A considerable body of research suggests that a large portion of the scalp-recorded P50 response may be explained by contributions from the temporal lobes (Huang et al., 2003
). Our findings in the present study are consistent with these results. We demonstrated that a substantial part of the P50 generators found by the LORETA solutions are localized in temporal lobe areas. In addition to temporal lobe generators of P50, our results demonstrate frontal lobe activity during P50 generation in half of our subjects (on both left and right sides). This result is in line with EEG and animal studies demonstrating frontal lobe involvement in P50 generation (Grunwald et al., 2003
; Mears et al., 2006
; Weisser et al., 2001
Since GDW is relatively new approach in P50 gating research for adequate interpretation of GDW results several aspects of these results should be taken in to consideration. First, GDW reflect changes that emerge in the brain activity before, during, and after S2 is presented. Therefore GDW at the P50 time range is reflecting changes of brain activity directly related to the process of gating. Second, brain localization of GDW does not explicitly show where response to the S1 or S2 is located but it provides direct information about the locations where changes of activity associated with gating occurring in the brain. Third, in the present GDW study we focused our interest to the maximum of gating related changes within P50 time range. While global maximums of GDW were found to be localized at the frontal lobe the local maximums apparently can be found at the temporal lobe areas.
Observation of the frontal lobe activity - especially frontal lobe activity changes during the process of gating - provide new empirical information about brain mechanisms of auditory gating. The difference between our findings in the frontal lobe and results from the previous attempts to model P50 generators might be explained in terms of differences between electric and magnetic signals recorded from the brain. While magnetic fields originating from neurons in Heschl's gyrus are usually oriented tangentially with respect to the head surface, and therefore may be readily detected, frontal lobe activity might have predominantly radial orientation, and thus may not be well evaluated with MEG sensors. In contrast to MEG studies (Edgar et al., 2003
; Hanlon et al., 2005
; Huang et al., 2003
; Onitsuka et al., 2000
; Reite et al., 1988
; Thoma et al., 2003
), the present study reflected electric signals sampled from relatively limited cortical areas using high density electrode arrays. These considerations may explain differences between our LORETA results and previous MEG-derived models of P50/M50 generators. It is possible that since the analog of frontal gating-related changes that was found in the present study was never reported in the MEG studies of gating it might mean that the frontal neuronal generators that underlie these gating related changes are less detectable by MEG due to their orientation with respect to MEG sensors.
Our finding that frontal lobe generators can contribute to auditory sensory gating (as assessed by GDW) is consistent with results demonstrating that patients with dorsolateral prefrontal damage have atypical sensory gating (Knight et al., 1999
), and previous findings of our group indicating the participation of prefrontal cortex (Brodmann's areas 6 and 24) in P50 sensory gating (Grunwald et al., 2003
). The most interesting aspect of our GDW modeling results is the finding that localization of frontal gating related changes were nearly identical with frontal P50 generators for the S1 stimulus (see Subjects 1, 4, 6, 7), which might suggests that gating related portion of the activity originated from frontal generators of P50 was absent as a response to the S1 stimulus. It is possible to suggest that this portion is reflection of inhibitory activity that might suppress or modulate activity of temporal generators of P50 resulting in the phenomenon of gating.
Summarizing, the data presented here provide new insights in the behavior of P50 generators at the moment of gating. Although these data should be interpreted with caution, as more subjects are needed before any firm conclusions can be drawn, current results raise the possibility that (along with other possible contributing factors) the following neuronal mechanisms might underlie the reduction of amplitude of the P50 when a second identical auditory event is processed by the auditory system. First, since major maximums of gating-related changes (GDW results) were localized in the frontal lobe areas it is possible to suggest that a cortical network localized at the frontal lobe plays an important role in providing mechanisms of gating. Second, since in the present study the amount of gating-related activity at the frontal lobe was relatively larger than at the temporal and number of MEG studies (Thoma et al., 2003
; Huang et al., 2003
) showed significant gating-related changes in the temporal lobe it is reasonable to suggest that combination of neuronal activity in these two brain regions result in the phenomenon of gating observable from the scalp recordings. Taking into account differences between the present results and MEG studies, it is possible that there is a difference in brain mechanisms of gating inherent in the frontal and temporal lobes. It is possible that a combination of these two mechanisms ultimately results in a reduction of the P50 amplitude to the second tone measured at Cz.
Since the frontal lobe generator of the P50 is activated about 10 ms later in time than the temporal lobe generator (Weisser et al., 2001
), it can be regarded as a higher level of auditory processing that collects and probably stores the outcome of S1 processing, such as information about the physical parameters of the first stimulus.
The above observations suggest a number of possible pathophysiological mechanisms to explain the gating deficit of P50 component in schizophrenia. First, it is possible that the deficit can be explained entirely based on aberrations of the temporal sources of the P50 (intracortical synaptic depression mechanisms; Wehr and Zador, 2005
). Alternatively, the data raise the possibility that an aberration of fronto-temporal interaction might contribute to the gating deficit.