The functional role of cross-frequency coupling

Recent studies suggest that cross-frequency coupling (CFC) might play a functional role in neuronal computation, communication and learning. In particular, the strength of phase-amplitude CFC differs across brain areas in a task-relevant manner, changes quickly in response to sensory, motor and cognitive events, and correlates with performance in learning tasks. Importantly, whereas high-frequency brain activity reflects local domains of cortical processing, low-frequency brain rhythms are dynamically entrained across distributed brain regions by both external sensory input and internal cognitive events. CFC might thus serve as a mechanism to transfer information from large-scale brain networks operating at behavioral timescales to the fast, local cortical processing required for effective computation and synaptic modification, thus integrating functional systems across multiple spatiotemporal scales.     

Convergence of biological and psychological perspectives on cognitive coordination in schizophrenia

The concept of locally specialized functions dominates research on higher brain function and its disorders. Locally specialized functions must be complemented by processes that coordinate those functions, however, and impairment of coordinating processes may be central to some psychotic conditions. Evidence for processes that coordinate activity is provided by neurobiological and psychological studies of contextual disambiguation and dynamic grouping. Mechanisms by which this important class of cognitive functions could be achieved include those long-range connections within and between cortical regions that activate synaptic channels via NMDA-receptors, and which control gain through their voltage-dependent mode of operation. An impairment of these mechanisms is central to PCP-psychosis, and the cognitive capabilities that they could provide are impaired in some forms of schizophrenia. We conclude that impaired cognitive coordination due to reduced ion flow through NMDA-channels is involved in schizophrenia, and we suggest that it may also be involved in other disorders. This perspective suggests several ways in which further research could enhance our understanding of cognitive coordination, its neural basis, and its relevance to psychopathology.     

Functional networks involved in spatial learning strategies in middle-aged rats

Our aim was to assess the way that middle-aged rats solve spatial learning tasks that can be performed using different strategies. We assessed the brain networks involved in these spatial learning processes using Principal Component Analysis. Two tasks were performed in a complex context, a four-arm radial maze, in which each group must use either an allocentric or an egocentric strategy. Another task was performed in a simple T-maze in which rats must use an egocentric strategy. Brain metabolic activity was quantified to evaluate neural changes related to spatial learning in the described tasks. Our findings revealed that two functional networks are involved in spatial learning in aged rats. One of the networks, spatial processing, is composed of brain regions involved in the integration of sensory and motivational information. The other network, context-dependent processing, mainly involves the dorsal hippocampus and is related to the processing of contextual information from the environment. Both networks work together to solve spatial tasks in a complex spatial environment.     

Attentional functions of cortical cholinergic inputs: what does it mean for learning and memory?

The hypothesis that cortical cholinergic inputs mediate attentional functions and capacities has been extensively substantiated by experiments assessing the attentional effects of specific cholinotoxic lesions of cortical cholinergic inputs, attentional performance-associated cortical acetylcholine release, and the effects of pharmacological manipulations of the excitability of basal forebrain corticopetal cholinergic projections on attentional performance. At the same time, numerous animal experiments have suggested that the integrity of cortical cholinergic inputs is not necessary for learning and memory, and a dissociation between the role of the cortical cholinergic input system in attentional functions and in learning and memory has been proposed. We speculate that this dissociation is due, at least in part, to the use of standard animal behavioral tests for the assessment of learning and memory which do not sufficiently tax defined attentional functions. Attentional processes and the allocation of attentional capacities would be expected to influence the efficacy of the acquisition and recall of declarative information and therefore, persistent abnormalities in the regulation of the cortical cholinergic input system may yield escalating impairments in learning and memory. Furthermore, the cognitive effects of loss of cortical cholinergic inputs are augmented by the disruption of the top-down regulation of attentional functions that normally acts to optimize information processing in posterior cortical areas. Because cortical cholinergic inputs play an integral role in the mediation of attentional processing, the activity of cortical cholinergic inputs is hypothesized to also determine the efficacy of learning and memory.     

Proactive control and episodic binding in context processing effects

Decision making often involves using prior contextual information to evaluate relevant events. A laboratory equivalent of context processing situations, the AX-Continuous Performance Task (AX-CPT), yields errors when a target probe appears in a nontarget context, or when a nontarget probe appears in a target context. According to goal-driven accounts, context information is used for top-down preparation towards processing of context-appropriate information. Performance costs in nontarget trials are attributed to inefficient cognitive control. In contrast, the episodic binding account predicts that prior experiences with combinations of a context, probe, and response are bound in episodic memory and thus bias future actions. Performance costs in this view are caused by the need to overrule prepotent associations. The current experiments tested the relative importance of proactive cognitive control versus episodic learning of appropriate stimulus-response relations for CPT performance. Support was obtained for both contributions.     

Retrieval experience as a modifier of future encoding: another test effect

Research on how individuals monitor their level of comprehension during study paints a picture of learners as being insensitive to many of the factors or conditions of learning that can enhance long-term retention and transfer. In previous research, however, deWinstanley and Bjork (2004) demonstrated that learners--if made sensitive to the memorial benefits of generation in the context of an informative test following study of a text passage in which they had encoded both to-be-read and to-be-generated critical items--then became more effective processors of future to-be-read information presented in a 2nd text passage. In Experiments 1 and 2 of the present research, we explored the potential applicability of this effect by testing whether it could survive certain types of activity-filled delays. In Experiments 3 and 4, we tested whether enhanced processing of contextual information, an encoding strategy that could possibly have been discovered by participants during the testing episode for the 1st text passage, was a potential underlying cause of this effect. Together, our results bring to light an additional benefit of test taking and point to what might be considered necessary and sufficient conditions for leading learners to become more effective processors of future to-be-learned information.     

Context Memory in Korsakoff’s Syndrome

Memory for contextual information and target-context integration are crucial for successful episodic memory formation and are impaired in patients with Korsakoff's syndrome. In this paper we review the evidence for the notion that a context memory deficit makes an important contribution to the amnesia in these patients. First, we focus on anterograde memory for contextual (spatial and temporal) information. Next, the use of contextual cues in memory retrieval is examined and their role in retrograde amnesia and confabulation. Evidence on the role of contextual cues and associations in working memory is discussed in relation to the underlying neurocognitive mechanisms and their dissociation from long-term encoding. Finally, we focus on implicit learning of contextual information in Korsakoff patients. It can be concluded that Korsakoff patients are impaired in the explicit processing of contextual information and in target-context binding, both in long-term (retrograde and anterograde) memory and in working memory. These results extend the context memory deficit hypothesis. In contrast, implicit contextual learning is relatively preserved in these patients. These findings are discussed in relation to evidence of dysfunction of the extended diencephalic-hippocampal memory circuit in Korsakoff's syndrome.     

Enhanced cholinergic suppression of previously strengthened synapses enables the formation of self-organized representations in olfactory cortex

Computational modeling assists in analyzing the specific functional role of the cellular effects of acetylcholine within cortical structures. In particular, acetylcholine may regulate the dynamics of encoding and retrieval of information by regulating the magnitude of synaptic transmission at excitatory recurrent connections. Many abstract models of associative memory function ignore the influence of changes in synaptic strength during the storage process and apply the effect of these changes only during a so-called recall-phase. Efforts to ensure stable activity with more realistic, continuous updating of the synaptic strength during the storage process have shown that the memory capacity of a realistic cortical network can be greatly enhanced if cholinergic modulation blocks transmission at synaptic connections of the association fibers during the learning process. We here present experimental data from an olfactory cortex brain slice preparation showing that previously potentiated fibers show significantly greater suppression (presynaptic inhibition) by the cholinergic agonist carbachol than unpotentiated fibers. We conclude that low suppression of non-potentiated fibers during the learning process ensures the formation of self-organized representations in the neural network while the higher suppression of previously potentiated fibers minimizes interference between overlapping patterns. We show in a computational model of olfactory cortex, that, together, these two phenomena reduce the overlap between patterns that are stored within the same neural network structure. These results further demonstrate the contribution of acetylcholine to mechanisms of cortical plasticity. The results are consistent with the extensive evidence supporting a role for acetylcholine in encoding of new memories and enhancement of response to salient sensory stimuli.     

Empathy and contextual social cognition

Empathy is a highly flexible and adaptive process that allows for the interplay of prosocial behavior in many different social contexts. Empathy appears to be a very situated cognitive process, embedded with specific contextual cues that trigger different automatic and controlled responses. In this review, we summarize relevant evidence regarding social context modulation of empathy for pain. Several contextual factors, such as stimulus reality and personal experience, affectively link with other factors, emotional cues, threat information, group membership, and attitudes toward others to influence the affective, sensorimotor, and cognitive processing of empathy. Thus, we propose that the frontoinsular-temporal network, the so-called social context network model (SCNM), is recruited during the contextual processing of empathy. This network would (1) update the contextual cues and use them to construct fast predictions (frontal regions), (2) coordinate the internal (body) and external milieus (insula), and (3) consolidate the context–target associative learning of empathic processes (temporal sites). Furthermore, we propose these context-dependent effects of empathy in the framework of the frontoinsular-temporal network and examine the behavioral and neural evidence of three neuropsychiatric conditions (Asperger syndrome, schizophrenia, and the behavioral variant of frontotemporal dementia), which simultaneously present with empathy and contextual integration impairments. We suggest potential advantages of a situated approach to empathy in the assessment of these neuropsychiatric disorders, as well as their relationship with the SCNM.     

Behavioural context and a distributed system: metabolic mapping studies of the basal ganglia.

Behavioural context is known to affect neural activity in the striatum. Responses of single cells increase to rewarding stimuli, or drop out as a bar press or saccade is learned. Networks that can accomplish a unique response to changing contexts are of particular interest to systems neuroscience and were a part of Hebb's interest in perception and learning. An overall map of the striatum that localizes changes related to this remarkable phenomenon of contextual responses contributes to our understanding of anatomical substrates of neural systems that integrate information, and may lead us to new striatal regions to study synaptic mechanisms of learning.     

Coarse threat images reveal theta oscillations in the amygdala: A magnetoencephalography study

Neurocognitive models propose a specialized neural system for processing threat-related information, in which the amygdala plays a key role in the analysis of threat cues. fMRI research indicates that the amygdala is sensitive to coarse visual threat relevant information—for example, low spatial frequency (LSF) fearful faces. However, fMRI cannot determine the temporal or spectral characteristics of neural responses. Consequently, we used magnetoencephalography to explore spatiotemporal patterns of activity in the amygdala and cortical regions with blurry (LSF) and normal angry, fearful, and neutral faces. Results demonstrated differences in amygdala activity between LSF threat-related and LSF neutral faces (50–250 msec after face onset). These differences were evident in the theta range (4–8 Hz) and were accompanied by power changes within visual and frontal regions. Our results support the view that the amygdala is involved in the early processing of coarse threat related information and that theta is important in integrating activity within emotion-processing networks.     

Generative models, brain function and neuroimaging

The representational capacity and inherent function of any neuron, neuronal population or cortical area in the brain is dynamic and context-sensitive. Functional integration, or interactions among brain systems, that employ driving (bottom up) and backward (top-down) connections, mediate this adaptive and contextual specialisation. A critical consequence is that neuronal responses, in any given cortical area, can represent different things at different times. This can have fundamental implications for the design of brain imaging experiments and the interpretation of their results. Our arguments are developed under generative models of brain function, where higher-level systems provide a prediction of the inputs to lower-level regions. Conflict between the two is resolved by changes in the higher-level representations, which are driven by the ensuing error in lower regions, until the mismatch is "cancelled". From this perspective the specialisation of any region is determined both by bottom-up driving inputs and by top-down predictions. Specialisation is therefore not an intrinsic property of any region but depends on both forward and backward connections with other areas. Because the latter have access to the context in which the inputs are generated they are in a position to modulate the selectivity or specialisation of lower areas. The implications for classical models (e.g., classical receptive fields in electrophysiology, classical specialisation in neuroimaging and connectionism in cognitive models) are severe and suggest these models may provide incomplete accounts of real brain architectures. Here we focus on the implications for cognitive neuroscience in the context of neuroimaging.     

Local intracortical circuitry not only for feature binding but also for rapid neuronal responses

Neurons of primary sensory cortices are known to have specific responsiveness to elemental features. To express more complex sensory attributes that are embedded in objects or events, the brain must integrate them. This is referred to as feature binding and is reflected in correlated neuronal activity. We investigated how local intracortical circuitry modulates ongoing-spontaneous neuronal activity, which would have a great impact on the processing of subsequent combinatorial input, namely, on the correlating (binding) of relevant features. We simulated a functional, minimal neural network model of primary visual cortex, in which lateral excitatory connections were made in a diffusive manner between cell assemblies that function as orientation columns. A pair of bars oriented at specific angles, expressing a visual corner, was applied to the network. The local intracortical circuitry contributed not only to inducing correlated neuronal activation and thus to binding the paired features but also to making membrane potentials oscillate at firing-subthreshold during an ongoing-spontaneous time period. This led to accelerating the reaction speed of principal cells to the input. If the lateral excitatory connections were selectively (instead of “diffusively”) made, hyperpolarization in ongoing membrane potential occurred and thus the reaction speed was decelerated. We suggest that the local intracortical circuitry with diffusive connections between cell assemblies might endow the network with an ongoing subthreshold neuronal state, by which it can send the information about combinations of elemental features rapidly to higher cortical stages for their full and precise analyses.     

Doing without schema hierarchies: a recurrent connectionist approach to normal and impaired routine sequential action

In everyday tasks, selecting actions in the proper sequence requires a continuously updated representation of temporal context. Previous models have addressed this problem by positing a hierarchy of processing units, mirroring the roughly hierarchical structure of naturalistic tasks themselves. The present study considers an alternative framework, in which the representation of context depends on recurrent connections within a network mapping from environmental inputs to actions. The ability of this approach to account for human performance was evaluated by applying it, through simulation, to a specific everyday task. The resulting model learned to deal flexibly with a complex set of sequencing constraints, encoding contextual information at multiple time scales within a single, distributed internal representation. Degrading this representation led to errors resembling those observed both in everyday behavior and in apraxia. Analysis of the model's function yielded numerous predictions relevant to both normal and apraxic performance.     

Stimulus generalization, context change, and forgetting

Forgetting is often attributed to retrieval failure caused by background contextual cues changing over time. However, generalization between stimuli may increase over time and make them increasingly interchangeable. If this effect occurs with contextual cues, it might cancel any effect of a changing context. The authors review the evidence and suggest a resolution of this paradox. Although generalization gradients can change over time, the effect is not always strong. Increased responding to nontarget stimuli is not often shown, and few studies have demonstrated such changes with contextual cues in a way that rules out other interpretations. Even this example of forgetting may be caused by retrieval failure. The physical contexts manipulated in learning and memory experiments themselves occur within a superordinate temporal context and can thus be forgotten with no inherent challenge to a context-change account of forgetting.     

Linking major depression and the neural substrates of associative processing

It has been proposed that mood correlates with the breadth of associative thinking. Here we set this hypothesis to the test in healthy and depressed individuals. Generating contextual associations engages a network of cortical regions including the parahippocampal cortex (PHC), retrosplenial complex, and medial prefrontal cortex. The link between mood, associative processing, and its underlying cortical infrastructure provides a promising avenue for elucidating the mechanisms underlying the cognitive impairments in major depressive disorder (MDD). The participants included 15 nonmedicated individuals with acute major depressive episodes and 15 healthy matched controls. In an fMRI experiment, participants viewed images of objects that were either strongly or weakly associated with a specific context (e.g., a beach chair vs. a water bottle) while rating the commonality of each object. Analyses were performed to examine the brain activation and structural differences between the groups. Consistent with our hypothesis, controls showed greater activation of the contextual associations network than did depressed participants. In addition, PHC structural volume was correlated with ruminative tendencies, and the volumes of the hippocampal subfields were significantly smaller in depressed participants. Surprisingly, depressed participants showed increased activity in the entorhinal cortex (ERC), as compared with controls. We integrated these findings within a mechanistic account linking mood and associative thinking and suggest directions for the future.     

Contextual cueing of visual attention

Visual context information constrains what to expect and where to look, facilitating search for and recognition of objects embedded in complex displays. This article reviews a new paradigm called contextual cueing, which presents well-defined, novel visual contexts and aims to understand how contextual information is learned and how it guides the deployment of visual attention. In addition, the contextual cueing task is well suited to the study of the neural substrate of contextual learning. For example, amnesic patients with hippocampal damage are impaired in their learning of novel contextual information, even though learning in the contextual cueing task does not appear to rely on conscious retrieval of contextual memory traces. We argue that contextual information is important because it embodies invariant properties of the visual environment such as stable spatial layout information as well as object covariation information. Sensitivity to these statistical regularities allows us to interact more effectively with the visual world.     

Integrating face and voice in person perception

Integration of information from face and voice plays a central role in our social interactions. It has been mostly studied in the context of audiovisual speech perception: integration of affective or identity information has received comparatively little scientific attention. Here, we review behavioural and neuroimaging studies of face-voice integration in the context of person perception. Clear evidence for interference between facial and vocal information has been observed during affect recognition or identity processing. Integration effects on cerebral activity are apparent both at the level of heteromodal cortical regions of convergence, particularly bilateral posterior superior temporal sulcus (pSTS), and at 'unimodal' levels of sensory processing. Whether the latter reflects feedback mechanisms or direct crosstalk between auditory and visual cortices is as yet unclear.     

Priming visual face-processing mechanisms: electrophysiological evidence

Accumulated evidence from electrophysiology and neuroimaging suggests that face perception involves extrastriate visual mechanisms specialized in processing physiognomic features and building a perceptual representation that is categorically distinct and can be identified by face-recognition units. In the present experiment, we recorded event-related brain potentials in order to explore possible contextual influences on the activity of this perceptual mechanism. Subjects were first exposed to pairs of small shapes, which did not elicit any face-specific brain activity. The same stimuli, however, elicited face-specific brain activity after subjects saw them embedded in schematic faces, which probably primed the subjects to interpret the shapes as schematic eyes. No face-specific activity was observed when objects rather than faces were used to form the context. We conclude that the activity of face-specific extrastriate perceptual mechanisms can be modulated by contextual constraints that determine the significance of the visual input.     

Dissociated roles for the lateral and medial septum in elemental and contextual fear conditioning

Extensive evidence indicates that the septum plays a predominant role in fear learning, yet the direction of this control is still a matter of debate. Increasing data suggest that the medial (MS) and lateral septum (LS) would be differentially required in fear conditioning depending on whether a discrete conditional stimulus (CS) predicts, or not, the occurrence of an aversive unconditional stimulus (US). Here, using a tone CS-US pairing (predictive discrete CS, context in background) or unpairing (context in foreground) conditioning procedure, we show, in mice, that pretraining inactivation of the LS totally disrupted tone fear conditioning, which, otherwise, was spared by inactivation of the MS. Inactivating the LS also reduced foreground contextual fear conditioning, while sparing the higher level of conditioned freezing to the foreground (CS-US unpairing) than to the background context (CS-US pairing). In contrast, inactivation of the MS totally abolished this training-dependent level of contextual freezing. Interestingly, inactivation of the MS enhanced background contextual conditioning under the pairing condition, whereas it reduced foreground contextual conditioning under the unpairing condition. Hence, the present findings reveal a functional dissociation between the LS and the MS in Pavlovian fear conditioning depending on the predictive value of the discrete CS. While the requirement of the LS is crucial for the appropriate processing of the tone CS-US association, the MS is crucial for an appropriate processing of contextual cues as foreground or background information.