To understand schizophrenia, a linking hypothesis is needed that shows how brain mechanisms lead to behavioral functions in normals, and also how breakdowns in these mechanisms lead to behavioral symptoms of schizophrenia. Such a linking hypothesis is now available that complements the discussion offered by Phillips & Silverstein (P&S).

Although research on the mismatch negativity (MMN) has been ongoing for 40 years, the generation process of the MMN remains largely unknown. In this study, we used a single-trial EEG-fMRI coupling method which can analyse neural activity with both high temporal and high spatial resolution and thus assess the generation process of the MMN. We elicited the MMN with an auditory oddball paradigm while recording simultaneous EEG and fMRI. We divided the MMN into five equal-durational phases. Utilizing the single-trial variability (...) of the MMN, we analysed the neural generators of the five phases, thereby determining the spatiotemporal generation process of the MMN. We found two distinct bottom-up prediction error propagations: first from the auditory cortex to the motor areas and then from the auditory cortex to the inferior frontal gyrus (IFG). Our results support the regularity-violation hypothesis of MMN generation. (shrink)

Numerous searches have failed to identify a single co-occurrence of total blindness and schizophrenia. Evidence that blindness causes loss of certain NMDA-receptor functions is balanced by reports of compensatory gains. Connections between visual and anterior cingulate NMDA-receptor systems may help to explain how blindness could protect against schizophrenia.

N-methyl-d-aspartate receptor (NMDAR) dysfunction plays a crucial role in schizophrenia, leading to impairments in cognitive coordination. NMDAR agonists (e.g., glycine) ameliorate negative and cognitive symptoms, consistent with NMDAR models. However, not all types of cognitive coordination use NMDAR. Further, not all aspects of cognitive coordination are impaired in schizophrenia, suggesting the need for specificity in applying the cognitive coordination construct.

This commentary compares clinical aspects of ketamine with the amphetamine model of schizophrenia. Hallucinations and loss of insight, associated with amphetamine, seem more schizophrenia-like. Flat affect encountered with ketamine is closer to the clinical presentation in schizophrenia. We argue that flat affect is not a sign of schizophrenia, but rather, a risk factor for chronic schizophrenia.

Encoding sensory events entails processing of several physical attributes. Is the processing of any of these attributes a pre-requisite of conscious awareness? This selective review examines a recent set of behavioral and event-related potentials, studies conducted in patients with visual and auditory unilateral neglect or extinction, with the aim of establishing what aspects of initial processing are impaired in these patients. These studies suggest that extinguished visual stimuli excite the sensory cortices, but perhaps to a lesser degree than acknowledged stimuli (...) do. However, encoding spatial attributes of auditory and visual stimuli appear to be preferentially impaired. In light of results from patients with other neuro-behavioral deficits, it is argued that egocentric spatial information is an essential pre-requisite for knowing that an external event occurred. In contrast, information handled by mostly domain-specific circuits, such as in the ventral temporal lobe, supports awareness of the identity of a stimulus, but not of its mere presence. Without spatial information, the stimulus identity will remain implicit. (shrink)

Detecting and correcting execution errors is crucial for safe and efficient goal-directed behavior. Despite intensive investigations on error processing, the cognitive foundations of this process remain unclear. Based on the presumed relation between executive attention and error processing, we implemented a seven-day EA intervention by adopting the Posner cueing paradigm to test the potential causal link from EA to error processing in healthy adults. The experimental group was trained on the Posner cueing paradigm, with a ratio of invalid cue trials (...) to valid cue trials of 5:1 and a corresponding ratio of 1:1 in the active control group. We found that the EA intervention improved EA across intervention sessions. Critically, after the EA intervention, the HEA group showed that post-error accuracy was restored to the same level as the post-correct accuracy. However, post-error slowing and the flanker effect were not modulated by the EA intervention. Furthermore, we observed that the changes in the accuracy of VC trials positively predicted the changes in PEA and that the two groups were classified according to the changes in PEA with a 61.3% accuracy. Based on these results, we propose that EA causally drives error processing. And the capabilities of the “actively catch” more attention resources and the automatic mismatch processing developed after EA intervention is transferable to error processing, thereby directly resulting in the gains in post-error adjustments. Our work informs the potential cognitive mechanisms underlying this causal link. (shrink)

The claim that the disorganized subtype of schizophrenia results from glutamate hypofunction is enhanced by consideration of current subtypology of schizophrenia, symptom definition, interdependence of neurotransmitters, and the nature of the data needed to support the hypothesis. Careful specification clarifies the clinical reality of disorganization as a feature of schizophrenia and increases the utility of the subtype.

Phillips & Silverstein emphasize the gain-control properties of NMDA synapses in cognitive coordination. We endorse their view and suggest that NMDA synapses play a crucial role in biased attentional competition and (visual) working memory. Our simulations show that NMDA synapses can control the storage rate of visual objects. We discuss specific predictions of our model about cognitive effects of NMDA-antagonists and schizophrenia.

Phillips & Silverstein offer an exciting synthesis of ongoing efforts to link the clinical and cognitive manifestations of schizophrenia with cellular accounts of its pathophysiology. We applaud their efforts but wonder whether the highly inclusive notion of “context” adequately captures some important details regarding schizophrenia and NMDA/glutamate function that are suggested by work on language processing and cognitive electrophysiology.

In this comment, a picture of ERP research is sketched that is slightly different from Hardcastle's account, in that it emphasises the functional characterisation of ERP components rather than the neurophysiological connections. It is suggested that selection pressure of ERP work on cognitive and neurophysiological theories and vice versa is a more apt metaphor for intertheoretical relations in this field than explanatory extension. Secondly, it is argued that the temporal characteristics of ERP components do not support Hardcastle's claim that they (...) may be used to fix timing in phenomenal consciousness. Although I agree that ERP components, cautiously interpreted, can contribute to the identification of substages of information processing, rather than refuting Dennett and Kinsbourne, her ERP data seem compatible with a multiple drafts model. (shrink)

Impairments in cognitive coordination in schizophrenia are supported by phenomenological data that suggest deficits in the processing of visual context. Although the target article is sympathetic to such a phenomenological perspective, we argue that the relevance of phenomenological data for a wider understanding of consciousness in schizophrenia is not sufficiently addressed by the authors.

Neurophysiological investigations of the past two decades have consistently demonstrated a deficit in sensory gating associated with schizophrenia. Phillips & Silverstein interpret this impairment as being consistent with cognitive coordination dysfunction. However, the physiological mechanisms that underlie sensory gating have not been shown to involve gamma-band oscillations or NMDA-receptors, both of which are critical neural elements in the cognitive coordination model.

It is proposed that cortical activity is normally coordinated across synaptically connected areas and that this coordination supports cognitive coherence relations. This view is consistent with the NMDA- hypoactivity hypothesis of the target article in regarding disorganization symptoms in schizophrenia as arising from disruption of normal interareal coordination. This disruption may produce abnormal contextual effects in the cortex that lead to anomalous cognitive coherence relations.

This work "cardiosensitivity, emotion processing and behavior" is concerned with the relevance of interoceptive sensitivity for emotion processing and behavioral control. The first part of the monograph elaborately outlines theoretical models underscoring the importance of somatic markers and bodily signals for feelings, emotion, decision making and behavior. Ongoing insights of emotion research and neuroanatomic fundamentals of emotion processing and visceroception are illustrated based on current neuroscientific results. In the second part of the work these models and findings provide a basis (...) for the examination of the relationship between interoceptive sensitivity and a) emotion processing using paradigms of EEG research, analyzing both the higher-order processing and the rapid, early processing of emotional and neutral, visual stimuli, and b) behavioral control of mental, emotional and physical stress, analyzing behavioral and physiological variables. The results of the studies demonstrated that interoceptive sensitivity is remarkably positively related to the intensity of both higher-order processing of emotional, visual stimuli and early, visual processing of rapidly presented emotional pictures at temporo-occipital brain regions. Behavioral and physiological data from the behavioral studies showed that persons with good interoceptive sensitivity demonstrate a more subtle and cautious behavioral self-control of mental, emotional as well as physical stress than persons with poor interoceptive sensitivity. The findings are discussed within the context of the described models by James and Damasio as well as topical findings from neuroscientific emotion research. Finally, the results are integrated within a detailed survey on future research on interoception. (shrink)

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. Key Words: attention; cerebral cortex; cognitive coordination; cognitive neuropsychiatry; cognitive neuropsychology; context disorganization; Gamma rhythms; Gestalt theory; glutamate; grouping; memory; NMDA-receptors; PCP-psychosis; perceptual organization; schizophrenia. (shrink)

Automatic detection of information changes in the visual environment is crucial for individual survival. Researchers use the oddball paradigm to study the brain’s response to frequently presented stimuli and occasionally presented stimuli. The component that can be observed in the difference wave is called visual mismatch negativity, which is obtained by subtracting event-related potentials evoked by the deviant from ERPs evoked by the standard. There are three hypotheses to explain the vMMN. The sensory fatigue hypothesis considers that weakened neural activity (...) caused by repetition results in decreased ERPs of the standard. The memory trace hypothesis proposes that vMMN results from increased responses to the deviant. The predictive coding hypothesis attributes the difference to enhanced responses for deviants and suppression for standards. However, when distinguishing between these effects, previous researchers did not consider the effect of low-level features on the vMMN. In this experiment, we used face sequences composed of different emotions and presented an oddball sequence, a reverse oddball sequence, and an equiprobable sequence to participants. The deviant of the oddball sequence was subtracted from the standard of the oddball sequence, the reverse oddball sequence, and the same type of stimulus of the equiprobable sequence to get oddball-vMMN, reverse oddball-vMMN, and equiprobable-vMMN, respectively. The results showed no significant difference between vMMN2 and vMMN3 in 100–350 ms following stimulus onset, while the vMMN effect was significant, indicating that the probability of the standard did not affect vMMN, which supported the memory trace hypothesis. Additionally, the fearful-related vMMN were more negative than the neutral-related vMMN within the range of 100–150 ms, suggesting a negative bias. We analyzed the source location of different vMMNs. There was no significant difference in brain regions between different vMMNs. Time-frequency analysis showed that the deviant had stronger theta-band oscillatory than the standard. However, there was no difference between vMORs2 and vMORs3, indicating that vMORs reflect an enhanced response to the deviant in terms of neural oscillation, supporting the memory trace hypothesis. (shrink)

The cognitive mind-brain is haunted by the ghost of consciousness. Cognitive science must face this ghost, since consciousness is perhaps the most important mental phenomenon: it forms a seemingly united, multimodal phenomenological world around the subject who experiences this world from a certain point of view. Many current approaches to consciousness fail to illuminate the nature of this “experienced world”. Some philosophers want to eliminate consciousness from science for good, others build theories in which the concept of consciousness is distorted (...) beyond recognition. I argue that elimination and Daniel Dennett's “multiple drafts” model do not offer genuine explanations for consciousness. However, certain empirically-based approaches to consciousness succeed in exorcising its ghostly reputation and, at the same time, in preserving the experienced world of consciousness as an important explanandum. (shrink)

Using a classical conditioning technique, this study investigated whether nonconscious associative learning could be indexed by event-related brain activity . There were three phases. In a preconditioning baseline phase, pleasant and unpleasant facial schematics were presented in awareness . A conditioning phase followed, in which stimuli were presented outside awareness , with an unpleasant face linked to an aversive shock and a pleasant face not linked to a shock. The third, postconditioning phase, involved stimulus presentations in awareness . Evidence for (...) acquisition of a conditional response was sought by comparing suprathreshold pre- and postconditioning phases, as well as in the subthreshold conditioning phase itself. For the pre-postconditioning phase analyses, significant ERP component differences differentiating CS+ and CS− were observed for N1, P2, and especially P3. For the conditioning phase, significant differences were observed in the 100–400 ms. post-stimulus region reflecting a CS+ processing negativity. Brain activity does indeed index the acquisition of a conditional response to subthreshold stimuli. Associative learning can occur outside awareness. (shrink)

The target article presents a model for schizophrenia extending four levels of abstraction: molecules, cells, cognition, and syndrome. An important notion in the model is that of coordination, applicable to both the level of cells and of cognition. The molecular level provides an “implementation” of the coordination at the cellular level, which in turn underlies the coordination at the cognitive level, giving rise to the clinical symptoms.

Phillips & Silverstein argue that a range of cognitive disturbances in schizophrenia result from a deficit in cognitive coordination attributable to NMDA receptor dysfunction. We suggest that the viability of this hypothesis would be further supported by explicit implementation in a computational framework that can produce quantitative estimates of the behavior of both healthy individuals and individuals with schizophrenia.

In the cocktail party situation, people with normal hearing usually follow a single speaker among multiple concurrent ones. However, there is no agreement in the literature as to whether the background is segregated into multiple streams/speakers. The current study varied the number of concurrent speech streams and investigated target detection and memory for the contents of a target stream as well as the processing of distractors. A male-voiced target stream was either presented alone (single-speech), together with one male-voiced distractor (one-distractor), (...) or a male- and a female-voiced distractor (two-distractor). Behavioral measures of target detection and content tracking performance as well as target- and distractor detection related event-related brain potentials (ERPs) were assessed. We found that the N2 amplitude decreased whereas the P3 amplitude increased from the single-speech to the concurrent speech streams conditions. Importantly, the behavioral effect of distractors differed between the conditions with one vs. two distractor speech streams and the non-zero voltages in the N2 time window for distractor numerals and in the P3 time window for syntactic violations appearing in the non-target speech stream significantly differed between the one- and two-distractor conditions for the same (male) speaker. These results support the notion that the two background speech streams are segregated, as they show that distractors and syntactic violations appearing in the non-target streams are processed even when two speech non-target speech streams are delivered together with the target stream. (shrink)

Schizophrenics exhibit a deficit in theory of mind (ToM), but an intact theory of biology (ToB). One explanation is that ToM relies on an independent module that is selectively damaged. Phillips & Silverstein's analyses suggest an alternative: ToM requires the type of coordination that is impaired in schizophrenia, whereas ToB is spared because this type of coordination is not involved.

The Phillips & Silverstein model of NMDA-mediated coordination deficits provides a useful heuristic for the study of schizophrenic cognition. However, the model does not specifically account for the development of schizophrenia-spectrum disorders. The P&S model is compared to Meehl's seminal model of schizotaxia, schizotypy, and schizophrenia, as well as the model of schizophrenic cognitive dysfunction posited by McCarley and colleagues.

Although context-processing deficits may be core features of schizophrenia, context remains a poorly defined concept. To test Phillips & Silverstein's model, we need to operationalize context more precisely. We offer several useful ways of framing context and discuss enhancing or facilitating schizophrenic patients' performance under different contextual situations. Furthermore, creativity may be a byproduct of cognitive uncoordination.

This commentary challenges the authors to use their computational modeling techniques to support one of their central claims: that schizophrenic deficits in bottom-up (Gestalt-type tasks) and top-down (cognitive control tasks) context processing tasks arise from the same dysfunction. Further clarification about the limits of cognitive coordination would also strengthen the hypothesis.

Evidence for a dysfunction in cognitive coordination in schizophrenia is emerging, but it is not specific enough to prove (or disprove) this long-standing hypothesis. Many aspects of the external world are spatially mapped in the brain. A comprehensive internal representation relies on integration of information across space. Focus on spatial integration in the perceptual and cognitive processes will generate empirical data that shed light on the pathophysiology of schizophrenia.

Using a classical conditioning technique, this study investigated whether nonconscious associative learning could be indexed by event-related brain activity . There were three phases. In a preconditioning baseline phase, pleasant and unpleasant facial schematics were presented in awareness . A conditioning phase followed, in which stimuli were presented outside awareness , with an unpleasant face linked to an aversive shock and a pleasant face not linked to a shock. The third, postconditioning phase, involved stimulus presentations in awareness . Evidence for (...) acquisition of a conditional response was sought by comparing suprathreshold pre- and postconditioning phases, as well as in the subthreshold conditioning phase itself. For the pre-postconditioning phase analyses, significant ERP component differences differentiating CS+ and CS− were observed for N1, P2, and especially P3. For the conditioning phase, significant differences were observed in the 100–400 ms. post-stimulus region reflecting a CS+ processing negativity. Brain activity does indeed index the acquisition of a conditional response to subthreshold stimuli. Associative learning can occur outside awareness. (shrink)

The emotion of surprise entails a complex of immediate responses, such as cognitive interruption, attention allocation to, and more systematic processing of the surprising stimulus. All these processes serve the ultimate function to increase processing depth and thus cognitively master the surprising stimulus. The present account introduces phasic negative affect as the underlying mechanism responsible for this switch in operating mode. Surprising stimuli are schema-discrepant and thus entail cognitive disfluency, which elicits immediate negative affect. This affect in turn works like (...) a phasic cognitive tuning switching the current processing mode from more automatic and heuristic to more systematic and reflective processing. Directly testing the initial elicitation of negative affect by surprising events, the present experiment presented high and low surprising neutral trivia statements to N = 28 participants while assessing their spontaneous facial expressions via facial electromyography. High compared to low surprising trivia elicited higher corrugator activity, indicative of negative affect and mental effort, while leaving zygomaticus (positive affect) and frontalis (cultural surprise expression) activity unaffected. Future research shall investigate the mediating role of negative affect in eliciting surprise-related outcomes. (shrink)

Phillips & Silverstein's focus on schizophrenia as a failure of “cognitive coordination” is welcome. They note that a simple hypothesis of reduced Gamma synchronisation subserving impaired coordination does not fully account for recent observations. We suggest that schizophrenia reflects a dynamic compensation to a core deficit of coordination, expressed either as hyper- or hyposynchronisation, with neurotransmitter systems and arousal as modulatory mechanisms.

Mechanisms that contribute to perceptual processing dysfunction in schizophrenia were examined by Phillips & Silverstein, and formulated as involving disruptions in both local and higher-level coordination of signals. We agree that dysfunction in the coordination of cognitive functions (disconnection) is also indicated for many of the linguistic processing deficits documented for schizophrenia. We suggest, however, that it may be necessary to add a timing mechanism to the theoretical account.

In chronic schizophrenic patients with both positive and negative symptoms (see Table 1), interhemispheric connections at the high frequency beta2-rhythm are absent during cognitive tasks, in contrast to normal controls, who have many interhemispheric connections at this frequency in the same situation. Connectivity is a fundamental brain feature, evidently greatly promoted by the NMDA system. It is a more reliable measure of brain function than the spectral power of this rhythm.

Although interesting, the hypotheses proposed by Phillips & Silverstein lack unifying structure both in specific mechanisms and in cited evidence. They provide little to support the notion that low-level sensory processing and high-level cognitive coordination share dynamic grouping by synchrony as a common processing mechanism. We suggest that more realistic large-scale modeling at multiple levels is needed to address these issues.

This commentary highlights methods for using scalp EEG to make inferences about contextual field interactions, which, in view of the target article, may be specially relevant to the study of schizophrenia. Although scalp EEG has limited spatial resolution, prior knowledge combined with experimental manipulations may be used to strengthen inferences about underlying brain processes. Both spatial and temporal context are discussed within the framework of nonlinear interactions. Finally, results from a visual contour integration EEG pilot study are summarized in view (...) of a hypothesis that relates receptive field and contextual field processing to evoked and induced activity, respectively. (shrink)

Context, connection, and coordination (CCC) describe well where the problems that apply to thought-disordered patients with schizophrenia lie. But they may be part of the experience of those with other symptom constellations. Switching is an important mechanism to allow context to be applied appropriately to changing circumstances. In some cases, NMDA-voltage modulations may be central, but gain and shift are also functions that monoaminergic systems express in CCC.

Studies suggest that reward and emotion are interdependent. However, there are discrepancies regarding the interaction between these variables. Some researchers speculate that the inconsistent findings may be due to different targets being used. Although reward and emotion both affect attention, it is not clear whether their impacts are independent. This study examined the impact of reward anticipation on emotion processing for different targets. A cue-target paradigm was used, and behavior and eye-tracking data were recorded in an emotion or sex recognition (...) task under the conditions of reward and non-reward anticipation. The results showed that when the target was related to the emotional attribute of the stimulus, the reward promoted the processing target information, thereby generating reward-oriented attention. When the target was unrelated to the emotional attributes of the stimulus, the reward did not promote the processing target information, and at the same time, individuals had negative emotional biases toward the emotional faces. The results revealed that, in addition to affecting the attention to emotional faces independently, the target regulated the promotion of reward anticipation to emotional attention and attention bias towards negative stimuli. (shrink)