A background to the study, including reference to previous work in the area leading up to this study, including hypotheses

Unilateral spatial neglect (USN), also referred to as Hemispatial neglect, is a common neurological syndrome that most often accompanies damage to the right hemisphere and is typically associated with stroke patients (Corbetta & Shulman, 2011). (Bartolomeo & Chokron, 2002). The most salient behavioural marker of unilateral spatial neglect is the failure of the injured individual to attend and respond to stimuli presented within the contralesional hemispace. A patient with UNS will often fail to complete the left side of a drawing (see figure 1), many not see the words on the left of a page he is reading, may collide with a wall on his left when walking and so on.

Figure 1: Copy of a figure by a right brain-damaged patient presenting a left unilateral spatial neglect (top: model, bottom: patient's copy; taken from Chokron, Dupierrix, Tabert, & Bartolomeo, 2007).

For example, a stroke patient who had damage to the right hemisphere may behave as if the left side of their (visual field?/ sensory space) does not exist. The literature has documented many cases of patients who experience USN(), with many descriptions consisting of different situations. For example, nnn described case of xxxx who failed to shave Moreover,

these patients frequently have accidents as their failure to attend to the left side of space results in many collisions with objects such as doors etc ().
Spatial neglect is caused by lesions, typically strokes, in a number of different cortical and subcortical areas. Although acutely both left and right hemisphere lesions can cause neglect, only right hemisphere lesions cause severe and persistent deficits (Stone et al. 1993), which is the primary basis for the widely held view that the right hemisphere is dominant for attention. features of unilateral spatial neglect: a reduction of arousal and speed of processing; an inability to attend to and report stimuli on the side opposite the lesion (contralesional) despite apparently normal visual perception; a spatial bias for directing actions toward the hemi-space or hemi-body on the same side as the lesion (ipsilesional); and several disorders of awareness, including a degree of obliviousness toward being ill and confabulation about body ownership. Spatial neglect is unique among the behavioral disorders resulting from focal lesions because its severity can be modulated by behavioral interventions over very short timescales (e.g., seconds). Deficits in attending to and reporting objects in contralesional space can be lessened by (a) encouraging a patient to attend to the previously ignored stimuli using verbal cues (Riddoch & Humphreys 1983); (b) presenting salient sensory stimuli, such as noises (Robertson et al. 1998); (c) asking the patient to perform hand movements controlled by the injured hemisphere (Robertson & North 1992); or (d ) training patients to increase their alertness (Robertson et al. 1995). These observations suggest that the neural mechanisms underlying the spatial deficit can be dynamically modulated by signals from other parts of the brain reflecting endogenous or exogenous attention, movement, and arousal. Moreover, in a matter of days or weeks, most patients with spatial neglect recover from the more obvious spatial impairments, which continue to negatively influence their ability to return to a productive life (Denes et al. 1982, Paolucci et al. 2001).

Cognitive neuropsychologists have been carrying out increasingly elegant experimental manipulations in an attempt to tease apart the components of UNS.

Investigators have used many different methods to investigate the mechanisms underlying UNS. For example, Di Pellegrino and De Renzi (1995) used a computer based procedure in which they recorded the reaction times (RTs) of a UNS patient when presented simultaneous stimuli (in both left and right hemispace). They patient was required to elicit a response based on which he saw first (look this paper up). In this study the patient responded in accordance with right hemispace neglect in 100% of trials. The only exception was when the patient was instructed to attend to previously ignored stimuli using verbal cues (Riddoch & Humphreys, 1983 ).

Early studies focused on increasing leftward visual scanning. For example many studies

What is unique about neglect is that it can be improved xxx Many different methods and procedures have been used to enhance the patients ability to Description of the study, including an overview of the methodology used.

Method Participants: This study contained eight stoke patients with right hemisphere damage (2 female, 6 males, mean age=64.6 years), whose mean number of weeks post stroke was 35. The criterion for entry to the study was right hemisphere lesions, which were confirmed by computerised tomography (CT). Follow up study: Only two of the original eight patients were available to participate in follow up study (D.M. and S.B.). Control group: A control group which contained seven patients with left- hemisphere damage (4 females, 3 males) were matched for age (mean age= 60.1) and extent of damage to the right- hemisphere group, and were tested on average of 34.4 days post stroke. Sequence of events (see figure 3)

The visual stimuli were presented on an LCD computer monitor. All visual stimuli were presented on a white background. First each participant was presented with an image of a cross that was at the centre of the display and was instructed to fixate and maintain their gaze on the cross. The participants performance was monitored by an observer. Visual targets contained two horizontal bars (height and width). The bars appeared at equal locations of both left and right visual fields and were the same height as the fixation cross (except patient S.G.), with the outer edges 9.8x from fixation point. The sequence of events for a warned trial: Figure 1.

Figure 3: The sequences of events for testing were as follows: First, a fixation cross appeared alone for 600ms. Next, In a subset of trials (25%) a 300- ms tone burst (either 400hz or 1000hz randomized) was presented centrally (centre of screen?) from two loudspeakers (Makintosh Multimedia Model SK-A10) concealed behind the monitor (in follow up experiment they were placed to the right of the monitor). After a random delay (why?) of

300-1,100ms after warning tone had ceased, the two bars appeared to the left and right of the fixation point, with a variable SOA between them of 0-1,296ms. The remaining 75% of trials contained the same sequence of events except a 300ms silence replaced the tone. In each trial subjects were forced to make a choice (2AFC) as to which of the two bars appeared first. The bars remained on the screen until the participant elicited a verbal response. Each participant underwent eight separate but concurrent psychophysiological staircases in a randomly intermingled sequence of trials. Of the eight staircases, six were unwarned and two were warned. In all cases half of the staircases commenced with an extreme left lead (1, 296ms) and half an extreme right lead (1, 296ms). Each staircase independently adapted (why?) to the participants responses, adjusting SOA to the point where left-first reponses were as common as right-first responses for that staircase, with the steps in SOA adjusted by the PEST algorithim. The trials did not cease until the participant had made at least ten reversals of responses in at one or two of the reversed staircases (typically occurred after 200 trials per subject).

Summary of results, detailing the main findings.

Less than 10% of trials were excluded due to participants failure to maintain fixation on the fixation cross. In line with standard psychological practice, the threshold for subjective simultaneity was computed from each staircase by averaging the SOAs in all trials after the fifth response reversal only in that staircase (to allow responses to settle).

Figure 2: Mean thresholds of subjective simultaneity for each participant.

A positive value represents responding if the left event appeared first (consistent with a rightward bias in attention). A negative value indicated that a right lead was required (responding consistent with a leftward bias in attention). The data from the initial experiment howed that in the unwarned trials the average threshold for perceiving (subjective simultaneity) was +497ms (ms range (-304 to +1,069 ms).

In unwarned trials, the average threshold for subjective simultaneity was +497ms (s.d. 358 ms; range 1491,069 ms), consistent with severe left neglect.

Summary of findings
The authors found that the pathological asymmetry of spatial attentional selection indeed was alleviated by such a phasic enhancement of alertness

Consistent with the hypothesis the results indicated that a phasic enhancement of alertness did indeed alleviate the pathological asymmetry found in neglect patients. . The left spatial neglect patients with right hemisphere damage in the initial study showed a significant decrease in their pathological bias for the right side resulting in a more balanced distribution of attention. The follow up experiment, in which the tone was moved to the right as opposed to the centre in the initial study, showed similar results suggesting that where the tone is located is unimportant. Considering all three conditions within this study (initial, follow up, control) the data overwhelmingly supports the notion that an alert tone can reduce spatial neglect in right- hemisphere lesion patients temporarily. This study implied that alertness, which is a non spatial constituent of attention, interacts with the allocation of spatial attention (Weinbach & Henik, 2011).

Why this article is an important contribution to the field. This study was the first to directly study the causal relationship between alertness changes induced by the unexpected presentation of tones and its impact on the rightward spatial bias present in neglect patients on a trial by trial basis (Finke, et al., 2012). The findings showed that a brief tone alert shifted the typical judgement of right bar as coming first in the judgement task to a more balanced spatial evaluation (?). This results highlighted the potential of the severely damaged attentional system in neglect patients ability to adapt in response to an alert tone such that their inattention to the left field is momentarily overcome.

The fact that left hemisphere damaged patients in the control study showed no consistent advantage for either left or right stimuli adds credence to the hypothesis that rightlateralization is correlated with spatial attention and non- spatial alertness.

What makes the design ingenious, innovative or novel. The method used in this experiment was novel because it was the first to provide a primarily perceptual measure of .as it did not require a manual response, thus reducing the chance of confounding the results with the possibility of the influence of motor readiness rather than the perceptual processes on the output. Additionally the simultaneous representation of left and right stimuli allowed the direct comparison of perceptual processing of both sides of the .

How this study may have influenced research in this area of neuroscience.
The rapid development of new theory-driven rehabilitation strategies shows promise, and some studies demonstrate generalization from the rehabilitation task to everyday behaviors which, in some cases, lasts for weeks to months (e.g., Frassinetti et al. 2002; Robertson et al. 1995, 1997). It is often difficult to tease apart spontaneous recovery from recovery as a result of rehabilitation, but in clinical practice, perhaps this does not matter.

Because Robertson and colleagues have demonstrated that patients with left neglect have a problem with sustaining attention on the left, they have additionally shown that neglect can be decreased by increasing alertness. This has led to the adaptation of this method (tonic alerting) to a rehabilitation technique for patients with UNS.

Several studies have previously examined the role of tonic alerting processes in CP, both in neurologically intact observers and in visual neglect patients. Manly, Dobler, Dodds, and George (2005) examined the role of diminished levels of alertness induced by sleep deprivation in pseudoneglect, a reliable though modest leftward attentional bias exhibited by the adult healthy population on horizontal line bisection or its variants, such as judgments of length of line segments in pre-bisected lines (landmark task). Manly et al. (2005) showed that sleep deprived participants shifted visual attention towards the right on a landmark task, thus demonstrating an effect of tonic alertness on spatial awareness. Van Vleet and Robertson (2006) reported that, in visual neglect patients, auditory tonic alerting ameliorated visuospatial attention deficits. They presented an auditory tonic alerting tone together with a visual target in a series of search tasks. The tone was presented bilaterally, or in a congruent or incongruent spatial location with respect to the target. They found that the tone always facilitated target detection, irrespective of location. Together, these studies suggest that increased tonic alertness may directly mediate spatial awareness.

What appeals to you about this study.

The method utilised in this study was novel in that it specifically enabled the researchers to parse out the effects of tonic alerting versus no alerting on participants responding. The use of 75% of non alert tasks was particularly important as it showed that the effects of the phasic alerting were not due to chance. Moreover, it showed that rather than an inability to perceive stimuli on the left side, instead it is rather a lack of attentional focus in this area.

This method has subsequently been used in a variety of studies. For example, this method was employed by Dobler and colleagues (2003) with a child aged seven who had been diagnosed with ADHD.

Limitations: As with most studies there were however some limitations It was not clarified what threshold was the forced choice was worked from (e.g. 75%). A small sample size may be considered disadvantageous; however as the follow up studies described have shown these findings can and have been replicated. The heterogeneity of the lesions of patients within the study could be considered a caveat of this study, however as heterogeneity is atypical in this group of patients it is plausible to suggest that instead this actually increases the ecological validity of the results.

. suggesting the phasic warning tone was effective in An interesting follow up study could be a similare study except requiring patients to copy pictures whilst tone With control group does not specify whether the repeated with tone on right.

Consistent with previous accounts of UNS the data showed that patients with right hemisphere dampage

As there is already a 50% chance of a correct response with 2AFC, threshold is commonly considered as 75% (See Fig. 14).

A possible indication for this comes from studies that show how alertness, a non-spatial component of attention, interacts with allocation of spatial attention (DeGutis & Van Vleet, 2010; Manly, Dobler, Dodds, & George, 2005; Matthias et al., 2010; Robertson, Mattingley, Rorden, & Driver, 1998; Thimm, Fink, Kst, Karbe, & Sturm, 2006). Recently, Van Vleet, Hoang-duc, DeGutis, and Robertson (2010) reported that alertness can interact with global and local processing of visual information.