Dynamic shifts in brain network activation during supracapacity working memory task performance.

Despite significant advances in understanding how brain networks support working memory (WM) and cognitive control, relatively little is known about how these networks respond when cognitive capabilities are overtaxed. We used a fine-grained manipulation of memory load within a single trial to exceed WM capacity during functional magnetic resonance imaging to investigate how these networks respond to support task performance when WM capacity is exceeded. Analyzing correct trials only, we observed a nonmonotonic (inverted-U) response to WM load throughout the classic WM network (including bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and presupplementary motor areas) that peaked later in individuals with greater WM capacity. We also observed a relative increase in activity in medial anterior prefrontal cortex, posterior cingulate/precuneus, and lateral temporal and parietal regions at the highest WM loads, and a set of predominantly subcortical and prefrontal regions whose activation was greatest at the lowest WM loads. At the individual subject level, the inverted-U pattern was associated with poorer performance while expression of the early and late activating patterns was predictive of better performance. In addition, greater activation in bilateral fusiform gyrus and right occipital lobe at the highest WM loads predicted better performance. These results demonstrate dynamic and behaviorally relevant changes in the level of activation of multiple brain networks in response to increasing WM load that are not well accounted for by present models of how the brain subserves the cognitive ability to hold and manipulate information on-line.

Capacity estimates in working memory: Reliability and interrelationships among tasks.

The concept of capacity has become increasingly important in discussions of working memory (WM), in so far as most models of WM conceptualize it as a limited-capacity mechanism for maintaining information in an active state, and as capacity estimates from at least one type of WM task-complex span-are valid predictors of real-world cognitive performance. However, the term capacity is also often used in the context of a distinct set of WM tasks, change detection, and may or may not refer to the same cognitive capability. We here develop maximum-likelihood models of capacity from each of these tasks-as well as from a third WM task that places heavy demands on cognitive control, the self-ordered WM task (SOT)-and show that the capacity estimates from change detection and complex span tasks are not correlated with each other, although capacity estimates from change detection tasks do correlate with those from the SOT. Furthermore, exploratory factor analysis confirmed that performance on the SOT and change detection load on the same factor, with performance on our complex span task loading on its own factor. These findings suggest that at least two distinct cognitive capabilities underlie the concept of WM capacity as it applies to each of these three tasks.

Examining encoding imprecision in spatial working memory in schizophrenia.

BACKGROUND: Visuospatial working memory is not a unitary sketch pad but comprises independent dimensions of target distance and direction and at least two levels of detail (fine-grained and category level). The aim of this study was to examine these multiple aspects of encoding in patients with schizophrenia using a modified delayed response task. METHOD: 42 patients with schizophrenia and 48 healthy controls pointed, as accurately as possible from a fixed starting position, to the visual location of target stimuli presented to a touch-sensitive screen. An adaptive staircase procedure was used to equate stimulus duration for each individual. Encoding accuracy and maintenance of distance (mm) and direction ( degrees ) information was examined following a 0-second (immediate) or 4-second (unfilled) delay. Analyses utilized both absolute (unsigned) and signed data. RESULTS: The results showed that the average duration required to detect a target was significantly longer in patients than controls. When stimulus duration was equated, (a) the absolute accuracy of distance and direction responses was not significantly different between groups at 0-second delay but was significantly reduced at 4-second delay in patients with schizophrenia, and (b) signed direction errors at 4-second delay were significantly different between groups at stimulus angles greater than 90 degrees . CONCLUSIONS: The findings challenge previous suggestions of deficits in fine-grained encoding of spatial information in schizophrenia but confirm a difficulty maintaining both direction and distance details in working memory. Imprecision in spatial memory in schizophrenia also introduced greater bias from category level (prior) representations, especially in left hemi-space.

A comparative study of digital PCR and real-time qPCR for the detection and quantification of HPV mRNA in sentinel lymph nodes of cervical cancer patients.

BACKGROUND: Qualitative analyses showed that the presence of HPV mRNA in sentinel lymph nodes of cervical cancer patients with pN0 status is associated with significantly decreased recurrence free survival. To further address the clinical potential of the strategy and to define prognostic threshold levels it is necessary to use a quantitative assay. Here, we compare two methods of quantification: digital PCR and standard quantitative PCR. METHODS: Serial dilutions of 5 ng-5 pg RNA (≙ 500-0.5 cells) of the cervical cancer cell line SiHa were prepared in 5 µg RNA of the HPV-negative human keratinocyte cell line HaCaT. Clinical samples consisted of 10 sentinel lymph nodes with varying HPV transcript levels. Reverse transcription of total RNA (5 µg RNA each) was performed in 100 µl and cDNA aliquots were analyzed by qPCR and dPCR. Digital PCR was run in the RainDrop® Digital PCR system (RainDance Technologies) using a probe-based detection of HPV E6/E7 cDNA PCR products with 11 µl template. qPCR was done using a Rotor Gene Q 5plex HRM (Qiagen) amplifying HPV E6/E7 cDNA in a SYBR Green format with 1 µl template. RESULTS: For the analysis of both, clinical samples and serial dilution samples, dPCR and qPCR showed comparable sensitivity. With regard to reproducibility, both methods differed considerably, especially for low template samples. Here, we found with qPCR a mean variation coefficient of 126% whereas dPCR enabled a significantly lower mean variation coefficient of 40% (p = 0.01). Generally, we saw with dPCR a substantial reduction of subsampling errors, which most likely reflects the large cDNA amounts available for analysis. CONCLUSIONS: Compared to real-time PCR, dPCR shows higher reliability. Thus, our HPV mRNA dPCR assay holds promise for the clinical evaluation of occult tumor cells in histologically tumor-free lymph nodes in future studies.

Working memory binding of visual object features in older adults.

Accurate mental representation of visual stimuli requires retaining not only the individual features but also the correct relationship between them. This associative process of binding is mediated by working memory (WM) mechanisms. The present study re-examined reports of WM-related binding deficits with aging. In Experiment 1, 31 older and 31 younger adults completed a visual change detection task with feature-location relations presented either simultaneously or sequentially; the paradigm was also designed specifically to minimize the impact of lengthy retention intervals, elaborative rehearsal, and processing demands of multi-stimulus probes. In Experiment 2, 38 older and 42 younger adults completed a modified task containing both feature-location relations and feature-feature conjunctions. In Experiment 1 although feature-location binding was more difficult with sequential compared with simultaneous presentation, the effect was independent of age. In Experiment 2 while older adults were overall slower and less accurate than young adults, there were no age-specific deficits in WM binding. Overall, after controlling for methodological factors, there was no evidence of an age-related visual WM binding deficit for surface or location features. However, unlike younger adults, older adults appeared less able to restrict processing of irrelevant features, consistent with reported declines with age in strategic capacities of WM.

Psychiatric comorbidity following traumatic brain injury.

PRIMARY OBJECTIVE: Survivors of traumatic brain injury (TBI) are at increased risk for development of severe, long-term psychiatric disorders. However, the aetiology of these disorders remains unclear. This article systematically reviews the most current prevalence rates and evidence for causality, in terms of established criteria. MAIN OUTCOME AND RESULTS: Psychiatric syndromes are consistently present at an elevated rate following TBI. Survivors of TBI are particularly susceptible to major depression, generalized anxiety disorder and post-traumatic stress disorder. Evidence for a biological gradient is generally lacking, although this criterion may not be appropriate in the case of TBI. The temporal pattern of onset is variable and reliable critical periods for the post-injury development of a psychiatric disorder remain to be identified; however, individuals appear to remain at risk for years following injury. CONCLUSIONS: Non-organic factors, including pre-morbid personality traits and post-injury psychological reactions to disability and trauma, are implicated in the generation and maintenance of post-TBI psychiatric disorder. There remains insufficient evidence to conclude what role the neuropathological consequences of TBI play in the development of post-TBI psychiatric disorder.