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PubMed1987

Programming and execution of movement in Parkinson's disease.

Programming and execution of arm movements in Parkinson's disease were investigated in choice and simple reaction time (RT) situations in which subjects made aimed movements at a target. A no-aiming condition was also studied. Reaction time was fractionated using surface EMG recording into premotor (central) and motor (peripheral) components. Premotor RT was found to be greater for parkinsonian patients than normal age-matched controls in the simple RT condition, but not in the choice condition. This effect did not depend on the parameters of the impending movement. Thus, paradoxically, parkinsonian patients were not inherently slower at initiating aiming movements from the starting position, but seemed unable to use advance information concerning motor task demands to speed up movement initiation. For both groups, low velocity movements took longer to initiate than high velocity ones. In the no-aiming condition parkinsonian RTs were markedly shorter than when aiming, but were still significantly longer than control RTs. Motor RT was constant across all conditions and was not different for patient and control subjects. In all conditions, parkinsonian movements were around 37% slower than control movements, and their movement times were more variable, the differences showing up early on in the movement, that is, during the initial ballistic phase. The within-subject variability of movement endpoints was also greater in patients. The motor dysfunction displayed in Parkinson's disease involves a number of components: (1) a basic central problem with simply initiating movements, even when minimal programming is required (no-aiming condition); (2) difficulty in maintaining computed forces for motor programs over time (simple RT condition); (3) a basic slowness of movement (bradykinesia) in all conditions; and (4) increased variability of movement in both time and space, presumably caused by inherent variability in force production.

Adult↗

PubMed1993

Reading in pure alexia. The effect of strategy.

A number of investigators have demonstrated that patients with pure alexia comprehend briefly presented words which they are unable to explicitly identify. We suggested previously that these patients may read by means of two distinct procedures: a laborious letter-by-letter method and a 'whole-word' procedure which, at least initially, does not support explicit word identification. We report a test of this proposal in a patient with pure alexia. We reasoned that if the patient had access to two distinct and incompatible procedures, he might be induced to switch from one to the other by changing task demands. We found that when instructed to name words, the patient employed a letter-by-letter strategy; in contrast, when instructed to make lexical decision or semantic judgements about rapidly presented words, he appeared to use a 'whole-word' strategy. These data support the hypothesis that two distinct procedures are available to this patient. We argue, further, that is necessary to suppress use of the letter-by-letter strategy to demonstrate whole word reading capability in pure alexics, and that failure to do so may account for negative findings in other cases reported in the literature.

Cerebral Infarction↗

PubMed1998

The effects of transcranial magnetic stimulation over the dorsolateral prefrontal cortex on suppression of habitual counting during random number generation.

Random number generation is an attention-demanding task that engages working memory and executive processes. Random number generation requires holding information 'on line', suppression of habitual counting, internally driven response generation and monitoring of responses. Evidence from PET studies suggests that the dorsolateral prefrontal cortex (DLPFC) is involved in the generation of random responses. We examined the effects of short trains of transcranial magnetic stimulation (TMS) over the left or right DLPFC or medial frontal cortex on random number generation in healthy normal participants. As in previous evidence, in control trials without stimulation participants performed poorly on the random number generation task, showing repetition avoidance and a tendency to count. Brief disruption of processing with TMS over the left DLPFC changed the balance of the individuals' counting bias, increasing the most habitual counting in ones and reducing the lower probability response of counting in twos. This differential effect of TMS over the left DLPFC on the balance of the subject's counting bias was not obtained with TMS over the right DLPFC or the medial frontal cortex. The results suggest that, with disruption of the left DLPFC with TMS, habitual counting in ones that has previously been suppressed is released from inhibition. From these findings a network modulation model of random number generation is proposed, whereby suppression of habitual responses is achieved through the modulatory influence of the left DLPFC over a number-associative network in the superior temporal cortex. To allow emergence of appropriate random responses, the left DLPFC inhibits the superior temporal cortex to prevent spreading activation and habitual counting in ones.

Adult↗

PubMed2000

A systematic study of visual extinction. Between- and within-field deficits of attention in hemispatial neglect.

Mechanisms of visual extinction were investigated in four patients with right hemisphere damage using a partial report paradigm. Different shapes (star or triangle) were displayed in one, two or four possible locations so that double simultaneous stimuli occurred either across the two hemifields or within the same hemifield. Patients attended either to the location (right, left or both), number (one, two or four) or shape (no, one or two stars among the shapes presented) of stimuli in three separate experiments using the same displays and exposure duration. Reporting the location (Experiment 1) produced marked contralesional extinction, although reaction time was delayed compared with unilateral right trials, indicating unconscious processing. Reaction time was also delayed on correct bilateral and unilateral left trials. In contrast, enumerating stimuli (Experiment 2) caused no significant contralesional extinction on bilateral displays and reaction time was similar on bilateral and unilateral right trials, suggesting that information from both fields was grouped in a single numerable percept in this task. However, patients often detected only one of two stimuli within the left field. Whereas similarity of shapes improved localization and did not affect enumeration, identifying stars among shapes (Experiment 3) revealed a severe inability to detect two similar targets between hemifields as well as within each of the hemifields. Distracting triangles were generally less detrimental to the perception of a concurrent target on either side, but slowed the reaction time regardless of whether they were in the same or the opposite field. Relative difficulty in ignoring distractors correlated with neglect severity on a cancellation task, and was most prominent in one patient with a large amount of frontal damage. These findings suggest that (i) allocation of attention to identical stimuli can be modulated by task demand; (ii) enumerating a small set of items across fields may not require attending to individual stimuli but relies on preattentive subitizing ability, as found in normal subjects; (iii) location information may be critical for attentional mechanisms subserved by the parietal cortex and pathological competition for awareness in extinction; (iv) extinction entails a bilateral deficit in attending to two concurrent similar targets when their features must be identified; and (v) the relevance of the stimuli can modulate the distribution of attention, possibly through frontal top-down control. These findings are consistent with recent neurophysiological evidence of parietal and frontal attentional influences on ventral visual pathways.

Aged↗

PubMed2002

Optic ataxia as a result of the breakdown of the global tuning fields of parietal neurones.

Optic ataxia is characterized by an impaired visual control of the direction of arm reaching to a visual target, accompanied by defective hand orientation and grip formation. In humans, optic ataxia is associated with lesions of the superior parietal lobule (SPL), which also affect visually guided saccades and other forms of eye-hand coordination. In the last 10 years, anatomical and physiological studies of the SPL have shed new light on the role of parietal cortex in the control of combined eye-hand movements to visual targets, and on the underlying distributed network which links parietal to frontal cortex. A main emerging functional feature of SPL neurones seems to be their capacity to combine, in a spatially congruent fashion, different directional eye- and hand-related information, that any coding scheme so far proposed, considers essential for the composition of motor commands for reaching. This integration occurs within the global tuning field of parietal neurones, is context-dependent and involves eye and hand information that shares the same directional properties. Depending on task demands, this integration of signals can result in the representation of different reference frames for coordinated eye-hand movements. The dynamic operations occurring within the global tuning fields might depend, at least in part, on the reciprocal sets of association connections linking the SPL and the premotor areas of the frontal lobe. From this picture, the SPL emerges as both a main source of visual input to the frontal cortex and a key structure for visuomotor integration based on re-entrant signalling and, therefore, as a crucial node in the visual control of movement. It is hypothesized that in parietal patients, the directional errors that characterize reaching are a consequence of the breakdown of the combination of directional eye and hand information within the global tuning fields of parietal neurones. In these patients, the spatial match among information about target location, eye and hand position, and movement direction would be prevented, so as to impair the composition of visually guided eye-hand movements. This breakdown could be dependent, at least in part, on the failure of a re-entrant frontoparietal signalling, an obvious consequence of the degeneration of the cortico-cortical systems linking parietal and frontal cortex. Cortico-cortical connections are, in fact, essential for shaping the dynamic properties of cortical neurones.

Animals↗

PubMed2003

Pure agnosia for mirror stimuli after right inferior parietal lesion.

This study reports the experimental investigation of G.R., a patient suffering from a highly specific disorder in discriminating mirror stimuli following a right temporoparietal cerebrovascular accident. G.R. showed intact perceptual, attentional, mnestic, linguistic and executive abilities. Object recognition was accurate even under unusual viewing conditions. He was highly accurate in defining the canonical orientation of common objects and in discriminating misoriented objects among identical distracters. However, he was severely impaired in tasks requiring mirror-stimulus discrimination, a deficit that persisted even when the object's coordinates were systematically misaligned with respect to his body. The disorder was also dependent upon the frame of reference (allocentric versus egocentric) activated on the basis of task demands. These results demonstrate the existence of a highly specific disorder in discriminating mirror stimuli defined in object-based coordinates, suggesting a failure in processing the directionality of an object's intrinsic x-axis.

Aged↗

PubMed2005

Brain motor system function after chronic, complete spinal cord injury.

Most therapies under development to restore motor function after spinal cord injury (SCI) assume intact brain motor functions. To examine this assumption, 12 patients with chronic, complete SCI and 12 controls underwent functional MRI during attempted, and during imagined, right foot movement, each at two force levels. In patients with SCI, many features of normal motor system function were preserved, however, several departures from normal were apparent: (i) volume of activation was generally much reduced, e.g. 4-8% of normal in primary sensorimotor cortex, in the setting of twice normal variance in signal change; (ii) abnormal activation patterns were present, e.g. increased pallido-thalamocortical loop activity during attempted movement and abnormal processing in primary sensorimotor cortex during imagined movement; and (iii) modulation of function with change in task or in force level did not conform to patterns seen in controls, e.g. in controls, attempted movement activated more than imagined movement did within left primary sensorimotor cortex and right dorsal cerebellum, while imagined movement activated more than attempted movement did in dorsolateral prefrontal cortex and right precentral gyrus. These modulations were absent in patients with SCI. Many features of brain motor system function during foot movement persist after chronic complete SCI. However, substantial derangements of brain activation, poor modulation of function with change in task demands and emergence of pathological brain events were present in patients. Because brain function is central to voluntary movement, interventions that aim to improve motor function after chronic SCI likely also need to attend to these abnormalities of brain function.

Adult↗

PubMed2006

Neural basis of irony comprehension in children with autism: the role of prosody and context.

While individuals with autism spectrum disorders (ASD) are typically impaired in interpreting the communicative intent of others, little is known about the neural bases of higher-level pragmatic impairments. Here, we used functional MRI (fMRI) to examine the neural circuitry underlying deficits in understanding irony in high-functioning children with ASD. Participants listened to short scenarios and decided whether the speaker was sincere or ironic. Three types of scenarios were used in which we varied the information available to guide this decision. Scenarios included (i) both knowledge of the event outcome and strong prosodic cues (sincere or sarcastic intonation), (ii) prosodic cues only or (iii) knowledge of the event outcome only. Although children with ASD performed well above chance, they were less accurate than typically developing (TD) children at interpreting the communicative intent behind a potentially ironic remark, particularly with regard to taking advantage of available contextual information. In contrast to prior research showing hypoactivation of regions involved in understanding the mental states of others, children with ASD showed significantly greater activity than TD children in the right inferior frontal gyrus (IFG) as well as in bilateral temporal regions. Increased activity in the ASD group fell within the network recruited in the TD group and may reflect more effortful processing needed to interpret the intended meaning of an utterance. These results confirm that children with ASD have difficulty interpreting the communicative intent of others and suggest that these individuals can recruit regions activated as part of the normative neural circuitry when task demands require explicit attention to socially relevant cues.

Adolescent↗

PubMed2000

Evidence for the transient nature of a neural system supporting goal-directed action.

Disruption of a neural system supporting goal-directed action gives rise to lapses of intention in healthy individuals and disorganized behavior in patients with prefrontal lesions. Evidence from behavioral studies indicates that the occurrence of lapses in selective attention, working memory and prospective memory tasks is transient in nature. In the current study, we used event-related brain potentials to demonstrate that lapses are associated with a slow wave over the frontal region that begins well before stimulus onset and lasts for several hundred milliseconds. The magnitude of this slow wave was modulated by task demands, indicating that attentional processes can be flexibly allocated in the service of goal-directed action. Together the findings of these experiments indicate that lapses result from a transient inability to bring to bear the goals of the individual upon the action selection system.

Adult↗

PubMed2003

NMDA receptors in the rat orbital prefrontal cortex are involved in guidance of instrumental behaviour under reversal conditions.

The orbital prefrontal cortex (OPFC) might be particularly involved in adapting instrumental responses to changes of stimulus-reward contingencies. We investigated whether signals in the OPFC transmitted via N-methyl-D-aspartate (NMDA) receptors are critical for learning a reversal of stimulus-reward contingencies. Rats were trained in a reaction time (RT) task demanding conditioned lever release with discriminative stimuli signalling in advance the upcoming reward magnitude (one or five pellets). After acquisition, RT of responses with expectancy of high reward magnitude were significantly shorter. Thereafter, stimulus-reward contingencies were reversed and rats received intra-OPFC infusions of saline or of the NMDA receptor antagonist AP5. Reversal learning was tested for 6 days, with microinfusions being given on days 1, 3 and 5. Intra-OPFC blockade of NMDA receptors impaired the learning of a reversal of previously acquired stimulus-reward magnitude contingencies: (i) latencies of correct responses were generally shortened, regardless of the response-associated reward magnitude; (ii) the proportion of premature responses was increased; and (iii) responses were not guided by the current significance of the reward-predicting stimuli. These findings provide novel evidence for NMDA-receptor-dependent plasticity in the OPFC in reversal learning.

2-Amino-5-phosphonovalerate↗

PubMed2004

Right temporoparietal cortex activation during visuo-proprioceptive conflict.

The conflict between vision and proprioception has been proposed to explain why healthy subjects perform worse than proprioceptively deafferented patients in conditions with optical displacement, e.g. novel mirror drawing. It is not known which brain processes depend upon the successful integration of visual and proprioceptive information and are therefore impaired when these modalities disagree. With fMRI in healthy subjects we compared brain activity across two conditions with similar visual and proprioceptive stimulation and similar task demands that differed by the congruence of movement showed by the two modalities. Subjects felt the passive movement of the right index finger on a rectangular field and watched a cursor moving on a computer screen. Cursor and finger locations either mapped onto each other (congruent condition) or did not (incongruent condition). Monitoring incongruent compared with congruent movement activated the premotor area bilaterally and the right temporoparietal junction. These brain areas have previously been associated with shifts in the attended location in the visual space. These findings suggest an interaction between vision and proprioception in orienting to spatial locations.

Adult↗

PubMed2004

Cognitive control involved in overcoming prepotent response tendencies and switching between tasks.

A dissociable set of regions was active for the executive processing associated with overcoming a prepotent response tendency and task switching. Regions associated with overcoming prepotency were primarily frontal and may be part of a system involved in top-down biasing for conflict reduction. Posterior regions were recruited for switching between tasks and likely play a role in reconfiguring stimulus-response mappings. Precuneus activity was common to both manipulations and may reflect increased visual attention due to more difficult task demands.

Adult↗

PubMed2006

Sex differences in semantic processing: event-related brain potentials distinguish between lower and higher order semantic analysis during word reading.

Behavioral studies suggest that women and men differ in the strategic elaboration of verbally encoded information especially in the absence of external task demand. However, measuring such covert processing requires other than behavioral data. The present study used event-related potentials to compare sexes in lower and higher order semantic processing during the passive reading of semantically related and unrelated word pairs. Women and men showed the same early context effect in the P1-N1 transition period. This finding indicates that the initial lexical-semantic access is similar in men and women. In contrast, sexes differed in higher order semantic processing. Women showed an earlier and longer lasting context effect in the N400 accompanied by larger signal strength in temporal networks similarly recruited by men and women. The results suggest that women spontaneously conduct a deeper semantic analysis. This leads to faster processing of related words in the active neural networks as reflected in a shorter stability of the N400 map in women. Taken together, the findings demonstrate that there is a selective sex difference in the controlled semantic analysis during passive word reading that is not reflected in different functional organization but in the depth of processing.

Adult↗

PubMed1997

Preventive care for patients following myocardial infarction. The Wessex Research Network (WReN).

OBJECTIVE: We aimed to assess general practice care for patients following a myocardial infarction (MI). METHOD: A structured review was carried out of general practice records of patients identified from hospital administration data. A total of 266 survivors following MI were identified from the discharge data of 13 hospitals in Southern England and registered with 71 GPs belonging to the Wessex Research Network. Median time since hospital discharge was 2.1 years. The main outcome measures were the provision of appropriate preventive care, including cardiac rehabilitation, drug therapy, and lifestyle advice for modifiable risk factors. RESULTS: Basic care was provided to nearly all patients; 253 (95.1%, 95% Cl 91.8-97.4) had blood pressure documented after their MI, 216 of 234 patients eligible for aspirin (92.3%; 88.1-95.4) had been recommended treatment, and the provision of advice on smoking cessation was documented for 27 of 33 continuing smokers (81.8%; 64.5-93.0). However, only 73 of 236 patients eligible to attend a structured rehabilitation programme (30.9%; 25.0-36.8) were documented as having received rehabilitation. Of 89 patients with heart failure following MI, 33 (37.1%; 27.1-48.0) had no record of having been offered treatment with an ACE inhibitor. Total cholesterol measurement was documented for only 144 patients (54.1%; 48.1-60.1). We estimate that there is still the potential to prevent between 4 and 9 deaths in this group of 266 surviving patients in the next 2 years by further improving the quality of follow-up care. CONCLUSIONS: Preventive care in patients with proven ischaemic heart disease in general practice remains haphazard, even among doctors enthusiastic to participate in research and to audit their quality of care. As general practitioners we should ensure that we are providing high quality preventive care to patients with clinical disease before we focus on the even more demanding task of primary prevention.

Adult↗

PubMed2025

Phylogenetic Methods Meet Deep Learning.

Deep learning (DL) has been widely used in various scientific fields, but its integration into phylogenetics has been slower, primarily due to the complex nature of phylogenetic data. The studies that apply DL to sequencing data often limit analyses to four-taxon trees. Many of these studies serve as "proof of principle" and perform similarly to traditional phylogeny reconstruction methods. New ways of using training data, such as encoding with compact bijective ladderized vectors or transformers, enable the handling of much larger trees and genomic data sets. This short perspective focuses on the application of DL in phylogenetics, introducing prevalent DL architectures. We highlight potential problems in the field by discussing the risks of using simulation-based training data and emphasize the importance of reproducibility and robustness in computational estimates. Finally, we explore promising research areas, including the combination of phylogenetics and population genetics in DL, the analysis of neighbor dependencies, and the potential to significantly reduce computational cost compared to traditional methods. This perspective illustrates the potential of DL in complementing traditional phylogeny reconstruction methods and aiding the advancement of phylogenetic analysis, especially in performing computationally demanding tasks such as model selection or estimating branch support values.

Humans↗

PubMed2006

The generalization of perceptual-motor intra-individual variability in young and old adults.

We examined the generalizability of intra-individual perceptual-motor variability in young and old adults. Participants completed four motor tasks that all required the maintenance of a steady state: finger tremor, and single-digit, two-digit, and three-digit isometric force production. Older adults had a greater amount of variability and an increased time and frequency structure of variability, except in the tremor task. There was a moderate association between the magnitudes of variability across tasks in the oldest age group, but the structural measures of variability were more highly related across tasks and the strength of this relationship increased with age. These findings support the hypothesis that older adults are less able than younger adults to adapt the structure of their perceptual-motor variability to task demands.

Adaptation, Psychological↗

PubMed1978

Orienting task effects on EDR and free recall in three age groups.

The present investigation was designed to examine the effects of orienting task-controlled processing on electrodermal response and free recall at two delay intervals for 94 young, 49 young-old (age 55 to 70), and 61 old-old (age 71 to 85) individuals. Subjects were presented with a list of 25 words and performed one of the following tasks: semantic, nonsemantic, or passive listening, presented in an incidental memory paradigm, or intentional memorization. Recall was obtained 2 min or 48 hours after list presentation. At the 2-min delay, the pattern of recall across tasks for the young-old and old-old subjects was similar to that of college students. Overall, the old-old recalled fewer words than the young and young-old, while the young-old recalled as many words as the young. After 48 hours, the task-related recall pattern was observed only in the young group. The skin conductance data indicated that task effects were similar across the three age groups and that response magnitude was lower in the old-old than the two younger groups. No differences in skin conductance were found between the young and young-old. Age differences in memory processing suggest that difficulties in delayed retrieval of semantically encoded words may increase during late adult years. Differences in electrodermal responses in the old-old compared to the young and young-old suggest that the range of autonomic responsivitiy to task demands may become restricted in advanced age.

Aged↗

PubMed1998

Institutional respite care: breaking chores or breaking social bonds?

This article addresses the question of why respite care is evaluated positively by caregivers, yet is often not used by those considered to be in need of the service. Data from interviews with 144 caregivers in Canberra, Australia, are the basis for examining the relationships between five appraisal dimensions and respite care usage, both in the past and in the future. These data show that use of respite care is higher when the task demands of caregiving are high and when caregivers and care receivers are bound together in dysfunctional caregiving relationships. The factor that is most likely to reduce the likelihood that respite care will be used in the future when past use is controlled is the caregiver's appraisal of an intimate and loving relationship between caregiver and care receiver.

Adult↗