Neurocognitive mechanisms of conceptual processing in healthy adults and patients with schizophrenia

Abstract

This overview outlines findings of cognitive and neurocognitive studies on comprehension of verbal, pictorial, and video stimuli in healthy participants and patients with schizophrenia. We present evidence for a distinction between two complementary neurocognitive streams of conceptual analysis during comprehension. In familiar situations, adequate understanding of events may be achieved by mapping the perceived information on the associative and similarity-based connections between concepts in semantic memory — a process reflected by an N400 waveform of event-related electrophysiological potentials (ERPs). However, in less conventional contexts, a more flexible mechanism may be needed. We suggest that this alternative processing stream, reflected by a P600 ERP waveform, may use discrete, rule-like goal-related requirements of real-world actions to comprehend relationships between perceived people, objects, and actions. This neurocognitive model of comprehension is used as a basis in discussing studies in schizophrenia. These studies suggest an imbalanced engagement of the two conceptual streams in schizophrenia, whereby patients may rely on the associative and similarity-based networks in semantic memory even when it would be more adaptive to recruit mechanisms that draw upon goal-related requirements. Finally, we consider the roles that these conceptual mechanisms may play in real-life behavior, and the consequences that their dysfunction may have for disorganized behavior and inability to plan actions to achieve behavioral goals in schizophrenia.

Introduction

Deficits in goal-directed behavior contribute to disability in schizophrenia (Poole et al., 1999, Velligan et al., 1997). Behavioral abnormalities may include context-inappropriate commission errors — actions that appear bizarre and are out of place, which constitute part of the disorganization syndrome of schizophrenia (American_Psychiatric_Association, 1994, Andreasen, 1984b, Andreasen et al., 1995a, Andreasen et al., 1995b, John et al., 2003, Liddle, 1987). Schizophrenia patients may also manifest global reduction in goal-directed behavior, which constitutes part of negative symptoms of avolition-apathy (Andreasen, 1984b, Kiang et al., 2003, van Reekum et al., 2005). In the paragraphs below, we outline neurocognitive mechanisms that may play an important role in normal goal-directed behavior, and consider how disease-related alterations in these mechanisms may contribute to the symptoms of schizophrenia.

The ability to find means to achieve behavioral goals is critical for goal-directed behavior. Traditionally, much research has focused on how humans are able to facilitate this process by mapping goals on semantic memory templates, or schemas, of common combinations between actions and entities (Bower et al., 1979, Fischler & Bloom, 1985, Hutchison, 2003, Zacks & Tversky, 2001). For instance, serving a cake may be effortlessly planned by accessing knowledge that cutting is usually done with a knife, and that this activity usually involves steps such as placing a piece of cake on a plate, passing the plate to a guest, etc.

Even though using such associative semantic memory is effective in familiar situations, it may be counterproductive in non-routine contexts when common connections between concepts must be overridden and the available objects and actions may need to be combined in an unusual way to achieve behavioral goals. For example, at an office birthday party, if a knife is unavailable, a reasonable substitute might be a stretched piece of dental floss. Recent research suggests that adaptive goal-directed behavior may be supported by a distinct type of real-world knowledge, coding goal-related requirements of actions, which can be applied to novel combinations between actions and entities (Sitnikova et al., 2008a). Goal-related requirements are properties that are necessary for the successful completion of an action, and exclude properties that are commonly present but are not necessary. In the above office party scenario, a ‘cutting’ implement must have <a sharp and sturdy enough edge>, but other properties such as <has handle> are not relevant. One can acquire an instrument with this goal-relevant element by pulling a few inches of dental floss out of a dispenser and stretching it tight between two hands. This knowledge of goal-related requirements of actions may also contribute to combining individual actions into goal-directed sequences. At each stage of a goal-directed activity, only a small subset of actions is possible given the current state of environment. For example, serving a piece of a cake is possible only after it has been cut.

In schizophrenia, abnormalities in neural activity mediating associative semantic memory have been previously linked to conceptual disorganization, which is often evident in the patients' speech (Aloia et al., 1996, Goldberg & Weinberger, 1995, Kuperberg et al., 2007a, Maher, 1983, Maher et al., 2005, Spitzer et al., 1994, Titone et al., 2000, Titone et al., 2002). We propose that a similar neurocognitive dysfunction may contribute to the behavioral disorganization in schizophrenia. However, a distinct neurocognitive deficit in operations necessary to construct plans for goal-directed actions may underlie the avolition-apathy symptoms (Godbout et al., 2007, Gold et al., 2008, Levy & Dubois, 2006, Rempfer et al., 2003). We suggest that schizophrenia patients may under-recruit conceptual knowledge encoding goal-related requirements of behavioral actions, particularly when planning more complex, non-routine tasks (Sitnikova et al., 2008a, Sitnikova et al., 2008b).

Growing evidence suggests similarities between neurocognitive systems mediating real-world knowledge that are recruited in execution and comprehension of behavioral actions (Humphreys & Forde, 1998, Raposo et al., 2009, Rizzolatti et al., 2001, Ruby et al., 2002, Sokolov et al., 2009, Tettamanti et al., 2005). Experimental paradigms in which participants are asked to comprehend presented stimuli are ideal for examining specific conceptual processes while controlling for confounding variables. In this overview, we discuss findings from comprehension studies both in healthy and schizophrenia participants, and consider their implications for models of goal-directed behavior and its abnormalities in schizophrenia. We also describe our own work that assayed real-world knowledge mechanisms during comprehension of goal-directed activities conveyed in video clips. This video paradigm is especially attractive for studies of psychiatric populations as it taps into naturalistic cognitive processing of real-world behaviors, while spontaneously engaging patients' attention (Levin and Simons, 2000).

Throughout this overview, we highlight experiments that aimed to characterize rapid conceptual processes of interest by recording event-related potentials (ERPs), which measure electrophysiological brain activity with the millisecond temporal resolution (Cohen et al., 1980, Williamson et al., 1978). ERPs are recorded at electrode sensors placed on participants' scalp and are time-locked to the onset of experimental trials of interest (e.g., presentation of target words, object pictures, or visual scenes). In a typical ERP study, electrophysiological data is collected in 30–50 trials per experimental condition, and is selectively averaged to obtain a single waveform for each condition. The changes in the neurophysiological activity that give rise to ERPs appear as positive-going or negative-going deflections in the recorded waveform, often referred to as ERP components. These components vary in their distribution across the scalp. Usually, differences in the polarity and/or topography of ERP components between experimental conditions or study groups are interpreted as reflecting distinctions in the underlying neuronal sources of these components (Holcomb et al., 1999, Kutas, 1993). In the studies described below, such polarity and topography information is used to distinguish between the neural mechanisms mediating different conceptual processes. In contrast, changes merely in the amplitude or timing of an ERP component are usually interpreted as indexing modulation of the same neurocognitive processes (Holcomb et al., 1999, Kutas, 1993). In the studies described below, the onset, peak latency, and duration of the amplitude changes are used to characterize the time-course of the corresponding neurocognitive processes.