Neural fate of seen and unseen faces in visuospatial neglect: a combined event-related functional MRI and event-related potential study.

To compare neural activity produced by visual events that escape or reach conscious awareness, we used event-related MRI and evoked potentials in a patient who had neglect and extinction after focal right parietal damage, but intact visual fields. This neurological disorder entails a loss of awareness for stimuli in the field contralateral to a brain lesion when stimuli are simultaneously presented on the ipsilateral side, even though early visual areas may be intact, and single contralateral stimuli may still be perceived. Functional MRI and event-related potential study were performed during a task where faces or shapes appeared in the right, left, or both fields. Unilateral stimuli produced normal responses in V1 and extrastriate areas. In bilateral events, left faces that were not perceived still activated right V1 and inferior temporal cortex and evoked nonsignificantly reduced N1 potentials, with preserved face-specific negative potentials at 170 ms. When left faces were perceived, the same stimuli produced greater activity in a distributed network of areas including right V1 and cuneus, bilateral fusiform gyri, and left parietal cortex. Also, effective connectivity between visual, parietal, and frontal areas increased during perception of faces. These results suggest that activity can occur in V1 and ventral temporal cortex without awareness, whereas coupling with dorsal parietal and frontal areas may be critical for such activity to afford conscious perception.

Response selection in the human anterior cingulate cortex.

The anterior cingulate cortex (ACC) has been proposed as part of the brain's attentional control network, but the exact nature of its involvement in cognitive and motor operations is under debate. Assessing effects of human ACC damage directly addresses the problem of ACC function. We report that executive control processes of a patient with a focal right hemisphere anterior cingulate lesion were not compromised. However, her performance level depended on the response modality used. Under the same task requirements, she was impaired when giving manual responses, but not vocal responses. Thus, we provide neuropsychological evidence for functional specialization within the human ACC.

Contributions of prefrontal cortex to recognition memory: electrophysiological and behavioral evidence.

To clarify the involvement of prefrontal cortex in episodic memory, behavioral and event-related potential (ERP) measures of recognition were examined in patients with dorsolateral prefrontal lesions. In controls, recognition accuracy and the ERP old-new effect declined with increasing retention intervals. Although frontal patients showed a higher false-alarm rate to new words, their hit rate to old words and ERP old-new effect were intact, suggesting that recognition processes were not fundamentally altered by prefrontal damage. The opposite behavioral pattern was observed in patients with hippocampal lesions: a normal false-alarm rate and a precipitous decline in hit rate at long lags. The intact ERP effect and the change in response bias during recognition suggest that frontal patients exhibited a deficit in strategic processing or postretrieval monitoring, in contrast to the more purely mnemonic deficit shown by hippocampal patients.

Prefrontal cortex regulates inhibition and excitation in distributed neural networks.

Prefrontal cortex provides both inhibitory and excitatory input to distributed neural circuits required to support performance in diverse tasks. Neurological patients with prefrontal damage are impaired in their ability to inhibit task-irrelevant information during behavioral tasks requiring performance over a delay. The observed enhancements of primary auditory and somatosensory cortical responses to task-irrelevant distractors suggest that prefrontal damage disrupts inhibitory modulation of inputs to primary sensory cortex, perhaps through abnormalities in a prefrontal-thalamic sensory gating system. Failure to suppress irrelevant sensory information results in increased neural noise, contributing to the deficits in decision making routinely observed in these patients. In addition to a critical role in inhibitory control of sensory flow to primary cortical regions, and tertiary prefrontal cortex also exerts excitatory input to activity in multiple sub-regions of secondary association cortex. Unilateral prefrontal damage results in multi-modal decreases in neural activity in posterior association cortex in the hemisphere ipsilateral to damage. This excitatory modulation is necessary to sustain neural activity during working memory. Thus, prefrontal cortex is able to sculpt behavior through parallel inhibitory and excitatory regulation of neural activity in distributed neural networks.

Verb generation in patients with focal frontal lesions: a neuropsychological test of neuroimaging findings.

What are the neural bases of semantic memory? Traditional beliefs that the temporal lobes subserve the retrieval of semantic knowledge, arising from lesion studies, have been recently called into question by functional neuroimaging studies finding correlations between semantic retrieval and activity in left prefrontal cortex. Has neuroimaging taught us something new about the neural bases of cognition that older methods could not reveal or has it merely identified brain activity that is correlated with but not causally related to the process of semantic retrieval? We examined the ability of patients with focal frontal lesions to perform a task commonly used in neuroimaging experiments, the generation of semantically appropriate action words for concrete nouns, and found evidence of the necessity of the left inferior frontal gyrus for certain components of the verb generation task. Notably, these components did not include semantic retrieval per se.

Effects of prefrontal lesions on lexical processing and repetition priming: an ERP study.

The role of left prefrontal cortex in lexical-semantic processing remains a matter of some debate. Functional neuroimaging experiments have reported blood flow changes in left inferior prefrontal cortex (LIPC) during tasks that involve word retrieval and semantic processing. Some of these studies have also implicated LIPC in repetition priming. To determine the necessity of prefrontal cortex for these types of memory and to elucidate their time-course, behavioral and event-related potential (ERP) correlates of lexical processing and repetition priming were examined in 11 stroke patients with lesions centered in dorsolateral prefrontal cortex (areas 9 and 46). Damage extended inferiorly and posteriorly to areas 6, 8, 44, and 45 in some subjects, so patients were subdivided into anterior and posterior frontal subgroups. Visually presented words and pronounceable non-words were repeated after one of three delays. Subjects categorized stimuli as either words or non-words in a lexical decision task. Controls showed significant word priming at all three delays. Old words elicited more positive-going potentials than new words, beginning at 300 ms and lasting until 500-700 ms. This ERP repetition effect was reduced, but not eliminated, by both anterior and posterior frontal lesions. However, behavioral priming was intact in the patients, suggesting that prefrontal cortex may modulate the neural generators in posterior cortical regions that are critical for priming. Left posterior frontal lesions resulted in impaired performance in the lexical decision task and a reduction in the amplitude of the late positive component (LPC). These latter findings suggest that left posterior prefrontal cortex is important for the categorization and selection processes required by lexical-semantic tasks.

Submersion injuries in children.

Submersion injures, also known as drowning or near drowning, are a serious threat to the life and health of children. They are the third leading cause of death in the pediatric population (18 years and less), behind motor vehicle crashes and cancer in the United States. This article discusses epidemiologic factors, the pathophysiologic characteristics of submersion injuries, treatment, outcome identifiers, and methods used for prevention.

Event-related potentials differentiate the effects of aging on word and nonword repetition in explicit and implicit memory tasks.

Explicit memory declines with age while implicit memory remains largely intact. These experiments extended behavioral findings by recording event-related potentials (ERPs) in young and elderly adults during repetition priming and recognition memory paradigms. Words and pronounceable nonwords repeated after 1 of 3 delays. Stimuli were categorized as either word-nonword or old-new. Repeated items elicited more positive-going potentials in both tasks. Hemispheric asymmetries for word and nonword processing were observed during lexical decision: Repetition effects were larger over the left hemisphere for words and over the right hemisphere for nonwords. For the young, ERP repetition effects were larger during recognition memory. For old adults, conversely, repetition produced more positive-going waveforms during lexical decision. The elderly had ERP and behavioral deficits at long recognition delays. ERP repetition effects in the elderly, like behavioral performance, were preserved in an implicit task but impaired in an explicit memory task.

Is prefrontal cortex involved in cued recall? A neuropsychological test of PET findings.

Positron emission tomography (PET) experiments have detected blood flow activations in right anterior prefrontal cortex during performance of a word stem cued recall task [3, 38]. Based on findings from a variety of PET studies, the "hemispheric encoding/retrieval asymmetry model" [44] was proposed to explain the role of the frontal lobes in episodic memory. This model asserts that left prefrontal cortex is preferentially involved in the encoding of new information into episodic memory, whereas right prefrontal cortex is more involved in episodic memory retrieval. As a neuropsychological test of this hypothesis, a group of frontal patients with lesions in areas 6, 8, 9, 10, 44, 45 and/or 46 (11 left, five right) were run on word stem cued recall under two semantic study conditions. As a group, these patients were not significantly impaired in cued recall. In the first but not the second experiment, left frontal patients recalled fewer words than controls. Right frontal patients were not impaired on either list. Right prefrontal cortex could be activated by several strategic aspects of the cued recall paradigm that were minimized in the present experiment. Brain reorganization in the lesioned patients could also account for their intact performance. The regions of prefrontal cortex activated in PET studies of young controls are not necessary for patients to perform the task.

Contributions of right inferior temporal-occipital cortex to visual word and non-word priming.

Little is known about the neural substrates of indirect forms of memory such as priming. Electrophysiological (ERP) and behavioral data were recorded from controls and three patients with damage in the right parahippocampal and lingual gyri, with variable extension into posterior hippocampus and striate/extrastriate cortex. Visually presented words and non-words were repeated after one of three delays in a lexical decision task. The late positive ERP deflection related to stimulus repetition was diminished at all scalp sites, suggesting dysfunction in a neural system associated with priming. The patients also failed to show significant reaction time priming at intermediate and long delays. These results demonstrate the importance of right inferior temporal-occipital cortex for ERP and behavioral manifestations of verbal priming.

Locus coeruleus neuronal activity in awake monkeys: relationship to auditory P300-like potentials and spontaneous EEG.

These experiments were designed to test the hypothesis that novel auditory stimuli lead to phasic and/or tonic increases in locus coeruleus (LC) cell firing, which may be a necessary condition for the occurrence of P300 potentials. Event-related potentials (ERPs) and LC unit activity were simultaneously recorded from three awake macaque monkeys exposed to an auditory "oddball" paradigm. Oddball stimuli resulted in probability-sensitive potentials resembling the human P3a component. Twenty-five percent (3/12) of LC units showed small phasic enhancements of LC firing after infrequent but not frequent tones. A comparison between histograms elicited by the two types of stimuli revealed significant effects of stimulus sequence. This pattern suggested a slight activation by rare tones, followed by a brief inhibition of firing in the subsequent trial. These data suggest that changes in LC activity during oddball paradigms are subtle, heterogeneous, and influenced by the subject's level of arousal and vigilance.

Effects of systemic clonidine on auditory event-related potentials in squirrel monkeys.

Event-related potential (ERP), electroencephalographic (EEG), and behavioral data were collected from squirrel monkeys (Saimiri sciureus) in a 90-10 auditory oddball paradigm. Background or target tones were presented once every 2 s, and responses to the targets were rewarded. ERPs were recorded from epidural electrodes following systemic administration of clonidine (0.1 mg/kg) or a saline placebo. EEG power spectral and behavioral performance were assessed simultaneously as indices of behavioral state. Clonidine significantly decreased the area and increased the latency of a P300-like potential. The amplitude and areas of the earlier P1, N1, and P2 components and a later slow wave-like potential were not reduced, nor were ther latencies altered. Clonidine produced increased EEG power in the alpha range (7.5-12 Hz) and decreased power in the upper beta range (20-40 Hz) but did not affect performance in the oddball task. Because two major effects of clonidine are to substantially reduce activity in the noradrenergic nucleus locus coeruleus (LC) and to reduce norepinephrine (NE) release from axons, the present results support the hypothesis that the LC and its efferent projection system are important in modulating the activity of P300-like potentials.

Visual P3-like potentials in squirrel monkey: effects of a noradrenergic agonist.

Event-related potentials (ERPs) were recorded from squirrel monkeys (Saimiri sciureus) in a 90-10 visual "oddball" paradigm. A small, blue rectangle was presented every 2 s on 90% of the trials (background), whereas a yellow rectangle occurred on 10% on the trials (oddball). Electrical activity time-locked to these stimulus events was recorded from epidural electrodes before and following systemic administration of the alpha-2 noradrenergic agonist clonidine (0.1 mg/kg intramuscularly, IM). Baseline data in response to oddball stimuli showed a large, P3-like potential exhibiting a fronto-central maximum along midline electrodes and a parietal maximum along lateral electrodes. A frontally dominant, long-latency, negative slow wave (SN) consistently followed this P3-like potential. Amplitudes for P3 were larger following 10% than 50% probable oddball events. These results suggest that monkeys exhibit large, probability-sensitive P3-like potentials similar to the visual potentials reported in humans. Administration of clonidine had no effect on the amplitude, area, or latency of the monkey P3 component. This contrasts with our previous findings that the same dose of clonidine significantly decreases auditory P3s in these monkeys. Such differences may reflect distinct functional roles for norepinephrine in the processing of low-probability acoustic versus visual signals and argues against the hypothesis that norepinephrine is a common neurotransmitter substrate for auditory and visual P3-like potentials.

Brain-stem auditory evoked potentials in squirrel monkey (Saimiri sciureus).

To more fully characterize brain-stem auditory evoked potentials (BAEPs) in non-human primates, BAEPs were recorded from chronically implanted epidural electrodes in 10 squirrel monkeys (Saimiri sciureus). The effects of stimulus intensity, repetition rate, and anesthesia (ketamine 20 mg/kg i.m.) on peak latencies and inter-peak intervals were evaluated. Monkey wave forms consisted of approximately 7 peaks (I-VII), each exhibiting similar latencies across sessions, with later peaks exhibiting greater variability. In some subjects, additional peaks (IIa, IIIa) and slow potentials were recorded. The slow potentials provided a substratum for peaks IV through VII. As with human, monkey peaks exhibited systematic changes in latency with changes in stimulus intensity or repetition rate. These shifts included significant decreases in latency with increasing intensity for peaks I-IV and increases in latency with increases in repetition rate for peaks III, V, and VI. Inter-peak intervals were similar to those observed in human. Furthermore, ketamine anesthesia significantly delayed the latencies of most peaks (except I, V, and VII). Some differences between monkey and human BAEPs were evident in the relative amplitude of specific peaks. For example, peak V is typically most prominent in human, while this was true for peak III in monkey. The similarities between unanesthetized monkey and human inter-peak intervals suggest that the times required for impulses to reach particular brain-stem areas are conserved across primate species that vary in brain size. This supports the hypothesis that comparably numbered BAEP peaks in monkey and human index homologous processes. The data also suggest that the differences between animal and human BAEPs commonly reported may result from the use of anesthetics. In summary, unanesthetized monkey BAEPs resemble human BAEPs in morphology, number of peaks, polarity, latency variability, inter-peak intervals, slow potentials superimposed on the high-frequency peaks, and variations in morphology, amplitude, and resolution of peaks as a function of recording site. Thus, unanesthetized monkey BAEPs may be an excellent model for investigating the neural substrates of human BAEP or for determining species differences in acoustic processing among primates.

Audiogenic stress response: behavioral characteristics and underlying monoamine mechanisms.

Behavioral characterization of the audiogenic stress response in rats revealed an intensity related multiphasic pattern including an initial, transient activation followed by prolonged periods of response suppression during the remainder of the noise exposure and excitation after noise offset. These observations emphasize the need to consider the temporal proximity between exposure to a stressor and either behavioral characterization and/or determinations of neurochemical changes relevant to the stress response. In a second series of studies, the effect of the NE alpha 2 agonist clonidine and the NE alpha 2 antagonist yohimbine were evaluated on the different components of the audiogenic stress response. The effects of intracerebroventricular xylamine-induced depletion of NE were also examined. The results seem to indicate that CNS noradrenergic systems may not be specifically implicated in regulating the responsiveness to noise stimulation but instead may subserve a more general role in adjusting baseline levels of motoric output in response to environmental conditions.