Search results

Integration of goal- and stimulus-related visual signals revealed by damage to human parietal cortex.

Where we look is determined both by our current intentions and by the tendency of visually salient items to "catch our eye." After damage to parietal cortex, the normal process of directing attention is often profoundly impaired. Here, we tracked parietal patients' eye movements during visual search to separately map impairments in goal-directed orienting to targets versus stimulus-driven gaze shifts to salient but task-irrelevant probes. Deficits in these two distinct types of attentional selection are shown to be identical in both magnitude and spatial distribution, consistent with damage to a "priority map" that integrates goal- and stimulus-related signals to select visual targets. When goal-relevant and visually salient items compete for attention, the outcome depends on a biased competition in which the priority of contralesional targets is undervalued. On the basis of these findings, we further demonstrate that parietal patients' spatial bias (neglect) in goal-directed visual exploration can be corrected and even reversed by systematically manipulating the spatial distribution of stimulus salience in the visual array.

Functional neuroanatomy: the locus of human intelligence.

A new study mapping the functional effects of brain lesions has revealed a surprising map of human intelligence, stimulating a re-evaluation of data from purely correlative methods such as functional magnetic resonance imaging.

Volition and conflict in human medial frontal cortex.

Controversy surrounds the role of human medial frontal cortex in controlling actions. Although damage to this area leads to severe difficulties in spontaneously initiating actions, the precise mechanisms underlying such "volitional" deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring and the control of voluntary action, suggesting that these key processes are functionally related or share neural substrates. Here, we combine a novel behavioral paradigm with functional imaging of the oculomotor system to reveal, for the first time, a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas that respond exclusively to either volition or conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict.

A new method for automated high-dimensional lesion segmentation evaluated in vascular injury and applied to the human occipital lobe.

Making robust inferences about the functional neuroanatomy of the brain is critically dependent on experimental techniques that examine the consequences of focal loss of brain function. Unfortunately, the use of the most comprehensive such technique-lesion-function mapping-is complicated by the need for time-consuming and subjective manual delineation of the lesions, greatly limiting the practicability of the approach. Here we exploit a recently-described general measure of statistical anomaly, zeta, to devise a fully-automated, high-dimensional algorithm for identifying the parameters of lesions within a brain image given a reference set of normal brain images. We proceed to evaluate such an algorithm in the context of diffusion-weighted imaging of the commonest type of lesion used in neuroanatomical research: ischaemic damage. Summary performance metrics exceed those previously published for diffusion-weighted imaging and approach the current gold standard-manual segmentation-sufficiently closely for fully-automated lesion-mapping studies to become a possibility. We apply the new method to 435 unselected images of patients with ischaemic stroke to derive a probabilistic map of the pattern of damage in lesions involving the occipital lobe, demonstrating the variation of anatomical resolvability of occipital areas so as to guide future lesion-function studies of the region.

Effects of cholinergic enhancement on visual stimulation, spatial attention, and spatial working memory.

We compared behavioral and neural effects of cholinergic enhancement between spatial attention, spatial working memory (WM), and visual control tasks, using fMRI and the anticholinesterase physostigmine. Physostigmine speeded responses nonselectively but increased accuracy selectively for attention. Physostigmine also decreased activations to visual stimulation across all tasks within primary visual cortex, increased extrastriate occipital cortex activation selectively during maintained attention and WM encoding, and decreased parietal activation selectively during maintained attention. Finally, lateralization of occipital activation as a function of the visual hemifield toward which attention or memory was directed was decreased under physostigmine. In the case of attention, this effect correlated strongly with a decrease in a behavioral measure of selective spatial processing. Our results suggest that, while cholinergic enhancement facilitates visual attention by increasing activity in extrastriate cortex generally, it accomplishes this in a manner that reduces expectation-driven selective biasing of extrastriate cortex.

The role of visual salience in directing eye movements in visual object agnosia.

Symmetries in human brain language pathways correlate with verbal recall.

Lateralization of language to the left hemisphere is considered a key aspect of human brain organization. We used diffusion tensor MRI to perform in vivo virtual dissection of language pathways to assess the relationship between brain asymmetry and cognitive performance in the normal population. Our findings suggest interhemispheric differences in direct connections between Broca's and Wernicke's territories, with extreme leftward lateralization in more than half of the subjects and bilateral symmetrical distribution in only 17.5% of the subjects. Importantly, individuals with more symmetric patterns of connections are better overall at remembering words using semantic association. Moreover, preliminary analysis suggests females are more likely to have a symmetrical pattern of connections. These findings suggest that the degree of lateralization of perisylvian pathways is heterogeneous in the normal population and, paradoxically, bilateral representation, not extreme lateralization, might ultimately be advantageous for specific cognitive functions.

Vision: Visual space is not what it appears to be.

The location of visual objects in the world around us is reconstructed in a complex way from the image falling on the retina. Recent studies have begun to reveal the different ways in which the brain dynamically re-maps retinal information across eye movements to compute object locations for perception and directing actions.

Expert cognitive control and individual differences associated with frontal and parietal white matter microstructure.

Although many functional imaging studies have reported frontal activity associated with "cognitive control" tasks, little is understood about factors underlying individual differences in performance. Here we compared the behavior and brain structure of healthy controls with fighter pilots, an expert group trained to make precision choices at speed in the presence of conflicting cues. Two different behavioral paradigms--Eriksen Flanker and change of plan tasks--were used to assess the influence of distractors and the ability to update ongoing action plans. Fighter pilots demonstrated superior cognitive control as indexed by accuracy and postconflict adaptation on the Flanker task, but also showed increased sensitivity to irrelevant, distracting choices. By contrast, when pilots were examined on their ability to inhibit a current action plan in favor of an alternative response, their performance was no better than the control group. Diffusion weighted imaging revealed differences in white matter radial diffusivity between pilots and controls not only in the right dorsomedial frontal region but also in the right parietal lobe. Moreover, analysis of individual differences in reaction time costs for conflict trials on the Flanker task demonstrated significant correlations with radial diffusivity at these locations, but in different directions. Postconflict adaptation effects, however, were confined to the dorsomedial frontal locus. The findings demonstrate that in humans expert cognitive control may surprisingly be mediated by enhanced response gain to both relevant and irrelevant stimuli, and is accompanied by structural alterations in the white matter of the frontal and parietal lobe.

Testing memory for unseen visual stimuli in patients with extinction and spatial neglect.

Visual extinction after right parietal damage involves a loss of awareness for stimuli in the contralesional field when presented concurrently with ipsilesional stimuli, although contralesional stimuli are still perceived if presented alone. However, extinguished stimuli can still receive some residual on-line processing, without awareness. Here we examined whether such residual processing of extinguished stimuli can produce implicit and/or explicit memory traces lasting many minutes. We tested four patients with right parietal damage and left extinction on two sessions, each including distinct study and subsequent test phases. At study, pictures of objects were shown briefly in the right, left, or both fields. Patients were asked to name them without memory instructions (Session 1) or to make an indoor/outdoor categorization and memorize them (Session 2). They extinguished most left stimuli on bilateral presentation. During the test (up to 48 min later), fragmented pictures of the previously exposed objects (or novel objects) were presented alone in either field. Patients had to identify each object and then judge whether it had previously been exposed. Identification of fragmented pictures was better for previously exposed objects that had been consciously seen and critically also for objects that had been extinguished (as compared with novel objects), with no influence of the depth of processing during study. By contrast, explicit recollection occurred only for stimuli that were consciously seen at study and increased with depth of processing. These results suggest implicit but not explicit memory for extinguished visual stimuli in parietal patients.

Unconscious inhibition separates two forms of cognitive control.

In the human brain, cognitive-control processes are generally considered distinct from the unconscious mechanisms elicited by subliminal priming. Here, we show that cognitive control engaged in situations of response conflict interacts with the negative (inhibitory) phase of subliminal priming. Thus, cognitive control may surprisingly share common processes with nonconscious brain mechanisms. In contrast, our findings reveal that subliminal inhibition does not, however, interact with control adaptation--the supposed modulation of current control settings by previous experience of conflict. Therefore, although influential models have grouped immediate cognitive control and control adaptation together as products of the same conflict detection and control network, their relationship to subliminal inhibition separates them. Overall, these results suggest that the important distinction lies not between cognitive or top-down processes on the one hand and nonconscious priming mechanisms on the other hand but between responsive (poststimulus) mechanisms that deal with sensorimotor activation after it has occurred and preparatory (prestimulus) mechanisms that are modulated before stimulus arrival.

Abnormal attentional modulation of retinotopic cortex in parietal patients with spatial neglect.

Brain regions beyond visual cortex are thought to be responsible for attention-related modulation of visual processing [1, 2], but most evidence is indirect. Here, we applied functional magnetic resonance imaging (fMRI), including retinotopic mapping of visual areas, to patients with focal right-parietal lesions and left spatial neglect [3, 4]. When attentional load at fixation was minimal, retinotopic areas in right visual cortex showed preserved responses to task-irrelevant checkerboards in the contralateral left hemifield, analogously to left visual cortex for right-hemifield checkerboards, indicating a "symmetric" pattern in both hemispheres with respect to contralateral stimulation under these conditions. But when attentional load at fixation was increased, a functional asymmetry emerged for visual cortex, with contralateral responses in right visual areas being pathologically reduced (even eliminated for right V4/TEO), whereas left visual areas showed no such reduction in their contralateral response. These results reveal attention-dependent abnormalities in visual cortex after lesions in distant (parietal) regions. This may explain otherwise puzzling aspects of neglect [5, 6], as confirmed here by additional behavioral testing.

Response to Comment on "Dynamic Shifts of Limited Working Memory Resources in Human Vision"

Cowan & Rouder suggest that a modification to the four-slot model of visual working memory fits the available data better than our distributed resource model. However their comparisons of statistical fit are biased in favour of the slot model. Here we compare the predictions of the two models and present further evidence against the division of visual memory into slots.

Individual differences in subconscious motor control predicted by GABA concentration in SMA.

Subliminal visual stimuli affect motor planning, but the size of such effects differs greatly between individuals. Here, we investigated whether such variation may be related to neurochemical differences between people. Cortical responsiveness is expected to be lower under the influence of more of the main inhibitory neurotransmitter, GABA. Thus, we hypothesized that, if an individual has more GABA in the supplementary motor area (SMA)--a region previously associated with automatic motor control--this would result in smaller subliminal effects. We measured the reversed masked prime--or negative compatibility--effect, and found that it correlated strongly with GABA concentration, measured with magnetic resonance spectroscopy. This occurred specifically in the SMA region, and not in other regions from which spectroscopy measurements were taken. We replicated these results in an independent cohort: more GABA in the SMA region is reliably associated with smaller effect size. These findings suggest that, across individuals, the responsiveness of subconscious motor mechanisms is related to GABA concentration in the SMA.

Motor role of human inferior parietal lobe revealed in unilateral neglect patients.

The exact role of the parietal lobe in spatial cognition is controversial. One influential hypothesis proposes that it subserves spatial perception, whereas other accounts suggest that its primary role is to direct spatial movement. For humans, it has been suggested that these functions may be divided between inferior and superior parietal lobes, respectively. In apparent support of a purely perceptual function for the inferior parietal lobe (IPL), patients with lesions to this structure, particularly in the right hemisphere, exhibit unilateral spatial neglect (deficient awareness for the side of space opposite to that of their lesion). Here we show that patients with right IPL lesions also have a specific difficulty in initiating leftward movements towards visual targets on the left side of space. This motor impairment was not found in neglect patients with frontal lesions, contrary to previous proposals that motor aspects of neglect are particularly associated with anterior damage. Our results suggest that the human IPL operates as a sensorimotor interface, rather than subserving only perceptual functions.

Binding deficits in memory following medial temporal lobe damage in patients with voltage-gated potassium channel complex antibody-associated limbic encephalitis.

Some prominent studies have claimed that the medial temporal lobe is not involved in retention of information over brief intervals of just a few seconds. However, in the last decade several investigations have reported that patients with medial temporal lobe damage exhibit an abnormally large number of errors when required to remember visual information over brief intervals. But the nature of the deficit and the type of error associated with medial temporal lobe lesions remains to be fully established. Voltage-gated potassium channel complex antibody-associated limbic encephalitis has recently been recognized as a form of treatable autoimmune encephalitis, frequently associated with imaging changes in the medial temporal lobe. Here, we tested a group of these patients using two newly developed visual short-term memory tasks with a sensitive, continuous measure of report. These tests enabled us to study the nature of reporting errors, rather than only their frequency. On both paradigms, voltage-gated potassium channel complex antibody patients exhibited larger errors specifically when several items had to be remembered, but not for a single item. Crucially, their errors were strongly associated with an increased tendency to report the property of the wrong item stored in memory, rather than simple degradation of memory precision. Thus, memory for isolated aspects of items was normal, but patients were impaired at binding together the different properties belonging to an item, e.g. spatial location and object identity, or colour and orientation. This occurred regardless of whether objects were shown simultaneously or sequentially. Binding errors support the view that the medial temporal lobe is involved in linking together different types of information, potentially represented in different parts of the brain, regardless of memory duration. Our novel behavioural measures also have the potential to assist in monitoring response to treatment in patients with memory disorders, such as those with voltage-gated potassium channel complex antibody limbic encephalitis.

Where the eye looks, the hand follows; limb-dependent magnetic misreaching in optic ataxia.

The posterior parietal cortex (PPC) is thought to play an important role in the sensorimotor transformations associated with reaching movements. In humans, damage to the PPC, particularly bilateral lesions, leads to impairments of visually guided reaching movements (optic ataxia). Recent accounts of optic ataxia based upon electrophysiological recordings in monkeys have proposed that this disorder arises because of a breakdown in the tuning fields of parietal neurons responsible for integrating spatially congruent retinal, eye, and hand position signals to produce coordinated eye and hand movements . We present neurological evidence that forces a reconceptualization of this view. We report a detailed case study of a patient with a limb-dependent form of optic ataxia who can accurately reach with either hand to objects that he can foveate (thereby demonstrating coordinated eye-hand movements) but who cannot effectively decouple reach direction from gaze direction for movements executed using his right arm. The demonstration that our patient's misreaching is confined to movements executed using his right limb, and only for movements that are directed to nonfoveal targets, rules out explanations based upon simple perceptual or motor deficits but indicates an impairment in the ability to dissociate the eye and limb visuomotor systems when appropriate.

Control over conflict during movement preparation: role of posterior parietal cortex.

Flexible behavior in humans often requires that rapid choices be made between conflicting action plans. Although much attention has focused on prefrontal regions, little is understood about the contribution of parietal cortex under situations of response conflict. Here we show that right parietal damage associated with spatial neglect leads to paradoxical facilitation (speeding) of rightward movements in the presence of conflicting leftward response plans. These findings indicate a critical role for parietal regions in action planning when there is response competition. In contrast, patients with prefrontal damage have an augmented cost of conflict for both leftward and rightward movements. The results suggest involvement of two independent systems in situations of response conflict, with right parietal cortex being a crucial site for automatic activation of competing motor plans and prefrontal regions acting independently to inhibit action plans irrelevant to current task goals.

Real-time functional magnetic resonance imaging neurofeedback for treatment of Parkinson's disease.

Self-regulation of brain activity in humans based on real-time feedback of functional magnetic resonance imaging (fMRI) signal is emerging as a potentially powerful, new technique. Here, we assessed whether patients with Parkinson's disease (PD) are able to alter local brain activity to improve motor function. Five patients learned to increase activity in the supplementary motor complex over two fMRI sessions using motor imagery. They attained as much activation in this target brain region as during a localizer procedure with overt movements. Concomitantly, they showed an improvement in motor speed (finger tapping) and clinical ratings of motor symptoms (37% improvement of the motor scale of the Unified Parkinson's Disease Rating Scale). Activation during neurofeedback was also observed in other cortical motor areas and the basal ganglia, including the subthalamic nucleus and globus pallidus, which are connected to the supplementary motor area (SMA) and crucial nodes in the pathophysiology of PD. A PD control group of five patients, matched for clinical severity and medication, underwent the same procedure but did not receive feedback about their SMA activity. This group attained no control of SMA activation and showed no motor improvement. These findings demonstrate that self-modulation of cortico-subcortical motor circuits can be achieved by PD patients through neurofeedback and may result in clinical benefits that are not attainable by motor imagery alone.

Vision and touch through the looking glass in a case of crossmodal extinction.

When observing ourselves in a mirror, we see our body and adjacent objects (e.g. a comb or razor) projecting the image of distant objects. Are these recoded by the brain as reflecting stimuli in peripersonal space? To address this, we exploited the neuropsychological phenomenon of crossmodal, visual-tactile extinction, as shown by patient BV following right-hemisphere stroke. In such crossmodal extinction, a right visual event impairs the perception of a simultaneous left tactile event. In BV, the right visual stimulus (an LED flash) induced more extinction of touch on the contralesional left hand when presented near the ipsilesional right hand, than when distant from it. This agrees with previous data in patients and monkeys showing that visual-tactile interactions are strongest within peripersonal space. Crucially, we also found that an ipsilesional flash produced more extinction when observed as the distant mirror-reflection of an LED that lay close to the ipsilesional hand, rather than as a distant LED flash projecting an equivalent visual image directly. This suggests that in BV, seeing his own hand via a mirror activates a representation of peripersonal space around that hand, not of the extrapersonal space suggested by the distant visual image in the mirror. We discuss the possible neural basis of interpreting mirror reflections.