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Biomedical subjects

R T Knight

Publications and source records attributed to R T Knight.

At least 37 records · Page 2Linked to original sources

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.

Adult↗

Spatial deficits in ideomotor limb apraxia. A kinematic analysis of aiming movements.

Ideomotor limb apraxia is a classic neurological disorder manifesting as a breakdown in co-ordinated limb control with spatiotemporal deficits. We employed kinematic analyses of simple aiming movements in left hemisphere-damaged patients with and without limb apraxia and a normal control group to examine preprogramming and response implementation deficits in apraxia. Damage to the frontal and parietal lobes was more common in apraxics, but neither frontal nor parietal damage was associated with different arm movement deficits. Limb apraxia was associated with intact preprogramming but impaired response implementation. The response implementation deficits were characterized by spatial but not temporal deficits, consistent with decoupling of spatial and temporal features of movement in limb apraxia. While the apraxics' accuracy was normal when visual feedback was available, it was impaired when visual feedback of either target location or hand position was unavailable. This finding suggests that ideomotor limb apraxia is associated with disruption of the neural representations for the extrapersonal (spatial location) and intrapersonal (hand position) features of movement. The non-apraxic group's normal kinematic performance demonstrates that the deficits demonstrated in the apraxic group are not simply a reflection of left hemisphere damage per se.

Analysis of Variance↗

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.

Adult↗

A distributed cortical network for auditory sensory memory in humans.

Auditory sensory memory is a critical first stage in auditory perception that permits listeners to integrate incoming acoustic information with stored representations of preceding auditory events. Here, we investigated the neural circuits of sensory memory using behavioral and electrophysiological measures of auditory processing in patients with unilateral brain damage to dorsolateral prefrontal cortex, posterior association cortex, or the hippocampus. We used a neurophysiological marker of an automatic component of sensory memory, the mismatch negativity (MMN), which can be recorded without overt attention. In comparison with control subjects, temporal-parietal patients had impaired auditory discrimination and reduced MMN amplitudes with both effects evident only following stimuli presented in the ear contralateral to the lesioned hemisphere. This suggests that auditory sensory memories are predominantly stored in auditory cortex contralateral to the ear of presentation. Dorsolateral prefrontal damage impaired performance and reduced MMNs elicited by deviant stimuli presented in either ear, implying that dorsolateral prefrontal cortices have a bilateral facilitatory effect on sensory memory storage. Hippocampal lesions did not affect either performance or electrophysiological measures. The results provide evidence of a temporal-prefrontal neocortical network critical for the transient storage of auditory stimuli.

Acoustic Stimulation↗

Cortical networks underlying mechanisms of time perception.

Precise timing of sensory information from multiple sensory streams is essential for many aspects of human perception and action. Animal and human research implicates the basal ganglia and cerebellar systems in timekeeping operations, but investigations into the role of the cerebral cortex have been limited. Individuals with focal left (LHD) or right hemisphere (RHD) lesions and control subjects performed two time perception tasks (duration perception, wherein the standard tone pair interval was 300 or 600 msec) and a frequency perception task, which controlled for deficits in time-independent processes shared by both tasks. When frequency perception deficits were controlled, only patients with RHD showed time perception deficits. Time perception competency was correlated with an independent test of switching nonspatial attention in the RHD but not the LHD patients, despite attention deficits in both groups. Lesion overlays of patients with RHD and impaired timing showed that 100% of the patients with anterior damage had lesions in premotor and prefrontal cortex (Brodmann areas 6, 8, 9, and 46), and 100% with posterior damage had lesions in the inferior parietal cortex. All LHD patients with normal timing had damage in these same regions, whereas few, if any, RHD patients with normal timing had similar lesion distributions. These results implicate a right hemisphere prefrontal-inferior parietal network in timing. Time-dependent attention and working memory functions may contribute to temporal perception deficits observed after damage to this network.

Aged↗

Unilateral medial temporal lobe memory impairment: type deficit, function deficit, or both?

Previous research has characterized memory deficits resulting from unilateral hippocampal system damage as 'material specific', suggesting that left damage results in verbal memory impairment with preservation of visuospatial function and the converse with right damage. Implicit within this hypothesis are the assumptions that the systems are independent and memory is lateralized for each type of material. To test the verbal component of this hypothesis, unilateral hippocampal lesion and commissurotomy patients were compared with controls on a multiple-list free-recall task. The material specific hypothesis predicts severe impairment only with left lesions; right lesions and commissurotomy patients should be only minimally impaired. However, secondary memory was compromised at immediate recall for all patient groups, with both unilateral groups showing comparable and severe verbal episodic memory deficits. Final testing across all lists also revealed severe impairment in commissurotomy patients. Finding both unilateral groups to be similarly impaired for verbal material is taken as evidence against a material specific deficit during this verbal episodic memory task. Although previous data suggest that left patients are considerably more impaired during some verbal tasks, this may not be specific to the material, but rather the combination of material and task demands. Implications for the material specific hypothesis are discussed.

Adult↗

Recollection and familiarity deficits in amnesia: convergence of remember-know, process dissociation, and receiver operating characteristic data.

Previous studies using the process dissociation and the remember-know procedures led to conflicting conclusions regarding the effects of anterograde amnesia on recollection and familiarity. We argue that these apparent contradictions arose because different models were used to interpret the results and because differences in false-alarm rates between groups biased the estimates provided by those models. A reanalysis of those studies with a dual-process signal-detection model that incorporates response bias revealed that amnesia led to a pronounced reduction in recollection and smaller but consistent reduction in familiarity. To test the assumptions of the model and to further assess recognition deficits in amnesics, we examined receiver operating characteristics (ROCs) in amnesics and controls. The ROCs of the controls were curved and asymmetrical, whereas those of the amnesics were curved and symmetrical. The results supported the predictions of the model and indicated that amnesia was associated with deficits in both recollection and familiarity.

Aged↗

Contribution of human prefrontal cortex to delay performance.

Neurological patients with focal lesions in the dorsolateral prefrontal cortex and age-matched control subjects were tested on an auditory version of the delayed-match-to-sample task employing environmental sounds. Subjects had to indicate whether a cue (s/S1) and a subsequent target sound (S2) were identical. On some trials, S1 and S2 were separated by a silent period of 5 sec. On other trials, the 5-sec delay between S1 and S2 was filled with irrelevant tone pips that served as distractors. Behaviorally, frontal patients were impaired by the presence of distractors. Electrophysiologically, patients generated enhanced primary auditory cortex-evoked responses to the tone pips, supporting a failure in inhibitory control of sensory processing after prefrontal damage. Intrahemispheric reductions of neural activity generated in the auditory association cortex and additional intrahemispheric reductions of attention-related frontal activity were also observed in the prefrontal patients. Together, these findings suggest that the dorsolateral prefrontal cortex is crucial for gating distracting information as well as maintaining distributed intrahemispheric neural activity during auditory working memory.

Acoustic Stimulation↗

Frontal lobe contributions to theory of mind.

"Theory of mind," the ability to make inferences about others" mental states, seems to be a modular cognitive capacity that underlies humans" ability to engage in complex social interaction. It develops in several distinct stages, which can be measured with social reasoning tests of increasing difficulty. Individuals with Asperger"s syndrome, a mild form of autism, perform well on simpler theory of mind tests but show deficits on more developmentally advanced theory of mind tests. We tested patients with bilateral damage to orbito-frontal cortex (n = 5) and unilateral damage in left dorsolateral prefrontal cortex (n = 5) on a series of theory of mind tasks varying in difficulty. Bilateral orbito-frontal lesion patients performed similarly to individuals with Asperger"s syndrome, performing well on simpler tests and showing deficits on tasks requiring more subtle social reasoning, such as the ability to recognize a faux pas. In contrast, no specific theory of mind deficits were evident in the unilateral dorsolateral frontal lesion patients. The dorsolateral lesion patients had difficulty only on versions of the tasks that placed demands on working memory.

Adult↗

Cortico-limbic circuits and novelty: a review of EEG and blood flow data.

Novelty detection is a fundamental capacity of all mammalian nervous systems /64/. The ability to orient to unexpected events is critical for both survival and normal memory function /82/. The mechanisms whereby the brain detects and responds to novelty have become of increasing interest to neuroscientists. A review is provided of human electrophysiological and blood flow data focused on delineating the neural systems engaged by novelty. Electrophysiological recording of event-related potentials (ERPs) has shown that novel stimuli activate a distributed network involving prefrontal and posterior association cortex as well as the hippocampus /4,23,24,32,33,36,86,88/. Activation of this network facilitates subsequent memory for novel events /27/. Neural modeling provides additional support for a prominent role of novelty in normal memory function /43/. Blood flow studies employing PET and fMRI have also begun to define the neural regions activated by novelty. The blood flow data provide converging evidence on the role of the hippocampus and cortical association regions in the processing of novelty /30,66,75,76/. The results of the behavioral, ERP and blood flow research confirm that a distributed neocortical-limbic circuit is activated by stimulus novelty. These distributed circuits maintain a template of the recent past /74/. Deviations from the template activate a neocortical-limbic network facilitating behavioral response to and memory storage of novel events.

Cerebral Cortex↗

Impaired word-stem priming in patients with temporal-occipital lesions.

In the word-stem priming test, words are presented (e.g., MOTEL, PARADE), and later subjects are shown three-letter word stems (e.g., MOT, PAR) and asked to complete each stem with the first word that comes to mind. Word-stem priming, as well as other aspects of implicit memory, are intact in amnesic patients with medial temporal lesions. However, this form of priming has been shown to be impaired in patients with Alzheimer's disease, suggesting that damage to neocortical areas outside the medial temporal lobe contributes to impaired priming in these patients. To examine the role of posterior cortical areas on word-stem priming, we administered the test to patients with unilateral temporal-occipital lesions. Patients with temporal-occipital lesions exhibited significantly impaired priming on this test. The findings suggest a critical role of the inferior posterior neocortex in the expression of this form of implicit memory.

Aged↗

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.

Adolescent↗

Retrieval of old memories: the temporofrontal hypothesis.

Extensive neuropsychological testing is reported on two chronic patients with combined temporopolar and prefrontal damage, dominantly left-hemispheric, and, as control, one chronic patient with bi-hemispheric prefrontal damage. The principal finding is that combined temporofrontal damage, but not substantial prefrontal damage alone, results in marked retrograde memory deficits while leaving intelligence and new learning relatively unimpaired. Although their general world knowledge was good, the temporopolar patients demonstrated retrograde memory impairments on several tests of past events and faces of previously famous people. With respect to retrograde autobiographical memory, one of the temporopolar patients was severely impaired and the other was judged to be moderately impaired. The control patient appeared to be normal. These results, together with corresponding data from related single case and dynamic imaging studies, strongly support a crucial role of the temporofrontal junction area in the ecphory of old memories.

Adult↗

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.

Adult↗

Prefrontal and posterior cortical activation during auditory working memory.

The present study investigated brain mechanisms underlying auditory memory. In a modified Sternberg memory scanning task, 11 subjects indicated whether a probe sound was part of a previously presented 4-item memory set by a button press. Behaviorally, subjects responded fastest and most accurately to probes that matched the last memory set items and slowest and least accurately to negative probes and to positive probes to the first two memory set items. Electrophysiologically, probes to the last memory set items elicited the largest amplitude and earliest latency P3 components while other probes elicited smaller amplitude, prolonged P3s as well as a negativity around 400 ms. These results suggest that subjects utilized a trace strength/self-terminating search model to perform the memory scanning task. Subjects only generated the P3 component during the matching phase of the auditory memory task while a sustained frontal negativity was elicited during both the encoding and matching phase. Taken together these findings provide evidence of differential activation of distributed neural activity during non-linguistic auditory memory.

Acoustic Stimulation↗