Highlights • During the normal waking state, the brain is in a constant state of internal exploration through the formation and dissolution of resting-state functional networks. • Based on large-scale computer models of the brain, the best fit to observed data comes when the networks are at the ‘edge of instability’. • Such a position is a distinct advantage for the efficiency and speed of network mobilization for perception and action. • We provide theoretical and empirical questions to better link resting-state networks to cognitive architectures.
Highlights • How proteinopathies damage brain networks is a key issue in neurodegenerative disease. • Here, we outline a solution based on the concept of ‘molecular nexopathies’. • The concept is founded on specific interactions of network and protein properties. • This new paradigm has far-reaching biological and clinical implications.
A basic feature of intelligent systems such as the cerebral cortex is the ability to freely associate aspects of perceived experience with an internal representation of the world and make predictions about the future. Here, a hypothesis is presented that the extraordinary performance of the cortex derives from an associative mechanism built in at the cellular level to the basic cortical neuronal unit: the pyramidal cell. The mechanism is robustly triggered by coincident input to opposite poles of the neuron, is exquisitely matched to the large- and fine-scale architecture of the cortex, and is tightly controlled by local microcircuits of inhibitory neurons targeting subcellular compartments. This article explores the experimental evidence and the implications for how the cortex operates.
Synchronised neuronal oscillations at beta frequencies are prevalent in the human motor system, but their function is unclear. In this Opinion article, we propose that the levels of beta oscillations provide a measure of the likelihood that a new voluntary action will need to be actuated. Oscillatory beta activity is in turn modulated by net dopamine levels at sites of cortical input to the basal ganglia. We hypothesise that net dopamine levels are modulated in response to salient internal and external cues. Crucially, the resulting modulation of beta activity is predictive, enabling the appropriate prospective resourcing and preparation of potential actions. Loss of dopamine, as in Parkinson's disease, annuls this function, unless net dopaminergic activity can be elevated through medication.
Neuroelectric oscillations reflect rhythmic shifting of neuronal ensembles between high and low excitability states. In natural settings, important stimuli often occur in rhythmic streams, and when oscillations entrain to an input rhythm their high excitability phases coincide with events in the stream, effectively amplifying neuronal input responses. When operating in a ‘rhythmic mode’, attention can use these differential excitability states as a mechanism of selection by simply enforcing oscillatory entrainment to a task-relevant input stream. When there is no low-frequency rhythm that oscillations can entrain to, attention operates in a ‘continuous mode’, characterized by extended increase in gamma synchrony. We review the evidence for early sensory selection by oscillatory phase-amplitude modulations, its mechanisms and its perceptual and behavioral consequences.
Information that is congruent with existing knowledge (a schema) is usually better remembered than less congruent information. Only recently, however, has the role of schemas in memory been studied from a systems neuroscience perspective. Moreover, incongruent (novel) information is also sometimes better remembered. Here, we review lesion and neuroimaging findings in animals and humans that relate to this apparent paradoxical relationship between schema and novelty. In addition, we sketch a framework relating key brain regions in medial temporal lobe (MTL) and medial prefrontal cortex (mPFC) during encoding, consolidation and retrieval of information as a function of its congruency with existing information represented in neocortex. An important aspect of this framework is the efficiency of learning enabled by congruency-dependent MTL–mPFC interactions.
A recent paradigm shift in systems neuroscience is the division of the human brain into functional networks. Functional networks are collections of brain regions with strongly correlated activity both at rest and during cognitive tasks, and each network is believed to implement a different aspect of cognition. We propose here that anxiety disorders and high trait anxiety are associated with a particular pattern of functional network dysfunction: increased functioning of the cingulo-opercular and ventral attention networks as well as decreased functioning of the fronto-parietal and default mode networks. This functional network model can be used to differentiate the pathology of anxiety disorders from other psychiatric illnesses such as major depression and provides targets for novel treatment strategies.
Several theories have proposed possible functions of adult neurogenesis in learning processes on a systems level, such as the avoidance of catastrophic interference and the encoding of temporal and contextual information, and in emotional behavior. Under the assumption of such functionality of new neurons, the question arises: what are the consequences of adult hippocampal neurogenesis beyond the temporally immediate computational benefit? What might provide the evolutionary advantage of maintaining neurogenesis in the dentate gyrus but almost nowhere else? I propose that over the course of life, activity-dependently regulated adult neurogenesis reveals its true significance in the retained ability for lasting and cumulative network adaptations. The hippocampal precursor cells that generate new neurons with their particular acute function represent a ‘neurogenic reserve’: the potential to remain flexible and plastic in hippocampal learning when the individual is exposed to novelty and complexity.
The retrieval of a memory places it into a plastic state, the result of which is that the memory can be disrupted or even enhanced by experimental treatment. This phenomenon has been conceptualised within a framework of memories being reactivated and then reconsolidated in repeated rounds of cellular processing. The reconsolidation phase has been seized upon as crucial for the understanding of memory stability and, more recently, as a potential therapeutic target in the treatment of disorders such as post-traumatic stress and drug addiction. However, little is known about the reactivation process, or what might be the adaptive function of retrieval-induced plasticity. Reconsolidation has long been proposed to mediate memory updating, but only recently has this hypothesis been supported experimentally. Here, the adaptive function of memory reconsolidation is explored in more detail, with a strong emphasis on its role in updating memories to maintain their relevance.
Caspase-3 has been identified as a key mediator of neuronal programmed cell death. This protease plays a central role in the developing nervous system and its activation is observed early in neural tube formation and persists during postnatal differentiation of the neural network. Caspase-3 activation, a crucial event of neuronal cell death program, is also a feature of many chronic neurodegenerative diseases. This traditional apoptotic function of caspase-3 is challenged by recent studies that reveal new cell death-independent roles for mitochondrial-activated caspase-3 in neurite pruning and synaptic plasticity. These findings underscore the need for further research into the mechanism of action and functions of caspase-3 that may prove useful in the development of novel pharmacological treatments for a diverse range of neurological disorders.