This study sought to determine whether the reduced LRP amplitude exhibited by schizophrenia patients is related to a difficulty in overcoming competition from the incorrect response or whether it instead reflects impaired response activation. In other words, the present study was designed to determine whether the LRP impairment in schizophrenia is related to cognitive control deficits or to more basic motor abnormalities. Both in a task that manipulated highly learned stimulus-response mappings (Experiment 1) and a task that manipulated the compatibility of flanker stimuli with a central target (Experiment 2), patients with schizophrenia showed a significant attenuation of LRP amplitude compared to controls. These results are consistent with previous reports of reduced LRPs in schizophrenia (Karayanidis et al., 2006
; Kieffaber et al., 2007
; Luck et al., 2009
; Mathalon et al., 2002
The key new result of the present study is that the patient LRP reduction was no greater under conditions of high than low response competition, indicating that the LRP reduction in schizophrenia is not driven by a failure to overcome competition from the incorrect response. A substantial deficit was observed even when, for example, a left-hand response was given in response to the word “Left” or a right-hand response was given in response to a set of right-pointing arrows. It is implausible that the amount of response competition was as great on these compatible trials as it was on the incompatible trials. Moreover, even when the overall decrease in the size of the LRP in the patients was taken into account, the patients and controls were similarly affected by the compatibility manipulation. The finding of equivalent patient LRP reductions on compatible and incompatible trials provides strong evidence against the hypothesis that these reductions are a consequence of an impaired ability to suppress activation of the incorrect response. Instead, these results indicate that patients have an overall deficit in the activation of the correct response.
What might be causing the reduction in response activation in the patients? There are two primary mechanisms that could lead to this result. First, the cognitive processes responsible for sending the motor command for the selected response to motor cortex might be impaired, independent of the processes that precede the selection of this response, leading to decreased input to the motor cortex. Second, the neural circuit that generates the LRP in primary motor cortex might be impaired, which would lead directly to reduced LRP amplitude. This is plausible given that motor cortex—where the LRP is largely generated—operates through a dopamine-mediated loop with the basal ganglia. Either of these possibilities would be consistent with the observed reduction in response activation in patients with schizophrenia.
Although little is known about the specific motor abnormalities that occur in schizophrenia, we can look to other disorders that affect the motor system for insight into the proposed mechanisms of LRP impairment in schizophrenia. Specifically, the LRP has been measured in two disorders of the basal ganglia that result in significant disruptions of the motor system—Parkinson’s Disease and Huntington’s Disease. Surprisingly, this research has shown that despite significant disruption of the motor system in these disorders, resulting in the generation of abnormal movements (e.g., tremor, choreiform movements, etc.), no reduction in LRP amplitude is found in patients with Parkinson’s Disease (Praamstra, Plat, Meyer, & Horstink, 1999
) or patients with Huntington’s Disease (Beste, Saft, Andrich, Gold, & Falkenstein, 2008
) compared with healthy controls. Neither the disruption of GABAergic inhibition within the basal ganglia that characterizes Huntington’s Disease nor the disruption of dopaminergic inputs to the basal ganglia present in Parkinson’s Disease produces the pattern of decreased LRP amplitude that is exhibited in schizophrenia. This suggests that the LRP reduction observed in schizophrenia is not a result of a disruption of the basal ganglia portion of the motor loop. A similar dissociation between schizophrenia and Parkinson’s Disease has been observed in the context of sequence learning (Sullivan et al., 2001
). However, we cannot rule out the possibility that some other form of disruption in the basal ganglia—such as the prefrontal-striatal disruption implicated in reward learning studies (Gold, Waltz, Prentice, Morris, & Heerey, 2008
)—is responsible for the LRP reduction in schizophrenia.
It is worth considering whether the LRP abnormalities exhibited by the patients could be a consequence of either medication or nicotine use in the patients. Although we cannot conclusively exclude the possibility that antipsychotic medications are contributing to the LRP effect, the pervasive response-related abnormalities (such as RT slowing) in schizophrenia patients do not seem to be caused by antipsychotic medications (Medalia, Gold, & Merriam, 1988
; Zahn, Pickar, & Haier, 1994
). In addition, motor abnormalities were well documented in the preneuroleptic era (Reiter, 1926
), and have been reliably observed in medication-naïve patients (Peralta & Cuesta, 2001
). Such evidence is indirect, and it is important for future research to examine the LRP in unmedicated, first-episode, and prodromal patients to fully assess the possible relationship between antipsychotic medications and LRP abnormalities. It also seems unlikely that the increased use of nicotine in patients with schizophrenia is contributing to the LRP deficit, because nicotine increases the amplitude and decreases the onset latency of the LRP (Houlihan, Pritchard, Guy, & Robinson, 2002
), contrary to the pattern shown by the patients in the present study. Thus, the reduced LRP in schizophrenia likely reflects a response activation impairment from the disease itself rather than pharmacological confounds.
It is important to note that the present study manipulated stimulus-response compatibility by disrupting highly learned stimulus-response mappings, such as the correspondence between a left-pointing arrow and a left-hand response. This allowed us to examine response preparation processes while minimizing other processes that may differ between patients with schizophrenia and controls, such as learning rate, working memory, etc. The LRP has also been examined in patients with schizophrenia in the context of more arbitrary stimulus-response mappings (Karayanidis, et al., 2006
; Kieffaber, et al., 2007
; Luck, et al., 2009
), and these studies have found a similar reduction in LRP amplitude in patients. Therefore, the LRP reduction observed here generalizes to contexts in which arbitrarily defined stimulus-response mappings are used. However, it is also possible that deficits in the high-level cognitive processes that lead to selection of a response contribute to the patient LRP deficit in contexts with complex stimulus-response mappings that rely heavily on cognitive processes. Therefore, it is possible that a larger deficit would be observed on incompatible trials in these contexts. This remains an important issue for future research.
It is also worth asking whether the response-related effects in the present study may be driven by sensory processing deficits in the patients. This question was directly addressed in a previous study (Luck et al., 2009
), in which both response-related processing and stimulus categorization were examined in patients with schizophrenia. As in the present study, a substantial reduction in LRP amplitude was found in the patients; however, the timing and amplitude of the rare-minus-frequent P3 difference wave was virtually identical in patients and controls, indicating that both groups were equally able to classify the stimuli as belonging to the rare or the frequency category. These results indicate that patients with schizophrenia were unimpaired in stimulus evaluation (for simple alphanumeric visual stimuli) but differed in response-related processing. Therefore, response-related deficits in patients with schizophrenia can exist independent of early sensory processing deficits.