Christopher J. Cannistraci

The relationship between delirium duration, white matter integrity, and cognitive impairment in intensive care unit survivors as determined by diffusion tensor imaging: the VISIONS prospective cohort magnetic resonance imaging study*.

Objective:Evidence is emerging that delirium duration is a predictor of long-term cognitive impairment in intensive care unit survivors. Relationships between 1) delirium duration and brain white matter integrity, and 2) white matter integrity and long-term cognitive impairment are poorly understood and could be explored using magnetic resonance imaging. Design, Setting, Patients:A two-center, prospective cohort study incorporating delirium monitoring, neuroimaging, and cognitive testing in intensive care unit survivors. Measurements:Delirium was evaluated with the Confusion Assessment Method for the Intensive Care Unit and cognitive outcomes were tested at 3 and 12-month follow-up. Following the intensive care unit stay, fractional anisotropy, a measure of white matter integrity, was calculated quantitatively using diffusion tensor imaging with a 3-T magnetic resonance imaging scanner at hospital discharge and 3-month follow-up. We examined associations between 1) delirium duration and fractional anisotropy and 2) fractional anisotropy and cognitive outcomes using linear regression adjusted for age and sepsis. Results:A total of 47 patients with a median age of 50 yrs completed the diffusion tensor imaging-magnetic resonance imaging protocol. Greater duration of delirium (3 vs. 0 days) was associated with lower fractional anisotropy (i.e., reduced fractional anisotropy = white matter disruption) in the genu (−0.02; p = .04) and splenium (−0.01; p = .02) of the corpus callosum and anterior limb of the internal capsule (−0.02; p =.01) at hospital discharge. These associations persisted at 3 months for the genu (−0.02; p =.02) and splenium (−0.01; p = .004). Lower fractional anisotropy in the anterior limb of internal capsule at discharge and in genu of corpus callosum at three months was associated with worse cognitive scores at 3 and 12 months. Conclusions:In this pilot investigation, delirium duration in the intensive care unit was associated with white matter disruption at both discharge and 3 months. Similarly, white matter disruption was associated with worse cognitive scores up to 12 months later. This hypothesis-generating investigation may help design future studies to explore these complex relationships in greater depth.

The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: the VISIONS cohort magnetic resonance imaging study*.

Objective:Delirium duration is predictive of long-term cognitive impairment in intensive care unit survivors. Hypothesizing that a neuroanatomical basis may exist for the relationship between delirium and long-term cognitive impairment, we conducted this exploratory investigation of the associations between delirium duration, brain volumes, and long-term cognitive impairment. Design, Setting, and Patients:A prospective cohort of medical and surgical intensive care unit survivors with respiratory failure or shock. Measurements:Quantitative high resolution 3-Tesla brain magnetic resonance imaging was used to calculate brain volumes at discharge and 3-month follow-up. Delirium was evaluated using the confusion assessment method for the intensive care unit; cognitive outcomes were tested at 3- and 12-month follow-up. Linear regression was used to examine associations between delirium duration and brain volumes, and between brain volumes and cognitive outcomes. Results:A total of 47 patients completed the magnetic resonance imaging protocol. Patients with longer duration of delirium displayed greater brain atrophy as measured by a larger ventricle-to-brain ratio at hospital discharge (0.76, 95% confidence intervals [0.10, 1.41]; p = .03) and at 3-month follow-up (0.62 [0.02, 1.21], p = .05). Longer duration of delirium was associated with smaller superior frontal lobe (−2.11 cm3 [−3.89, −0.32]; p = .03) and hippocampal volumes at discharge (−0.58 cm3 [−0.85, −0.31], p < .001)—regions responsible for executive functioning and memory, respectively. Greater brain atrophy (higher ventricle-to-brain ratio) at 3 months was associated with worse cognitive performances at 12 months (lower Repeatable Battery for the Assessment of Neuropsychological Status score −11.17 [−21.12, −1.22], p = .04). Smaller superior frontal lobes, thalamus, and cerebellar volumes at 3 months were associated with worse executive functioning and visual attention at 12 months. Conclusions:These preliminary data show that longer duration of delirium is associated with smaller brain volumes up to 3 months after discharge, and that smaller brain volumes are associated with long-term cognitive impairment up to 12 months. We cannot, however, rule out that smaller preexisting brain volumes explain these findings.

An FMRI study of number processing in children with fetal alcohol syndrome.

BACKGROUND Number processing deficits are frequently seen in children exposed to alcohol in utero. METHODS Functional magnetic resonance imaging was used to examine the neural correlates of number processing in 15 right-handed, 8- to 12-year-old children diagnosed with fetal alcohol syndrome (FAS) or partial FAS (PFAS) and 18 right-handed, age- and gender-matched controls from the Cape Coloured (mixed ancestry) community in Cape Town, South Africa, using Proximity Judgment and Exact Addition tasks. RESULTS Control children activated the expected fronto-parietal network during both tasks, including the anterior horizontal intraparietal sulcus (HIPS), left posterior HIPS, left precentral sulcus, and posterior medial frontal cortex. By contrast, on the Proximity Judgment task, the exposed children recruited additional parietal pathways involving the right and left angular gyrus and posterior cingulate/precuneus, which may entail verbally mediated recitation of numbers and/or subtraction to assess relative numerical distances. During Exact Addition, the exposed children exhibited more diffuse and widespread activations, including the cerebellar vermis and cortex, which have been found to be activated in adults engaged in particularly challenging number processing problems. CONCLUSIONS The data suggest that, whereas control children rely primarily on the fronto-parietal network identified in previous studies to mediate number processing, children with FAS/PFAS recruit a broader range of brain regions to perform these relatively simple number processing tasks. Our results are consistent with structural neuroimaging findings indicating that the parietal lobe is relatively more affected by prenatal alcohol exposure and provide the first evidence for brain activation abnormalities during number processing in children with FAS/PFAS, effects that persist even after controlling statistically for group differences in total intracranial volume and IQ.

Working memory in survivors of childhood acute lymphocytic Leukemia: Functional neuroimaging analyses†

Research on the physical and psychological late effects of treatment of childhood cancer has led to the identification of significant long‐term neurocognitive deficits experienced by some survivors, particularly in the areas of memory and executive functioning. Despite indications of deficits based on cognitive assessment, the identification of specific mechanisms of neurocognitive deficits using neuroimaging techniques has yet to be adequately considered.

Aberrant Functional Activation in School Age Children At-Risk for Mathematical Disability: A Functional Imaging Study of Simple Arithmetic Skill.

We used functional magnetic resonance imaging (fMRI) to explore the patterns of brain activation associated with different levels of performance in exact and approximate calculation tasks in well-defined cohorts of children with mathematical calculation difficulties (MD) and typically developing controls. Both groups of children activated the same network of brain regions; however, children in the MD group had significantly increased activation in parietal, frontal, and cingulate cortices during both calculation tasks. A majority of the differences occurred in anatomical brain regions associated with cognitive resources such as executive functioning and working memory that are known to support higher level arithmetic skill but are not specific to mathematical processing. We propose that these findings are evidence that children with MD use the same types of problem solving strategies as TD children, but their weak mathematical processing system causes them to employ a more developmentally immature and less efficient form of the strategies.

The neural correlates of calculation ability in children: an fMRI study

Most studies investigating mental numerical processing involve adult participants and little is known about the functioning of these systems in children. The current study used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of numeracy and the influence of age on these correlates with a group of adults and a group of third graders who had average to above average mathematical ability. Participants performed simple and complex versions of exact and approximate calculation tasks while in the magnet. Like adults, children activated a network of brain regions in the frontal and parietal lobes during the calculation tasks, and they recruited additional brain regions for the more complex versions of the tasks. However, direct comparisons between adults and children revealed significant differences in level of activation across all tasks. In particular, patterns of activation in the parietal lobe were significantly different as a function of age. Findings support previous claims that the parietal lobe becomes more specialized for arithmetic tasks with age.

Sensorimotor-independent prefrontal activity during response inhibition

A network of brain regions involving the ventral inferior frontal gyrus/anterior insula (vIFG/AI), presupplementary motor area (pre‐SMA) and basal ganglia has been implicated in stopping impulsive, unwanted responses. However, whether this network plays an equal role in response inhibition under different sensorimotor contexts has not been tested systematically. Here, we conducted an fMRI experiment using the stop signal task, a sensorimotor task requiring occasional withholding of the planned response upon the presentation of a stop signal. We manipulated both the sensory modality of the stop signal (visual versus auditory) and the motor response modality (hand versus eye). Results showed that the vIFG/AI and the preSMA along with the right middle frontal gyrus were commonly activated in response inhibition across the various sensorimotor conditions. Our findings provide direct evidence for a common role of these frontal areas, but not striatal areas in response inhibition independent of the sensorimotor contexts. Nevertheless, these three frontal regions exhibited different activation patterns during successful and unsuccessful stopping. Together with the existing evidence, we suggest that the vIFG/AI is involved in the early stages of stopping such as triggering the stop process while the preSMA may play a role in regulating other cortical and subcortical regions involved in stopping. Hum Brain Mapp 35:2119–2136, 2014.

Auditory Attraction: Activation of Visual Cortex by Music and Sound in Williams Syndrome

Williams syndrome is a genetic neurodevelopmental disorder with a distinctive phenotype, including cognitive-linguistic features, nonsocial anxiety, and a strong attraction to music. we preformed functional MRI studies examining brain responses to musical and other types of stimuli in young adults with Williams syndrome and typically developing controls. In Study 1, the Williams syndrome group exhibited unforeseen activations of the visual cortex to musical stimuli, and it was this novel finding that became the focus of two subsequent studies. Using retinotopy, color localizers, and additional sound conditions, we identified specific visual areas in subjects with Williams syndrome that were activated by both musical and nonmusical auditory stimuli. The results, similar to synthetic-like experiences, have implications for cross-modal sensory processing in typical and atypical neurodevelopment.

An fMRI study of magnitude comparison and exact addition in children

By contrast to the adult literature, in which a consistent parietofrontal network for number processing has been identified, the data from studies of number processing in children have been less consistent, probably due to differences in study design and control conditions. Number processing was examined using functional magnetic resonance imaging in 18 right-handed children (8-12 years) from the Cape Coloured community in Cape Town, South Africa, using Proximity Judgment and Exact Addition (EA) tasks. The findings were consistent with the hypothesis that, as in adults, the anterior horizontal intraparietal sulcus (HIPS) plays a major role in the representation and manipulation of quantity in children. The posterior medial frontal cortex, believed to be involved in performance monitoring in more complex arithmetic manipulations in adults, was extensively activated even for relatively simple symbolic number processing in the children. Other areas activated to a greater degree in the children included the left precentral sulcus, which may mediate number knowledge and, for EA, the head of the caudate nucleus, which is part of a fronto-subcortical circuit involved in the behavioral execution of sequences. Two regions that have been linked to number processing in adults - the angular gyrus and posterior superior parietal lobule - were not activated in the children. The data are consistent with the inference that although the functional specialization of the anterior HIPS may increase as symbolic number processing becomes increasingly automatic, this region and other elements of the parietofrontal network identified in adults are already reliably and robustly activated by middle childhood.

Neuroimaging of Executive Function in Survivors of Pediatric Brain Tumors and Healthy Controls

OBJECTIVE Research on the long-term sequelae of treatment for pediatric brain tumors has identified significant neurocognitive deficits experienced by many survivors. Despite indications of deficits based on cognitive assessment, the identification of specific neurobiological mechanisms of these deficits using neuroimaging techniques has yet to be considered. METHOD This study used norm-referenced standardized assessment and functional MRI (fMRI) to examine attention and executive functioning deficits of survivors of pediatric brain tumors, as compared with healthy children. RESULTS Survivors of pediatric brain tumors performed more poorly than healthy children on measures of overall cognitive ability, attention, and executive function during testing, as well as on a working memory task during fMRI. Survivors showed lower blood-oxygen level dependent (BOLD) signal in bilateral frontal regions associated with sustained attention (BA6/8) and greater BOLD signal in left cingulate regions associated with complex problem-solving and performance monitoring (BA32) during working memory task completion. Both group and brain activation accounted for significant variance in neurocognitive functioning. CONCLUSIONS Survivors of pediatric brain tumor and healthy children differed in brain activation during completion of a working memory task, and brain activation was associated with deficits noted in testing. These findings may improve understanding of mechanisms of cognitive deficits and avenues for intervention for children with brain tumors.