Paresh Malhotra

Role of right posterior parietal cortex in maintaining attention to spatial locations over time

Recent models of human posterior parietal cortex (PPC) have variously emphasized its role in spatial perception, visuomotor control or directing attention. However, neuroimaging and lesion studies also suggest that the right PPC might play a special role in maintaining an alert state. Previously, assessments of right-hemisphere patients with hemispatial neglect have revealed significant overall deficits on vigilance tasks, but to date there has been no demonstration of a deterioration of performance over time—a vigilance decrement—considered by some to be a key index of a deficit in maintaining attention. Moreover, sustained attention deficits in neglect have not specifically been related to PPC lesions, and it remains unclear whether they interact with spatial impairments in this syndrome. Here we examined the ability of right-hemisphere patients with neglect to maintain attention, comparing them to stroke controls and healthy individuals. We found evidence of an overall deficit in sustaining attention associated with PPC lesions, even for a simple detection task with stimuli presented centrally. In a second experiment, we demonstrated a vigilance decrement in neglect patients specifically only when they were required to maintain attention to spatial locations, but not verbal material. Lesioned voxels in the right PPC spanning a region between the intraparietal sulcus and inferior parietal lobe were significantly associated with this deficit. Finally, we compared performance on a task that required attention to be maintained either to visual patterns or spatial locations, matched for task difficulty. Again, we found a vigilance decrement but only when attention had to be maintained on spatial information. We conclude that sustaining attention to spatial locations is a critical function of the human right PPC which needs to be incorporated into models of normal parietal function as well as those of the clinical syndrome of hemispatial neglect.

Priming of Color and Position during Visual Search in Unilateral Spatial Neglect

We examined priming of visual search by repeated target location or color in two patients with left visual neglect and extinction, following strokes centered on the right inferior parietal lobe. Both patients, like the healthy controls we tested, showed intact priming, with performance speeded when either the location or color of a singleton target was repeated over successive trials in a standard search condition (Experiment 1). This was observed both from and to targets on the contralesional (left) side. Moreover, priming of search was still observed even when a return of fixation back to display-center was required between successive trials (Experiment 2). When briefer displays were used (Experiment 3), the patients often failed to detect left targets. This situation revealed an important dissociation: Whereas location priming only arose from preceding left targets that had been consciously detected, color priming (possibly arising within the intact ventral stream) did not depend on awareness of the preceding target. There was considerable color priming from missed targets. These findings demonstrate relatively intact priming of visual search by color and location in patients with right parietal damage, and also reveal that location priming may differ from color priming in requiring awareness.

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.

Impaired spatial working memory: one component of the visual neglect syndrome?

Both impaired spatial working memory (SWM) and unilateral neglect may follow damage to the right parietal lobe. We propose that impaired SWM can exacerbate visual neglect, due to failures in remembering locations that have already been searched. When combined with an attentional bias to the ipsilesional right side, such a SWM impairment should induce recursive search of ipsilesional locations. Here we studied a left neglect patient with a right temporoparietal haemorrhage. On a nonlateralised, purely vertical SWM task, he was impaired in retaining spatial locations. In a visual search task, his eye position was monitored while his spatial memory was probed. He recursively searched through right stimuli, re-fixating previously inspected items, and critically treated them as if they were new discoveries, consistent with the SWM deficit. When his recovery was tracked over several months, his SWM deficit and left neglect showed concurrent improvements. We argue that impaired SWM may be one important component of the visual neglect syndrome.

The effects of the dopamine agonist rotigotine on hemispatial neglect following stroke

Hemispatial neglect following right-hemisphere stroke is a common and disabling disorder, for which there is currently no effective pharmacological treatment. Dopamine agonists have been shown to play a role in selective attention and working memory, two core cognitive components of neglect. Here, we investigated whether the dopamine agonist rotigotine would have a beneficial effect on hemispatial neglect in stroke patients. A double-blind, randomized, placebo-controlled ABA design was used, in which each patient was assessed for 20 testing sessions, in three phases: pretreatment (Phase A1), on transdermal rotigotine for 7–11 days (Phase B) and post-treatment (Phase A2), with the exact duration of each phase randomized within limits. Outcome measures included performance on cancellation (visual search), line bisection, visual working memory, selective attention and sustained attention tasks, as well as measures of motor control. Sixteen right-hemisphere stroke patients were recruited, all of whom completed the trial. Performance on the Mesulam shape cancellation task improved significantly while on rotigotine, with the number of targets found on the left side increasing by 12.8% (P = 0.012) on treatment and spatial bias reducing by 8.1% (P = 0.016). This improvement in visual search was associated with an enhancement in selective attention but not on our measures of working memory or sustained attention. The positive effect of rotigotine on visual search was not associated with the degree of preservation of prefrontal cortex and occurred even in patients with significant prefrontal involvement. Rotigotine was not associated with any significant improvement in motor performance. This proof-of-concept study suggests a beneficial role of dopaminergic modulation on visual search and selective attention in patients with hemispatial neglect following stroke.

Attention modulates the visual field in healthy observers and parietal patients

Recent attention research suggests that factors other than low-level sensory processes modulate perception across the visual field, with right parieto-temporal cortex playing a critical role in directing visual attention to peripheral events. Here we examine how different degrees of attentional demand at fixation dynamically affect detection of abrupt visual onsets in the periphery. In young healthy subjects, peripheral detection was significantly disrupted bilaterally when there was high attention demand at fixation. Right parieto-temporal lesioned patients, tested with a simplified version of task, demonstrated bilateral shrinkage of their available visual field, worse to the contralesional side, under increased attentional demand at fixation. These findings demonstrate how the effective visual field is dynamically modulated by the deployment of attention in health and, more severely, following right parieto-temporal damage.

Hemispatial neglect, balance and eye-movement control

Purpose of reviewDisorders of spatial awareness and balance following stroke are common but often under-diagnosed. They lead to poor outcome and frequently coexist. Here we focus on recent progress in the understanding of the mechanisms underlying these disorders and potential therapeutic advances. Recent findingsRight-hemisphere networks are important for both spatial attention and postural awareness. Neglect patients show multiple oculomotor impairments including reduced saccade amplitude and difficulty retaining spatial locations across saccades. There has been controversy regarding the brain regions associated with neglect, although most studies show the right inferior parietal lobe to be crucial and new imaging modalities have provided insight into neglect caused by subcortical stroke. The ‘pusher syndrome’ is a poorly understood balance disorder where patients push towards their paretic side, resulting in falls. It may involve impairment of subjective verticality but experimental studies have reported diverse findings. Advances in treatment for neglect include the successful use of prism adaptation and pilot data suggesting noradrenergic stimulation may improve search in selected patients. SummaryNew experimental techniques have provided insight into the debilitating disorders of spatial and postural awareness that often follow stroke. There are currently no widely used therapies for neglect but both new behavioural techniques and pharmacological methods are promising.

Thalamic Control of Human Attention Driven by Memory and Learning

Summary The role of the thalamus in high-level cognition—attention, working memory (WM), rule-based learning, and decision making—remains poorly understood, especially in comparison to that of cortical frontoparietal networks [1–3]. Studies of visual thalamus have revealed important roles for pulvinar and lateral geniculate nucleus in visuospatial perception and attention [4–10] and for mediodorsal thalamus in oculomotor control [11]. Ventrolateral thalamus contains subdivisions devoted to action control as part of a circuit involving the basal ganglia [12, 13] and motor, premotor, and prefrontal cortices [14], whereas anterior thalamus forms a memory network in connection with the hippocampus [15]. This connectivity profile suggests that ventrolateral and anterior thalamus may represent a nexus between mnemonic and control functions, such as action or attentional selection. Here, we characterize the role of thalamus in the interplay between memory and visual attention. We show that ventrolateral lesions impair the influence of WM representations on attentional deployment. A subsequent fMRI study in healthy volunteers demonstrates involvement of ventrolateral and, notably, anterior thalamus in biasing attention through WM contents. To further characterize the memory types used by the thalamus to bias attention, we performed a second fMRI study that involved learning of stimulus-stimulus associations and their retrieval from long-term memory to optimize attention in search. Responses in ventrolateral and anterior thalamic nuclei tracked learning of the predictiveness of these abstract associations and their use in directing attention. These findings demonstrate a key role for human thalamus in higher-level cognition, notably, in mnemonic biasing of attention.

Dynamic attentional modulation of vision across space and time after right hemisphere stroke and in ageing

Introduction Attention modulates the availability of sensory information to conscious perception. In particular, there is evidence of pathological, spatial constriction of the effective field of vision in patients with right hemisphere damage when a central task exhausts available attentional capacity. In the current study we first examined whether this constriction might be modulated across both space and time in right hemisphere stroke patients without neglect. Then we tested healthy elderly people to determine whether non-pathological ageing also leads to spatiotemporal impairments of vision under conditions of high attention load. Methods Right hemisphere stroke patients completed a task at fixation while attempting to discriminate letters appearing in the periphery. Attentional load of the central task was modulated by increasing task difficulty. Peripheral letters appeared simultaneously with the central task or at different times (stimulus onset asynchronies, SOAs) after it. In a second study healthy elderly volunteers were tested with a modified version of this paradigm. Results Under conditions of high attention load right hemisphere stroke patients have a reduced effective visual field, over a significantly extended ‘attentional blink’, worse for items presented to their left. In the second study, older participants were unable to discriminate otherwise salient items across the visual field (left or right) when their attention capacity was loaded on the central task. This deficit extended temporally, with peripheral discrimination ability not returning to normal for up to 450 msec. Conclusions Dynamically tying up attention resources on a task at fixation can have profound effects in patient populations and in normal ageing. These results demonstrate that items can escape conscious detection across space and time, and can thereby impact significantly on visual perception in these groups.

Reward modulates spatial neglect

Background Reward has been shown to affect attention in healthy individuals, but there have been no studies addressing whether reward influences attentional impairments in patients with focal brain damage. Methods Using two novel variants of a widely-used clinical cancellation task, we assessed whether reward modulated impaired attention in 10 individuals with left neglect secondary to right hemisphere stroke. Results Reward exposure significantly reduced neglect, as measured by total targets found, left-sided targets found and centre of cancellation, across the patient group. Lesion analysis showed that lack of response to reward was associated with damage to the ipsilateral striatum. Conclusions This is the first experimental evidence that reward can modulate attentional impairments following brain damage. These results have significant implications for the development of behavioural and pharmacological therapies for patients with attentional disorders.