Individuals with schizophrenia frequently experience difficulty discriminating relevant information from the unimportant (Freedman et al., 1996
; McGhie & Chapman, 1961
). Confronted with an ever-changing environment and the need to focus selectively while filtering out distracting information, ongoing challenges present as patients with schizophrenia attempt to work productively, live independently, and function socially. The capacity to maintain and control attention, frequently referred to as top-down processing, along with the inhibition of responses to distracters, typically achieved with bottom-up processes, are central to effective neurocognitive functioning but are impaired in schizophrenia (Gold, Fuller, Robinson, Braun, & Luck, 2007
; Gur et al., 2007
). Though often viewed as separate processes involving distinct brain networks (Posner, 2004
), these two systems also can interact dynamically, such that attention to sensory stimuli may be modulated by bottom-up and top-down processes (Hillyard, Vogel, & Luck, 1998
; Posner, 2004
; Woldorff et al., 1993
). Given such a relationship between the two systems, it is possible that deficits in one domain are amenable to improvement by intact aspects of the other network among individuals with schizophrenia. If it can be established, for example, that deficits in the inhibitory response to distracting information are responsive to improvement by attentional control systems, this information would provide a potential pathway for future pharmacological interventions and cognitive remediation techniques.
Although neurocognitive dysfunction is extensive in schizophrenia, not all attentional processes are compromised by the illness. Notably, top-down modulation of early auditory attention appears to be spared. Relying upon the high temporal resolution offered by event-related potentials (ERPs), Mathalon, Heinks and Ford (2004)
demonstrated that frontally-mediated control of attention is intact in schizophrenia patients up until about 75 ms in the processing stream. It is possible, therefore, that early attention can be utilized to influence disrupted processes occurring within this temporal domain.
The compromised capacity to gate or inhibit responses to distracting information in schizophrenia has been studied extensively by presenting paired auditory stimuli to assess the degree of suppression of the P50 ERP component to the second stimulus (“S2”) relative to the response elicited by the first stimulus (“S1”), when separated by a 500 ms interstimulus interval. The relationship between the two stimuli is often quantified as the S2/S1 ratio, with healthy individuals typically scoring below .50 and schizophrenia patients exceeding this value (Adler et al., 2004
; Freedman et al., 2000
; Patterson et al., 2008
; Waldo et al., 1991
). Meta-analytic studies reveal a robust effect size for the P50 deficit in schizophrenia that exceeds most other abnormalities (Bramon, Rabe-Hesketh, Sham, Murray, & Frangou, 2004
; Heinrichs, 2001
; Patterson et al., 2008
). Although deficits in P50 suppression can be restored by pharmacological agents, such as nicotine and a subset of second-generation antipsychotics (Adler, Hoffer, Wiser, & Freedman, 1993
; Adler et al., 2004
; Light, Geyer, Clementz, Cadenhead, & Braff, 2000
; Olincy et al., 2006
), it has yet to be established whether voluntary control of attention can be engaged to improve or even normalize P50 gating in schizophrenia. Thus, the objective of the present study was to determine the extent to which early attentional control might improve inhibitory processing of the P50 component of the ERP in schizophrenia within the context of a sensory gating paradigm.
In evaluating another neurophysiological deficit in schizophrenia, we found that enhanced attention to the target stimulus improved eye tracking performance to such a degree that schizophrenia patients with a recent onset of illness were able to track as accurately as healthy individuals (Yee, Nuechterlein, & Dawson, 1998
). Similar findings have been obtained in chronic schizophrenia patients (Holzman, Levy, & Proctor, 1976
; Iacono, Tuason, & Johnson, 1981
) with the level of improvement generally less than that observed in patients closer to their first episode of illness, possibly as a result of degenerative processes, sustained neuroleptic treatment, adaptation to a recurring illness or other factors associated with the chronic phase of schizophrenia.
The relative absence of research investigating the malleability of the P50 in schizophrenia patients, aside from pharmacological interventions, can be attributed to two factors. From a theoretical perspective, P50 gating has been conceptualized within the framework of an automatic, inhibitory process
model (Braff & Light, 2004
; Freedman et al., 1996
). The prevailing view is that P50 suppression provides an index of sensory gating whereby S1 automatically activates an inhibitory process which then suppresses responsiveness to S2. In schizophrenia patients, the suggestion is that the initial stimulus fails to activate an inhibitory response to the second stimulus and thereby allows S2 to interfere with the processing of S1. The initial stimulus, therefore, is viewed as failing to close off processing of a subsequent auditory event that ensues almost immediately. Under this model, P50 suppression does not require voluntary attention and occurs automatically (Freedman et al., 1987
; Freedman et al., 1996
Second, the preattentive nature of P50 suppression is supported by studies in which healthy individuals were instructed to allocate voluntary attention towards each of the two stimuli but without any detectable influence on P50 or its suppression (Jerger, Biggins, & Fein, 1992
; White & Yee, 1997
). Relying upon normal variations in attentiveness among healthy participants, Cardenas, Gill and Fein (1997)
further determined that P50 and its suppression are not affected by differing levels of wakefulness. There is some suggestion, however, that maintaining a running count of the second stimulus may serve to disrupt suppression (Guterman, Josiassen, & Bashore, 1992
To our knowledge, there have been no investigations examining whether the P50 deficit in schizophrenia is also impervious to attentional manipulations. P50 suppression may be unaffected by voluntary attention in healthy individuals because the inhibitory process is intact and fully functional whereas, in schizophrenia patients, recruitment of voluntary attention could improve the deficit by compensating for a faulty preattentive inhibitory process. Alternatively, allocation of attentional processes might serve to further disrupt a process that is already compromised, depending upon how or when voluntary attention is engaged. Because it remains to be demonstrated how voluntary attention might influence P50 suppression in schizophrenia patients, three possible outcomes were evaluated in the current study.
Consistent with the automatic, inhibitory process model described above and with available evidence from healthy subjects, voluntary attention directed at either S1 or S2 should have no effect on P50 gating in schizophrenia patients. As an alternative, we examined the possibility that schizophrenia patients fail to allocate sufficient attention towards the incoming, initial stimulus which, in turn, leads to a failure to activate the P50 inhibitory process. In this case, P50 suppression is not entirely automatic but instead may be enhanced by top-down processes directed towards the auditory channel. Instructing schizophrenia patients to direct attention to S1, therefore, should help to fully engage the P50 inhibitory mechanism and lead to normal levels of P50 suppression. This option is described as a compensatory attention model.
A third scenario is that because the automatic P50 inhibitory mechanism is only partially intact in schizophrenia patients, it is easily disrupted when attention is allocated to other stimuli that may be generated internally or externally. Accordingly, impairments in P50 suppression should be exacerbated when voluntary attention is directed towards S2. This possibility, an attention disruption model, is not incompatible with the compensatory attention model because both alternatives allow for attentional effects but attribute them to different manners of action.
In the present study, moderating effects of phase of illness on the attentional manipulations also were examined, as the eye tracking results suggest that greater gains with voluntary attention may be achieved with individuals closer to the onset of schizophrenia. Consistent with a compensatory attention
model, we predicted that directing voluntary attention towards S1 would activate an inhibitory response to S2 and result in improved P50 suppression, with more significant gains observed among patients with a recent onset of schizophrenia than those in the chronic phase. As suggested by an attention disruption
model, we also hypothesized that because of its tenuous nature in schizophrenia, P50 and its suppression will be further compromised when voluntary attention is directed at the second, interfering stimulus, with the most deleterious effect on chronic patients who also were expected to show greatest P50 impairment overall (Brockhaus-Dumke et al., 2008