a unique, annotated view of neuroanatomical consilience (integration of knowledge)

MOTOR CORTEX REGULATION OF THALAMIC-CORTICAL ACTIVITY IN THE SOMATOSENSORY SYSTEM

A prominent feature of thalamocortical circuitry in sensory systems is the extensive and highly organized feedback projection from the cortex to thalamic neurons that provide input to it. Intriguingly, many corticothalamic (CT) neurons are weakly responsive to peripheral stimuli, or silent altogether. Here using the whisker-to-barrel system, we examine whether the responses of CT neurons and their related thalamic neurons are affected by motor cortex, a prominent source of input to deep layers of the somatosensory cortex. Pharmacological facilitation of motor cortex activity produced using focal, microiontophoresis leads to enhanced whisker-evoked firing of topographically aligned layer 6 neurons, including identified CT cells, and of cells in corresponding regions of the thalamic ventral posterior medial nucleus (VPm barreloids). Together, the findings raise the possibility that cortico-thalamo-cortical circuitry in primary sensory areas is engaged by other functionally related cortical centers, providing a means for context-dependent regulation of information processing within thalamocortical circuits.We investigated how vMCx influence activity in thalamic VPm nucleus in a freely behaving rat. We examine afferent-evoked thalamic activity in animals that are either alert but voluntarily relatively motionless or actively whisking in the air without object contact. Afferent activity is evoked in VPm by means of electrical microstimulation of a single whisker follicle. In some experiments, neural processing in brainstem trigeminal nuclei was either by-passed by means of medial lemniscus stimulation, or altered by pharmacological intervention. We found that sensory responses during voluntary whisker movements, when motor cortex is likely to be active, are reduced relative to responses that occur during periods of wakeful quiescence. Enhancement of thalamic activity during whisking can be observed, however, when signal processing in sub-thalamic centers is either by-passed or experimentally altered. Findings suggest that during voluntary movement activity within the lemniscal system is globally diminished, perhaps at early, brainstem levels at the same time that activity within specific thalamocortical neuronal populations is facilitated. Though activity levels are reduced system-wide, activity within some local circuits may be subject to less net suppression. This decrease in suppression may occur on a moment-to-moment basis in a context-dependent manner. Thus, during voluntary whisker movement, sensory transmission in thalamocortical circuits may be modulated according to specific activation patterns distributed across the motor map

Perspective on the Multiple Pathways to Changing Brain States

In this review article, we highlight several disparate ideas that are linked to changes in brain state (i.e., sleep to arousal, Down to Up, synchronized to de-synchronized). In any discussion of the brain state, we propose that the cortical pyramidal neuron has a central position. EEG recordings, which typically assess brain state, predominantly reflect the activity of cortical pyramidal neurons. This means that the dominant rhythmic activity that characterizes a particular brain state ultimately has to manifest globally across the pyramidal neuron population. During state transitions, it is the long-range connectivity of these neurons that broadcast the resultant changes in activity to many subcortical targets. Structures like the thalamus, brainstem/hypothalamic neuromodulatory systems, and respiratory systems can also strongly influence brain state, and for many decades we have been uncovering bidirectional pathways that link these structures to state changes in the cerebral cortex. More recently, movement and active behaviors have emerged as powerful drivers of state changes. Each of these systems involve different circuits distributed across the brain. Yet, for a system-wide change in brain state, there must be a collaboration between these circuits that reflects and perhaps triggers the transition between brain states. As we expand our understanding of how brain state changes, our current challenge is to understand how these diverse sets of circuits and pathways interact to produce the changes observed in cortical pyramidal neurons

Gamma Band Activity in the Reticular Activating System

This review considers recent evidence showing that cells in three regions of the reticular activating system (RAS) exhibit gamma band activity, and describes the mechanisms behind such manifestation. Specifically, we discuss how cells in the mesopontine pedunculopontine nucleus (PPN), intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD) all fire in the beta/gamma band range when maximally activated, but no higher. The mechanisms behind this ceiling effect have been recently elucidated. We describe recent findings showing that every cell in the PPN have high-threshold, voltage-dependent P/Q-type calcium channels that are essential, while N-type calcium channels are permissive, to gamma band activity. Every cell in the Pf also showed that P/Q-type and N-type calcium channels are responsible for this activity. On the other hand, every SubCD cell exhibited sodium-dependent subthreshold oscillations. A novel mechanism for sleep–wake control based on well-known transmitter interactions, electrical coupling, and gamma band activity is described. The data presented here on inherent gamma band activity demonstrates the global nature of sleep–wake oscillation that is orchestrated by brainstem–thalamic mechanism, and questions the undue importance given to the hypothalamus for regulation of sleep–wakefulness. The discovery of gamma band activity in the RAS follows recent reports of such activity in other subcortical regions like the hippocampus and cerebellum. We hypothesize that, rather than participating in the temporal binding of sensory events as seen in the cortex, gamma band activity manifested in the RAS may help stabilize coherence related to arousal, providing a stable activation state during waking and paradoxical sleep. Most of our thoughts and actions are driven by pre-conscious processes. We speculate that continuous sensory input will induce gamma band activity in the RAS that could participate in the processes of pre-conscious awareness, and provide the essential stream of information for the formulation of many of our actions

Up and down states and memory consolidation across somatosensory, entorhinal, and hippocampal cortices

In the course of a day, brain states fluctuate, from conscious awake information-acquiring states to sleep states, during which previously acquired information is further processed and stored as memories. One hypothesis is that memories are consolidated and stored during "offline" states such as sleep, a process thought to involve transfer of information from the hippocampus to other cortical areas. Up and Down states (UDS), patterns of activity that occur under anesthesia and sleep states, are likely to play a role in this process, although the nature of this role remains unclear. Here we review what is currently known about these mechanisms in three anatomically distinct but interconnected cortical areas: somatosensory cortex, entorhinal cortex, and the hippocampus. In doing so, we consider the role of this activity in the coordination of "replay" during sleep states, particularly during hippocampal sharp-wave ripples. We conclude that understanding the generation and propagation of UDS may provide key insights into the cortico-hippocampal dialogue linking archi- and neocortical areas during memory formation

Dissociable contributions of mediodorsal and anterior thalamic nuclei in visual attentional performance: a comparison using nicotinic and muscarinic cholinergic receptor antagonists

Background: Thalamic subregions mediate various cognitive functions, including attention, inhibitory response control and decision making. Such neuronal activity is modulated by cholinergic thalamic afferents and deterioration of such modulatory signaling has been theorised to contribute to cognitive decline in neurodegenerative disorders. However, the thalamic subnuclei and cholinergic receptors involved in cognitive functioning remain largely unknown. Aims: We investigated whether muscarinic or nicotinic receptors in the mediodorsal thalamus and anterior thalamus contribute to rats’ performance in the five-choice serial reaction time task, which measures sustained visual attention and impulsive action. Methods: Male Long-Evans rats were trained in the five-choice serial reaction time task then surgically implanted with guide cannulae targeting either the mediodorsal thalamus or anterior thalamus. Reversible inactivation of either the mediodorsal thalamus or anterior thalamus were achieved with infusions of the γ-aminobutyric acid-ergic agonists muscimol and baclofen prior to behavioural assessment. To investigate cholinergic mechanisms, we also assessed the behavioural effects of locally administered nicotinic (mecamylamine) and muscarinic (scopolamine) receptor antagonists. Results: Reversible inactivation of the mediodorsal thalamus severely impaired discriminative accuracy and response speed and increased omissions. Inactivation of the anterior thalamus produced less profound effects, with impaired accuracy at the highest dose. In contrast, blocking cholinergic transmission in these regions did not significantly affect five-choice serial reaction time task performance. Conclusions/interpretations: These findings show the mediodorsal thalamus plays a key role in visuospatial attentional performance that is independent of local cholinergic neurotransmission

Simulating Idiopathic Parkinson\u27s Disease by In Vitro and Computational Models

In general there is a wide gap between experimental animal results, especially with respect to neuroanatomical data, and computational modeling. In order to be able to investigate the anatomical and functional properties of afferent and efferent connections between the different nuclei of the basal ganglia, similar studies need to be performed as described in this review for the Substantia Nigra. These studies, though very time-consuming, are essential to decide which pathways play important roles in normal functioning and therefore need to be included in modeling studies. In addition, it should be known what neuroanatomical changes take place resulting from the neurodegeneration associated with Parkinson’s disease and how they affect network behavior. For instance, the direct effects of DBS on motor control are of interest, but since DBS has a low threshold to side effects, additional non-motor pathways are expected to be involved. Including these pathways in network models may shed light on the extent and effect of stimulation. Similarly, as PPN stimulation may have a beneficial influence on gait and balance, different pathways are important regarding the different motor symptoms of Parkinson’s disease