How serially organized working memory information interacts with timing.

The temporary storage of serial order information in working memory (WM) has been demonstrated to be crucial to higher order cognition. The previous studies have shown that the maintenance of serial order can be a consequence of the construction of position markers to which to-be-remembered information will be bound. However, the nature of these position markers remains unclear. In this study, we demonstrate the crucial involvement of time in the construction of these markers by establishing a bidirectional relationship. First, results of the first experiment show that the initial items in WM result in faster responding after shorter time presentations, while we observe the opposite for items stored further in WM. Second, in the next experiment, we observe an effect of temporal cueing on WM retrieval; longer time cues facilitate responding to later WM items compared with items stored at the beginning of WM. These findings are discussed in the context of position marker theories, reviewing the functional involvement of time in the construction of these markers and its association with space.

Neural conflict-control mechanisms improve memory for target stimuli.

According to conflict-monitoring models, conflict serves as an internal signal for reinforcing top-down attention to task-relevant information. While evidence based on measures of ongoing task performance supports this idea, implications for long-term consequences, that is, memory, have not been tested yet. Here, we evaluated the prediction that conflict-triggered attentional enhancement of target-stimulus processing should be associated with superior subsequent memory for those stimuli. By combining functional magnetic resonance imaging (fMRI) with a novel variant of a face-word Stroop task that employed trial-unique face stimuli as targets, we were able to assess subsequent (incidental) memory for target faces as a function of whether a given face had previously been accompanied by congruent, neutral, or incongruent (conflicting) distracters. In line with our predictions, incongruent distracters not only induced behavioral conflict, but also gave rise to enhanced memory for target faces. Moreover, conflict-triggered neural activity in prefrontal and parietal regions was predictive of subsequent retrieval success, and displayed conflict-enhanced functional coupling with medial-temporal lobe regions. These data provide support for the proposal that conflict evokes enhanced top-down attention to task-relevant stimuli, thereby promoting their encoding into long-term memory. Our findings thus delineate the neural mechanisms of a novel link between cognitive control and memory.

Correction: Serial Position Markers in Space: Visuospatial Priming of Serial Order Working Memory Retrieval.

[This corrects the article DOI: 10.1371/journal.pone.0116469.].

Selective laser trabeculoplasty as replacement therapy in medically controlled glaucoma patients.

PURPOSE: We examined selective laser trabeculoplasty (SLT) as a replacement therapy for medically controlled open-angle glaucoma (OAG) or ocular hypertensive patients. METHODS: A prospective randomized interventional clinical trial on 143 glaucoma patients. Patients were randomized to either receiving SLT or to the control group that continued on pressure lowering medication. Data were recorded 1 hr, 1 week, 1, 3, 6, 12 and 18 months after SLT. Primary outcome was number of medications at 12 and 18 months while maintaining a predetermined target intraocular pressure (IOP). RESULTS: Selective laser trabeculoplasty (SLT) reduced number of medications from a mean of 1.5 at baseline, to 0.35 after 12 months and 0.29 after 18 months. Meanwhile, SLT achieved more than 20% IOP lowering in 95% of eyes and more than 30% IOP lowering in 86% of eyes after 18 months. Seventy-seven per cent of our eyes no longer needed any medication after SLT at 18 months. CONCLUSION: Selective laser trabeculoplasty (SLT) enabled a reduction in number of medications while maintaining good IOP control. Selective laser trabeculoplasty (SLT) was able to completely replace medical therapy in 77% of eyes after 18 months. Selective laser trabeculoplasty (SLT) as replacement therapy may reduce local and systemic side-effects and prevent adherence issues.

Impaired Processing of Serial Order Determines Working Memory Impairments in Alzheimer's Disease.

BACKGROUND: Working memory (WM) problems are commonly observed in Alzheimer's disease (AD), but the affected mechanisms leading to impaired WM are still insufficiently understood. The ability to efficiently process serial order in WM has been demonstrated to be fundamental to fluent daily life functioning. The decreased capability to mentally process serial position in WM has been put forward as the underlying explanation for generally compromised WM performance. OBJECTIVE: Determine which mechanisms, such as order processing, are responsible for deficient WM functioning in AD. METHOD: A group of AD patients (n = 32) and their partners (n = 25), assigned to the control group, were submitted to an extensive battery of neuropsychological and experimental tasks, assessing general cognitive state and functioning of several aspects related to serial order WM. RESULTS: The results revealed an impaired ability to bind item information to serial position within WM in AD patients compared to controls. It was additionally observed that AD patients experienced specific difficulties with directing spatial attention when searching for item information stored in WM. CONCLUSION: The processing of serial order and the allocation of attentional resources are both disrupted, explaining the generally reduced WM functioning in AD patients. Further studies should now clarify whether this observation could explain disease-related problems for other cognitive functions such as verbal expression, auditory comprehension, or planning.

Selective laser trabeculoplasty in pseudophakic and phakic eyes: a prospective study.

AIM: To compare the efficacy of selective laser trabeculoplasty (SLT) in replacing medical therapy in pseudophakic and phakic eyes. METHODS: Subgroup of a prospective randomized clinical trial including patients with primary open angle glaucoma or ocular hypertension controlled with medication. Of 38 pseudophakic eyes were matched with 38 phakic eyes. SLT was offered as a way to decrease medication while maintaining the same low eye pressure. SLT was performed over 360°, at 3ns, spotsize 400 µm, 100 spots. Data [intraocular pressure (IOP), number of medications needed] were measured at 1h, 1wk, 1, 3, 6 and 12mo. An independent-samples t-test was performed to compare baseline characteristics of the phakic and the pseudophakic group and differences in evolution of mean IOP and number of used medications. Chi-squared analysis was performed to investigate proportions of fast, slow and non-responders. RESULTS: The mean IOP measurement was 13.00± 2.88 mm Hg in the phakic group (38 eyes) and 13.51±3.06 mm Hg in the pseudophakic group (38 eyes) (P>0.05). This changed little after SLT and IOP lowering effect was comparable between the two groups. Main aim however was to lower the amount of medication needed. In the phakic group medication lowered from 1.29±0.62 at baseline, to 0.15±0.46 after 12mo; a reduction of 88.37%. In the pseudophakic group, used medication changed from 1.71±1.04, to 0.41±0.61; a 76.02% reduction. The differences were not statistically significant at any time point (P>0.05). IOP lowering occurred slightly faster in the pseudophakic group (50% of patients after one week) than in the phakic group (68% of patients after more than 4wk). The difference was not significant (P>0.05). CONCLUSION: IOP lowering effect of SLT is comparable between phakic and pseudophakic eyes.

Quality of life in glaucoma patients after selective laser trabeculoplasty.

AIM: To compare quality of life and treatment satisfaction between patients who had selective laser trabeculoplasty (SLT) and those on medication. METHODS: A prospective clinical trial on 143 glaucoma patients that received SLT and a control group that continued using anti glaucoma medication was conducted. Tear break-up time (BUT), punctuate keratitis, need for help, use of artificial tears and the treatment satisfaction survey of intraocular pressure (IOP) were measured at baseline, 6 and 12mo. RESULTS: SLT was able to reduce the mean number of medications needed from 1.56±0.81 to 0.42±0.66 at six months and to 0.33±0.69 at one year. Punctuate keratitis was observed significantly less often (12.24%) after SLT than before (35.94%; P=0.03). Use of artificial tears and BUT did not change significantly after SLT (P>0.05). At baseline, patients in the SLT group were significantly less convinced of medication effectiveness (P=0.006) and complained more about side effects (P=0.003). After SLT, these patients had significantly more confidence in their therapy (P<0.001), showed less side effects (P=0.006), complained less about changes in appearance of the eyes (P=0.003) and were less inconvenienced by the use of eye drops (P<0.001). CONCLUSION: SLT is able to improve treatment-related quality of life in glaucoma patients.

Randomized Prospective Study of the Use of Anti-Inflammatory Drops After Selective Laser Trabeculoplasty.

PURPOSE: Evaluating the use of Indomethacin, Dexamethasone, and no anti-inflammatory treatment immediately after selective laser trabeculoplasty (SLT). MATERIALS AND METHODS: Prospective randomized clinical trial of 132 eyes. Both eyes of the patient underwent SLT. One of the eyes was treated with Indomethacin 0.1% or Dexamethasone 0.1% 3 times daily for 1 week; the other eye did not receive any anti-inflammatory treatment. Intraocular pressure (IOP) and inflammatory parameters were recorded at 1 hour, 1 week, 1, 3, and 6 months. RESULTS: Cells in the anterior chamber were present in 57% to 71% of the patients after 1 hour. About 16% to 37% of the patients reported pain/discomfort after 1 hour. Redness was present before SLT in 29% to 34% of the patients, probably due to antiglaucoma medication. After 1 hour, the amount of redness recorded raised to 32% to 42%, but the amount of patients with redness returned to pretreatment levels after 1 week. An IOP peak of >5 mm Hg above baseline IOP 1 hour after laser was present in 3% to 9% of the patients. IOP lowered 11% to 21% compared with IOP at baseline. The number of medications needed changed from 1.45 to 1.49 before, to 0.23 to 0.45 six months after SLT.No differential effects based on the kind of anti-inflammatory treatment or no treatment were found for any of the parameters. CONCLUSIONS: SLT induces little inflammation: anti-inflammatory drops do not make a significant difference in pain, redness, cells in anterior chamber, or peak IOP following SLT.The IOP-lowering effect of the SLT is not influenced by the use of Indomethacin or Dexamethasone.

Where does selective laser trabeculoplasty stand now? A review.

BACKGROUND: Chronic treatment of glaucoma can present a challenge in patients who lack the means and/or the discipline to use daily glaucoma medication. We wondered if selective laser trabeculoplasty (SLT) could be a useful alternative. INCLUSION CRITERIA: controlled trials comparing efficacy of SLT in adult patients with any form of open angle glaucoma or ocular hypertension and case reports on side effects of SLT. Two recent meta-analyses identified eight randomized clinical trials (RCTs) comparing the effect of SLT with medication (prostaglandin analogs) and with argon laser trabeculoplasty (ALT). We took these eight RCTs as reference base and calculated their success rates where they were not given. Other articles were added to elaborate on technique and side effects. RESULTS: Mean intraocular pressure (IOP) reduction after SLT was 3.8-8.0 mmHg after 6 months to 1 year. Mean success rate of SLT at 6 months to 1 year is 55-82 %. Higher IOP before laser predicts a higher IOP-lowering effect. In terms of mean IOP reduction, reduction in number of medications and treatment success, the effect of SLT was found to show no clinically relevant difference from that of contemporary medication (prostaglandin analogs) and from ALT. CONCLUSIONS: The evidence indicates that SLT is an efficacious primary or adjunctive therapy for treating glaucoma.

Associative reinstatement memory measures hippocampal function in Parkinson's Disease.

In Parkinson's Disease (PD), hippocampal atrophy is associated with rapid cognitive decline. Hippocampal function is typically assessed using memory tests but current clinical tools (e.g., free recall) also rely on executive functions or use material that is not optimally engaging hippocampal memory networks. Because of the ubiquity of executive dysfunction in PD, our ability to detect true memory deficits is suboptimal. Our previous behavioural and neuroimaging work in other populations suggests that an experimental memory task - Associative Reinstatement Memory (ARM) - may prove useful in investigating hippocampal function in PD. In this study, we investigated whether ARM is compromised in PD and we assessed its convergent and divergent validity by comparing it to standardized measures of memory and of attention and executive functioning in PD, respectively. Using fMRI, we also investigated whether performance in PD relates to degree of hippocampal engagement. Fifteen participants with PD and 13 age-matched healthy controls completed neuropsychological testing as well as an ARM fMRI recognition paradigm in which they were instructed to identify word pairs comprised of two studied words (intact or rearranged pairs) and those containing at least one new word (new or half new pairs). ARM is measured by the differences in hit rates between intact and rearranged pairs. Behaviourally, ARM was poorer in PD relative to controls and was correlated with verbal memory measures, but not with attention or executive functioning in the PD group. Hippocampal activation associated with ARM was reduced in PD relative to controls and covaried with ARM scores in both groups. To conclude, ARM is a sensitive measure of hippocampal memory function that is unaffected by attention or executive dysfunction in PD. Our study highlights the benefit of integrating cognitive neuroscience frameworks and novel experimental tasks to improve the practice of clinical neuropsychology in PD.

Serial position markers in space: visuospatial priming of serial order working memory retrieval.

Most general theories on serial order working memory (WM) assume the existence of position markers that are bound to the to-be-remembered items to keep track of the serial order. So far, the exact cognitive/neural characteristics of these markers have remained largely underspecified, while direct empirical evidence for their existence is mostly lacking. In the current study we demonstrate that retrieval from verbal serial order WM can be facilitated or hindered by spatial cuing: begin elements of a verbal WM sequence are retrieved faster after cuing the left side of space, while end elements are retrieved faster after cuing the right side of space. In direct complement to our previous work--where we showed the reversed impact of WM retrieval on spatial processing--we argue that the current findings provide us with a crucial piece of evidence suggesting a direct and functional involvement of space in verbal serial order WM. We outline the idea that serial order in verbal WM is coded within a spatial coordinate system with spatial attention being involved when searching through WM, and we discuss how this account can explain several hallmark observations related to serial order WM.

Diffusion Kurtosis Imaging: A Possible MRI Biomarker for AD Diagnosis?

The purpose of this explorative study was to investigate whether diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) parameter changes are reliable measures of white matter integrity changes in Alzheimer's disease (AD) patients using a whole brain voxel-based analysis (VBA). Therefore, age- and gender-matched patients with mild cognitive impairment (MCI) due to AD (n = 18), dementia due to AD (n = 19), and age-matched cognitively healthy controls (n = 14) were prospectively included. The magnetic resonance imaging protocol included routine structural brain imaging and DKI. Datasets were transformed to a population-specific atlas space. Groups were compared using VBA. Differences in diffusion and mean kurtosis measures between MCI and AD patients and controls were shown, and were mainly found in the splenium of the corpus callosum and the corona radiata. Hence, DTI and DKI parameter changes are suggestive of white matter changes in AD.