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Biomedical subjects

R T Knight

Publications and source records attributed to R T Knight.

At least 19 recordsLinked to original sources

Human prefrontal lesions increase distractibility to irrelevant sensory inputs.

Neurological patients with focal lesions in either the dorsolateral prefrontal cortex, temporal-parietal junction or the posterior hippocampus, and control subjects, were tested on a task requiring short-term retention of environmental sounds. Subjects had to indicate whether initial and subsequent test sounds were identical in two conditions. The initial and test sounds were separated by either a silent period varying from 4 to 12.6 s (no-distractor condition) or a series of irrelevant tones (distractor condition). Prefrontal patients were significantly impaired by distractors at all delays, hippocampal patients were impaired only at longer delays, while temporal-parietal patients performed similar to controls. The findings suggest that dorsolateral prefrontal cortex is crucial for gating of distracting information during delay tasks.

Aged

Auditory event-related potentials dissociate early and late memory processes.

Event-related potentials (ERPs) to environmental sounds were recorded from 15 young control subjects in an auditory recognition memory task. Subjects listened to a continuous string of binaurally presented sounds, 20% of which were presented once and 80% were repeated. Of the repeated sounds, some repeated immediately after the initial presentation (2 sec; short delay repetition) while others repeated after 2-6 intervening sounds (4-12 sec; long delay repetition). Subjects were instructed to indicate whether they had heard the sounds before by pressing a "yes" or "no" button. The initial stimulus presentation and long delay repetition stimuli generated both an N4 component and a prolonged latency P3 component while the short delay repetition stimuli elicited no N4 component and an earlier latency P3 component. Subjects' responses were faster and more accurate for short delay repetition. All stimuli generated a sustained frontal negative component (SFN). These data indicate that auditory recognition memory for environmental sounds may involve two processes. The P3 generated by both short and long delay repetition stimuli may index activation of a neocortical template matching system. The N4 generated by initial stimulus presentations and long delay repetition is proposed to measure additional activation of limbic memory systems at long retention intervals.

Acoustic Stimulation

Role of human prefrontal cortex in attention control.

Without a functioning dorsolateral prefrontal cortex, humans are stimulus bound and have little confidence in their ability to interact with the environment. Deficits in inhibitory control of external and internal processes coupled with impaired temporal coding of stimuli and detection capacity for novel events leave the patient functioning in a noisy internal environment without critical spatiotemporal cues. Some of these proposals are similar to those of Nauta (104). Based on connectivity of the prefrontal cortex, Nauta suggested that this region was ideally suited to generate and evaluate internal models of action. It is proposed that, in addition to this generation function, the prefrontal cortex is crucial for detecting changes in the external environment and for discriminating internally and externally derived models of the world. This chapter has described a cascade of deficits that result from damage to the dorsolateral prefrontal cortex. Awareness of the sensory world, and of the apparent stream of internal and external events, is impaired by deficits in novelty detection. Changes in the world, internal or external, may not be noticed in a noisy internal milieu. These deficits contribute to impaired reality monitoring and to a subsequent lack of confidence in behavior. An inability to bridge temporal gaps and temporally sequence internal events, together with deficits in inhibitory control systems, contribute to an impairment in the ability to generate coherent representations of alternate or counterfactual realities.

Animals

Electrophysiological dissociation of rapid memory mechanisms in humans.

Human memory involves an interaction between transient working memory and a long-term store. We found electrophysiological evidence supporting the existence of two distinct mechanisms subserving these processes. Stimuli held in memory for less than 4 s generate large, early latency P300 potentials which may index activation of a frontally-mediated rapid working memory system. Stimuli held in memory for over 4 s selectively generate N400 potentials which may reflect activation of mesial temporal cortices involved in access to the long-term store. These results suggest that memory processing in the initial 10 s after stimulus detection involves at least two distinct distributed cortical-limbic systems.

Adult

Lesions of frontal cortex diminish the auditory mismatch negativity.

Event-related brain potentials to non-attended auditory stimuli were recorded from patients with dorsolateral prefrontal cortex (DPFCx) lesions and from age-matched control subjects as they performed a visual reaction time task. Auditory stimuli consisted of monaural sequences of repetitive standard tones (1000 Hz) and occasional deviant tones of a higher frequency (1300 Hz). In comparison with control subjects, DPFCx patients showed enhanced P1 amplitudes (mean peak latency 50 msec), consistent with reduced frontally mediated gating of sensory input to the auditory cortex. The mismatch negativity (MMN) elicited by deviant tones was reduced in DPFCx patients over a broad latency range (130-210 msec), especially over the lesioned hemisphere and for tones delivered to the ear ipsilateral to the lesion. The results suggest that DPFCx and DPFCx-temporal projections play a critical role in involuntary orienting to physical changes in sequences of non-attended auditory stimuli.

Acoustic Stimulation

A dry electrode for EEG recording.

This paper describes the design, fabrication and testing of a prototype dry surface electrode for EEG signal recording. The new dry electrode has the advantages of no need for skin preparation or conductive paste, potential for reduced sensitivity to motion artifacts and an enhanced signal-to-noise ratio. The electrode's sensing element is a 3 mm stainless steel disk which has a 2000 A (200 nm) thick nitride coating deposited onto one side. The back side of the disk is attached to an impedance converting amplifier. The prototype electrode was mounted on a copper plate attached to the scalp by a Velcro strap. The performance of this prototype dry electrode was compared to commercially available wet electrodes in 3 areas of electroencephalogram (EEG) recording: (1) spontaneous EEG, (2) sensory evoked potentials, and (3) cognitive evoked potentials. In addition to the raw EEG, the power spectra of the signals from both types of electrodes were also recorded. The results suggest that the dry electrode performs comparably to conventional electrodes for all types of EEG signal analysis. This new electrode may be useful for the production of high resolution surface maps of brain activity where a large number of electrodes or prolonged recording times are required.

Electrodes

CT findings of hypoxic basal ganglia damage.

The outcome of hypoxic ischemic injury ranges from complete recovery to a persistent vegetative state or death, depending on the length of time the patient remains unconscious and the degree of associated cardiac failure. We describe three patients who were comatose from a hypoxic and/or ischemic injury and whose principal computed tomographic (CT) finding was bilateral basal ganglia hypodensities. Two of these patients were discharged from the hospital with minimal residual neurologic deficits. These cases and review of the literature suggest that ischemic basal ganglia signs on CT scan are not necessarily a predictor of severe neurologic sequelae.

Adult

Multiple brain systems generating the rat auditory evoked potential. I. Characterization of the auditory cortex response.

The objectives of this study were to characterize the auditory cortex response in the rat and to examine its contributions to the auditory evoked potentials (AEPs) recorded from the dorsal and lateral skull. This was accomplished by simultaneously recording AEPs from the cortical surface and from skull screw electrodes in anesthetized animals. The initial positive-negative response (P17-N32) was largely restricted to the cortical region corresponding to area 41. More detailed examination of the AEP mapping revealed multiple subcomponents (P9, P14, P17, P19) underlying the initial positivity, with differing topographies. Stimulus-response properties further dissociated the multiple positive subcomponents. Reversible local neurochemical suppression confirmed the auditory cortical origin of these AEPs. The auditory cortex-generated AEPs were refractory to barbiturate anesthesia which eliminated all dorsal skull AEPs, indicating that primary auditory cortical AEPs do not make a significant contribution to the dorsal skull-recorded ('vertex') AEPs. The findings raise issues regarding multiple parallel auditory processing systems and their associated AEPs.

Acoustic Stimulation

Multiple brain systems generating the rat auditory evoked potential. II. Dissociation of auditory cortex and non-lemniscal generator systems.

This study addressed the issue of multiple parallel auditory processing systems and their relationship to the skull-recorded auditory evoked potentials (AEPs) in the unanesthetized, unrestrained rat. In the preceding paper (Brain Res., 602 (1993) 240-250) it has been shown that auditory cortex activity does not contribute significantly to the vertex maximal AEPs recorded from the dorsal skull of the rat. In the present study, mapping of the AEP skull distribution revealed two sets of components: one set maximal at the dorsal skull vertex, and another set at the lateral skull), but not the early (P7-P11, N15) lateral skull components generated in auditory cortex. Bilateral auditory cortex ablation eliminated the lateral skull maximal AEP components, but not the dorsal skull maximal components. These findings support extensive parallel processing of auditory inputs (reflected by the dorsal AEPs) in the absence of primary auditory cortex. Ablation of primary auditory cortex did result in a modulation of the dorsal skull AEPs, indicative of an interaction between the geniculocortical system and the parallel system which generates the dorsal AEPs.

Anesthesia

Factors of the Wisconsin Card Sorting Test as measures of frontal-lobe function in schizophrenia and in chronic alcoholism.

The purpose of this study was to examine the factor structure of the Wisconsin Card Sorting Test (WCST). The scores of 22 patients with schizophrenia, 20 patients with chronic alcoholism, and 16 normal control subjects were entered into a principal components analysis, which yielded three factors: Perseveration, Inefficient Sorting, and Nonperseverative Errors. WCST performance of seven patients with lesions invading the dorsolateral prefrontal cortex, available from another study, provided criterion validity for the Perseveration factor and, less strongly, for the Inefficient Sorting factor. Two patterns of performance characterized the three patient groups: the schizophrenic group and frontal lobe group had the highest Perseveration factor scores, whereas the alcoholic group had the highest Inefficient Sorting scores; the Nonperseverative Errors factor showed no significant group differences. Construct validity of these factors involved assessing, in all but the frontal group, the degree of overlap (convergent validity) and separation (discriminant validity) of each WCST factor with scores from tests of other cognitive functions. The convergent and discriminant validity of the Perseveration factor, but not the remaining two factors, received support only within the group of schizophrenic patients.

Adult

The Royal Marsden Hospital pelvic radiotherapy trial: technical aspects and quality assurance.

Planning and quality control procedures are described for a randomised trial designed to measure the effect on normal tissue toxicity of reducing the volume of normal tissue irradiated through the introduction of Beams-Eye-View designed customised blocks. Consideration is given to the accuracy with which blocks can be designed and to the potential application of multi-leaf collimator technology.

Adult

Anatomical substrates of auditory selective attention: behavioral and electrophysiological effects of posterior association cortex lesions.

Event-related brain potentials (ERPs) and reaction times (RTs) were recorded in an auditory selective attention task in control subjects and two groups of patients with lesions centered in (1) the temporal/parietal junction (T/P, n = 9); and (2) the inferior parietal lobe (IPL, n = 7). High pitched tones were presented to one ear and low pitched tones to the other in random sequences that included infrequent longer-duration tones and occasional novel sounds. Subjects attended to a specified ear and pressed a button to the longer-duration tones in that ear. IPL and T/P lesions slowed reaction times (RTs) and increased error rates, but improved one aspect of performance--patients showed less distraction than controls when targets followed novel sounds. T/P lesions reduced the amplitude of early sensory ERPs, initially over the damaged hemisphere (N1a, 70-110 ms) and then bilaterally (N1b, 110-130 ms, and N1c 130-160 ms). The reduction was accentuated for tones presented contralateral to the lesion, suggesting that N1 generators receive excitatory input primarily from the contralateral ear. IPL lesions reduced N1 amplitudes to both low frequency tones and novel sounds. Nd components associated with attentional selection were diminished over both hemispheres in the T/P group and over the lesioned hemisphere in the IPL group independent of ear of stimulation. Target and novel N2s tended to be diminished by IPL lesions but were unaffected by T/P lesions. The mismatch negativity was unaffected by either T/P or IPL lesions. The results support different roles of T/P and IPL cortex in auditory selective attention.

Acoustic Stimulation

Cognitive neuropsychology is more than single-case studies.

S. M. Sokol et al. (1991) claim that "The Cognitive Neuropsychology Approach" (p. 355) is limited to the single-case study design. The present article takes issue with this claim. Contrary to the beliefs of Sokol et al., we argue (a) that cognitive modularity is best studied by group design, (b) that the possibility of neural reorganization in patients should be tested through converging evidence from different populations using various methods, and (c) that cognitive neuropsychology can benefit from being a part of cognitive neuroscience where both neural and cognitive mechanisms underlying normal cognition are relevant.

Bias

Effects of posterior association cortex lesions on brain potentials preceding self-initiated movements.

To assess the role of subregions of the posterior association cortex in movement control, we recorded movement-related potentials (MRPs) in patients who had lesions centered in the temporal-parietal junction (T-PCx; damaged areas 22, caudal 39, 40, and 42; n = 7), superior parietal cortex (ParCx; damaged areas 5, 7, rostral 39, and 40; n = 5), and posterior association cortex lesions involving both the temporal-parietal junction and the superior parietal structures (PosCx; damaged areas 7, 22, 39, 40, 41, and 42; n = 5) and in 14 age-matched normal controls. MRPs were recorded in a self-paced button-press task in which subjects performed a switch closure with the right, left, or both hands (experiment I, experiment II, and experiment III, respectively) under counter-balanced experimental conditions. Data epochs beginning 1400 msec prior to and extending to 600 msec after each motor response were recorded from scalp sites over the precentral, central, and parietal regions. Normal controls and patients with T-PCx lesions generated comparable vertex maximal, symmetrical readiness potentials (onset 1000 msec), contralaterally enhanced NS' values (onset 500 msec), and MP values (onset 100 msec) preceding voluntary self-paced movements. Extensive lesions involving the posterior association cortex reduced MRP amplitudes. Patients with selective ParCx lesions also had marked reduction of MRPs under all experimental conditions. The MRP findings coupled with clinical and behavioral data on patients with parietal-cortex lesions indicate that the superior parietal regions are part of a neural system necessary for movement preparation.

Aged

Intact implicit memory in patients with frontal lobe lesions.

Patients with frontal lobe lesions and control subjects were administered tests of word-stem completion priming. In this implicit memory test, subjects are first presented words (e.g. MOTEL, PARADE) in an incidental learning paradigm. Following word presentation, subjects are shown word stems (e.g. MOT, PAR) and asked to produce the first word that comes to mind. Patients with frontal lobe lesions exhibited normal levels of word-stem completion. These findings indicate that implicit memory can operate normally despite damage to the prefrontal cortex. The present results substantiate previous neuropsychological and positron emission tomography findings which indicate that word priming depends critically on posterior cortical areas.

Brain Damage, Chronic

Abnormal premovement brain potentials in schizophrenia.

We assessed scalp-recorded movement related potentials (MRPs) generated prior to voluntary movements in chronic, medicated schizophrenics (n = 9) and age matched normal controls (n = 9). MRPs were recorded in a self-paced button press task in which subjects pressed a button with either their right, left or both thumbs (experimental condition I, II and III respectively). Controls generated a slowly rising readiness potential (RP) at about 1000 ms, a negative shift (NS') at about 450 ms and a motor potential (MP) at about 100 ms prior to movement. The initial MRP components (RP and NS') were reduced in schizophrenics indicating an impairment of the voluntary preparatory process in schizophrenia. Results of the present study indicate a similarity of MRP findings in schizophrenics and reported MRPs (Singh and Knight, 1990) in patients with unilateral lesions of the dorsolateral prefrontal cortex. These findings provide further support for frontal lobe dysfunction in schizophrenia.

Adult

P300 generation by novel somatosensory stimuli.

Event-related potentials (ERPs) to task-relevant target and task-irrelevant novel stimuli were recorded in a somatosensory discrimination task. Subjects pressed a button to mechanical taps of the fifth finger (targets, P = 0.12), randomly interposed in sequences of taps to the second finger (standards, P = 0.76). Two types of infrequent novel stimuli were delivered; one was a mechanical tap to the third or fourth finger (tactile novels, P = 0.06), another was an electric shock at the wrist (shock novels, P = 0.06). Correctly detected targets generated a parietal maximal P300 (P3b, latency 335 msec). Shock novels generated a central maximal P300 with a shorter peak latency (298 msec) than the P3b. Tactile novels generated a P300 with a scalp distribution comparable to the shock novels. Unlike the P3b, P300 amplitude to both the shock and tactile novel stimuli habituated by 20-30% across the first several stimulus presentations. These results indicate that, similar to the auditory and visual modality, task-irrelevant novel somatosensory stimuli generate a novelty P300 ERP. Differences in scalp distribution, latency and habituation characteristics suggest that the novelty P300 may have contributions from intracranial generators independent from target P300 sources.

Adolescent

Differential auditory processing continues during sleep.

Auditory evoked potentials (AEPs) were used to examine selective stimulus processing in sleep. In waking, repetitive stimuli generate exogenous P1, N1 and P2 components of the auditory evoked potential (AEP). Deviant stimuli generate endogenous cognitive components including the mismatch negativity (MMN), N2 and P3 components. We examined long-latency auditory evoked potentials elicited by repetitive and deviant stimuli during waking and stage II-IV sleep to assess whether stimulus deviance is detected during sleep. The waking P1, N1b and P2 had maximal amplitudes at fronto-central scalp sites, with additional peaks (N1a, N1c) at temporal sites. Deviant tones generated a frontal maximal MMN, and complex novel tones generated an additional P3 component maximal at centro-parietal sites. During stages II-IV sleep N1a, b, c amplitudes were reduced. During stage II sleep all stimuli generated increased P2 amplitudes and a late negative component (N340). Deviant stimuli generated greater P2 and N340 amplitudes than frequent stimuli in stage II sleep, as well as an additional P420 component. In stage III-IV sleep the P420 was absent and the AEP was dominated by a negativity of long duration whose amplitude increased in response to deviant stimuli. These data indicate that auditory evoked activity changes from wakefulness to sleep. The differential response to deviant sounds observed during waking and all sleep stages supports the theory that selective processing of auditory stimuli persists during sleep.

Adolescent