DISCUSSION

The data presented here complement those of previous functional imaging as well as electrophysiologic studies, in that few if any fMRI studies in the past have focused on the time courses of the signal changes, and most electrophysiologic studies do not afford the whole-brain coverage included in our data. These findings extend the previous results (Kraut et al., 2002a, 2002b; Slotnick et al., 2002) in two important ways. First, they demonstrate two distinct loci of thalamic signal change, one in the dorsomedial region, and the other more posteriorly, in the pulvinar. Second, analysis of the regionally specific signal change waveform morphology demonstrates distinct patterns that are likely, at least in part, reflective of different time courses of neural activity in different brain regions.

The data show that the signal changes centered in BA6 have a steep climb toward an early peak, and an early drop-off; this latter contention is strengthened by the relative concavity of the falling edge of the signal changes here. The ventral temporo-occipital regions exhibit a later increase in signal, and the waveform is prolonged compared to that of BA6 (Figure 4). The signal changes detected in primary visual cortex and the dorsomedial thalamus demonstrate almost identical rising phases, with the thalamic signal changes falling off slightly more slowly. Interestingly, the signal changes in the primary visual region both rise and fall more slowly than those in the non-primary, ventral temporo–occipital region. Finally, the signal changes in the pulvinar exhibit distinctly slower signal increase and decrease phases than the other regions in which we evaluated the signal change dynamics.

Our data help inform further development of a neural-based model of semantic object recall referred to as the Neural Hybrid Model (Ver. 1.0; Hart et al., 2002). In the framework of this model, we have proposed that there are cortical and subcortical regions that likely encode for representations associated with objects in sensorimotor and higher order cognitive systems (e.g., lexical–semantic). Both feature- and category-based representations have been proposed for several sensorimotor/cognitive domains. While there are variable proposals as to the functional-anatomic organization of these representations, there is little disagreement that these types of representations exist in some cognitive domains (but see Devlin et al., 2002; Moore & Price, 1999). For example, objects that intuitively possess a manipulable feature have been associated with signal changes in premotor areas on functional imaging studies, independent of their category designation (Kraut et al., 2002c). Alternatively, there have been several examples in lesion studies of at least a categorical organization to the lexical semantic system (Caramazza & Shelton, 1998) with a suggestion of a featural organization as well (Hart & Gordon, 1992; Haxby et al., 2001; Miceli et al., 2001). Irrespective of the specific functional anatomic assignments, there have been suggestions of some aspects of these representations for objects in the tactile, somatomotor, lexical–semantic, and visual domains, with the visual representations appearing to be the most salient given that the target stimuli are objects.

Another notion that has emerged from both the lesion and functional imaging findings has been the suggestion that there are focal, circumscribed brain regions that regularly are activated in functional imaging studies or disrupted in lesion studies for specific semantic processes or operations (e.g., category membership, feature identification) across object types. For example, providing a verb/action for a noun/object has been associated in multiple functional imaging studies (including PET and fMRI) with a focal circumscribed region in the left dorsolateral prefrontal cortex (Binder et al., 1996; Fiez, 1997), with further investigations suggesting that the specific role the region plays is in semantic selection (Thompson-Schill et al., 1997). Data gathered in patients with focal lesions (Kemmerer & Tranel, 2000; Thompson-Schill et al., 1998) corroborated the critical role that the left inferior frontal gyrus plays in verb generation, as have the data from cortical stimulation studies (Ojemann et al., 2002). In contrast, the temporoparietal junction region has been shown to mediate object-based category, property, definition and synonym functions during stimulus presentation from multiple modalities (auditory-word, visual-word, and pictures; Hart & Gordon, 1990) and with knowledge of associations between concepts and attribute judgment for these concepts during functional imaging studies (Vandenberghe et al., 1996). Thus far, although the regions detected have been associated with multimodal processing, it appears theoretically plausible that unimodal regions may be isolated with more sensitive investigative techniques.

The mechanisms by which these brain regions function in concert to integrate mental representations are not understood. The present study and previous related experiments using fMRI (Kraut et al., 2002a, 2002b) and electrophysiologic measures (Slotnick et al., 2002) have directly explored semantic object recall from features to assess plausible neural mechanisms that mediate such recall across multiple memory representations. The study by Slotnick et al. is one of the few that have explored rigorously the relationships between cortical and subcortical fMRI signal changes and their electrophysiological concomitants, and emphasizes the specific changes in regional neural ensemble activity that occur with successful object recall. Slotnick et al. showed that during all trials of the semantic object recall task there is a global decrease in alpha band EEG power which was followed by an increase in spatially specific gamma band EEG power in the thalamus and occipital scalp electrodes for only those trials where feature binding resulted in semantic object recall.

In cats, the analogs of the low frequency electrical rhythms detected by Slotnick et al. appear to be controlled by means of spatially widespread, inhibitory (i.e., GABA-ergic) projections from the thalamic reticular nucleus (RE) to thalamocortical (TC) cells in other thalamic nuclei and mediate cyclic activity by rebound excitation. Spatially widespread connections from cortex to RE have also been shown to modulate low-frequency synchronization. In contrast, high-frequency thalamocortical rhythms in the cat have been proposed to reflect spatially specific, monosynaptic excitatory (e.g., glutamatergic) cortico–thalamo–cortical pathways that do not necessarily engage RE.

Based upon these findings and the framework of this semantic object recall task, the low-frequency synchronization may functionally represent a tonic state of cortical inhibition, and thus the widespread decrease in low-frequency EEG power could reflect cortical disinhibition. The spatially specific fast rhythm burst (gamma), may mediate or at least be related to feature binding during recall via the synchronization of neural regions associated with feature representations of the object to be recalled (Joliot et al., 1994; Klimesch, 1996; Singer, 1993; Singer & Gray, 1995; Steriade, 2000).

Within this framework, not every sensorimotor/cognitive domain will necessarily have featural information about an object, nor will all features have the same strength of association to a given object. The varying strength of association for each cognitive domain's featural component of semantic memory for a given object is likely based on the individual's encoding process and experience with that object over time, thus allowing for the individual variability noted. Obversely, common distinguishing features across groups of objects likely allow for the observed regularities in object recall across individuals (e.g., all animals have a strong visual–perceptual loading for features). The network of feature representations for each object thus will vary by object and reflect varying weights and saliency of each feature to that object's overall representation. In addition, how that network is accessed can vary, and this access may be reflected in the strength of activation of all or part of the network. It may be that some features or set/domain of features may have stronger links to others and function as “pointers” in the network. For example, referent and associated connections for a hammer (hammer, tool, nail, repair, etc.) may serve as pointers to some of the sensorimotor features and trigger their activation, lower their activation threshold, or activate the entire feature network for hammer more effectively than the tactile feature of a hammer does. The extent or presence of such triggering may differ, depending upon the specific item or task.

Our data show that the dynamics of both the cortical and subcortical task related signal changes are complex, likely reflecting recurring inter-regional interactions. Taken in conjunction with the electrophysiology results, these findings suggest that the pulvinar region engages later in the process and is thus likely the mediator/modulator of the selective gamma burst rhythm that we propose binds or unites the features in this instance of object recall. The prolonged fMRI response suggests that the pulvinar is more likely engaged after the semantic fields of each feature have been searched and a common object is detected. From the previous studies, the gamma synchronizing rhythm is most readily detected when an actual object is recalled and thus is likely not the principal mechanism for the search for the object. However, whether the gamma rhythm heralds the detection of the common object or unites the features to represent the object is unclear and cannot be determined from the present studies. Further elucidation will require investigation with electrophysiological markers with more precise temporal resolution and optimally with electrode tip placement closer to or in the pulvinar nucleus itself.

The multiple reciprocal connections between the pulvinar and numerous cortical association cortices provide many potential pathways by which this nucleus could mediate integration of features to form object representations. For example, a role for pulvinar in binding of shape and color has been proposed (Ward et al., 2002). The region of the pulvinar most strongly activated in these experiments appears to be medial pulvinar. In macaques, the medial pulvinar connects particularly widely—including prefrontal cortex, auditory-related and multimodal parts of the superior temporal gyrus, and vision-related posterior parietal cortex. Medial portions of the pulvinar connect with inferotemporal visual cortex as well as somatosensory cortex of the insula and with the amygdala (for review, see Gutierrez et al., 2000). Thus, the V1/occipitotemporal–pulvinar connections as well as medial pulvinar connections with wide array of cortical areas (superior temporal gyrus, inferior parietal lobule) may well be involved in a semantic object recall network.

Given its numerous anatomic connections, the dorsomedial nucleus (DM) activity more likely is involved as part of a search or object generation pathway in conjunction with BA6, to which it has direct connections (Ilinsky et al., 1985; Inase et al., 1996), setting or monitoring criteria that an object would meet to fulfill the search. The dorsomedial nucleus may interact with or trigger the pulvinar via corticothalamic feedback connections, since sectors of prefrontal cortex interconnect with both DM and the pulvinar (Gutierrez et al., 2000; Preuss & Goldman-Rakic, 1987; Yeterian & Pandya, 1988). Finally, DM may directly activate other specific prefrontal portions of the network. This is relevant given that prefrontal cortex has been shown to be involved in spatial and object-centered working memory (Wilson et al., 1993), as well as language functions.

There are several possibilities as regards the role of the pre-SMA region (BA6). Crosson et al. (1999) showed that this region is active during word generation. Kraut et al. (2002a, 2002b) suggested that this activation is likely associated with a search strategy, which may be semantic or language related, while others have suggested that its function is in preparedness to make a motor response (Thompson-Schill et al., 1997). However, the absence of its activation in very similar tasks requiring a motor response suggests either (1) semantic or generic search strategy; or (2) generation of an object concept framework from featural input. Nadeau and Crosson (1997) have suggested that the frontal lobe, via the inferior thalamic peduncle, reticular nucleus, and centromedian complex selectively engages portions of a network of regions necessary to represent an object or concept. We would suggest that BA 6, along with its dorsomedial nucleus connections, could be playing a role in this process.

The somewhat prolonged time course of activation for primary visual cortex is intriguing in that this likely would have been one of the initial regions activated in a visually driven task. We would thus have expected to see the signal in primary visual cortex increase early, and perhaps decrease early, with completion of visual evaluation of the stimuli. The delay in primary visual cortex response with respect to that of higher-order regions, suggests that this region is mediating some mental visualization of the target object stimulus or features that are contributing to the integrated object concept in memory during task performance (subjectively, subjects do report seeing internal images of the objects recalled). This is further supported indirectly by there being no significant differences in time course between primary visual cortex and pulvinar, given pulvinar's putative role in feature binding during integrated semantic object recall.

It is clear that when evaluating the time courses of fMRI signal changes, one must take into account the considerable likelihood that regionally disparate hemodynamics will contribute to differences in the morphologic features of the waveforms. Nonetheless, the data presented here provide motivation for further studies using electro- or magneto-encephalographic techniques, as well as further functional imaging studies in which stimulus and task parameters are varied in an effort to accentuate differences in the timing of regional activation. We also acknowledge that some aspects of semantic object recall presented here have been accounted for in other cognitive frameworks, particularly feature and category representation (Devlin et al., 2002; Gainotti, 2000; Moore & Price, 1999; Tyler & Moss, 2001; Warrington & McCarthy, 1994). Overall, however, we believe that coordinated processing of category-level information is fundamental to object recall and likely integrated within the proposed mechanism. Irrespective of the hypotheses for functional organization of some components of the object memories (e.g., categories, features), the present model is one possible set of mechanisms by which semantic object recall could be instantiated, and could be applied to several of the models of knowledge organization that have not specified comparable mechanisms. We do not posit that it operates exclusively to accomplish such object recall; however, we also believe schema analogous to that presented here could well exist in other cognitive domains. We are currently carrying out experiments to test these hypotheses.