Publications by authors named "Helmet T Karim"

32 Publications

Midazolam and Ketamine Produce Distinct Neural Changes in Memory, Pain, and Fear Networks during Pain.

Anesthesiology 2021 Apr 19. Epub 2021 Apr 19.

Background: Despite the well-known clinical effects of midazolam and ketamine, including sedation and memory impairment, the neural mechanisms of these distinct drugs in humans are incompletely understood. The authors hypothesized that both drugs would decrease recollection memory, task-related brain activity, and long-range connectivity between components of the brain systems for memory encoding, pain processing, and fear learning.

Methods: In this randomized within-subject crossover study of 26 healthy adults, the authors used behavioral measures and functional magnetic resonance imaging to study these two anesthetics, at sedative doses, in an experimental memory paradigm using periodic pain. The primary outcome, recollection memory performance, was quantified with d' (a difference of z scores between successful recognition versus false identifications). Secondary outcomes were familiarity memory performance, serial task response times, task-related brain responses, and underlying brain connectivity from 17 preselected anatomical seed regions. All measures were determined under saline and steady-state concentrations of the drugs.

Results: Recollection memory was reduced under midazolam (median [95% CI], d' = 0.73 [0.43 to 1.02]) compared with saline (d' = 1.78 [1.61 to 1.96]) and ketamine (d' = 1.55 [1.12 to 1.97]; P < 0.0001). Task-related brain activity was detected under saline in areas involved in memory, pain, and fear, particularly the hippocampus, insula, and amygdala. Compared with saline, midazolam increased functional connectivity to 20 brain areas and decreased to 8, from seed regions in the precuneus, posterior cingulate, and left insula. Compared with saline, ketamine decreased connectivity to 17 brain areas and increased to 2, from 8 seed regions including the hippocampus, parahippocampus, amygdala, and anterior and primary somatosensory cortex.

Conclusions: Painful stimulation during light sedation with midazolam, but not ketamine, can be accompanied by increased coherence in brain connectivity, even though details are less likely to be recollected as explicit memories.

Editor’s Perspective:
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ALN.0000000000003774DOI Listing
April 2021

Midazolam and Ketamine Produce Distinct Neural Changes in Memory, Pain, and Fear Networks during Pain.

Anesthesiology 2021 Apr 19. Epub 2021 Apr 19.

Background: Despite the well-known clinical effects of midazolam and ketamine, including sedation and memory impairment, the neural mechanisms of these distinct drugs in humans are incompletely understood. The authors hypothesized that both drugs would decrease recollection memory, task-related brain activity, and long-range connectivity between components of the brain systems for memory encoding, pain processing, and fear learning.

Methods: In this randomized within-subject crossover study of 26 healthy adults, the authors used behavioral measures and functional magnetic resonance imaging to study these two anesthetics, at sedative doses, in an experimental memory paradigm using periodic pain. The primary outcome, recollection memory performance, was quantified with d' (a difference of z scores between successful recognition versus false identifications). Secondary outcomes were familiarity memory performance, serial task response times, task-related brain responses, and underlying brain connectivity from 17 preselected anatomical seed regions. All measures were determined under saline and steady-state concentrations of the drugs.

Results: Recollection memory was reduced under midazolam (median [95% CI], d' = 0.73 [0.43 to 1.02]) compared with saline (d' = 1.78 [1.61 to 1.96]) and ketamine (d' = 1.55 [1.12 to 1.97]; P < 0.0001). Task-related brain activity was detected under saline in areas involved in memory, pain, and fear, particularly the hippocampus, insula, and amygdala. Compared with saline, midazolam increased functional connectivity to 20 brain areas and decreased to 8, from seed regions in the precuneus, posterior cingulate, and left insula. Compared with saline, ketamine decreased connectivity to 17 brain areas and increased to 2, from 8 seed regions including the hippocampus, parahippocampus, amygdala, and anterior and primary somatosensory cortex.

Conclusions: Painful stimulation during light sedation with midazolam, but not ketamine, can be accompanied by increased coherence in brain connectivity, even though details are less likely to be recollected as explicit memories.

Editor’s Perspective:
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ALN.0000000000003774DOI Listing
April 2021

An Effect of Education on Memory-Encoding Activation in Subjective Cognitive Decline.

J Alzheimers Dis 2021 Apr 3. Epub 2021 Apr 3.

Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.

Background: Subjective cognitive decline (SCD) may be an early manifestation of pre-clinical Alzheimer's disease. Elevated amyloid-β (Aβ) is a correlate of SCD symptoms in some individuals. The underlying neural correlates of SCD symptoms and their association with Aβ is unknown. SCD is a heterogeneous condition, and cognitive reserve may explain individual differences in its neural correlates.

Objective: We investigated the association between brain activation during memory encoding and SCD symptoms, as well as with Aβ, among older individuals. We also tested the moderating role of education (an index of cognitive reserve) on the associations.

Methods: We measured brain activation during the "face-name" memory-encoding fMRI task and Aβ deposition with Pittsburgh Compound-B (PiB)-PET among cognitively normal older individuals (n = 63, mean age 73.1 ± 7.4 years). We tested associations between activation and SCD symptoms by self-report measures, Aβ, and interactions with education.

Results: Activation was not directly associated with SCD symptoms or Aβ. However, education moderated the association between activation and SCD symptoms in the executive control network, salience network, and subcortical regions. Greater SCD symptoms were associated with greater activation in those with higher education, but with lower activation in those with lower education.

Conclusion: SCD symptoms were associated with different patterns of brain activation in the extended memory system depending on level of cognitive reserve. Greater SCD symptoms may represent a saturation of neural compensation in individuals with greater cognitive reserve, while it may reflect diminishing neural resources in individuals with lower cognitive reserve.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-201087DOI Listing
April 2021

Understanding the Neurocomputational Mechanisms of Antidepressant Placebo Effects.

J Psychiatr Brain Sci 2021 15;6. Epub 2021 Feb 15.

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Over the last two decades, neuroscientists have used antidepressant placebo probes to examine the biological mechanisms implicated in antidepressant placebo effects. However, findings from these studies have not yet elucidated a model-based theory that would explain the mechanism through which antidepressant expectancies evolve to induce persistent mood changes. Emerging evidence suggests that antidepressant placebo effects may be informed by models of reinforcement learning (RL). Such that an individual's expectation of improvement is updated with the arrival of new sensory evidence, by incorporating a reward prediction error (RPE), which signals the mismatch between the expected (expected value) and perceived improvement. Consistent with this framework, neuroimaging studies of antidepressant placebo effects have demonstrated placebo-induced μ-opioid activation and increased blood-oxygen-level dependent (BOLD) responses in regions tracking expected values (e.g., ventromedial prefrontal cortex (vmPFC)) and RPEs (e.g., ventral striatum (VS)). In this study, we will demonstrate the causal contribution of reward learning signals (expected values and RPEs) to antidepressant placebo effects by experimentally manipulating expected values using transcranial magnetic stimulation (TMS) targeting the vmPFC and μ-opioid striatal RPE signal using pharmacological approaches. We hypothesized that antidepressant placebo expectancies are represented in the vmPFC (expected value) and updated by means of μ-opioid-modulated striatal learning signal. In a 3 × 3 factorial double-blind design, we will randomize 120 antidepressant-free individuals with depressive symptoms to one of three between-subject opioid conditions: the μ-opioid agonist buprenorphine, the μ-opioid antagonist naltrexone, or an inert pill. Within each arm, individuals will be assigned to receive three within-subject counterbalanced forms of TMS targeting the vmPFC-intermittent Theta Burst Stimulation (TBS) expected to potentiate the vmPFC, continuous TBS expected to de-potentiate the vmPFC, or sham TBS. These experimental manipulations will be used to modulate trial-by-trial reward learning signals and related brain activity during the Antidepressant Placebo functional MRI (fMRI) Task to address the following aims: (1) investigate the relationship between reward learning signals within the vmPFC-VS circuit and antidepressant placebo effects; (2) examine the causal contribution of vmPFC expected value computations to antidepressant placebo effects; and (3) investigate the causal contribution of μ-opioid-modulated striatal RPEs to antidepressant placebo effects. The proposed study will be the first to investigate the causal contribution of μ-opioid-modulated vmPFC-VS learning signals to antidepressant placebo responses, paving the way for developing novel treatments modulating learning processes and objective means of quantifying and potentially reducing placebo effects during drug development.

Trial Registration: ClinicalTrials.gov Identifier: NCT04276259.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20900/jpbs.20210001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963355PMC
February 2021

Effect of Experimental Manipulation of the Orbitofrontal Cortex on Short-Term Markers of Compulsive Behavior: A Theta Burst Stimulation Study.

Am J Psychiatry 2021 Mar 17:appiajp202020060821. Epub 2021 Mar 17.

Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).

Objective: Compulsive behaviors are a core feature of obsessive-compulsive spectrum disorders but appear across a broad spectrum of psychological conditions. It is thought that compulsions reflect a failure to override habitual behaviors "stamped in" through repeated practice and short-term distress reduction. Animal models suggest a possible causal role of the orbitofrontal cortex (OFC) in compulsive behaviors, but human studies have largely been limited by correlational designs. The goal of this study was to establish the first experimental evidence in humans for a mechanistic model in order to inform further experimental work and the eventual development of novel mechanistic treatments involving synergistic biological-behavioral pairings.

Methods: After a baseline assessment, 69 individuals with compulsive behavior disorders were randomly assigned, in a double-blind, between-subjects design, to receive a single session of one of two active stimulation conditions targeting the left OFC: intermittent theta burst stimulation (iTBS), expected to increase OFC activity, or continuous TBS (cTBS), expected to decrease activity (both conditions, 600 pulses at 110% of target resting motor threshold). In both conditions, brain modulation was paired with a subsequent computer task providing practice in overriding a clinically relevant habit (an overlearned shock avoidance behavior), delivered during the expected window of OFC increase or decrease. Pre- and post-TBS functional MRI assessments were conducted of target engagement and compulsive behaviors performed in response to an idiographically designed stressful laboratory probe.

Results: cTBS and iTBS modulated OFC activation in the expected directions. cTBS, relative to iTBS, exhibited a beneficial impact on acute laboratory assessments of compulsive behaviors 90 minutes after TBS. These acute behavioral effects persisted 1 week after cTBS.

Conclusions: Experimental modulation of the OFC, within the behavioral context of habit override training, affected short-term markers of compulsive behavior vulnerability. The findings help delineate a causal translational model, serving as an initial precursor to mechanistic intervention development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1176/appi.ajp.2020.20060821DOI Listing
March 2021

Aging faster: worry and rumination in late life are associated with greater brain age.

Neurobiol Aging 2021 Jan 20;101:13-21. Epub 2021 Jan 20.

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

Older adults with anxiety have lower gray matter brain volume-a component of accelerated aging. We have previously validated a machine learning model to predict brain age, an estimate of an individual's age based on voxel-wise gray matter images. We investigated associations between brain age and anxiety, depression, stress, and emotion regulation. We recruited 78 participants (≥50 years) along a wide range of worry severity. We collected imaging data and computed voxel-wise gray matter images, which were input into an existing machine learning model to estimate brain age. We conducted a multivariable linear regression between brain age and age, sex, race, education, worry, anxiety, depression, rumination, neuroticism, stress, reappraisal, and suppression. We found that greater brain age was significantly associated with greater age, male sex, greater worry, greater rumination, and lower suppression. Male sex, worry, and rumination are associated with accelerated aging in late life and expressive suppression may have a protective effect. These results provide evidence for the transdiagnostic model of negative repetitive thoughts, which are associated with cognitive decline, amyloid, and tau.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2021.01.009DOI Listing
January 2021

Accelerated brain aging in chronic low back pain.

Brain Res 2021 Mar 7;1755:147263. Epub 2021 Jan 7.

Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

Chronic low back pain (CLBP) is a leading cause of disability and is associated with neurodegenerative changes in brain structure. These changes lead to impairments in cognitive function and are consistent with those seen in aging, suggesting an accelerated aging pattern. In this study we assessed this using machine-learning estimated brain age (BA) as a holistic metric of morphometric changes associated with aging. Structural imaging data from 31 non-depressed CLBP patients and 32 healthy controls from the Pain and Interoception Imaging Network were included. Using our previously developed algorithm, we estimated BA per individual based on grey matter density. We then conducted multivariable linear modeling for effects of group, chronological age, and their interaction on BA. We also performed two voxel-wise analyses comparing grey matter density between CLBP and control individuals and the association between gray matter density and BA. There was an interaction between CLBP and greater chronological age on BA such that the discrepancy in BA between healthy and CLBP individuals was greater for older individuals. In CLBP individuals, BA was not associated with sex, current level of pain, duration of CLBP, or mild to moderate depressive symptoms. CLBP individuals had lower cerebellar grey matter density compared to healthy individuals. Brain age was associated with lower gray matter density in numerous brain regions. CLBP was associated with greater BA, which was more profound in later life. BA as a holistic metric was sensitive to differences in gray matter density in numerous regions which eluded direct comparison between groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2020.147263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939694PMC
March 2021

Testing a new, intensified infusion-withdrawal protocol for urinary urgency provocation in brain-bladder studies.

Neurourol Urodyn 2021 01 29;40(1):131-136. Epub 2020 Oct 29.

Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Introduction: The brain's role in bladder control has become an important area of study in the last 15 years. Typically, the brain's role in urinary urgency has been studied by repeated infusion and withdrawal of fluid, per catheter, to provoke urgency sensation during a whole brain magnetic resonance imaging (MRI) scan. Since this technique generally requires a large group size, we tested a more intense infusion-withdrawal protocol in an attempt to improve signal to noise ratio and repeatability of the signal which would, in turn, allow us to further probe subtypes of urgency urinary incontinence.

Methods: A total of 12 women over the age of 60 were recruited to test a new "intense" infusion withdrawal protocol. They underwent this new protocol during a functional brain MRI scan. The primary outcome was comparison of activity within the insula, medial pre-frontal cortex and dorsal anterior cingulate cortex/supplementary motor area (dACC/SMA). Immediate test-retest repeatability was measured using intraclass correlation. Secondary exploratory evaluation of differences in the whole brain between protocols was conducted.

Results: There was no significant difference in signal in any of the a priori regions of interest between protocols. Test-retest repeatability in the new protocol was poor compared to the original protocol, and variability was higher. Three participants were not able to tolerate the "intense" protocol.

Conclusion: The small improvement in signal to noise ratio of the new protocol was not sufficient to overcome the poorly tolerated intense filling protocol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nau.24559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902294PMC
January 2021

Resting-state function connectivity associated with being a "morning-type" dementia caregiver and having lower depression symptom severity.

J Gerontol B Psychol Sci Soc Sci 2020 Aug 5. Epub 2020 Aug 5.

Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Objectives: A lack of "morningness" predicts greater depression symptom severity over time, including in a vulnerable group of older adults: family dementia caregivers (dCGs). Evidence regarding the neurobiological basis of these correlations is needed to guide future research towards biomarker-informed detection and prevention approaches. We therefore primarily aimed to identify simple resting-state biomarkers that correlated with a lack of "morningness" in dCGs.

Methods: We examined 54 dCGs (mean age=70, range: 61-84; 70% female) of whom 40% were definite "morning types" according to Composite Scale of Morningness (CSM). Using a 7 Tesla resting-state sequence, we compared the functional connectivity of nodes in networks previously implicated in depression (fronto-parietal, default mode, limbic, and salience) between caregivers who were and were not "morning types."

Results: Correcting for voxel-wise comparisons, "morning type" dCGs had less amygdala-posterior cingulate connectivity (Cohen's d=-1.3), which statistically mediated ~32% of the association between the degree of "morningness" and lower depression severity. Post-hoc analyses of CSM items found significant correlations, with both amygdala-posterior cingulate FC and depression severity, for: 4/6 items pertaining to difficulty, 2/5 items pertaining to preference, and 0/2 items pertaining to typical patterns.

Discussion: Prior research shows that amygdala-posterior cingulate connectivity increases when allocating attention to peripheral aspects of negative emotional stimuli. As such, difficulty with morning activation may relate to the ongoing direction of focus around distressing content; in contrast, morning activity participation may serve to limit focus on distress. Replication and experimental studies are required to confirm these associations and their modifiability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/geronb/gbaa115DOI Listing
August 2020

Regional Gray Matter Density Associated With Fast-Paced Walking in Older Adults: A Voxel-Based Morphometry Study.

J Gerontol A Biol Sci Med Sci 2020 07;75(8):1530-1536

Department of Epidemiology, University of Pittsburgh, Pennsylvania.

Background: Walking speed during fast-paced walking task has been associated with cognitive function. It is unclear what underlying brain structures are related to fast-paced walking. We investigated the association of gray matter (GM) density with fast-paced walking speed and usual-paced walking speed.

Methods: We collected data from 284 older adults from a subset of the Health, Aging, and Body composition study (mean age = 83 [SD = 2.8], 58% women, 41% black). Voxel-wise analyses on magnetic resonance imaging data identified regions of the brain where GM density was associated with fast-paced walking speed. We then extracted GM density for all identified regions and modeled the association with fast-paced walking speed after adjusting for demographic factors, clinical factors, and cognitive function. Analyses were repeated for usual-paced walking. Regions with beta coefficients ≥0.3 m/s were considered to be meaningfully correlated.

Results: GM density of clusters from cortical regions in the right middle and superior frontal gyrus, right postcentral gyrus, and left superior temporal gyrus were positively correlated with fast-paced walking speed in adjusted models. Adjustment for cognitive function had little impact on the findings. Caudate was correlated with usual paced walking speed at coefficient ≥0.3 m/s after adjustment of demographic factors and clinical factors, but not after further adjustment of cognitive function.

Conclusions: Fast-paced walking speed was correlated with GM density of right middle and superior frontal gyrus, right postcentral gyrus, and left superior temporal gyrus, and could potentially provide evidence about subclinical structural change of brain related to aging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gerona/glaa091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357587PMC
July 2020

The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults.

Alzheimers Res Ther 2020 01 6;12(1). Epub 2020 Jan 6.

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Background: Pathological processes contributing to Alzheimer's disease begin decades prior to the onset of clinical symptoms. There is significant variation in cognitive changes in the presence of pathology, functional connectivity may be a marker of compensation to amyloid; however, this is not well understood.

Methods: We recruited 64 cognitively normal older adults who underwent neuropsychological testing and biannual magnetic resonance imaging (MRI), amyloid imaging with Pittsburgh compound B (PiB)-PET, and glucose metabolism (FDG)-PET imaging for up to 6 years. Resting-state MRI was used to estimate connectivity of seven canonical neural networks using template-based rotation. Using voxel-wise paired t-tests, we identified neural networks that displayed significant changes in connectivity across time. We investigated associations among amyloid and longitudinal changes in connectivity and cognitive function by domains.

Results: Left middle frontal gyrus connectivity within the memory encoding network increased over time, but the rate of change was lower with greater amyloid. This was no longer significant in an analysis where we limited the sample to only those with two time points. We found limited decline in cognitive domains overall. Greater functional connectivity was associated with better attention/processing speed and executive function (independent of time) in those with lower amyloid but was associated with worse function with greater amyloid.

Conclusions: Increased functional connectivity serves to preserve cognitive function in normal aging and may fail in the presence of pathology consistent with compensatory models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-019-0573-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945413PMC
January 2020

Improving brain age prediction models: incorporation of amyloid status in Alzheimer's disease.

Neurobiol Aging 2020 03 14;87:44-48. Epub 2019 Nov 14.

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

Brain age prediction is a machine learning method that estimates an individual's chronological age from their neuroimaging scans. Brain age indicates whether an individual's brain appears "older" than age-matched healthy peers, suggesting that they may have experienced a higher cumulative exposure to brain insults or were more impacted by those pathological insults. However, contemporary brain age models include older participants with amyloid pathology in their training sets and thus may be confounded when studying Alzheimer's disease (AD). We showed that amyloid status is a critical feature for brain age prediction models. We trained a model on T1-weighted MRI images participants without amyloid pathology. MRI data were processed to estimate gray matter density voxel-wise, which were then used to predict chronological age. Our model performed accurately comparable to previous models. Notably, we demonstrated more significant differences between AD diagnostic groups than other models. In addition, our model was able to delineate significant differences in brain age relative to chronological age between cognitively normal individuals with and without amyloid. Incorporation of amyloid status in brain age prediction models ultimately improves the utility of brain age as a biomarker for AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2019.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064421PMC
March 2020

Association between increased theta cordance and early response to ECT in late-life depression.

Int J Geriatr Psychiatry 2020 02 1;35(2):147-152. Epub 2019 Dec 1.

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA.

Objectives: More than half of patients with major depression who do not respond to initial antidepressants become treatment resistant (TRD), and while electroconvulsive therapy (ECT) is effective, it involves anesthesia and other medical risks that are of concern in geriatric patients. Past studies have suggested that theta cordance (TC), a correlate of cerebral metabolism measured by electroencephalography, could guide treatment decisions related to patient selection and engagement of the therapeutic target.

Methods/design: Eight patients with late-life treatment resistant depression (LL-TRD) underwent magnetoencephalography (MEG) at baseline and following seven sessions of ECT. We tested whether the mean and regional frontal cortex TC were able to differentiate early responders from nonresponders.

Results: Five patients whose depression severity decreased by >30% after seven sessions were considered early responders. We found no baseline differences in mean frontal TC between early responders compared with nonresponders, but early responders exhibited a significant increase in TC following ECT. Further, we found that compared with nonresponders, early responders exhibited a greater change in TC specifically within the right prefrontal cortex.

Conclusions: These results support the hypothesis that increases in frontal TC are associated with antidepressant response. We expand on previous findings by showing that this change is specific to the right prefrontal cortex. Validation of this neural marker could contribute to improved ECT outcomes, by informing early clinical decisions about the acute efficacy of this treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gps.5220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047608PMC
February 2020

Disruption of Neural Homeostasis as a Model of Relapse and Recurrence in Late-Life Depression.

Am J Geriatr Psychiatry 2019 12 7;27(12):1316-1330. Epub 2019 Aug 7.

Department of Psychiatry and Behavioral Sciences (KA, WDT), The Center for Cognitive Medicine, Vanderbilt University Medical Center, Nashville, TN; Department of Veterans Affairs Medical Center (WDT), Geriatric Research, Education and Clinical Center, Tennessee Valley Healthcare System, Nashville, TN. Electronic address:

The significant public health burden associated with late-life depression (LLD) is magnified by the high rates of recurrence. In this manuscript, we review what is known about recurrence risk factors, conceptualize recurrence within a model of homeostatic disequilibrium, and discuss the potential significance and challenges of new research into LLD recurrence. The proposed model is anchored in the allostatic load theory of stress. We review the allostatic response characterized by neural changes in network function and connectivity and physiologic changes in the hypothalamic-pituitary-adrenal axis, autonomic nervous system, immune system, and circadian rhythm. We discuss the role of neural networks' instability following treatment response as a source of downstream disequilibrium, triggering and/or amplifying abnormal stress response, cognitive dysfunction and behavioral changes, ultimately precipitating a full-blown recurrent episode of depression. We propose strategies to identify and capture early change points that signal recurrence risk through mobile technology to collect ecologically measured symptoms, accompanied by automated algorithms that monitor for state shifts (persistent worsening) and variance shifts (increased variability) relative to a patient's baseline. Identifying such change points in relevant sensor data could potentially provide an automated tool that could alert clinicians to at-risk individuals or relevant symptom changes even in a large practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jagp.2019.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842700PMC
December 2019

Relationships Between Executive Control Circuit Activity, Amyloid Burden, and Education in Cognitively Healthy Older Adults.

Am J Geriatr Psychiatry 2019 12 19;27(12):1360-1371. Epub 2019 Jul 19.

Department of Psychiatry (HTK, DLT, AC, HJA), University of Pittsburgh, Pittsburgh, PA; Department of Bioengineering (HJA), University of Pittsburgh, Pittsburgh, PA. Electronic address:

Introduction: In cognitively healthy older adults, amyloid-beta (Aβ) burden is associated with greater activity on task-based functional magnetic resonance imaging. Higher levels of functional activation are associated with other factors along with amyloid and the authors investigated these relationships as well as how they relate to Aβ in cognitively healthy older adults.

Methods: The authors recruited cognitive healthy older adults (N = 50) from the Pittsburgh community that underwent extensive cognitive batteries, activation during a working memory (digit symbol substitution task, DSST), positron emission tomography scan for Pittsburgh Compound B (PiB, measuring amyloid), and other demographic measures. The authors tested the association between DSST activation and global PiB, neurocognitive batteries, and education.

Results: The authors found that the DSST robustly activated expected structures involved in working memory. The authors found that greater global Aβ deposition was associated with greater DSST activation in the right calcarine, precuneus, middle temporal as well as the left insula and inferior frontal gyrus. The authors also found that greater education was associated with lower DSST activation - however this was not significant after adjusting for Aβ.

Discussion: Greater amyloid was associated with greater activation, which may represent compensatory activation. Greater education was associated with lower activation, which may represent more efficient activation (i.e., less activation for the same task). After adjusting for amyloid, education was not significantly associated with activation suggesting that during the preclinical stage amyloid is the primary determinant of activation. Further, activation was not associated with cognitive function. Compensatory activation in the preclinical stage may help maintain cognitive function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jagp.2019.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047647PMC
December 2019

Impact of acute sleep restriction on cerebral glucose metabolism during recovery non-rapid eye movement sleep among individuals with primary insomnia and good sleeper controls.

Sleep Med 2019 03 4;55:81-91. Epub 2019 Jan 4.

Department of Psychiatry, Center for Sleep and Circadian Science, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Background: Restricting time in bed improves insomnia symptoms, but the neural mechanisms for this effect are unknown. Total and partial acute sleep restriction may be useful paradigms for elucidating these effects. We examined the impact of acute sleep restriction on cerebral glucose metabolism during non-rapid eye movement (NREM) sleep in individuals with primary insomnia (n = 17) and good sleep (n = 19).

Methods: Participants underwent [F]fluorodeoxyglucose positron emission tomography scans during baseline and recovery NREM sleep following one night of partial or total sleep restriction. We compared group differences in baseline-recovery changes, as well as main effects of group and condition (baseline vs. recovery NREM sleep), for relative regional cerebral metabolic rate for glucose (rCMR), whole-brain glucose metabolism, and sleep quality.

Results: Relative rCMR was significantly lower during recovery NREM sleep compared to baseline in the left frontoparietal cortex, medial frontal cortex, posterior cingulate cortex, and thalamus, with no significant group differences. Good sleepers, but not insomnia patients, had lower whole-brain glucose metabolism during recovery NREM sleep compared to baseline. Acute sleep restriction improved sleep quality in individual with insomnia. Subgroup analyses including only participants who underwent partial sleep restriction yielded the same pattern of findings.

Conclusion: Individuals with insomnia and good sleepers showed similar relative rCMR responses to acute sleep restriction. Brain regions showing the greatest baseline-recovery changes in both groups included regions previously shown to have smaller sleep-wake differences in patients with primary insomnia. Acute sleep restriction, and by extension sleep restriction therapy, may impact regional metabolic alterations that characterize insomnia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sleep.2018.12.007DOI Listing
March 2019

Amyloid deposition is associated with different patterns of hippocampal connectivity in men versus women.

Neurobiol Aging 2019 04 1;76:141-150. Epub 2018 Dec 1.

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

Compared to men, women are disproportionally affected by Alzheimer's disease (AD) and have an accelerated trajectory of cognitive decline and disease progression. Neurobiological factors underlying gender differences in AD remain unclear. This study investigated brain beta-amyloid (Aβ)-related neural system differences in cognitively normal older men and women (N = 61; 41 females, 65-93 years old). We found that men and women showed different associations between Aβ load and hippocampal functional connectivity. During associative memory encoding, in men greater Aβ burden was accompanied by greater hippocampus-prefrontal connectivity (i.e., more synchronized activities), whereas in women hippocampal connectivity did not vary by Aβ burden. For resting-state data, the interaction of gender × Aβ on hippocampal connectivity did not survive multiple comparison in the whole-brain analyses. In the region of interest-based analyses, resting-state hippocampal-prefrontal connectivity was positively correlated with Aβ load in men and was negatively correlated with Aβ load in women. The observed Aβ-related neural differences may explain the accelerated trajectory of cognitive decline and AD progression in women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2018.11.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584958PMC
April 2019

Low-dose augmentation with buprenorphine increases emotional reactivity but not reward activity in treatment resistant mid- and late-life depression.

Neuroimage Clin 2019 22;21:101679. Epub 2019 Jan 22.

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

Buprenorphine is currently being studied for treatment-resistant depression because of its rapid effect, relative safety, and unique pharmacodynamics. To understand the neural impact of buprenorphine in depression, we examined acute limbic and reward circuit changes during an intervention with low-dose buprenorphine augmentation pharmacotherapy. Mid and late-life adults with major depression (N = 31) who did not completely respond to an adequate trial of venlafaxine were randomized to augmentation with low-dose buprenorphine or matching placebo. We investigated early neural changes using functional magnetic resonance imaging (fMRI) from pre-randomization to 3 weeks using both an emotional reactivity task and a gambling task. We tested if: 1) there were significant neural changes acutely per intervention group, and 2) if acute neural changes were associated with depressive symptom change over 8 weeks using both the total score and the dysphoria subscale of the Montgomery Asberg Depression Rating Scale. Participants in both the buprenorphine and placebo groups showed similar changes in depressive symptoms. Neither the emotional reactivity nor gambling task resulted in significant neural activation changes from pre-randomization to 3-weeks. In both groups, increases in rostral anterior cingulate (rACC) and ventromedial prefrontal cortex (vmPFC) activation during the emotional reactivity task were associated with overall symptom improvement. In the buprenorphine but not the placebo group, increased activation in left anterior insula (aINS) and bilateral middle frontal gyrus (MFG) was associated with improvement on the dysphoria subscale. Activation changes in the reward task were not associated with buprenorphine. This is the first study to show an association between acute neural changes during emotion reactivity and changes in depression severity with buprenorphine treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2019.101679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356006PMC
January 2020

Neural architecture supporting active emotion processing in children: A multivariate approach.

Neuroimage 2019 03 8;188:171-180. Epub 2018 Dec 8.

Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA; Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Background: Adaptive emotion processing is critical for nearly all aspects of social and emotional functioning. There are distinct developmental trajectories associated with improved emotion processing, with a protracted developmental course for negative or complex emotions. The specific changes in neural circuitry that underlie this development, however are still scarcely understood. We employed a multivariate approach in order to elucidate distinctions in complex, naturalistic emotion processing between childhood and adulthood.

Method: Twenty-one adults (M±SD age = 26.57 ± 5.08 years) and thirty children (age = 7.75 ± 1.80 years) completed a free-viewing movie task during BOLD fMRI scanning. This task was designed to assess naturalistic processing of movie clips portraying positive, negative, and neutral emotions. Multivariate support vector machines (SVM) were trained to classify age groups based on neural activation during the task.

Results: SVMs were able to successfully classify condition (positive, negative, and neutral) across all participants with high accuracy (61.44%). SVMs could successfully distinguish adults and children within each condition (ps < 0.05). Regions that informed the age group SVMs were associated with sensory and socio-emotional processing (inferior parietal lobule), emotion regulation (inferior frontal gyrus), and sensory regions of the temporal and occipital lobes.

Conclusions: These results point to distributed differences in activation between childhood and adulthood unique to each emotional condition. In the negative condition specifically, there is evidence for a shift in engagement from regions of sensory and socio-emotional integration to emotion regulation regions between children and adults. These results provide insight into circuitry contributing to maturation of emotional processing across development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2018.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401267PMC
March 2019

Trajectories in Cerebral Blood Flow Following Antidepressant Treatment in Late-Life Depression: Support for the Vascular Depression Hypothesis.

J Clin Psychiatry 2018 10 23;79(6). Epub 2018 Oct 23.

Western Psychiatric Institute and Clinic, 3811 O'Hara St, Pittsburgh, PA 15213.

Objective: Studies have identified longitudinally that there exists an association between depression, cerebral blood flow (CBF), and white matter hyperintensities that are thought to be due to vascular pathologies in the brain. However, the changes in CBF, a measure that reflects cerebrovascular integrity, following pharmacotherapy are not well understood. In this study, we investigated the dynamic CBF changes over the course of antidepressant treatment and the association of these changes with depressive symptoms.

Methods: We used pseudocontinuous arterial spin labeling to investigate CBF changes in a sample of older patients (≥ 50 years of age; N = 46; 29 female) with a DSM-IV diagnosis of major depressive disorder. Participants had 5 magnetic resonance imaging scans (at baseline, the day after receiving a placebo, the day after receiving a first dose of venlafaxine, a week after starting venlafaxine treatment, and at the end of trial [12 weeks]). Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate depression severity and treatment outcome. We investigated the association between changes in depression severity with changes in voxel-wise CBF while adjusting for potential confounding factors.

Results: Increased CBF in the middle and posterior cingulate between baseline and end of treatment was significantly associated with percent decrease in MADRS score, independent of sex and Mini-Mental State Examination score (5,000 permutations, cluster forming threshold P < .005, family-wise error P < .05). No significant effects were detected between baseline and other scans (ie, placebo, acute [single dose], or subacute [after a week]).

Conclusions: Regional CBF increases were associated with decreases in depressive symptoms. This observation is consistent with the vascular depression hypothesis in late-life depression.

Trial Registration: ClinicalTrials.gov identifiers: NCT00892047 and NCT01124188.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4088/JCP.18m12106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419103PMC
October 2018

Functional connectivity of the brain in older women with urgency urinary incontinence.

Neurourol Urodyn 2018 11 27;37(8):2763-2775. Epub 2018 Jul 27.

Division of Geriatric Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.

Background: The brain's role in continence is critical but poorly understood. Although regions activated during bladder stimulation have been identified, little is known about the interaction between regions. In this secondary analysis we evaluate resting state and effective connectivity in older women treated for urgency urinary incontinence (UUI).

Method: 54 women ≥60 years old with UUI and 10 continent women underwent fMRI scanning during provocation of urinary urgency, both before and after therapy. Response was defined by >50% reduction in leaks on bladder diary. Regions of interest (RoIs) were selected a priori: right insula, medial prefrontal cortex, and dorsal anterior cingulate cortex. Generalized psycho-physiological interaction (gPPI) was used to calculate "effective connectivity" between RoIs during urgency. We performed a one-way ANOVA pre-treatment between groups (continent/responders/non-responders), as well as a two-way mixed ANOVA between group and time (responders/non-responders; pre-/post-therapy) using false discovery rate (FDR) correction. Principal component analysis was used to assess the variance within RoIs. Exploratory voxel-wise connectivity analyses were conducted between each RoI and the rest of the brain.

Results: RoI-RoI connectivity analysis showed connectivity differences between controls, responders, and non-responders, although statistical significance was lost after extensive correction. Principal component analysis confirmed appropriate RoI selection. Voxel-wise analyses showed that connectivity in responders became more like that of controls after therapy (cluster-wise correction P < 0.05). In non-responders, no consistent changes were seen.

Conclusion: These data support the postulate that responders and non-responders to therapy may represent different subsets of UUI, one with more of a central etiology, and one without.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nau.23766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469490PMC
November 2018

Functional connectivity of the brain in older women with urgency urinary incontinence.

Neurourol Urodyn 2018 11 27;37(8):2763-2775. Epub 2018 Jul 27.

Division of Geriatric Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.

Background: The brain's role in continence is critical but poorly understood. Although regions activated during bladder stimulation have been identified, little is known about the interaction between regions. In this secondary analysis we evaluate resting state and effective connectivity in older women treated for urgency urinary incontinence (UUI).

Method: 54 women ≥60 years old with UUI and 10 continent women underwent fMRI scanning during provocation of urinary urgency, both before and after therapy. Response was defined by >50% reduction in leaks on bladder diary. Regions of interest (RoIs) were selected a priori: right insula, medial prefrontal cortex, and dorsal anterior cingulate cortex. Generalized psycho-physiological interaction (gPPI) was used to calculate "effective connectivity" between RoIs during urgency. We performed a one-way ANOVA pre-treatment between groups (continent/responders/non-responders), as well as a two-way mixed ANOVA between group and time (responders/non-responders; pre-/post-therapy) using false discovery rate (FDR) correction. Principal component analysis was used to assess the variance within RoIs. Exploratory voxel-wise connectivity analyses were conducted between each RoI and the rest of the brain.

Results: RoI-RoI connectivity analysis showed connectivity differences between controls, responders, and non-responders, although statistical significance was lost after extensive correction. Principal component analysis confirmed appropriate RoI selection. Voxel-wise analyses showed that connectivity in responders became more like that of controls after therapy (cluster-wise correction P < 0.05). In non-responders, no consistent changes were seen.

Conclusion: These data support the postulate that responders and non-responders to therapy may represent different subsets of UUI, one with more of a central etiology, and one without.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nau.23766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469490PMC
November 2018

Association of Hippocampal Substructure Resting-State Functional Connectivity with Memory Performance in Older Adults.

Am J Geriatr Psychiatry 2018 06 13;26(6):690-699. Epub 2018 Mar 13.

Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, PA.

Objectives: Hippocampal hyperactivation marks preclinical dementia pathophysiology, potentially due to differences in the connectivity of specific medial temporal lobe structures. Our aims were to characterize the resting-state functional connectivity of medial temporal lobe sub-structures in older adults, and evaluate whether specific substructural (rather than global) functional connectivity relates to memory function.

Methods: In 15 adults (mean age: 69 years), we evaluated the resting state functional connectivity of medial temporal lobe substructures: dentate/Cornu Ammonis (CA) 4, CA1, CA2/3, subiculum, the molecular layer, entorhinal cortex, and parahippocampus. We used 7-Tesla susceptibility weighted imaging and magnetization-prepared rapid gradient echo sequences to segment substructures of the hippocampus, which were used as structural seeds for examining functional connectivity in a resting BOLD sequence. We then assessed correlations between functional connectivity with memory performance (short and long delay free recall on the California Verbal Learning Test [CVLT]).

Results: All the seed regions had significant connectivity within the temporal lobe (including the fusiform, temporal, and lingual gyri). The left CA1 was the only seed with significant functional connectivity to the amygdala. The left entorhinal cortex was the only seed to have significant functional connectivity with frontal cortex (anterior cingulate and superior frontal gyrus). Only higher left dentate-left lingual connectivity was associated with poorer CVLT performance (Spearman r = -0.81, p = 0.0003, Benjamini-Hochberg false discovery rate: 0.01) after multiple comparison correction.

Conclusions: Rather than global hyper-connectivity of the medial temporal lobe, left dentate-lingual connectivity may provide a specific assay of medial temporal lobe hyper-connectivity relevant to memory in aging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jagp.2018.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993618PMC
June 2018

Insulin sensitivity predicts brain network connectivity following a meal.

Neuroimage 2018 05 13;171:268-276. Epub 2018 Jan 13.

Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

There is converging evidence that insulin plays a role in food-reward signaling in the brain and has effects on enhancing cognition. Little is known about how these effects are altered in individuals with insulin resistance. The present study was designed to identify the relationships between insulin resistance and functional brain connectivity following a meal. Eighteen healthy adults (7 male, 11 female, age: 41-57 years-old) completed a frequently-sampled intravenous glucose tolerance test to quantify insulin resistance. On separate days at least one week apart, a resting state functional magnetic resonance imaging scan was performed: once after a mixed-meal and once after a 12-h fast. Seed-based resting state connectivity of the caudate nucleus and eigenvector centrality were used to identify relationships between insulin resistance and functional brain connectivity. Individuals with greater insulin resistance displayed stronger connectivity within reward networks following a meal suggesting insulin was less able to suppress reward. Insulin resistance was negatively associated with eigenvector centrality in the dorsal anterior cingulate cortex following a meal. These data suggest that individuals with less sensitivity to insulin may fail to shift brain networks away from reward and toward cognitive control following a meal. This altered feedback loop could promote overeating and obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2018.01.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857474PMC
May 2018

Subjective-Objective Sleep Discrepancy Is Associated With Alterations in Regional Glucose Metabolism in Patients With Insomnia and Good Sleeper Controls.

Sleep 2017 11;40(11)

Department of Psychiatry, Sleep and Chronobiology Center, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Objectives: Sleep discrepancies are common in primary insomnia (PI) and include reports of longer sleep onset latency (SOL) than measured by polysomnography (PSG) or "negative SOL discrepancy." We hypothesized that negative SOL discrepancy in PI would be associated with higher relative glucose metabolism during nonrapid eye movement (NREM) sleep in brain networks involved in conscious awareness, including the salience, left executive control, and default mode networks.

Methods: PI (n = 32) and good sleeper controls (GS; n = 30) completed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans during NREM sleep, and relative regional cerebral metabolic rate for glucose (rCMRglc) was measured. Sleep discrepancy was calculated by subtracting PSG-measured SOL on the PET night from corresponding self-report values the following morning. We tested for interactions between group (PI vs. GS) and SOL discrepancy for rCMRglc during NREM sleep using both a region of interest mask and exploratory whole-brain analyses.

Results: Significant group by SOL discrepancy interactions for rCMRglc were observed in several brain regions (pcorrected < .05 for all clusters). In the PI group, more negative SOL discrepancy (self-reported > PSG-measured SOL) was associated with significantly higher relative rCMRglc in the right anterior insula and middle/posterior cingulate during NREM sleep. In GS, more positive SOL discrepancy (self-reported < PSG-measured SOL) was associated with significantly higher relative rCMRglc in the right anterior insula, left anterior cingulate cortex, and middle/posterior cingulate cortex.

Conclusions: Although preliminary, these findings suggest regions of the brain previously shown to be involved in conscious awareness, and the perception of PSG-defined states may also be involved in the phenomena of SOL discrepancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/sleep/zsx155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819841PMC
November 2017

Neurodevelopmental maturation as a function of irritable temperament: Insights From a Naturalistic Emotional Video Viewing Paradigm.

Hum Brain Mapp 2017 10 24;38(10):5307-5321. Epub 2017 Jul 24.

Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.

Few studies have investigated the neural systems involved in decreasing behavioral reactivity to emotional stimuli as children age. It has been suggested that this process may interact with temperament-linked variations in neurodevelopment to better explain individual differences in the maturation of emotion regulation. In this investigation, children ages 4 to 12 (n = 30, mean age = 7.62 years, SD = 1.71 years) and adults (n = 21, mean age = 26.67 years) watched clips from popular children's films containing positive, negative, or neutral emotional content during functional magnetic resonance imaging. Compared to adults, children demonstrated greater activation in subcortical and visual regions (hippocampus, thalamus, visual cortex, fusiform) during negative clips and greater activation of subcortical and prefrontal regions during positive clips (hippocampus, thalamus, caudate, ACC, OFC, superior frontal cortex). In children only, we found an age by temperament interaction in frontal and subcortical regions indicating that activation increased as a function of age in the most irritable children, but decreased as a function of age in the least irritable children. Findings were not present in the temperament domain of fear. Findings replicate and extend the existing irritability literature, indicating that healthy children highest in irritability may develop comparatively greater activation of the lateral prefrontal cortex in order to support adaptive regulation during emotional challenges. These results are discussed within the context of the emerging literature on the utility of complex, multidimensional, and naturalistic stimuli, which present a complementary alternative to understanding ecologically valid and sustained neural responses to emotionally evocative stimuli. Hum Brain Mapp 38:5307-5321, 2017. © 2017 Wiley Periodicals, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.23742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752122PMC
October 2017

Reproducibility and Bias in Healthy Brain Segmentation: Comparison of Two Popular Neuroimaging Platforms.

Front Neurosci 2016 9;10:503. Epub 2016 Nov 9.

Department of Biostatistics, Bloomberg School of Public Health, John Hopkins University Baltimore, MD, USA.

We evaluated and compared the performance of two popular neuroimaging processing platforms: Statistical Parametric Mapping (SPM) and FMRIB Software Library (FSL). We focused on comparing brain segmentations using Kirby21, a magnetic resonance imaging (MRI) replication study with 21 subjects and two scans per subject conducted only a few hours apart. We tested within- and between-platform segmentation reliability both at the whole brain and in 10 regions of interest (ROIs). For a range of fixed probability thresholds we found no differences between-scans within-platform, but large differences between-platforms. We have also found very large differences between- and within-platforms when probability thresholds were changed. A randomized blinded reader study indicated that: (1) SPM and FSL performed well in terms of gray matter segmentation; (2) SPM and FSL performed poorly in terms of white matter segmentation; and (3) FSL slightly outperformed SPM in terms of CSF segmentation. We also found that tissue class probability thresholds can have profound effects on segmentation results. We conclude that the reproducibility of neuroimaging studies depends on the neuroimaging software-processing platform and tissue probability thresholds. Our results suggest that probability thresholds may not be comparable across platforms and consistency of results may be improved by estimating a probability threshold correspondence function between SPM and FSL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2016.00503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101202PMC
November 2016

Motor sequence learning-induced neural efficiency in functional brain connectivity.

Behav Brain Res 2017 02 11;319:87-95. Epub 2016 Nov 11.

Department of Physical Therapy, University of Pittsburgh, Pittsburgh PA, USA. Electronic address:

Previous studies have shown the functional neural circuitry differences before and after an explicitly learned motor sequence task, but have not assessed these changes during the process of motor skill learning. Functional magnetic resonance imaging activity was measured while participants (n=13) were asked to tap their fingers to visually presented sequences in blocks that were either the same sequence repeated (learning block) or random sequences (control block). Motor learning was associated with a decrease in brain activity during learning compared to control. Lower brain activation was noted in the posterior parietal association area and bilateral thalamus during the later periods of learning (not during the control). Compared to the control condition, we found the task-related motor learning was associated with decreased connectivity between the putamen and left inferior frontal gyrus and left middle cingulate brain regions. Motor learning was associated with changes in network activity, spatial extent, and connectivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2016.11.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5183470PMC
February 2017

Gray matter regions statistically mediating the cross-sectional association of eotaxin and set-shifting among older adults with major depressive disorder.

Int J Geriatr Psychiatry 2017 12 19;32(12):1226-1232. Epub 2016 Sep 19.

Department of Psychiatry, Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Objective: Eotaxin is a chemokine that exerts negative effects on neurogenesis. We recently showed that peripheral eotaxin levels correlate with both lower gray matter volume and poorer executive performance in older adults with major depressive disorder. These findings suggest that the relationship between eotaxin and set-shifting may be accounted for by lower gray matter volume in specific regions. Prior studies have identified specific gray matter regions that correlate with set-shifting performance, but have not examined whether these specific gray matter regions mediate the cross-sectional association between eotaxin and set-shifting.

Method: In 27 older adults (mean age: 68 ± 5.2 years) with major depressive disorder, we performed a whole brain (voxel-wise) analysis testing whether/where gray matter density statistically mediates the cross-sectional association of eotaxin and set-shifting performance.

Results: We found the association between eotaxin and set-shifting performance was fully statistically mediated by lower gray matter density in left middle cingulate, right pre-/post-central, lingual, inferior/superior frontal, cuneus, and middle temporal regions.

Conclusion: The regions identified above may be both susceptible to a potential neurodegenerative effect of eotaxin, and critical to preserving set-shifting function. Longitudinal and intervention studies are needed to further evaluate whether targeting eotaxin levels will prevent neurodegeneration and executive impairment in older adults with depression. Copyright © 2016 John Wiley & Sons, Ltd.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gps.4585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846473PMC
December 2017

Sleep-Wake Differences in Relative Regional Cerebral Metabolic Rate for Glucose among Patients with Insomnia Compared with Good Sleepers.

Sleep 2016 Oct 1;39(10):1779-1794. Epub 2016 Oct 1.

Department of Psychiatry, Sleep and Chronobiology Center, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Study Objectives: The neurobiological mechanisms of insomnia may involve altered patterns of activation across sleep-wake states in brain regions associated with cognition, self-referential processes, affect, and sleep-wake promotion. The objective of this study was to compare relative regional cerebral metabolic rate for glucose (rCMR) in these brain regions across wake and nonrapid eye movement (NREM) sleep states in patients with primary insomnia (PI) and good sleeper controls (GS).

Methods: Participants included 44 PI and 40 GS matched for age (mean = 37 y old, range 21-60), sex, and race. We conducted [F]fluoro-2-deoxy-D-glucose positron emission tomography scans in PI and GS during both morning wakefulness and NREM sleep at night. Repeated measures analysis of variance was used to test for group (PI vs. GS) by state (wake vs. NREM sleep) interactions in relative rCMR.

Results: Significant group-by-state interactions in relative rCMR were found in the precuneus/posterior cingulate cortex, left middle frontal gyrus, left inferior/superior parietal lobules, left lingual/fusiform/occipital gyri, and right lingual gyrus. All clusters were significant at P < 0.05.

Conclusions: Insomnia was characterized by regional alterations in relative glucose metabolism across NREM sleep and wakefulness. Significant group-by-state interactions in relative rCMR suggest that insomnia is associated with impaired disengagement of brain regions involved in cognition (left frontoparietal), self-referential processes (precuneus/posterior cingulate), and affect (left middle frontal, fusiform/lingual gyri) during NREM sleep, or alternatively, to impaired engagement of these regions during wakefulness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020360PMC
http://dx.doi.org/10.5665/sleep.6154DOI Listing
October 2016