Brain, Vol. 123, No. 5, 927-939,
May 2000
© 2000 Oxford University Press
The central role of the prefrontal cortex in directing attention to novel events
1 Brigham Behavioral Neurology Group and Laboratory of Higher Cortical Functions, Division of Cognitive and Behavioral Neurology, 2 MRI Division, Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 3 Harvard School of Public Health, Boston, Massachusetts, 4 Center for Behavioral and Cognitive Neurology, Northwestern University Medical School, Chicago, Illinois and 5 Department of Psychology, Tufts University, Medford, Massachusetts, USA
Correspondence to:
Kirk R. Daffner, MD, Division of Cognitive and Behavioral Neurology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA E-mail: kdaffner{at}partners.org
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Abstract |
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The physiological basis for the striking decrease of attention to novel events following frontal lobe injury is poorly understood. In this study, event-related potentials (ERPs) were recorded from patients with frontal lobe damage and matched subjects, who controlled the duration of viewing of background, novel and target stimuli. Frontal lobe patients did not differ from normal controls in terms of age, education, estimated IQ or mood. However, they were judged to be more apathetic as measured by self-report and informants' ratings. Patients with frontal lobe damage exhibited markedly reduced amplitude of the novelty P3 response and the duration of viewing of novel stimuli. In contrast, injury to the frontal lobes had a limited impact on P3 amplitude and behavioural responses (viewing duration and reaction time) to target stimuli. A strong correlation was found between measures of apathy and both attenuated P3 amplitude and viewing duration in response to novel but not target stimuli. Differences in amplitude of the novelty P3 response explained a large portion of the variance associated with duration of viewing of novel stimuli. After controlling for the influence of P3 amplitude, there was no association between frontal lobe injury and reduced viewing of novel stimuli. The results of this study suggest that frontal lobe damage leads to diminished visual attention to novel events through its disruption of neural processes underlying the novelty P3 response. These processes appear to regulate the allocation of attentional resources and early exploratory behaviours, and are not limited to immediate orienting responses. Damage to the frontal lobes may prevent the generation of a signal which indicates that a novel event in the environment requires additional attention due to its potential behavioural significance. The disruption of these processes is likely to contribute to the apathy observed in patients after injury to the frontal lobes.
frontal lobes; novelty; P3; attention; apathy
ERP = event-related potential
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Introduction |
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Novelty-seeking is an integral part of normal human behaviour, yet surprisingly little is known about the mechanisms which contribute to the impairment of attention to novel events in patients with frontal lobe damage (Luria, 1973
; Hutton et al., 1979; Knight, 1984, 1997; Daffner et al., 2000a). The novelty P3 response is characterized typically as an anteriorly distributed positive event-related potential (ERP) wave associated with the orienting response to novel stimuli (Courchesne et al., 1975; Squires et al., 1975; Snyder and Hillyard, 1976; Knight, 1984; Hillyard and Picton, 1987; Naatanen, 1992; Baudena et al., 1995; Daffner et al., 1998, 2000b). Both the novelty P3 and the orienting responses are usually considered involuntary and automatic (Courchesne et al., 1975; Squires et al., 1975; Snyder and Hillyard, 1976; Holdstock and Rugg, 1995; Knight and Scabini, 1998). However, there is evidence to suggest that the novelty P3 response marks the preferential allocation of attentional resources to potentially significant events (Kahneman, 1973; Ohman, 1979; Naatanen, 1992; Daffner et al., 1998a, 2000b; Escera et al., 1998).
Frontal lobe injury has been shown to reduce the amplitude of the novelty P3 response (Knight, 1984, 1997; Knight and Scabini, 1998). We investigated whether the reduction of the P3 response was a necessary correlate of diminished allocation of attention to novel stimuli in patients with frontal lobe damage. Previous work has demonstrated that when normal subjects control how long they look at stimuli, the amplitude of the novelty P3 response in frontal regions strongly predicts the duration of viewing of novel stimuli (Daffner et al., 1998), suggesting that the P3 might reflect the activity of a neural system that serves to link attentional resources to novel events. A more direct test of this theory was carried out in the current investigation of patients with focal damage to the prefrontal cortex.
We studied patients with chronic infarctions centred in the prefrontal cortex, and normal controls matched for age, education, estimated IQ and mood. ERPs were recorded from scalp electrode sites while subjects viewed a series of line drawings that included a frequent, repetitive background stimulus, an infrequent target stimulus and infrequent novel stimuli (e.g. fragmented or `impossible' objects). Task instructions emphasized that the study was investigating how people look at different kinds of visual stimuli. Subjects controlled viewing duration by a button press that led to the onset of the next stimulus and served as a measure of visual attention (Berlyne, 1960; Vurpillot, 1968; Loftus and Mackworth, 1978; Daffner et al., 1992, 1998, 2000b). Subjects also responded to target stimuli by pressing a foot pedal. Based on previous work, we hypothesized that the diminution of attention to novel stimuli following frontal lobe damage would be linked to a disruption of the novelty P3 response.
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Methods |
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Subjects
CT or MRI scans of patients discharged from the Brigham and Women's Hospital (BWH) with a diagnosis of stroke were reviewed. Patients whose infarctions were centred in the frontal lobes (with no extension into parietal cortex) were recruited. Patients with a history of previous strokes, alcohol abuse or dementia were excluded. Eight patients underwent research MRI scans, with three-dimensional reconstruction of images (Shenton et al., 1992
). In one of these patients, the frontal infarction that had been noted on the initial scans (done 18 months before) was not visible on MRI and thus, experimental data from this patient were not included. Two patients had only CT scans because pacemakers made them ineligible for MRI scans. We therefore report on nine patients with frontal infarctions.
Lesion localization was based on the Damasio template system (Damasio and Damasio, 1989). In patients who were able to have MRI scans, infarct localization was confirmed by reviewing the three-dimensional images that were reconstructed from the MRI data set (Shenton et al., 1992) after the boundaries of the lesion had been traced on each slice. Five patients had right frontal infarctions; three had left. One patient had suffered small, bilateral frontal infarctions. All infarctions were centred in the prefrontal cortex. Mean duration post stroke was 1.5 ± 0.8 years (Table 1).
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Normal controls (n = 20) were recruited through advertisements in the Boston community. Subjects were excluded if they had a history of cerebrovascular disease, alcohol abuse, dementia or a focal neurological exam. Informed consent was obtained from all subjects. The study was approved by the Human Research Committee at BWH.
Subjects completed the American version of the National Adult Reading Test (Nelson and O'Connell, 1978; Ryan and Paolo, 1992) and the Ravens Coloured Progressive Matrices Test (Raven et al., 1995) to determine an estimated IQ score. Subjects completed the Apathy Scale (Starkstein et al., 1993, 1995) (a 14-item survey that evaluates a subject's level of interest, motivation and concern) and the Zung Depression Scale (Zung, 1965) (a 20-item questionnaire about the subject's mood and affective state). Informants who knew the subjects well completed a Personality and Behavioural Inventory (Daffner et al., 1999) that included four items evaluating the subject's degree of apathy by assessing his/her level of initiation, participation, interest and motivation.
Experimental procedures
Three hundred line drawings, white on black background, were presented at the centre of a high resolution computer monitor. All stimuli subtended a visual angle of ~2.75° along their longest dimension. There were three categories of visual stimuli: (i) a repetitive background stimulus (a triangle), 70% frequency; (ii) a target stimulus (upside down triangle), 15% frequency; and (iii) novel stimuli, randomly drawn from a set of unusual/unfamiliar line drawings shown only once each, 15% frequency (Fig. 1). Many of the novel stimuli came from the collection of drawings that have been used by Kosslyn and colleagues (Kosslyn et al., 1994) and Kroll and Potter (Kroll and Potter, 1984). Stimuli appeared within a fixation box subtending a visual angle of approximately 3.5 x 3.5°, which remained on the screen at all times. Stimuli were presented in pseudorandom order with the additional constraints that no more than two deviant stimuli were shown consecutively, and that each block of 50 stimuli had the same number of background stimuli and approximately the same number of target and deviant stimuli.
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Procedure
Subjects were informed that the experiment involved the study of brain wave responses as they looked at different kinds of drawings. They were told that they would be viewing a set of drawings and that they could look at each picture for however long they liked. They controlled the viewing duration by a button press that triggered the onset of the next stimulus. Subjects were explicitly told that they would not be asked questions about the pictures at the conclusion of the experiment. Subjects were also told to respond to the designated target stimulus by pressing a foot pedal (ipsilateral to the button press). We called the targets `Sequence Markers' and indicated to subjects that they were included in the task to help the experimenters keep track of where they were in the sequence of drawings. In the stroke patients, the responding hand/foot used was ipsilateral to the lesion site. In normal controls and the patient with bilateral lesions, the response hand/foot was randomly assigned. Although viewing durations were calculated by subtracting the stimulus onset time from the button press time, all stimuli were displayed for a minimum duration of 600 ms. The interval between the offset of one stimulus and the onset of the next stimulus ranged between 1 and 1.5 s.
ERP recordings
An electrode cap (Electro-Cap International, Eaton, Ohio, USA) was used to hold the 29 active electrodes to the scalp, whose locations were based on the international 10–20 system. They included three midline sites (Pz, Cz, Fz) and 26 lateral sites arranged in four parasagittal rows [(i) CP1/2, FC1/2, FP1/2; (ii) O1/2, P3/4, C3/4, F3/4; (iii) CP5/6, FC5/6, AF7/8; (iv) T5/6, T3/4, F7/8].
All sites were referenced to the left mastoid, and the impedance between each recording site and the reference was reduced to less than 5 k
. An electrode was placed beneath the left eye (left mastoid reference) to check for eye blinks and vertical eye movements, and another electrode to the right of the subject's right eye (referenced to an electrode to the left of the left eye) to check for lateral eye movements. A final electrode was placed over the right mastoid (referenced to the left) to monitor asymmetrical mastoid activity (none was found).
The EEG was amplified by an SA Instrumentation acquisition system (model H & W 32BA, San Diego, Calif., USA) using a band filter with negative 3 db cut-offs of 0.01 and 40 Hz, and continuously digitized (200 Hz) by a computer yielding 1280 ms of data from each electrode site, beginning 100 ms before stimulus onset.
Data analysis
A continuous record of the raw EEG was stored on hard disk. Off-line, EEG epochs for the three stimulus types (background, target, novel) were averaged separately. Trials with eye movements or amplifier blocking were excluded from data analysis. In cases with excessive eye blinks, a blink correction programme was employed (Dale, 1994) that computed the impact of the blink on the wave forms in each channel. For the eight patients with unilateral infarctions, data are presented as a function of electrode site ipsilateral or contralateral to the lesion. In the figures, ERPs ipsilateral to the lesion are shown on the right side of the scalp. The P3 response was defined as the peak positive wave between 325 and 600 ms, measured with respect to the average of the 100 ms prestimulus baseline.
Data were analysed using repeated measures ANOVA (analysis of variance). There were two levels of group (normal controls, frontal lobe patients), and for ERP and duration data, three levels of stimulus type (background, target, novel). For ERP measurements, there were three midline electrode sites and 13 lateral electrode sites with two levels, one for each hemisphere. Between-group analyses that yielded significant interactions between group, stimulus type, electrode site or hemisphere resulted in planned contrasts between the levels of the variable. In looking at scalp site interactions with other variables, the data were normalized using a Z-score technique (Kounios and Holcomb, 1994) similar to the method recommended by McCarthy and Wood to avoid problems associated with interpreting site by factor interactions using ANOVA (McCarthy and Wood, 1985). The Geisser–Greenhouse correction (Geisser and Greenhouse, 1959) was applied for all repeated measures with >1 degree of freedom.
Data sets involving the behavioural results (e.g. viewing durations, reaction times) or demographic variables that were not normally distributed were transformed (e.g. inverse function) prior to statistical analyses. If assumptions for parametric analyses were still violated, non-parametric statistics (e.g. Mann–Whitney U tests) were employed. To examine the effects of frontal lobe injury and the novelty P3 response on viewing duration, a path analysis was conducted (Kerlinger and Pedhazur, 1973) based on the causal model in which frontal lobe damage affects viewing duration through its impact on the novelty P3 response. Correlation analysis (Spearman's rho) was used to determine the degree of association between severity of apathy and pertinent electrophysiological and behavioural variables. All P-values reported are two-tailed.
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Results |
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Subject characteristics
Patients with frontal lobe strokes and normal controls did not differ significantly in terms of age, education, estimated IQ (Nelson and O'Connell, 1978
; Ryan and Paolo, 1992; Raven et al., 1995) or Zung Depression Scale scores (Zung, 1965). Frontal lobe patients exhibited increased apathy as measured by self-report on the Apathy Scale (Starkstein et al., 1993, 1995) (P < 0.05) and informant-based judgements on the Personality and Behavioural Inventory (Daffner et al., 1999) (P < 0.001) (Table 2). According to these measures, the frontal lobe patients were mildly apathetic.
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P3 data
Figure 2
presents the grand average ERP plots for the group of normal control subjects and frontal lobe patients. P3 mean amplitude and latency data at midline sites are summarized in Table 3.
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The grand average plots revealed a similar pattern of response to that observed in individual subjects, as shown by an example of midline ERP plots from a normal control subject and a frontal lobe patient (Fig. 3
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P3 amplitude was significantly smaller for frontal lobe patients than normal controls [main effect of group, midline: F(1,27) = 14.26, P < 0.001; lateral: F(1,27) = 18.3, P < 0.001]. Moreover, P3 latency was longer for frontal lobe patients than normal controls across all stimulus types and midline electrode sites [F(1,27) = 7.91, P < 0.01]. P3 amplitude in response to different stimulus types varied across groups [stimulus type by group interaction, midline: F(2,54) = 7.77, P < 0.01; lateral: F(2,54) = 6.81, P < 0.01]. For normal controls, the amplitude of the P3 response to novel stimuli was equal to that of target stimuli (midline: P > 0.9; lateral: P > 0.4), both of which were larger than to background stimuli (midline and lateral: Ps < 0.001) (Fig. 2
). In contrast, for frontal lobe patients, the P3 response to novel stimuli was no larger than to background stimuli (midline: P > 0.3; lateral: P > 0.2), both of which were smaller than to target stimuli (midline: Ps < 0.01; lateral: Ps < 0.05). Figure 4A illustrates the voltage difference maps of the P3 response to target or novel stimuli minus the P3 response to background stimuli in normal controls and frontal lobe patients.
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P3 amplitude to novel stimuli was smaller for frontal lobe patients than for normal controls [midline: F(1,27) = 23.14, P < 0.001; lateral: F(1,27) = 26.35, P < 0.001] across all scalp locations (i.e. no group by electrode site interaction). In contrast, only at anterior sites was P3 amplitude to target stimuli smaller for frontal lobe patients than normal controls [group by electrode site interaction, midline: F(2,54) = 7.11, P < 0.01; lateral: F(12,324) = 3.14, P < 0.05]. Figure 4B
illustrates the voltage difference maps of the P3 amplitude of normal controls minus frontal lobe patients for each stimulus type, demonstrating the marked group difference in response to novel stimuli. For normal controls, the P3 response to all stimulus types was asymmetric (larger at right hemisphere sites) [main effect of hemisphere, F(1,19) = 11.66, P < 0.01]. In contrast, frontal lobe patients did not exhibit any difference in P3 amplitude between ipsi- and contralesional hemisphere sites (P > 0.2).
Note that as a further check of the reliability of our P3 peak amplitude measures, the data were also analysed using mean amplitude measurements between 325 and 600 ms. These analyses (not shown) yielded almost identical statistical results to those seen for the P3 peak amplitude data.
Behavioural data
There were significant differences in the length of time in which frontal lobe patients and normal controls viewed novel and background stimuli [stimulus type by group interaction: F(1,27) = 8.82, P < 0.01] (Fig. 5). Although there were no group differences in how long subjects looked at background stimuli (P > 0.3), frontal lobe patients spent significantly less time looking at novel stimuli than normal controls (P < 0.05). Both groups spent more time viewing novel than background stimuli, although the effect was much more robust in the normal control group (P < 0.001) than the frontal lobe group (P < 0.05).
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Subjects varied in terms of the rate at which they tended to move through the stimulus set. Response times in stroke subjects may have been affected by non-specific alterations in speed of motor or cognitive processing. To help control for these factors, we constructed a measure of proportionality (ratio of viewing duration of novels to viewing duration of backgrounds). This ratio is particularly informative since the novel stimuli are defined in terms of their deviance from background stimuli. Frontal lobe patients exhibited a significantly smaller ratio of viewing of duration novels to viewing of duration backgrounds than normal controls [frontal lobe patients: 1.40 (0.12) versus normal controls: 2.84 (0.41), F(1,28) = 12.00, P < 0.01].
In terms of responses to target stimuli, there were no significant group differences in reaction time, percentage of correct hits, number of false alarms, viewing duration of targets, or ratio of viewing duration of targets to viewing duration of backgrounds (Table 4).
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Path analysis
To further investigate the major hypothesis of this study, a path analysis was conducted of the relationship among the variables of group membership (frontal lobe patients versus normal controls), novelty P3 response and ratio of viewing duration of novels to viewing duration of backgrounds (Fig. 6
). It revealed a strong association between group membership and novelty P3 amplitude, with a correlation coefficient of 0.68 (P < 0.001). There was also a strong correlation between the amplitude of the novelty P3 response and ratio of viewing duration of novels to viewing duration of backgrounds, that remained significant after controlling for the impact of group membership (path coefficient = 0.54, P < 0.01). In contrast, after controlling for the impact of the novelty P3 response, there was no association between frontal lobe injury and reduced viewing duration of novel relative to background stimuli (correlation coefficient = 0.19, P > 0.4), suggesting that the neural processes indexed by the novelty P3 response mediate viewing duration of novel stimuli.
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Correlations between experimental variables and apathy scores
There was a strong inverse relationship between apathy scores and the ratio of viewing duration of novel stimuli to viewing duration of background stimuli, and between apathy scores and the ratio of the amplitude of the P3 response to novel stimuli to the amplitude of the P3 response to background stimuli (Table 5
). In contrast, there were no significant correlations between electrophysiological or behavioural responses to target stimuli and apathy measures (Table 5).
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Regional or lateralized differences within the prefrontal cortex
Given the small sample size, only limited analysis was conducted on the impact of different lesion sites within the prefrontal cortex on attention to novel stimuli. The three patients with the most circumscribed lesions within the dorsolateral prefrontal cortex (patients 7, 8 and 9) did not differ significantly from the three patients with the largest frontal lesions (patients 1, 2 and 3) in terms of the novelty P3 amplitude or viewing duration of novel relative to background stimuli. Similarly, there were no significant differences in these variables between the three patients with lesions in the left hemisphere (patients 1, 5 and 9) and the three patients with comparable lesions in the right hemisphere (patients 2, 3 and 4).
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Discussion |
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The process of orienting and attending to novel stimuli is essential for adapting to a rapidly changing environment (Berlyne, 1960
; Sokolov, 1963; Daffner et al., 1994, 1998). The frontal lobes appear to play an important role in this process. For example, monkeys with injury to frontal cortex exhibit autonomic or locomotive responses that do not differ between novel and repetitive stimuli, and fail to demonstrate a range of exploratory behaviours (Jacobsen, 1936; French and Harlow, 1955; Welker, 1961; Butter, 1964; Kimble et al., 1965; Mesulam, 1986, 1998). Novelty-seeking behaviour in humans appears to have a similar dependency on the frontal lobes. Thus, it is commonly observed that patients with injury to the frontal cortex are apathetic and uninterested in novel aspects of their environment. However, there has been very limited investigation of the physiology underlying these changes.
ERPs have helped to elucidate the neurophysiological underpinnings of novelty processing in humans. Unexpected novel stimuli evoke characteristic patterns of ERPs including the novelty P3 wave, an important index of the orienting response (Courchesne et al., 1975; Squires et al., 1975; Snyder and Hillyard, 1976; Knight, 1984; Hillyard and Picton, 1987; Naatanen, 1992; Baudena et al., 1995; Daffner et al., 1998, 2000b). Lesion studies in humans point to a major disruption of the novelty P3 response following focal injury, especially to frontolimbic circuits. For example, cerebrovascular infarctions in the prefrontal cortex and posterior hippocampus result in a markedly reduced surface novelty P3 amplitude in all three sensory modalities (Knight, 1984, 1996, 1997; Knight and Scabini, 1998). Furthermore, deviant visual or auditory stimuli evoke a novelty P3 wave with large local gradients or polarity inversions in dorsolateral prefrontal cortex, anterior cingulate gyrus and posterior parahippocampus in patients undergoing depth electrode studies for possible surgical treatment of epilepsy (Alain et al., 1989; Baudena et al., 1995; Halgren et al., 1995).
The current study confirms that damage to prefrontal cortex in humans profoundly disrupts the novelty P3 response. The decrease in the amplitude of the novelty P3 response was more widespread than that reported by Knight (Knight, 1984, 1997). This result may indicate that the decision-making task we employed placed greater demands on a more extensive part of the prefrontal cortex. The novelty P3 response is typically characterized in young and middle-aged adults as having an earlier latency and a more anterior scalp distribution than the target P3 response (Courchesne et al., 1975; Knight and Scabini, 1998), a pattern that was not found in our control subjects. The most likely explanation for the different pattern we observed is the age of our normal control subjects (mean of 68 years). Studies that have examined the impact of aging on the P3 wave have demonstrated a marked change in scalp distribution as subjects get older (Knight, 1987; Friedman et al., 1993, 1997; Fabiani and Friedman, 1995; Anderer et al., 1996), with a significant shift in P3 amplitude towards anterior sites in response to novel and target stimuli. Often, as in our study, no significant difference in the scalp distribution of novel versus target P3 waves has been found (Friedman et al., 1993; Fabiani and Friedman, 1995). Moreover, in older subjects, the novelty P3 latency is frequently not significantly shorter than the target P3 latency (Snyder and Hillyard, 1979; Friedman et al., 1993).
Frontal lobe damage significantly reduced attention to novel stimuli as measured by viewing duration. The amplitude of the novelty P3 response accounted for much of the variance associated with the preferential viewing of novel stimuli. The novelty P3 response thus appears to reflect cerebral activity that determines the enhanced allocation of attentional resources to potentially significant events. The absence of a significant association between frontal lobe injury and reduced viewing of novel stimuli after controlling for the impact of the novelty P3 response strongly suggests that frontal damage leads to diminished attention to novelty through a disruption of neural processes underlying the novelty P3 response. In keeping with other reports in the literature (Knight, 1984; Yamaguchi and Knight, 1991), frontal lobe injury had a limited effect on the P3 amplitude and behavioural responses to target stimuli.
Depth electrode studies (Alain et al., 1989; Baudena et al., 1995) have suggested that the P3 activity of frontal regions precedes that of posterior regions. Thus, damage to the frontal lobes may prevent the generation of a `signal' indicating that a novel event requires additional attention (Baudena et al., 1995; Daffner et al., 1998). Such impairment in orienting and allocating attention to novelty could be a critical early step in undermining more complex aspects of exploratory behaviour. Apathy (defined in terms of reduced motivation, initiative and exploration) (Marin, 1990, 1991) is a common feature of frontal lobe injury. Marin and colleagues have used experimental measures of interest in novelty to quantify apathy (Marin et al., 1991). In the current study, a strong negative correlation was found between measures of apathy and P3 amplitude as well as viewing of novel stimuli. The link between apathy and diminished responsiveness to novel stimuli appears to be selective, as no correlation was noted between apathy and electrophysiological or behavioural responses to target stimuli.
We found that patients with relatively circumscribed lesions within the dorsolateral prefrontal cortex exhibited a similar reduction of novelty P3 amplitude and viewing duration of novel relative to background stimuli as patients with the large lesions that involved much more of the frontal lobes. This suggests that the dorsolateral prefrontal cortex may make a particularly important contribution to responding to novelty, as has been shown in primate studies (Mesulam, 1986). However, the small size of the sample in this study limits conclusions about the function of specific prefrontal regions in the processing of novel events. It will be interesting to determine whether the right hemisphere plays a greater role than the left in distributing attention to novel stimuli, which would be consistent with other studies indicating a right hemisphere specialization for the orienting of attention (Mesulam, 1981, 1998; Heilman et al., 1993; Gitelman et al., 1999). In support of this possibility, normal controls exhibited larger P3 responses at right hemisphere sites, a finding in keeping with other results in the ERP literature (Alexander et al., 1995; Daffner et al., 1998). However, the three patients with left frontal damage did not differ significantly from the three patients with right-sided infarctions of similar size and distribution, in terms of P3 amplitude or proportional viewing of novel stimuli.
In summary, three conclusions can be drawn. First, the novelty P3 response reflects neural processes that actively allocate attentional resources to potentially significant events in the environment. Secondly, the prefrontal cortex serves as a critical component of this novelty processing system. Finally, damage to this system appears to contribute to the reduced attention to novel events and the emergence of apathy commonly observed in patients with frontal lobe injury.
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Acknowledgments |
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We wish to thank Dr S. M. Kosslyn, Dr J. F. Kroll and Dr M. C. Potter for allowing us to use their stimulus sets, and appreciate the expert administrative assistance of Barbara Vericker and Lise Bliss. This research was supported by NIH grant K20MH01378 to the first author.
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Received August 5, 1999. Revised October 28, 1999. Accepted December 6, 1999.
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