Pathophysiology underlying diminished attention to novel events in patients with early AD

BACKGROUND: Patients with mild to moderate AD often are apathetic and fail to attend to novel aspects of their environment. OBJECTIVE: To investigate the mechanisms underlying these changes by studying the novelty P3 response that measures shifts of attention toward novel events. METHODS: While event-related potentials were recorded, mildly impaired AD patients and matched normal controls (NC) viewed line drawings that included a repetitive background stimulus, an infrequent target stimulus, and infrequent novel stimuli. Subjects controlled how long they viewed each stimulus by pressing a button. This served as a measure of their allocation of attention. They also responded to targets by depressing a foot pedal. Patients did not differ from NC in age, education, estimated IQ, or mood but were judged by informants to be more apathetic. RESULTS: P3 amplitude to novel stimuli was significantly smaller for AD patients than NC. However, P3 amplitude to target stimuli did not differ between groups. For NC, P3 response to novel stimuli was much larger than to background stimuli. In contrast, for patients with AD, there was no difference in P3 response to novel vs background stimuli. Although NC spent more time looking at novel than background stimuli, patients with AD distributed their viewing time evenly. Remarkably, for patients with AD, the amplitude of the novelty P3 response powerfully predicted how long they would spend looking at novel stimuli (R2 = 0.52) and inversely correlated with apathy severity. CONCLUSIONS: The decreased attention to novel events exhibited by patients with AD cannot be explained by a nonspecific reduction in their attentional abilities. The novelty P3 response is markedly diminished in mild AD, at a time when the target P3 response is preserved. The disruption of the novelty P3 response predicts diminished attention to novel stimuli and is associated with the apathy exhibited by patients with AD.     

Disruption of attention to novel events after frontal lobe injury in humans

OBJECTIVE: To investigate whether frontal lobe damage in humans disrupts the natural tendency to preferentially attend to novel visual events in the environment. METHODS: Nine patients with chronic infarctions in the dorsolateral prefrontal cortex (DLPFC) and 23 matched normal controls participated in a study in which subjects viewed repetitive background stimuli, infrequent target stimuli, and novel visual stimuli (for example, fragmented or "impossible" objects). Subjects controlled viewing duration by a button press that led to the onset of the next stimulus. They also responded to targets by pressing a foot pedal. The amount of time spent looking at the different kinds of stimuli, and the target detection accuracy and speed served as dependent variables. RESULTS: Overall, normal controls spent significantly more time than frontal lobe patients looking at novel stimuli. Analysis of responses across blocks showed that initially frontal lobe patients behaved like normal controls by directing more attention to novel than background stimuli. However, they quickly began to distribute their viewing time evenly between novel and background stimuli, a pattern that was strikingly different from normal controls. By contrast, there were no differences between frontal lobe patients and normal controls for viewing duration devoted to background and target stimuli, target detection accuracy, or reaction time to targets. Frontal lobe patients did not differ from normal controls in terms of age, education, estimated IQ, or mood, but were more apathetic as measured by self report and informants' judgments. Attenuated responses to novel stimuli significantly correlated with degree of apathy. CONCLUSIONS: This study demonstrates that DLPFC injury selectively impairs the natural tendency to seek stimulation from novel and unusual stimuli. These data provide the first quantitative behavioural demonstration that the human frontal lobes play a critical part in directing and sustaining attention to novel events. The impairment of novelty seeking behaviour may contribute to the characteristic apathy found in patients with frontal lobe injury.     

Age-related changes in the electrophysiological response to visual stimulus novelty: A topographical approach

The relationship of task relevance and stimulus probability to P300 morphology, latency and distribution was assessed. Eight year olds and adults completed visual oddball tasks of recognition memory with frequent non-target (60%), infrequent target (20%), and infrequent novel (20%) stimuli. Stimuli consisted of 2 female faces posing neutral expressions, and 40 trial unique novel photographs depicting scenes, animals, objects or abstract patterns. Event-related potentials were recorded from 17 electrodes over frontal, central and parietal scalp, including lateral temporal sites. All stimuli elicited P300 responses at parietal electrodes, with the largest responses to the target stimuli (relevant and infrequent). The P300 responses of adults and children were morphologically dissimilar, with children showing broader peaks and latency shifts across electrodes. In addition, the eight year olds displayed a frontal negativity to novel stimuli which was absent in the responses of adult participants. Results suggest that different anatomical or functional circuitry may be involved in the processing of novelty for adults as compared to eight year olds.     

Total sleep deprivation and novelty processing: implications for frontal lobe functioning.

OBJECTIVE: Mounting evidence suggests that the frontal lobes are particularly vulnerable to total sleep deprivation (TSD). Detection of novelty involves the frontal lobes. The presentation of rare, novel stimuli elicits an event-related potential (novel P3), which maximizes over anterior regions of the scalp. We hypothesized that TSD would impair novelty detection, resulting in a smaller novel P3 over the frontal region, with a topographic shift toward posterior areas. METHODS: An auditory novelty oddball task was administered to a TSD group after 36 h of waking and again following recovery sleep, and to a control group after 12 h of waking. EEG was recorded from Fz, Cz and Pz. RESULTS: A large anterior P3 was elicited in the control group. In the TSD group, this novel P3 was smaller at Fz. A later novel positivity appeared in parietal areas. The novel P3 returned to baseline levels and the late novel P3 was difficult to observe following recovery sleep. CONCLUSIONS: TSD appears to compromise the usual automatic detection of novelty probably due to frontal deactivation. Participants may compensate by relying on posterior brain mechanisms involving active memory comparison. The late novel P3 component may also reflect a secondary effortful attempt to encode and to categorize novel stimuli. SIGNIFICANCE: This study suggests that TSD may compromise cognitive functioning in different regions of the brain. The detection of novelty, probably mediated by the frontal lobes, is particularly at risk.     

Contribution of subregions of human frontal cortex to novelty processing

Novelty processing was studied in patients with lesions centered in either OFC or lateral pFC (LPFC). An auditory novelty oddball ERP paradigm was applied with environmental sounds serving as task irrelevant novel stimuli. Lesions to the LPFC as well as the OFC resulted in a reduction of the frontal Novelty P3 response, supporting a key role of both frontal subdivisions in novelty processing. The posterior P3b to target sounds was unaffected in patients with frontal lobe lesions in either location, indicating intact posterior cortical target detection mechanisms. LPFC patients displayed an enhanced sustained negative slow wave (NSW) to novel sounds not observed in OFC patients, indicating prolonged resource allocation to task-irrelevant stimuli after LPFC damage. Both patient groups displayed an enhanced NSW to targets relative to controls. However, there was no difference in behavior between patients and controls suggesting that the enhanced NSW to targets may index an increased resource allocation to response requirements enabling comparable performance in the frontal lesioned patients. The current findings indicate that the LPFC and OFC have partly shared and partly differential contributions to the cognitive subcomponents of novelty processing.     

Attention orienting dysfunction during salient novel stimulus processing in schizophrenia

Schizophrenia is characterised by marked disturbances of attention and information processing. Patients experience difficulty focusing on relevant cues and avoiding distraction by irrelevant stimuli. Event-related potential recordings indicate an amplitude reduction in the P3a component elicited by involuntary orienting to task-irrelevant, infrequent novel stimuli presented during auditory oddball detection in patients with schizophrenia. The goal of the present study was to elucidate the functional abnormality underlying the disturbed orienting to novel stimuli in schizophrenia. Twenty-eight stable, partially remitted, medicated patients with schizophrenia and 28 healthy control participants completed a novelty oddball variant during event-related fMRI. Relative to healthy participants, patients with schizophrenia were characterised by underactivity during novel stimulus processing in the right amygdala-hippocampus, within paralimbic cortex in the rostral anterior cingulate and posterior cingulate cortices and the right frontal operculum, and in association cortex at the right temporo-parietal-occipital junction, bilateral intraparietal sulcus, and bilateral dorsal frontal cortex. Subcortically, relative hypoactivation during novelty processing was apparent in the cerebellum, thalamus, and basal ganglia. These results suggest that patients less efficiently reorient processing resources away from the ongoing task of detecting and responding to the task-relevant target stimuli. In addition, trend results suggest that patients experienced increased distraction by novel stimuli.     

Luminance and spatial attention effects on early visual processing

Event-related potentials (ERPs) were recorded from healthy subjects in response to unilaterally flashed high and low luminance bar stimuli presented randomly to left and right field locations. Their task was to covertly and selectively attend to either the left or right stimulus locations (separate blocks) in order to detect infrequent shorter target bars of either luminance. Independent of attention, higher stimulus luminance resulted in higher ERP amplitudes for the posterior N95 (80–110 ms), occipital P1 (110–140 ms), and parietal N1 (130–180 ms). Brighter stimuli also resulted in shorter peak latency for the occipital N1 component (135–220 ms); this effect was not observed for the N1 components over parietal, central or frontal regions. Significant attention-related amplitude modulations were obtained for the occipital P1, occipital, parietal and central N1, the occipital and parietal P2, and the parietal N2 components; these components were larger to stimuli at the attended location. In contrast to the relatively short latencies of both spatial attention and luminance effects, the first interaction between luminance and spatial attention effects was observed for the P3 component to the target stimuli (350–750 ms). This suggests that interactions of spatial attention and stimulus luminance previously reported for reaction time measures may not reflect the earliest stages of sensory/perceptual processing. Differences in the way in which luminance and attention affected the occipital P1, occipital N1 and parietal N1 components suggest dissociations among these ERPs in the mechanisms of visual and attentional processing they reflect. Nonetheless, scalp current density mappings of the attention effects throughout the latency ranges of the P1 and N1 components show the most prominent attention-related activity to be in lateral occipital scalp areas. Such a pattern is consistent with the spatially selective filtering of information into the ventral stream of visual processing which is reponsible for complex feature analysis and object identification.     

Anterior and posterior association cortex contributions to the somatosensory P300

A P300 (P3)-evoked response is generated in a variety of mammalian species upon detection of significant environmental events. The P3 component has been proposed to index a neural system involved in attention and memory capacity. We investigated the contribution of anterior and posterior association cortex to somatosensory P3 generation. Somatosensory event-related potentials (ERPs) were recorded in controls (n = 10) and patients with unilateral lesions in temporal-parietal junction (n = 8), lateral parietal cortex (n = 8), or dorsolateral frontal cortex (n = 10). Subjects pressed a button to mechanical taps of the fifth finger (targets; p = 0.12), randomly interposed in sequences of taps to the second (standards; p = 0.76) and the third or fourth finger (tactile novels; p = 0.06). Occasional shock stimuli were delivered to the wrist (shock novels; p = 0.06). The scalp-recorded P3 was differentially affected by anterior and posterior association cortex lesions. Subjects with temporal-parietal lesions showed markedly reduced P3s to all types of stimuli at all scalp locations. The reductions were largest at the parietal electrode site over the lesioned hemisphere. Parietal patients had normal P3s for all stimulus types except for contralateral shock novels, which generated reduced P3s. Frontal lesions had reductions of the novelty P3 over frontal sites with minimal changes in the target P3. The data support the existence of multiple intracranial P3 sources. The data further indicate that association cortex in the temporal-parietal junction is critical for generating the scalp-recorded target and novelty P3s, whereas dorsolateral frontal cortex contributes preferentially to novelty P3 generation. The N2 component was reduced by parietal and frontal lesions in patients who had intact target P3s, suggesting that different neural systems underlie N2 and P3 generation.     

Apathy and the processing of novelty in schizophrenia

Apathy is a common negative symptom in schizophrenia that has been associated with poor medication compliance and treatment outcome. Recent studies in neurological patients have observed an association between apathy and reduced attention to novel stimuli. We evaluated whether patients with schizophrenia demonstrate a similar relationship. Participants included 20 patients with schizophrenia and 20 healthy comparison subjects matched for age, sex, handedness, and parental education. A self-paced visual novelty task was presented which assessed the duration that participants looked at frequent standard stimuli, infrequent target stimuli, and novel stimuli. Attention to novelty was defined as the duration of viewing novel relative to standard stimuli. Apathy was assessed with the Marin Apathy Evaluation Scale. Results revealed significantly greater self- and informant-reported apathy, slower reaction time to target stimuli, and longer viewing times to the stimuli, but not reduced attention to the novel stimuli, in the patient group. Although greater self-report of apathy was associated with longer viewing times for all stimuli in the patient group, this was accounted for by depressed mood. The present findings indicate that schizophrenia is associated with slowed information processing, but do not support the hypothesis that apathy in schizophrenia is associated with abnormal processing of novelty.     

To ignore or explore: top-down modulation of novelty processing

Abstract Attending to novelty is a critical element of human behavior and learning. Novel events can serve as task-irrelevant distracters or as potential sources of engagement by interesting or important aspects of one's environment. An optimally functioning brain should have the capacity to respond differentially to novel events depending on the circumstances in which they occur. In the present study, a subject-controlled variant of the visual novelty oddball paradigm was employed under two different conditions in which novel stimuli were characterized either as distracters from a main task or as potentially meaningful "invitations" to explore the environment. Differences in context, derived from varying the emphasis of task instructions, strongly modulated both the behavioral and electrophysiological response to novelty. This modulation was not observed for processing earlier than the P3 component. Subjects who encountered novel events that served as distracters limited the amount of attention and processing resources they appropriated. Remarkably, under this condition, there were no differences in overall P3 amplitude, late positive slow-wave activity, or viewing duration between rare novel and frequent standard events. In contrast, subjects who encountered novel events as potential opportunities to explore augmented the attention and processing resources directed toward these events (as reflected by a larger P3 amplitude, late positive slow-wave activity, and longer viewing durations). Our results suggest that the processing of novelty within the visual modality involves several stages, including: (1) the relatively automatic detection of unfamiliar, novel stimuli (indexed by the N2); (2) the voluntary allocation of resources determined by the broader context in which a novel event occurs (indexed by the P3); and (3) the sustained processing of novelty (indexed by late positive slow-wave activity). This study provides evidence of the brain's ability to generate differential responses to novel events according to the circumstances under which they are encountered. It also points to a greater degree of top-down modulation of the processing of novelty than has been previously emphasized. We suggest that less commonly studied variables, such as subject control, may provide additional insight into the different ways in which novelty is processed.     

Predictive value of novel stimuli modifies visual event-related potentials and behavior.

OBJECTIVE: We examined how behavioral context influences novelty processing by varying the degree that a novel event predicted the occurrence of a subsequent target stimulus. METHODS: Visual event-related potentials (ERPs) and reaction times (RTs) were recorded in 3 detection experiments (23 subjects). The predictive value of a novel stimulus on the occurrence of a subsequent target was varied as was novel-target pairing intervals (200-900 ms). In Experiment 1, novel stimuli always preceded a target, in Experiment 2, 40% of novel stimuli were followed by a target, and in Experiment 3, novel stimuli occurred randomly. RESULTS: In Experiment 1, RTs following 100% predictive novels were shortened for targets at all spatial locations and novel-target pairing intervals. Novel stimuli predicting a target generated a central negativity peaking at 300 ms and reduced P3a and P3b ERPs. In Experiments 2 and 3, target RTs were prolonged only when novel and target stimuli were presented in the same spatial location at short ISIs (200 ms). The central novel N2 was smaller in amplitude in comparison to Experiment 1, and novelty P3a and target extrastriate N2 and posterior scalp P3b ERPs were enhanced. CONCLUSIONS: The enhanced N2 for 100% predictive novel stimuli appears to index an alerting system facilitating behavioral detection. The same novel stimuli with no predictive value distract attention and generate a different ERP pattern characterized by increased novelty P3a and target P3b responses. The results indicate that behavioral context determines how novel stimuli are processed and influence behavior.     

What can functional imaging reveal about the role of attention in visual awareness?

This review focuses on neuroimaging studies that address the relationship between selective attention, neural activity and visual awareness. Withdrawing attention from particular visual stimuli reduces modality-specific processing in posterior visual cortex, and when attention is fully engaged elsewhere, even highly salient but task-irrelevant stimuli can fail to evoke activity and reach awareness. However, the link between visual attention and awareness extends beyond posterior visual cortex to also encompass regions of parietal and prefrontal cortex. Activity in the posterior visual cortex may be necessary but not sufficient for awareness, without a contribution from frontal and parietal cortex. Consistent with this, enhanced interactions between parietal, frontal and posterior visual cortex are observed as a function of both visual attention and visual awareness; and lesions of parietal cortex disrupt both visual attention and awareness. Taken together, these data suggest that distributed interactions between modality-specific posterior visual cortex and frontoparietal areas subserve both visual attention and visual awareness.     

Decreased response to novel stimuli after prefrontal lesions in man

Experiments were conducted to study the contribution of prefrontal cortex to the generation and modulation of two varieties of P300 activity. Control subjects generated typical parietal maximal P300 responses to detected target stimuli. Unexpected, novel auditory stimuli presented to controls generated an earlier latency, fronto-centrally distributed P300 response. A similar earlier latency, fronto-central P300 is generated to unexpected, novel visual stimuli. The occurrence of this phenomenon in both the auditory and visual modalities suggests that it may reflect neural activity of a common CNS system involved in the orienting response. Subjects with unilateral prefrontal damage generated P300 complexes to target stimuli that did not differ from the control responses. Prefrontal damage, however, resulted in a specific defect in the P300 response to the unexpected novel stimulus. Prefrontal patients showed neither N200 enhancement nor the fronto-central P300 response to the novel stimulus that was found in control subjects. These findings indicate that prefrontal regions are critical for the organism's response to unexpected novel stimuli. Abnormalities in prefrontal control of sensory-limbic integration may be a critical element in the decreased P300 to novel stimuli found in these unilateral prefrontal lesioned patients. It is suggested that major features of the human frontal lobe syndrome may be explained by a physiological inability to control attention and orientation systems after prefrontal damage.     

Orbitofrontal cortex biases attention to emotional events

We examined the role of orbitofrontal (OF) cortex in regulating emotion-attention interaction and the balance between involuntary and voluntary attention allocation. We studied patients with OF lesion applying reaction time (RT) and event-related potential (ERP) measures in a lateralized visual discrimination task with novel task-irrelevant affective pictures (unpleasant, pleasant, or neutral) preceding a neutral target. This allowed for comparing the effects of automatic attention allocation to emotional versus neutral stimuli on subsequent voluntary attention allocation to target stimuli. N2-P3a and N2-P3b ERP components served as measures of involuntary and voluntary attention allocation correspondingly. Enhanced N2-P3a amplitudes to emotional distractors and reduced N2-P3b amplitudes to targets preceded by emotional distractors were observed in healthy subjects, suggesting automatic emotional orienting interfered with subsequent voluntary orienting. OF patients showed an opposite pattern with tendency towards reduced N2-P3a responses to emotional distractors, suggesting impaired automatic orienting to emotional stimuli due to orbitofrontal damage. Enhanced N2-P3b responses to targets preceded by any affective distractor were observed in OF patients, suggesting bias towards voluntary target-related attention allocation due to orbitofrontal lesion. Behavioral evidence indicated that left visual field (LVF) attention performance was modulated by emotional stimuli. Specifically, OF patients responded faster to LVF targets subsequent to pleasant emotional distractors. We suggest that damage to the orbitofrontal circuitry leads to dysbalance between voluntary and involuntary attention allocation in the context of affective distractors with predisposition to posterior target-related processing over frontal novelty and affect-related processing. Furthermore, we suggest that orbitofrontal influence on emotion-attention interaction is valence and hemisphere dependent.     

Impaired novelty detection and frontal lobe dysfunction in Parkinson's disease

Recent evidence suggests that the frontal lobe plays an important role in an orienting response to novel events, and that frontal lobe dysfunction is linked to attentional and cognitive deficits in Parkinson's disease (PD). We tested the hypothesis that the neural network involved in novelty detection may be impaired in PD patients by studying event-related brain potentials to target and novel stimuli and their correlation to performance in neuropsychological tests in non-demented PD patients. The PD patients showed prolonged P3 latency to novel stimuli compared with age-matched controls, whereas their P3 latency to target stimuli was not different from that in controls. The PD patients also manifested amplitude reduction and less habituation of the P3 to novel stimuli over frontal scalp sites compared with controls. The prolonged latency and frontal reduction of novelty P3 correlated with a poor performance in the Wisconsin Card Sorting Test. These results suggest that the orienting response of PD patients to novel events is impaired and that recording novelty P3 might provide a neurophysiological and quantitative measure of attentional and cognitive deficits linked to the frontal lobe in non-demented PD patients.     

Mapping early somatosensory evoked potentials in selective attention: critical evaluation of control conditions used for titrating by difference the cognitive P30, P40, P100 and N140

Detailed procedures are described for the study of somatosensory event-related potentials (ERPs) to electric stimulation of fingers. Control responses to homogeneous (100%) series of identical stimuli (thus eliminating input mismatch) while the subject reads a novel (thus providing a distinct attention-capturing activity and maintaining vigilance level) are validated as reflecting the exogenous obligatory profiles required for assessing cognitive component in ERPs to target relevant stimuli. With these 'neutral' conditions, the control responses have a similar profile even at larger ISIs such as those separating the infrequent targets in Attention runs. Conversely, series of stimuli identical to those in control runs can elicit cognitive components in a 'Lie' experiment when the subject is induced to treat the stimuli like targets even though there is no discrimination involved. On this basis, the somatosensory P30, P40, P100 and N140 components appearing in the target profiles are considered genuine cognitive components. They have been analyzed with scatter displays, electronic subtraction, bit-mapped displays and with calculation of Z and dilation factors. The cognitive P30 and P40 reflect selective attention-related enhancements of the neural generators in receiving somatosensory cortex. The early parietal positivity P27 can thus be modulated separately from the frontal N30 component and is thought to be generated by a radial dipole in area 1. The later cognitive P100 and N140 reflect the invocation of distinct processors in conjunction with the behavioral use of the sensory input. The evolving topographical patterns of the P100 and N140 electrogeneses, revealed by bit-mapped data, suggest complex interactions between posterior parietal and prefrontal cortex whereby the sensory information is placed into spatial coordinate systems and matched with representations of relevant objects or relationships in space for target processing in the sequential tasks.     

Contributions of temporal-parietal junction to the human auditory P3

The P3 component of the event-related potential (ERP) is generated in humans and other mammalian species when attention is drawn to infrequent stimuli. We assessed the role of subregions of human posterior association cortex in auditory P3 generation in groups of patients with focal cortical lesions. Auditory P3s were recorded to target (P3b) and unexpected novel stimuli (P3a) in monaural and dichotic signal detection experiments. Two groups of patients were studied with lesions of: (1) temporal-parietal junction including posterior superior temporal plane and adjacent caudal inferior parietal cortex; and (2) the lateral parietal lobe including the rostral inferior parietal lobe and portions of superior parietal lobe. Extensive lateral parietal cortex lesions had no effect on the P3. In contrast, discrete unilateral lesions centered in the posterior superior temporal plane eliminated both the auditory P3b and P3a at electrodes over the posterior scalp. The results indicate that auditory association cortex in the human temporal-parietal junction is critical for auditory P3 generation.     

Event-related brain potentials in response to novel sounds in dementia.

OBJECTIVE: Non-target, deviant stimuli generate an earlier latency, front-central novelty P3, whereas correctly detected task-relevant stimuli generate a parietal maximal target P3. We examined whether the P3 component to novel stimuli is affected by dementing processes, and is therefore useful for distinguishing Alzheimer's type dementia (AD) from vascular dementia (VD). METHODS: We recorded ERPs to task-relevant stimuli (target P3) and novel task-irrelevant stimuli (novelty P3) in an auditory oddball task in AD (n = 16), VD (n = 16), and age-matched controls (n = 18). The amplitude, latency, and scalp topography of target and novelty P3 were compared among 3 groups using ANOVA. The relationship between P3 measures and intelligence scores were evaluated by correlation analysis. RESULTS: The amplitude, latency and scalp topography of the target P3 were comparably affected by both AD and VD. However, the amplitude of the novelty P3 was markedly reduced in VD, but not in AD, and the scalp topographics were different in the 3 groups. The amplitude was maximal at frontal sites in controls, at central sites in AD, and at parietal sites in VD. The target P3 latency was prolonged in both AD and VD, whereas the novelty P3 latency was only prolonged in VD. AD was discriminated satisfactorily from VD by using the novelty amplitude at Cz and the ratio of the amplitudes at Fz and Pz as independent variables. CONCLUSIONS: These results suggest that the response to novel stimuli is differentially affected by dementia with degenerative and vascular etiology.     

Monitoring for target objects: activation of right frontal and parietal cortices with increasing time on task

The right prefrontal and parietal cortices have been implicated in attentional processing in both neuropsychological and functional neuroimaging literature. However, attention is a heterogeneous collection of processes, each of which may be underpinned by different neural networks. These attentional networks may interact, such that engaging one type of attentional process could influence the efficiency of another via overlapping neural substrates. We investigated the hypothesis that right frontal and parietal cortices provide the neuroanatomical location of the functional interaction between sustained attention and the process of selectively monitoring for target objects. Six healthy volunteers performed one of two tasks which required either selective or non-selective responding. The task lasted continuously for 18 min, during which time 3 Positron Emission Tomography (PET) scans were acquired for each task. This was repeated to obtain 12 PET measurements of regional cerebral blood flow (rCBF) for each subject. The right inferior frontal and parietal cortices were differentially activated by increasing time on task during the selective (S) vs non-selective (NS) task. Specifically, rCBF decreased with increasing time spent performing the NS task but not the S task. This result suggests that the normal deactivation in these areas as time on task increases is counteracted by the extra cognitive demands of selectively responding to target objects. Therefore, we have confirmed our hypothesis that right frontal and parietal cortices provide the neuroanatomical location for the modulation of object selection by sustained attention. We also identified the neuroanatomical correlates of each process separately, and confirmed earlier reports of prefrontal cortex and anterior cingulate activation associated with selective responding, and a fronto-parietal-thalamic network associated with sustained attention.     

Reproducibility of the hemodynamic response to auditory oddball stimuli: a six-week test-retest study

Determining the reliability and reproducibility of the hemodynamic response is important for the interpretation and understanding of the results of functional magnetic resonance imaging (fMRI) experiments. We describe a whole brain fMRI study designed to examine the reproducibility of the event-related hemodynamic response elicited by low-probability task-relevant target stimuli and low-probability task-irrelevant novel stimuli assessed 6 weeks apart. Reliable activation was observed during test and retest for processing of target stimuli in multiple frontal, temporal, parietal, cerebellar, and subcortical sites. Novel stimuli elicited reliable activation during test and retest in lateral frontal cortex, inferior parietal lobule, and lateral temporal cortex, though there was evidence of habituation at some cortical sites. The patterns of activation associated with target detection and novelty processing are consistent with the intracranial distribution of the neural sources generated during similar tasks and replicate the results of previous event-related fMRI studies. The observed pattern of results supports the hypothesis that the hemodynamic response to target and novel stimuli is highly reproducible over the 6-week test-retest period.