scholarly journals Persistent impairment in working memory following severe hyperglycemia in newly diagnosed type 2 diabetes

Author(s):  
Joseph Cerasuolo ◽  
Anthony Izzo

Summary Acute hyperglycemia has been shown to cause cognitive impairments in animal models. There is growing appreciation of the numerous effects of hyperglycemia on neuronal function as well as blood–brain barrier function. In humans, hypoglycemia is well known to cause cognitive deficits acutely, but hyperglycemia has been less well studied. We present a case of selective neurocognitive deficits in the setting of acute hyperglycemia. A 60-year-old man was admitted to the hospital for an episode of acute hyperglycemia in the setting of newly diagnosed diabetes mellitus precipitated by steroid use. He was managed with insulin therapy and discharged home, and later, presented with complaints of memory impairment. Deficits included impairment in his declarative and working memory, to the point of significant impairment in his overall functioning. The patient had no structural lesions on MRI imaging of the brain or other systemic illnesses to explain his specific deficits. We suggest that his acute hyperglycemia may have caused neurological injury, and may be responsible for our patient’s memory complaints. Learning points: Acute hyperglycemia has been associated with poor outcomes in several different central nervous system injuries including cerebrovascular accident and hypoxic injury. Hyperglycemia is responsible for accumulation of reactive oxygen species in the brain, resulting in advanced glycosylated end products and a proinflammatory response that may lead to cellular injury. Further research is needed to define the impact of both acute and chronic hyperglycemia on cognitive impairment and memory.

2020 ◽  
Vol 93 (1115) ◽  
pp. 20200245 ◽  
Author(s):  
Charles Limoli

Not surprisingly, our knowledge of the impact of radiation on the brain has evolved considerably. Decades of work have struggled with identifying the critical cellular targets in the brain, the latency of functional change and understanding how irradiation alters the balance between excitatory and inhibitory circuits. Radiation-induced cell kill following clinical fractionation paradigms pointed to both stromal and parenchymal targets but also defined an exquisite sensitivity of neurogenic populations of newly born cells in the brain. It became more and more apparent too, that acute (days) events transpiring after exposure were poorly prognostic of the late (months-years) waves of radiation injury believed to underlie neurocognitive deficits. Much of these gaps in knowledge persisted as NASA became interested in how exposure to much different radiation types, doses and dose rates that characterize the space radiation environment might impair central nervous system functionality, with possibly negative implications for deep space travel. Now emerging evidence from researchers engaged in clinical, translational and environmental radiation sciences have begun to fill these gaps and have uncovered some surprising similarities in the response of the brain to seemingly disparate exposure scenarios. This article highlights many of the commonalities between the vastly different irradiation paradigms that distinguish clinical treatments from occupational exposures in deep space.


2021 ◽  
Author(s):  
Kyra Schapiro ◽  
Kresimir Josic ◽  
Zachary Kilpatrick ◽  
Joshua I Gold

Deliberative decisions based on an accumulation of evidence over time depend on working memory, and working memory has limitations, but how these limitations affect deliberative decision-making is not understood. We used human psychophysics to assess the impact of working-memory limitations on the fidelity of a continuous decision variable. Participants decided the average location of multiple visual targets. This computed, continuous decision variable degraded with time and capacity in a manner that depended critically on the strategy used to form the decision variable. This dependence reflected whether the decision variable was computed either: 1) immediately upon observing the evidence, and thus stored as a single value in memory; or 2) at the time of the report, and thus stored as multiple values in memory. These results provide important constraints on how the brain computes and maintains temporally dynamic decision variables.


2020 ◽  
Author(s):  
Max Michael Owens ◽  
Nicholas Allgaier ◽  
Sage Hahn ◽  
Dekang Yuan ◽  
Matthew Albaugh ◽  
...  

Attention deficit/hyperactivity disorder is associated with numerous neurocognitive deficits including poor working memory and difficulty inhibiting undesirable behaviors that cause academic and behavioral problems in children. Prior work has attempted to determine how these differences are instantiated in the structure and function of the brain, but much of that work has been done in small samples, focused on older adolescents or adults, and used statistical approaches that were not robust to model overfitting. The current study used cross-validated elastic net regression to predict a continuous measure of ADHD symptomatology using brain morphometry and activation during tasks of working memory, inhibitory control, and reward processing, with separate models for each MRI measure. The best model using activation during the working memory task to predict ADHD symptomatology had an out-of-sample R2 = 2% and was robust to residualizing the effects of age, sex, race, parental income and education, handedness, pubertal status, and internalizing symptoms from ADHD symptomatology. This model used reduced activation in task positive regions and reduced deactivation in task negative regions to predict ADHD symptomatology. The best model with morphometry alone predicted ADHD symptomatology with an R2 = 1% but this effect dissipated when including covariates. The inhibitory control and reward tasks did not yield generalizable models. In summary, these analyses show, with a large and well-characterized sample, that the brain correlates of ADHD symptomatology are modest in effect size and captured best by brain morphometry and activation during a working memory task.


2017 ◽  
Vol 13 (01) ◽  
pp. 17 ◽  
Author(s):  
M Loredana Marcovecchio ◽  

Hyperglycemia is due to a dysregulation in the complex mechanisms implicated in glucose homeostasis. Chronic hyperglycemia, as measured by hemoglobin A1c (HbA1c), is a key risk factor for the development of microvascular and macrovascular complications, which in turn negatively influence the prognosis of patients with diabetes. Several studies have shown that acute hyperglycemia can add to the effect of chronic hyperglycemia in inducing tissue damage. Acute hyperglycemia can manifest as high fasting plasma glucose (FPG) or high postprandial plasma glucose (PPG) and can activate the same metabolic and hemodynamic pathways as chronic hyperglycemia. Glucose variability, as expressed by the intraday glucose fluctuations from peaks to nadirs, is another important parameter, which has emerged as an HbA1c-independent risk factor for the development of vascular complications, mainly in the context of type 2 diabetes. Treatments able to decrease HbA1c have been associated with positive effects in terms of reducing risk for the development and progression of complications. Further studies are required to clarify the impact of strategies more specifically targeting components of acute hyperglycemia, to improve outcomes in patients with diabetes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Max M. Owens ◽  
Nicholas Allgaier ◽  
Sage Hahn ◽  
DeKang Yuan ◽  
Matthew Albaugh ◽  
...  

AbstractAttention deficit/hyperactivity disorder is associated with numerous neurocognitive deficits, including poor working memory and difficulty inhibiting undesirable behaviors that cause academic and behavioral problems in children. Prior work has attempted to determine how these differences are instantiated in the structure and function of the brain, but much of that work has been done in small samples, focused on older adolescents or adults, and used statistical approaches that were not robust to model overfitting. The current study used cross-validated elastic net regression to predict a continuous measure of ADHD symptomatology using brain morphometry and activation during tasks of working memory, inhibitory control, and reward processing, with separate models for each MRI measure. The best model using activation during the working memory task to predict ADHD symptomatology had an out-of-sample R2 = 2% and was robust to residualizing the effects of age, sex, race, parental income and education, handedness, pubertal status, and internalizing symptoms from ADHD symptomatology. This model used reduced activation in task positive regions and reduced deactivation in task negative regions to predict ADHD symptomatology. The best model with morphometry alone predicted ADHD symptomatology with an R2 = 1% but this effect dissipated when including covariates. The inhibitory control and reward tasks did not yield generalizable models. In summary, these analyses show, with a large and well-characterized sample, that the brain correlates of ADHD symptomatology are modest in effect size and captured best by brain morphometry and activation during a working memory task.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Connor Cross ◽  
Roman H. Khonsari ◽  
Dawid Larysz ◽  
David Johnson ◽  
Lars Kölby ◽  
...  

AbstractSagittal synostosis is the most occurring form of craniosynostosis, resulting in calvarial deformation and possible long-term neurocognitive deficits. Several surgical techniques have been developed to correct these issues. Debates as to the most optimal approach are still ongoing. Finite element method is a computational tool that’s shown to assist with the management of craniosynostosis. The aim of this study was to compare and predict the outcomes of three reconstruction methods for sagittal craniosynostosis. Here, a generic finite element model was developed based on a patient at 4 months of age and was virtually reconstructed under all three different techniques. Calvarial growth was simulated to predict the skull morphology and the impact of different reconstruction techniques on the brain growth up to 60 months of age. Predicted morphology was then compared with in vivo and literature data. Our results show a promising resemblance to morphological outcomes at follow up. Morphological characteristics between considered techniques were also captured in our predictions. Pressure outcomes across the brain highlight the potential impact that different techniques have on growth. This study lays the foundation for further investigation into additional reconstructive techniques for sagittal synostosis with the long-term vision of optimizing the management of craniosynostosis.


2019 ◽  
Author(s):  
Johanna Norrlid ◽  
Jonas M.D. Enander ◽  
Hannes Mogensen ◽  
Henrik Jörntell

AbstractThe brain has a never-ending internal activity, whose spatiotemporal evolution interacts with external inputs to define how we perceive them. We used reproducible touch-related spatiotemporal inputs and recorded intracellularly from rat neocortical neurons to characterise this interaction. The synaptic responses, or the summed input of the networks connected to the neuron, varied greatly to repeated presentations of the same tactile input pattern delivered to the tip of digit 2. Surprisingly, however, these responses sorted into a set of specific response types, unique for each neuron. Further, using a set of eight such tactile input patterns, we found each neuron to exhibit a set of specific response types for each input provided. Response types were not determined by global cortical state, but instead likely depended on the time-varying state of the specific subnetworks connected to each neuron. The fact that some types of responses were recurrent, i.e. more likely than others, indicates that the cortical network had a non-continuous landscape of solutions for these tactile inputs. Therefore, our data suggests that sensory inputs combine with the internal dynamics of the brain networks, thereby causing them to fall into one of multiple possible perceptual attractor states. The neuron-specific instantiations of response types we observed suggest that the subnetworks connected to each neuron represent different components of those attractor states. Our results indicate that the impact of cortical internal states on external inputs is substantially more richly resolvable than previously shown.Key points summaryIt is known that the internal state of the neocortical network profoundly impacts cortical neuronal responses to sensory input.Little is known of how the internal neocortical activity combines with a given sensory input to generate the response.We used eight reproducible patterns of skin sensor activation and made intracellular recordings in neocortical neurons to explore the response variations in the specific subnetworks connected to each recorded neuron.We found that each neuron exhibited multiple, specific recurring response types to the exact same skin stimulation pattern and that each given stimulation pattern evoked a unique set of response types.The findings indicate a multi-structure internal state that combines with peripheral information to define cortical responses; we suggest this mechanism is a prerequisite for the formation of perception (and illusions) and indicates that the cortical networks work according to attractor dynamics.


2020 ◽  
Vol 63 (9) ◽  
pp. 3036-3050
Author(s):  
Elma Blom ◽  
Tessel Boerma

Purpose Many children with developmental language disorder (DLD) have weaknesses in executive functioning (EF), specifically in tasks testing interference control and working memory. It is unknown how EF develops in children with DLD, if EF abilities are related to DLD severity and persistence, and if EF weaknesses expand to selective attention. This study aimed to address these gaps. Method Data from 78 children with DLD and 39 typically developing (TD) children were collected at three times with 1-year intervals. At Time 1, the children were 5 or 6 years old. Flanker, Dot Matrix, and Sky Search tasks tested interference control, visuospatial working memory, and selective attention, respectively. DLD severity was based on children's language ability. DLD persistence was based on stability of the DLD diagnosis. Results Performance on all tasks improved in both groups. TD children outperformed children with DLD on interference control. No differences were found for visuospatial working memory and selective attention. An interference control gap between the DLD and TD groups emerged between Time 1 and Time 2. Severity and persistence of DLD were related to interference control and working memory; the impact on working memory was stronger. Selective attention was unrelated to DLD severity and persistence. Conclusions Age and DLD severity and persistence determine whether or not children with DLD show EF weaknesses. Interference control is most clearly impaired in children with DLD who are 6 years and older. Visuospatial working memory is impaired in children with severe and persistent DLD. Selective attention is spared.


2018 ◽  
Vol 29 (4) ◽  
pp. 249-258 ◽  
Author(s):  
Steffen Moritz ◽  
Insa Happach ◽  
Karla Spirandelli ◽  
Tania M. Lincoln ◽  
Fabrice Berna

Abstract. Neurocognitive deficits in patients with mental disorders are partially due to secondary influences. “Stereotype threat” denotes the phenomenon that performance is compromised when a participant is confronted with a devaluing stereotype. The present study examined the impact of stereotype threat on neuropsychological performance in schizophrenia. Seventy-seven participants with a self-reported diagnosis of schizophrenia were randomly assigned to either an experimental condition involving stereotype threat activation or a control condition in an online study. Participants completed memory and attention tests as well as questionnaires on motivation, self-efficacy expectations, cognitive complaints, and self-stigmatization. Contrary to our prediction, the two groups showed no significant differences regarding neuropsychological performance and self-report measures. Limitations, such as a possibly too weak threat cue, are discussed and recommendations for future studies are outlined.


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