The Impact of Financial Reward Contingencies on Cognitive Function Profiles in Adult ADHD

Objectives

Although it is well established that cognitive performance in children with attention-deficit/hyperactivity disorder (ADHD) is affected by reward and that key deficits associated with the disorder may thereby be attenuated or even compensated, this phenomenon in adults with ADHD has thus far not been addressed. Therefore, the aim of the present study was to examine the motivating effect of financial reward on task performance in adults with ADHD by focusing on the domains of executive functioning, attention, time perception, and delay aversion.

Methods

We examined male and female adults aged 18–40 years with ADHD (n = 38) along with a matched control group (n = 40) using six well-established experimental paradigms.

Results

Impaired performance in the ADHD group was observed for stop-signal omission errors, n-back accuracy, reaction time variability in the continuous performance task, and time reproduction accuracy, and reward normalized time reproduction accuracy. Furthermore, when rewarded, subjects with ADHD exhibited longer reaction times and fewer false positives in the continuous performance task, which suggests the use of strategies to prevent impulsivity errors.

Conclusions

Taken together, our results support the existence of both cognitive and motivational mechanisms for the disorder, which is in line with current models of ADHD. Furthermore, our data suggest cognitive strategies of “stopping and thinking” as a possible underlying mechanism for task improvement that seems to be mediated by reward, which highlights the importance of the interaction between motivation and cognition in adult ADHD.     

Vegetative versus Minimally Conscious States: A Study Using TMS-EEG,Sensory and Event-Related Potentials

Differential diagnoses between vegetative and minimally conscious states (VS and MCS, respectively) are frequently incorrect. Hence, further research is necessary to improve the diagnostic accuracy at the bedside. The main neuropathological feature of VS is the diffuse damage of cortical and subcortical connections. Starting with this premise, we used electroencephalography (EEG) recordings to evaluate the cortical reactivity and effective connectivity during transcranial magnetic stimulation (TMS) in chronic VS or MCS patients. Moreover, the TMS-EEG data were compared with the results from standard somatosensory-evoked potentials (SEPs) and event-related potentials (ERPs). Thirteen patients with chronic consciousness disorders were examined at their bedsides. A group of healthy volunteers served as the control group. The amplitudes (reactivity) and scalp distributions (connectivity) of the cortical potentials evoked by TMS (TEPs) of the primary motor cortex were measured. Short-latency median nerve SEPs and auditory ERPs were also recorded. Reproducible TEPs were present in all control subjects in both the ipsilateral and the contralateral hemispheres relative to the site of the TMS. The amplitudes of the ipsilateral and contralateral TEPs were reduced in four of the five MCS patients, and the TEPs were bilaterally absent in one MCS patient. Among the VS patients, five did not manifest ipsilateral or contralateral TEPs, and three of the patients exhibited only ipsilateral TEPs with reduced amplitudes. The SEPs were altered in five VS and two MCS patients but did not correlate with the clinical diagnosis. The ERPs were impaired in all patients and did not correlate with the clinical diagnosis. These TEP results suggest that cortical reactivity and connectivity are severely impaired in all VS patients, whereas in most MCS patients, the TEPs are preserved but with abnormal features. Therefore, TEPs may add valuable information to the current clinical and neurophysiological assessment of chronic consciousness disorders.     

FLT3 Mutations in Early T-Cell Precursor ALL Characterize a Stem Cell Like Leukemia and Imply the Clinical Use of Tyrosine Kinase Inhibitors

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup.     

Separable Roles for a Caenorhabditis elegans RMI1 Homolog in Promoting and Antagonizing Meiotic Crossovers Ensure Faithful Chromosome Inheritance

During the first meiotic division, crossovers (COs) between homologous chromosomes ensure their correct segregation. COs are produced by homologous recombination (HR)-mediated repair of programmed DNA double strand breaks (DSBs). As more DSBs are induced than COs, mechanisms are required to establish a regulated number of COs and to repair remaining intermediates as non-crossovers (NCOs). We show that the Caenorhabditis elegans RMI1 homolog-1 (RMH-1) functions during meiosis to promote both CO and NCO HR at appropriate chromosomal sites. RMH-1 accumulates at CO sites, dependent on known pro-CO factors, and acts to promote CO designation and enforce the CO outcome of HR-intermediate resolution. RMH-1 also localizes at NCO sites and functions in parallel with SMC-5 to antagonize excess HR-based connections between chromosomes. Moreover, RMH-1 also has a major role in channeling DSBs into an NCO HR outcome near the centers of chromosomes, thereby ensuring that COs form predominantly at off-center positions.     

Highly unsaturated fatty acids in nature: what we know and what we need to learn

The supply and demand of omega‐3 highly unsaturated fatty acids (ω‐3 HUFA) in natural ecosystems may lead to resource limitation in a diverse array of animal taxa. Here, we review why food quality in terms of ω‐3 HUFAs is important, particularly for neural tissue, across a diversity of animal taxa ranging from invertebrate zooplankton to vertebrates (including humans). Our review is focused on ω‐3 HUFAs rather than other unsaturated fatty acids because these compounds are especially important biochemically, but scarce in nature. We discuss the dichotomy between ω‐3 HUFA availability between aquatic primary producers, which are often rich in these compounds, and terrestrial primary producers, which are contain little to none of them. We describe the use of fatty acids as qualitative and quantitative tracers for reconstructing animal diets in natural ecosystems. Next, we discuss both direct and indirect ecological implications of ω‐3 HUFA limitation at the individual, population, food web, and ecosystem scales, which include: changes in behavior, species composition, secondary production rates, trophic transfer efficiency and cross‐ecosystem subsidies. We finish by highlighting future research priorities including a need for more research on ω‐3 HUFAs in terrestrial systems, more research their importance for higher order consumers, and more research on the food web and ecosystem‐scale effects of ω‐3 HUFA limitation. Synthesis Mismatches between the supply of and demand for omega‐3 highly unsaturated fatty acids (ω‐3 HUFA) in natural ecosystems have the potential to result in resource limitation across a diverse array of ecosystems. We combined perspectives from ecology and nutritional science to develop a unified synthesis of ω‐3 HUFA ecology. We reviewed the importance of ω‐3 HUFAs for animals, the striking differences in ω‐3 HUFA availability at the base of terrestrial versus aquatic food webs, and the implications of ω‐3 HUFA limitation for food webs. We finished by highlighting research priorities in the field including more research on ω‐3 HUFAs in terrestrial systems, on higher order consumers, and at the food web and ecosystem‐scales.     

Senescence‐associated tissue microenvironment promotes colon cancer formation through the secretory factor GDF15

The risk of colorectal cancer (CRC) varies between people, and the cellular mechanisms mediating the differences in risk are largely unknown. Senescence has been implicated as a causative cellular mechanism for many diseases, including cancer, and may affect the risk for CRC. Senescent fibroblasts that accumulate in tissues secondary to aging and oxidative stress have been shown to promote cancer formation via a senescence‐associated secretory phenotype (SASP). In this study, we assessed the role of senescence and the SASP in CRC formation. Using primary human colon tissue, we found an accumulation of senescent fibroblasts in normal tissues from individuals with advanced adenomas or carcinomas in comparison with individuals with no polyps or CRC. In in vitro and ex vivo model systems, we induced senescence using oxidative stress in colon fibroblasts and demonstrated that the senescent fibroblasts secrete GDF15 as an essential SASP factor that promotes cell proliferation, migration, and invasion in colon adenoma and CRC cell lines as well as primary colon organoids via the MAPK and PI3K signaling pathways. In addition, we observed increased mRNA expression of GDF15 in primary normal colon tissue from people at increased risk for CRC in comparison with average risk individuals. These findings implicate the importance of a senescence‐associated tissue microenvironment and the secretory factor GDF15 in promoting CRC formation.     

Do intraspecific life history patterns follow interspecific predictions? A test using latitudinal variation in ringed seals

Mammals adapted to unpredictable and low-energy environments often evolve a “bet-hedging” life history strategy characterized by less costly reproductive outputs over a longer and slower-growing life. In contrast, species adapted to more predictable (i.e., low variation) and higher energy environments may evolve greater fecundity over a shorter and faster-growing life. We tested whether this known interspecific pattern also occurs within a species. We compared life history traits of the ringed seal (Pusa hispida) in the Canadian High Arctic to those closer to the southern limit of the species' circumpolar distribution. We found that northern seals grew slower than southern seals (Brody growth coefficient), achieved a greater asymptotic body weight (82 and 69 kg vs. 74 and 54 kg female and male, respectively), reached sexual maturity later (6.1 years vs. 4.5 years), had lower fecundity (1.8 years vs. 1.3 years interbirth interval), longer average lifespan (5 years vs. 3 years median age), and greater movements (1,269 vs. 681 km). Mating systems also likely differed with northern seals showing morphological evidence of a promiscuous mating system with potential sperm competition as indicated by greater relative testes size. The northern region was also characterized by more unpredictable environmental timing of seasonal events, such as spring sea ice breakup. Life history variation between the intraspecific groups of seals appears to agree with interspecific patterns and provides a better understanding of how species' life history parameters shift in concert with environmental conditions.