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Biomedical subjects

M F S Rushworth

Publications and source records attributed to M F S Rushworth.

At least 19 recordsLinked to original sources

Probabilistic diffusion tractography with multiple fibre orientations: What can we gain?

We present a direct extension of probabilistic diffusion tractography to the case of multiple fibre orientations. Using automatic relevance determination, we are able to perform online selection of the number of fibre orientations supported by the data at each voxel, simplifying the problem of tracking in a multi-orientation field. We then apply the identical probabilistic algorithm to tractography in the multi- and single-fibre cases in a number of example systems which have previously been tracked successfully or unsuccessfully with single-fibre tractography. We show that multi-fibre tractography offers significant advantages in sensitivity when tracking non-dominant fibre populations, but does not dramatically change tractography results for the dominant pathways.

Brain↗

Weighing up the benefits of work: behavioral and neural analyses of effort-related decision making.

How we decide whether a course of action is worth undertaking is largely unknown. Recently, neuroscientists have been turning to ecological approaches to address this issue, examining how animals evaluate the costs and benefits of different options. We present here evidence from rodents and monkeys that demonstrate the degree to which they take into account work and energetic requirements when deciding what responses to make. These calculations appear to be critically mediated by the anterior cingulate cortex (ACC) and mesolimbic dopamine (DA) pathways, with damage to either causing a bias towards options that are easily obtained but yield relatively smaller reward rather than alternatives that require more work but result in greater reward. The evaluation of such decisions appears to be carried out in systems independent of those involved in delay-discounting. We suggest that top-down signals from ACC to nucleus accumbens (NAc) and/or midbrain DA cells may be vital for overcoming effort-related response costs.

Animals↗

A role for the macaque anterior cingulate gyrus in social valuation.

Complex human social interaction is disrupted when the frontal lobe is damaged in disease, and in extreme cases patients are described as having acquired sociopathy. We compared, in macaques, the effects of lesions in subdivisions of the anterior cingulate and the orbitofrontal cortices believed to be anatomically homologous to those damaged in such patients. We show that the anterior cingulate gyrus in male macaques is critical for normal patterns of social interest in other individual male or female macaques. Conversely, the orbitofrontal cortex lesion had a marked effect only on responses to mildly fear-inducing stimuli. These results suggest that damage to the anterior cingulate gyrus may be the cause of changes in social interaction seen after frontal lobe damage.

Analysis of Variance↗

Visual neglect after right posterior cerebral artery infarction.

OBJECTIVES: To investigate the characteristics and neuroanatomical correlates of visual neglect after right-sided posterior cerebral artery (PCA) infarction. METHODS: 15 patients with acute PCA strokes were screened for the presence of neglect on a comprehensive battery of cognitive tests. Extra tests of visual perception were also carried out on six patients. To establish which areas were critically associated with neglect, the lesions of patients with and without neglect were compared. RESULTS: Neglect of varying severity was documented in 8 patients. In addition, higher-order visual perception was impaired in 5 of the 6 patients. Neglect was critically associated with damage to an area of white matter in the occipital lobe corresponding to a white matter tract connecting the parahippocampal gyrus with the angular gyrus of the parietal lobe. Lesions of the thalamus or splenium of the corpus callosum did not appear necessary or sufficient to cause neglect, but may mediate its severity in these patients. CONCLUSIONS: PCA stroke can result in visual neglect. Interruption of the white matter fibres connecting the parahippocampal gyrus to the angular gyrus may be important in determining whether a patient will manifest neglect.

Aged↗

TMS in the parietal cortex: updating representations for attention and action.

Transcranial magnetic stimulation (TMS) is one of the most recent techniques to have been used in investigations of the parietal cortex but already a number of studies have employed it as a tool in investigations of attentional and sensorimotor processes in the human parietal cortices. The high temporal resolution of TMS has proved to be a particular strength of the technique and the experiments have led to hypotheses about when circumscribed regions of parietal cortex are critical for specific attentional and sensorimotor processes. A consistent theme that runs through many reports is that of a critical contribution of parietal areas when attention or movements are re-directed and representations for attention or action must be updated.

Animals↗

Connection patterns distinguish 3 regions of human parietal cortex.

Three regions of the macaque inferior parietal lobule and adjacent lateral intraparietal sulcus (IPS) are distinguished by the relative strengths of their connections with the superior colliculus, parahippocampal gyrus, and ventral premotor cortex. It was hypothesized that connectivity information could therefore be used to identify similar areas in the human parietal cortex using diffusion-weighted imaging and probabilistic tractography. Unusually, the subcortical routes of the 3 projections have been reported in the macaque, so it was possible to compare not only the terminations of connections but also their course. The medial IPS had the highest probability of connection with the superior colliculus. The projection pathway resembled that connecting parietal cortex and superior colliculus in the macaque. The posterior angular gyrus and the adjacent superior occipital gyrus had a high probability of connection with the parahippocampal gyrus. The projection pathway resembled the macaque inferior longitudinal fascicle, which connects these areas. The ventral premotor cortex had a high probability of connection with the supramarginal gyrus and anterior IPS. The connection was mediated by the third branch of the superior longitudinal fascicle, which interconnects similar regions in the macaque. Human parietal areas have anatomical connections resembling those of functionally related macaque parietal areas.

Adult↗

Components of attentional set-switching.

A series of distinct event-related potentials (ERPs) have been recorded from the scalp of human subjects as they switch from one task to another. It is possible that task switching may depend on different mechanisms depending on whether the switch requires a change in attentional set, in other words the redirecting of attention to different aspects of a sensory stimulus, or whether it requires a change in intentional set, in others words a change in the way that responses are selected. To address this issue, the current study recorded ERPs while subjects switched between attentional sets and the results were compared with those of a previous investigation in which subjects switched between intentional sets. Subjects selected stimuli according to two conflicting attentional sets, each emphasizing one visual stimulus dimension (colour, shape). Pairs of stimuli, only one of which was to be attended, were presented for between eight and seventeen trials then either a switch or a stay cue was shown. The switch cue instructed subjects to switch from the current attentional set to the other set, while the stay cue instructed subjects to maintain the current set. Comparing ERPs time-locked to the switch and stay cues revealed neural correlates of the initiation of a task switch. Comparing the ERPs time locked to the first stimuli after either stay or switch cues identified neural correlates of the implementation of a task switch. A similar modulation over parietal electrodes was seen when subjects were switching between either attentional or intentional sets. While an intentional set switch began with a medial frontal modulation, attentional set switching began with a lateral frontal modulation. Implementing a new attentional set was associated with modulation of relatively early visual potentials, while implementing a new intentional set was associated with modulation of later response-related potentials. The results confirm that task switching consists of a number of constituent processes which may be taxed to different degrees depending on whether a task-switch paradigm requires subjects to change the way in which they select stimuli or responses.

Attention↗

The mesocortical dopamine projection to anterior cingulate cortex plays no role in guiding effort-related decisions.

Both mesolimbic dopamine (DA) and the anterior cingulate cortex (ACC) have been implicated in enabling animals to expend effort to obtain greater reward. To investigate the role of the DA pathway to ACC in working for reward, the authors tested rats on a cost-benefit T-maze paradigm in which they could either climb a barrier to obtain large reward in 1 arm (high reward [HR]) or select the low-effort alternative containing less reward (low reward [LR]). Surprisingly, ACC DA depletions had no effect on choice performance. Manipulations of barrier and reward sizes demonstrated that lesioned rats were as sensitive to the costs and benefits of the alternatives as controls. These results imply that the DA projection to ACC is not involved in guiding effort-related decisions.

Animals↗

Differential involvement of serotonin and dopamine systems in cost-benefit decisions about delay or effort.

RATIONALE: Although tasks assessing the role of dopamine in effort-reward decisions are similar to those concerned with the role of serotonin in impulsive choice in that both require analysis of the costs and benefits of possible actions, they have never been directly compared. OBJECTIVES: This study investigated the involvement of serotonin and dopamine in two cost-benefit paradigms, one in which the cost was delay and the other in which it was physical effort. METHODS: Sixteen rats were trained on a T-maze task in which they chose between high and low reward arms. In one version, the high reward arm was obstructed by a barrier, in the other, delivery of the high reward was delayed by 15 s. Serotonin and dopamine function were manipulated using systemic pCPA and haloperidol injections, respectively. RESULTS: Haloperidol-treated rats were less inclined either to exert more effort or to countenance a delay for a higher reward. pCPA had no effect on the performance of the rats on the effortful task, but significantly increased the rats' preference for an immediate but smaller reward. All animals (drug treated and controls) chose the high reward arm on the majority of trials when the delay or effort costs were matched in both high and low reward arms. CONCLUSION: A dissociation was found between the neurotransmitter systems involved in different types of cost-benefit decision making. While dopaminergic systems were required for decisions about both effort and delay, serotonergic systems were only needed for the latter.

Animals↗

Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex.

A fundamental issue in neuroscience is the relation between structure and function. However, gross landmarks do not correspond well to microstructural borders and cytoarchitecture cannot be visualized in a living brain used for functional studies. Here, we used diffusion-weighted and functional MRI to test structure-function relations directly. Distinct neocortical regions were defined as volumes having similar connectivity profiles and borders identified where connectivity changed. Without using prior information, we found an abrupt profile change where the border between supplementary motor area (SMA) and pre-SMA is expected. Consistent with this anatomical assignment, putative SMA and pre-SMA connected to motor and prefrontal regions, respectively. Excellent spatial correlations were found between volumes defined by using connectivity alone and volumes activated during tasks designed to involve SMA or pre-SMA selectively. This finding demonstrates a strong relationship between structure and function in medial frontal cortex and offers a strategy for testing such correspondences elsewhere in the brain.

Adult↗

Action sets and decisions in the medial frontal cortex.

Activations in human dorsomedial frontal and cingulate cortices are often present in neuroimaging studies of decision making and action selection. Interpretations have emphasized executive control, movement sequencing, error detection and conflict monitoring. Recently, however, experimental approaches, using lesions, inactivation, and cell recording, have suggested that these are just components of the areas' functions. Here we review these results and integrate them with those from neuroimaging. A medial superior frontal gyrus (SFG) region centred on the pre-supplementary motor area (pre-SMA) is involved in the selection of action sets whereas the anterior cingulate cortex (ACC) has a fundamental role in relating actions to their consequences, both positive reinforcement outcomes and errors, and in guiding decisions about which actions are worth making.

Animals↗

Organization of action sequences and the role of the pre-SMA.

To understand the contribution of the human presupplementary motor area (pre-SMA) in sequential motor behavior, we performed a series of finger key-press experiments. Experiment 1 revealed that each subject had a spontaneous tendency to organize or "chunk" a long sequence into shorter components. We hypothesized that the pre-SMA might have a special role in initiating each chunk but not at other points during the sequence. Experiment 2 therefore examined the effect of 0.5-s, 10-Hz repetitive transcranial magnetic stimulation (rTMS) directed over the pre-SMA. As hypothesized, performance was disrupted when rTMS was delivered over the pre-SMA at the beginning of the second chunk but not when it was delivered in the middle of a chunk. Contrary to the hypothesis, TMS did not disrupt sequence initiation. Experiments 3 and 4 examined whether the very first movement of a sequence could be disrupted under any circumstances. Pre-SMA TMS did disrupt the initiation of sequences but only when subjects had to switch between sequences and when the first movement of each sequence was not covertly instructed by a learned visuomotor association. In conjunction, the results suggest that for overlearned sequences the pre-SMA is primarily concerned with the initiation of a sequence or sequence chunk and the role of the pre-SMA in sequence initiation is only discerned when subjects must retrieve the sequence from memory as a superordinate set of movements without the aid of a visuomotor association. Control experiments revealed such effects were not present when rTMS was applied over the left dorsal premotor cortex.

Adult↗

The effect of cingulate cortex lesions on task switching and working memory.

Anatomic interconnections between the prefrontal and anterior cingulate cortices suggest that these areas may have similar functions. Here we report the effect of anterior cingulate removal on task switching, error monitoring, and working memory. Neuroimaging studies have implicated the cingulate cortex in all these processes. Six macaques were taught task switching (TS) and delayed alternation (DA) paradigms. TS required switching between two conditional response tasks with mutually incompatible response selection rules. DA required alternation between two identically covered food-well positions. In the first set of experiments, anterior cingulate lesions did not consistently impair TS or DA performance. One animal performed worst on both TS and DA and in this animal the cingulate sulcus lesion was most complete. In the second set of experiments, we confirmed that larger anterior cingulate lesions, which included the sulcus, consistently impaired TS but only led to a mild and equivocal impairment of DA. The TS error pattern, however, did not suggest an impairment of TS per se. The consequence of a cingulate lesion is, therefore, distinct to that of a prefrontal lesion. TS error distribution analyses provided some support for a cingulate role in monitoring responses for errors and subsequent correction but the pattern of reaction time change in TS was also indicative of a failure to sustain attention to the task and the responses being made.

Animals↗

Towards understanding language organisation in the brain using fMRI.

Functional magnetic resonance imaging (fMRI), which allows non-invasive mapping of human cognitive functions, has become an important tool for understanding language function. An understanding of component processes and sources of noise in the images is contributing to increased confidence in the reproductability of studies. This allows clinical applications, e.g., for pre-surgical lateralisation of language functions in patients with temporal lobe epilepsy. fMRI is a sensitive method for mapping regions involved in language functions. We recently have applied it to study the effect of word surface form on reading with a comparison of responses to Chinese characters or alphabetical Pinyin. Interpretation of fMRI activations must be made with caution; fMRI suggests task-associated activation, but does not independently confirm that such activity is necessary. However, complementary studies can be performed using transcranial magnetic stimulation (TMS), which can be used to interfere with brain activity in a specific region transiently for characterisation of the behavioural effects. We describe how TMS combined with fMRI has confirmed a role for the left inferior frontal cortex in semantic processing.

Asian People↗

The left parietal and premotor cortices: motor attention and selection.

It is well established that the premotor cortex has a central role in the selection of movements. The role of parts of the parietal cortex in movement control has proved more difficult to describe but appears to be related to the preparation and the redirection of movements and movement intentions. We have referred to some of these processes as motor attention. It has been known since the time of William James that covert motor attention can be directed to an upcoming movement just as visuospatial attention can be directed to a location in space. While some parietal regions, particularly in the right hemisphere, are concerned with covert orienting and the redirecting of covert orienting it may be useful to consider other parietal regions, in the anterior inferior parietal lobule and in the posterior superior parietal lobule, particularly in the left hemisphere, as contributing to motor attention. Such parts of the parietal lobe are activated in neuroimaging experiments when subjects covertly prepare movements or switch intended movements. Lesions or transcranial magnetic stimulation (TMS) affect the redirecting of motor attention. The difficulties apraxic patients experience when sequencing movements may partly be due to an inability to redirect motor attention from one movement to another. The role of the premotor cortex in selecting movements is also lateralized to the left hemisphere. Damage to left hemisphere movement selection mechanisms may also contribute to apraxia. If, however, it remains intact after a stroke then the premotor cortex may contribute to the recovery of arm movements. A group of patients with unilateral left hemisphere lesions and impaired movements in the contralateral right hand was studied. Functional magnetic resonance imaging showed that in some cases the premotor cortex in the intact hemisphere was more active when the stroke-affected hand was used. TMS in the same area in the same patients had the most disruptive effect on movements. In summary, patterns of motor impairment and recovery seen after strokes can partly be explained with reference to the roles of the parietal and premotor cortices in motor attention and selection.

Attention↗

The effect of cingulate lesions on social behaviour and emotion.

Functional and structural neuroimaging of the human cingulate cortex has identified this region with emotion and social cognition and suggested that cingulate pathology may be associated with emotional and social behavioural disturbances. The importance of the cingulate cortex for emotion and social behaviour, however, has not been clear from lesion studies. Bilateral lesions in the cingulate cortex were made in three macaques and their social interactions were compared with those of controls. Subsequently, cingulate lesions were made in the three controls and their behaviour was compared before and after surgery. Cingulate lesions were associated with decreases in social interactions, time spent in proximity with other individuals, and vocalisations but an increase in manipulation of an inanimate object. The results are consistent with a cingulate role in social behaviour and emotion.

Animals↗

The anterior cingulate and reward-guided selection of actions.

Macaques were taught a reward-conditional response selection task; they learned to associate each of two different actions to each of two different rewards and to select actions that were appropriate for particular rewards. They were also taught a visual discrimination learning task. Cingulate lesions significantly impaired selection of responses associated with different rewards but did not interfere with visual discrimination learning or performance. The results suggest that 1) the cingulate cortex is concerned with action reward associations and not limited to just detecting when actions lead to errors and 2) that the cingulate cortex's function is limited to action reinforcer associations and it is not concerned with stimulus reward associations.

Animals↗