One particular area of inquiry that has been largely overlooked is the examination of impairments in the higher-order cognitive ability of foresight among this population. Foresight has been a key domain in cognitive research among a range of clinical populations (e.g, Atance & O'Neill, 2001; Lilienfeld et al., 1996; Petry et al., 1998; Wallace, 1956), and broadly refers to the ability to think of the long-term consequences of one's behavior and use this information to guide present and future actions. A review of the interdisciplinary, and at times disparate, literature surrounding foresight and future thinking suggests a multidimensional model of foresightfulness consisting of future orientation/time perspective, time horizon, delay of gratification, and consideration of future consequences. Future orientation refers to the degree to which a person generally thinks about the future (e.g., Lens, 1986; Lewin, 1951); time horizon concerns how far in the future someone thinks (e.g., Loewenstein & Elster, 1992); delay of gratification concerns the postponement of smaller, immediate for larger, delayed rewards (e.g., Metcalfe & Mischel, 1999); and consideration of future consequences is the degree to which a person thinks about the potential consequences of his/her behavior (e.g., Strathman, Gleicher, Boninger, & Edwards, 1994). Each of these dimensions of foresight is supported by its own empirical literature, and have been shown in several studies to be psychometrically distinguishable from each other and such related constructs as impulsivity (Fellows & Farah, 2005; Lane, Cherek, Rhoades, Pietras, & Tcheremissine, 2003; Strathman, Gleicher, Boninger, & Edwards, 1994; Zimbardo & Boyd, 1999), although some do conceptualize cognitive impulsivity as largely a deficit in these domains of foresightfulness and executive control (e.g., Barratt & Patton, 1983). Further, all of these abilities and foresight in general have been posited to have a substantial neurobiological basis and theorized to rely on the integration of a number of basic cognitive domains, particularly episodic memory and executive function systems (Suddendorf & Corballis, in press).

Recently we introduced this concept of foresight as a promising area of cognitive investigation in schizophrenia research. In a longitudinal study of foresight among early course patients with schizophrenia, we demonstrated that such individuals tended to exhibit low levels of foresight across the course of a 1 year study period. Furthermore, level of foresightfulness at baseline was shown to be a significant cross-sectional and longitudinal predictor of functional outcome, above and beyond negative symptomatology and deficits in neurocognitive function (Eack & Keshavan, 2008), signifying the clinical relevance of this area of investigation. In this research, we now turn to the question of whether impaired foresight in schizophrenia is a unique biobehavioral marker of the disease, by examining the association of impaired foresight with abnormalities in underlying neuroanatomy.

Several studies among other clinical populations have found abnormalities in ventromedial prefrontal and parietal cortical regions to be associated with impairments in foresightfulness. Perhaps the most famous case study linking brain anomalies to impaired foresight is that of Phineas Gage. After sustaining significant damage to the medial frontal lobes (Damasio et al., 1994), Gage was noted as becoming "impatient of restraint or advice when it conflicts with his desires" and "devising many plans of future operation, which are no sooner arranged than they are abandoned in turn for others appearing more feasible" (Harlow, 1868), demonstrating marked impairments in delay of gratification and future planning. More recent case control studies on individuals with brain lesions have continued to implicate the medial frontal lobes in foresightfulness. Specifically, several studies have shown that lesions in the ventromedial prefrontal (vmPFC) and orbitofrontal (OFC) cortices produce profound deficits in foresight with regard to both time perspective (Fellows & Farah, 2005) and sensitivity to future consequences (Bechara et al., 1994). In addition, a minority of functional neuroimaging studies among healthy and clinical samples has also implicated the cingulate cortex in foresightfulness, by demonstrating significant posterior cingulate cortex (PCC) activation during delay of gratification tasks (Wittmann et al., 2007).

Neuroimaging studies of constructs related to foresight, such as impulsivity and choice anticipation, among individuals with schizophrenia have also been illustrative in implicating the orbitofrontal and cingulate cortices. In one study with schizophrenia patients, Quintana and colleagues (2004) found reduced anterior cingulate cortex (ACC) activation during a choice anticipation task, which the investigators speculated may be generally associated with poor foresight. In a diffusion tensor imaging study, Hoptman and colleagues (2002) found preliminary evidence for an association between reduced fractional anisotropy and impulsiveness among individuals with schizophrenia. The findings of these investigators were confirmed in a subsequent investigation that indicated an association between self-reported impulsiveness and reduced fractional anisotropy in white matter tracts of the ACC and inferior frontal regions among a sample of males with schizophrenia (Hoptman et al., 2004).

The primary results of this research indicate the presence of significant positive associations between foresight and gray matter volume densities in the bilateral vmPFC, right OFC and PCC, as well as the left ACC, suggesting an association between poor foresight in schizophrenia and reduced gray matter volume in select regions of the medial frontal and cingulate cortices. Exploratory whole brain also revealed several interactions with gender, pointing to the potential additional impact of reductions in gray matter volume in the left orbitofrontal cortex, angular gyrus, and right dorsolateral prefrontal cortex in subverting foresightfulness among male patients. Further, these results could not be attributed to individual differences in psychopathology or illness duration. Consistent with previous research with other populations (e.g., Fellows & Farah, 2005), these findings largely highlight the role of the vmPFC, OFC, and cingulate cortex in supporting a capacity for foresight and increasingly point to its aberrance among persons with schizophrenia. When coupled with our previous findings indicating that foresight is a unique longitudinal contributor to functional outcome among this population, these results suggest that impaired foresight may represent a key biobehavioral marker of the disease and its functional course. In turn, the remediation of foresight and broader functional outcome in schizophrenia may depend on interventions that act on the neuronal systems associated with the medial frontal and cingulate cortices.

Firm conclusions regarding the significance of foresight impairments in schizophrenia and their neurobiological correlates, however, are admittedly premature as this exploratory investigation contains a number of important limitations. First, while our global, clinician-rated measurements of foresight provide an accurate and reliable description of the overall level of foresightfulness a person displays (Eack & Keshavan, 2008; Hogarty et al., 2004), such measures are less adept in separating the different dimensions of foresight (e.g., future orientation, delay of gratification), which may not necessarily be equally associated with gray matter volume in the medial frontal and cingulate cortices. Future research needs to employ more specific measures of foresight that adequately assess the range of dimensions of this concept, in order to clearly identify the neurobiological substrates most closely associated with different components of foresight. The development of performance-based assessments could be particularly promising, as such measures would allow for the assessment of not only the propensity, but also the capacity to use foresight, and allow for a broader range of neurobiological investigations (e.g., fMRI, DTI).

Second, it is important to remember that this study was not a controlled examination of foresight impairment in schizophrenia, but rather consisted of an investigation of how individual differences in foresight within schizophrenia patients are associated with alterations in brain morphology. A medial frontal neurobiologic deficit in schizophrenia seems clear, given that consistent evidence has pointed to the altered morphology and function of these regions in this population (Honea et al., 2005; Shenton et al., 2001). Less clear is the degree to which foresight deficits are present in and specific to schizophrenia, as no controlled studies of foresight among this population have been conducted. However, our initial longitudinal investigation of foresight in schizophrenia did show profound deficits in this domain throughout the course of a 1 year study period, which were significantly predictive of functional outcome (Eack & Keshavan, 2008). This study extends these findings by taking the initial step in showing that these impairments in foresight are related to the medial frontal deficit commonly described in schizophrenia. Nonetheless, controlled investigations are clearly needed not only to identify the magnitude and specificity of foresight impairments among this population, but also to clarify the degree to which reduced gray matter volume in the medial frontal and cingulate cortices adequately distinguishes foresight ability between persons with schizophrenia and healthy individuals.