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Biomedical subjects

R T Knight

Publications and source records attributed to R T Knight.

103 records · Page 6Linked to original sources

The effects of frontal cortex lesions on event-related potentials during auditory selective attention.

We compared electrophysiological indices of auditory selective attention in control subjects and in patients with unilateral lesions of the dorsolateral frontal lobes. In control subjects, ERPs following attended tones showed an enhanced negativity from 80 to 500 msec post-stimulus which had a different topographic distribution than the N120. Lesions of the frontal lobes reduced the attention-related negativity and impaired behavioral performance. The ERP reductions were equivalent in recordings obtained from electrodes placed over the damaged and intact cortex. A difference was noted between left and right frontal groups as a function of ear of delivery of the stimuli. Patients with left frontal lesions showed reduced attention effects following tones presented to either ear. Patients with right frontal lesions showed intact attention effects to right ear tones, but no attention-related negativity to left ear tones. When the left and right frontal groups were considered together, tones in ignored channels produced larger responses when presented to the ear contralateral to damaged cortex. These results underline the important role of the frontal lobes in processes of selective attention. Although the endogenous negativity produced in selective attention tasks does not appear to originate in dorsolateral frontal cortex, the frontal lobes exhibit a modulating influence upon it. In addition, the endogenous attention related negativity and exogenous N120 components apparently arise from different neural generators.

Adult↗

The effects of frontal and temporal-parietal lesions on the auditory evoked potential in man.

We compared the properties of long-latency auditory evoked potentials (AEPs) in patients with unilateral lesions of the dorsolateral frontal cortex (N = 10) or temporal-parietal cortex (N = 10) to those of a group of age-matched normal subjects. Extensive lesions of the frontal cortex had no effect on AEP amplitudes, scalp distributions or refractory properties. However, following frontal lesions AEPs were larger to tones presented in the ear contralateral to the lesion than they were for tones presented ipsilaterally. Following unilateral temporal-parietal lesions, the N1 component (98 msec latency) was markedly reduced in amplitude at all scalp sites, and no increase in N1 amplitude occurred with lengthening ISIs. The P2 component (200 msec), however, showed the same amplitude and refractory properties as in the normal subjects. The results underline the critical role played by the cortex of the posterior-superior temporal plane and the adjacent cortex of the parietal lobe in the production of the N1 component.

Adult↗

Auditory evoked potentials from the primary auditory cortex of the cat: topographic and pharmacological studies.

Wave VI (8.4 msec) of the brain-stem auditory evoked potential (BAEP) was maximal in a discrete region of primary auditory cortex (AI) of the anesthetized cat. Wave VI underwent rapid amplitude decrease over millimeter distances in the AI region and followed high stimulation rates. Wave VI did not show intracortical polarity inversion nor was it abolished by epicortical or intracortical GABA administration. The data are compatible with a wave VI source in the terminal axons of the thalamo-cortical radiations. Middle latency auditory responses (MAEPs) generated 10-40 msec after auditory stimulation were also recorded in a circumscribed area of AI. In contrast to wave VI, these primary auditory cortex potentials (Pa 18.3 msec; Nb 31.9 msec) underwent transcortical polarity inversion, correlated with intracortical multi-unit activity in the AI region and were reversibly altered or abolished by epicortical or intracortical GABA administration to the AI region. The data suggest that the Pa and Nb components of the cat MAEP are intracortically generated by neuronal elements in the AI region.

Acoustic Stimulation↗

Effects of temporal-parietal lesions on the somatosensory P3 to lower limb stimulation.

Temporal-parietal junction lesions reduce the auditory and upper limb somatosensory P3 event-related potential (ERP) to target and novel stimuli. The current study examined the somatosensory P3 to target and novel stimuli delivered to the sole of the foot in patients with unilateral temporal-parietal lesions (n = 6). Age-matched controls (n = 10) generated a parietal maximal target P3 and a frontal-central maximal novelty P3 ERP to foot stimulation. Unilateral temporal-parietal lesions abolished target and novelty P3 responses over all scalp sites for stimuli delivered contralateral to the lesion. The P3 was also reduced to ipsilateral stimuli at electrodes over the lesioned hemisphere with partial P3 preservation observed at electrode sites over the non-lesioned hemisphere. These results parallel the findings for upper limb stimulation and support the critical role of temporal-parietal cortex in P3 generation.

Aged↗

P3-like potential in rats.

Auditory event-related potentials (ERPs) were recorded from the skull surface in unrestrained, unanesthetized rats. Infrequent deviant tones presented randomly within a sequence of repetitive tones enhanced a long-latency positive component peaking at 240 msec. This rodent ERP was comparable to the human P3a component in latency and sensitivity to stimulus probability. The rodent may provide a useful model for investigation of the neural sources of the P3.

Acoustic Stimulation↗

Aging decreases auditory event-related potentials to unexpected stimuli in humans.

A P300 event-related potential (P3a) was recorded to unexpected, deviant auditory stimuli requiring no behavioral response. This brain potential underwent systematic latency prolongation and amplitude decrease with advancing age. The age-related changes paralleled those of the P300 (P3b) recorded in target detection tasks. These results provide physiological evidence of a decremented CNS response to unexpected stimuli with aging.

Acoustic Stimulation↗

Recovery from GABA-mediated hemiplegia in young and aged rats: effects of catecholaminergic manipulations.

We investigated the participation of catecholaminergic mechanisms in the functional recovery from motor cortex lesions in young (9 months) and aged (26 months) rats. The animals were studied during the recovery period from an hemiplegic syndrome secondary to small motor cortex lesions potentiated by the localized, chronic (7 days) infusion of GABA into the lesion site. Acute administration of haloperidol (0.1 mg/kg IP) to these recovered animals induced a re-emergence of the contralateral motor syndrome in both groups. In the young group, the haloperidol-induced hemiplegia lasted one day whereas in the aged animals the deficit was significantly prolonged lasting three days. Apomorphine administration (0.5 mg/kg IP) prior to or immediately after haloperidol injection failed to prevent or reverse the reappearance of the motor deficit. Adult animals recovered from motor cortex aspirations performed 7 to 12 months prior were refractory to haloperidol effects. Amphetamine administration to young rats treated chronically with saline or GABA infusion into the somatomotor region also failed to alter the clinical evolution of the motor deficit. The evidence suggests that dopaminergic mechanisms are involved in the functional recovery from brain lesions and that these mechanisms are most susceptible to neuroleptic blockade during the early post-lesional period. The deleterious effects of dopaminergic blockade are heightened in aged populations. The use of dopaminergic antagonists in brain-lesioned subjects, and particularly in geriatric populations, is considered potentially harmful, particularly in the early stages of the recovery process.

Aging↗

Age-related prefrontal alterations during auditory memory.

Event-related potentials were recorded from young and elderly subjects while they performed a modified auditory Sternberg memory task. Aging was associated with a decrease in frontal activation, suggesting that prefrontal alterations may be central to age-related impairments in auditory working memory. Young subjects showed significant serial position effects electrophysiologically, while elderly subjects showed no recency effects for P3 latency and no serial position effects for N4 and SFN amplitude. This finding, in combination with increased false alarm rates in the elderly, suggest that the two group of subjects employed different cortico-limbic circuits to perform the task.

Acoustic Stimulation↗

Cortical substrates supporting visual search in humans.

Serial and parallel visual search tasks were presented to patients with focal lesions in dorsolateral frontal, lateral parietal, or temporal-parietal cortex. In the unilateral display conditions, search efficiency in all patient groups was similar to the normal control group for stimuli both on the ipsi- and on the contralesional side of the displays. In contrast, in the bilateral display conditions, all patient groups showed a marked delay in initiating search on the side contralateral to the lesion as compared to normal controls. This delay was more pronounced when attention demands on the ipsilateral side increased, either by making target-distractor discrimination more difficult (serial search task), or by increasing the number of ipsilateral distractor items. The contralateral deficit was evident in all patient groups, supporting the notion that dorsolateral frontal as well as posterior parietal and temporal-parietal cortex plays a critical role in visual spatial attention.

Aged↗

Role of prefrontal cortex in generation of the contingent negative variation.

The contingent negative variation (CNV) is a brain potential generated during delay periods that has been proposed to measure prefrontal cortex (PFCx) activity. The CNV was recorded in neurological patients with PFCx damage centered in Brodmann areas 9, 44, 45, and 46 in a classical auditory S1-S2 paradigm employing a 3 sec interstimulus interval. Subjects pressed a button upon detection of an acoustically cued imperative tone (S2, 1000 Hz, GO). Responses were withheld if the warning tone (S1, 1500 Hz in GO trials) was lower in frequency (500 Hz, NOGO). The early phase of the CNV (500-700 msec after S1) was not reduced in patients with PFCx damage. PFCx lesions reduced the later phase of the CNV beginning about 1000 msec prior to S2. Reductions were maximal over PFCx sites but extended to posterior scalp electrodes over the lesioned hemisphere. The results are consistent with a late CNV generator in dorsolateral PFCx that also modulates generation of the potential in posterior regions of the ipsilateral hemisphere. The CNV findings coupled with behavioral evidence of impaired preparatory processes in these patients support the role of PFCx in sustaining distributed neural activity during delay periods.

Basal Ganglia↗

Prefrontal alterations during memory processing in aging.

Studies of human amnesia provide evidence for a short-term memory store with information transfer to long-term memory occurring within 60 sec of encoding. Frontal cortical activation is critical for maintenance of the short-term store, and limbic structure are necessary for access to the long-term store. The P3 and N4 components of the event-related potential (ERP) are generated during memory processes mediated by these brain regions. The current study examines the effects of age on ERPs generated to correctly identified stimuli presented at delays of 1-150 sec in a visual recognition memory task. Consistently different evoked potentials and performance were obtained to stimuli repeated at 1.2 sec delay as opposed to stimuli repeated at delays of over 4 sec in all subjects. At the 1.2 sec delay, the performance and posterior P3 amplitudes generated by old and young subjects were comparable. At longer delays, the older subjects had impaired performance and decreased P3 amplitude at posterior scalp sites. In addition, fronto-central N4 activity was reduced at long delays in the elderly. Older subjects generated a sustained frontal positivity (50-800 msec) to both short and long delay stimuli that was not observed in the younger group. The late phase of the frontal positivity was enhanced at long delays in the elderly. The data provide evidence of intact rapid and impaired delayed recognition memory in aging. Alternations in frontal cortical control of posterior and limbic regions may contribute to the memory changes observed in aging.

Adult↗

Prefrontal deficits in attention and inhibitory control with aging.

Event-related potentials and behavioral measures were obtained from young and elderly subjects while they performed two different auditory delayed match-to-sample tasks. In each experiment, subjects had to indicate whether an initial and a subsequent test sound were identical in two different conditions: one filled with distracting tone pips and one with no distractors. Electrophysiologically, elderly subjects had reduced attention-related activity over frontal regions. In addition, the distracting stimuli elicited an enhanced primary auditory evoked response in the elderly. The percentage of perseverative errors on the Wisconsin card sorting test, a putative measure of frontal lobe function, was positively correlated with the amplitude of the primary auditory evoked response in elderly subjects. Behaviorally, elderly subjects were impaired by distractors at long but not short delays. Taken together, these results suggest that increased distractibility and impaired sustained attention with aging may be due to altered prefrontal cortex function. These data support the loss of prefrontal suppression over the primary auditory regions with aging.

Adult↗

Status epilepticus manifesting as reversible Wernicke's aphasia.

Ictal aphasia in adults is a rare phenomenon, with the majority of reported cases showing a nonfluent Broca's or mixed aphasic speech pattern associated with disturbances of level of consciousness. There is usually only one prolonged episode of aphasia with evidence of lateralized neurological findings and structural pathology on CAT scan. We describe a patient with intermittent episodes over a 10-year period of a fluent Wernicke's aphasia associated with paroxysmal posterior temporoparietal spike-wave activity on the EEG. Interictally, the patient was clear of neurologic signs and symptoms. These episodes were repeatedly misdiagnosed as psychotic breaks and treated with antipsychotic medication and psychiatric hospitalization. Unless language performance is assessed, these cases of focal epilepsy may be diagnosed as schizophrenic "word-salad," leading to delay of appropriate treatment.

Aphasia↗