Publications by authors named "Mandelkern M"

Article Synopsis
  • - The study investigated the role of mGlu5 receptors in individuals with methamphetamine use disorder (MUD) compared to a control group, focusing on cognitive performance and brain activity measured by PET scans.
  • - Results showed no significant differences in mGlu5 levels between MUD participants and controls, but MUD individuals performed worse on certain cognitive tests, particularly in spatial working memory.
  • - Findings suggest that while mGlu5 receptors are not downregulated in abstinent MUD patients, targeting these receptors could potentially enhance cognitive functioning, especially in verbal learning tasks.
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Deep brain stimulation (DBS) holds promise for neuropsychiatric conditions where imbalance in network activity contributes to symptoms. Treatment-resistant Combat post-traumatic stress disorder (TR-PTSD) is a highly morbid condition and 50% of PTSD sufferers fail to recover despite psychotherapy or pharmacotherapy. Reminder-triggered symptoms may arise from inadequate top-down ventromedial prefrontal cortex (vmPFC) control of amygdala reactivity.

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Background: Escalating misuse of amphetamine-type stimulants, mainly methamphetamine, has led to a staggering rise in associated overdose deaths and a pressing need to understand the basis of methamphetamine use disorder (MUD). MUD is characterized by disadvantageous decision-making, and people with MUD perform below controls on the Balloon Analogue Risk Task (BART), a laboratory test of decision-making under uncertainty. The BART presents a series of choices with progressively higher stakes-greater risk of loss and greater potential monetary reward.

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Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for patients who misuse alcohol, especially in the context of comorbid depressive symptoms. Deficits in impulse control and decision-making are linked to routine alcohol consumption and alcohol dependence. The goal of this study was to determine the effects of a single dose of citalopram on measures of impulsivity, decision-making, and/or brain dopamine receptor availability in alcohol-dependent individuals.

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Although imaging glucose metabolism with positron emission tomography combined with X-ray CT (FDG-PET/CT) has become a standard diagnostic modality for the discovery and surveillance of malignant tumors and inflammatory processes, its origins extend back to more than a century of notable discoveries in the fields of inorganic and organic chemistry, nuclear physics, mathematics, biochemistry, solute transport physiology, metabolism, and imaging, accomplished by pioneering and driven investigators, of whom at least ten were recipients of the Nobel Prize. These tangled and diverse roots eventually coalesced into the FDG-PET/CT method, that through its many favorable characteristics inherent in the isotope used (F), the accurate imaging derived from coincidence detection of positron annihilation radiation combined with computed tomography, and the metabolic trapping of 2-deoxy-2-[F]fluoro-D-glucose (FDG) in tissues, provides safety, sensitivity, and specificity for tumor and inflammation detection. The authors hope that this article will increase the appreciation among its readers of the insight, creativity, persistence, and drive of the many investigators who made this technique possible.

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Mild, blast-induced traumatic brain injury (mbTBI) is a common combat brain injury characterized by typically normal neuroimaging findings, with unpredictable future cognitive recovery. Traditional methods of electroencephalography (EEG) analysis (e.g.

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Brain structural findings in chronic methamphetamine users have been inconsistent. Identifying contributing influences (e.g.

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Research using rodent models has established a relationship between the steroid hormone estrogen and dopamine function, by revealing changes throughout the estrous cycle and by directly manipulating neuroendocrine signaling through ovariectomy and administration of estrogen. However, a direct link between estrogen levels and dopamine signaling had not been established in humans. The goal of this study, therefore, was to assess the relationship between circulating 17β-estradiol and dopamine signaling in the human brain by testing for a relationship between two proxies for these variables: peripheral 17β-estradiol and striatal dopamine D-type receptor availability, measured with [F]fallypride and positron emission tomography (PET).

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Background: Radioligands for the translocator protein (TSPO) 18 kDa have been used with positron emission tomography (PET) to assess neuroinflammation and microglial activation in psychiatric disorders. One study using this approach showed substantial TSPO elevation throughout the brain in chronic methamphetamine users following long-term abstinence (0.5-4 years), but clients typically present for treatment earlier in abstinence.

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Alzheimer's disease and mild cognitive impairment are increasingly prevalent global health concerns in aging industrialized societies. There are only limited non-invasive biomarkers for the cognitive and functional impairment associated with dementia. Multifractal analysis of EEG has recently been proposed as having the potential to be an improved method of quantitative EEG analysis compared to existing techniques (e.

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Background: Selective serotonin reuptake inhibitors are often used in alcohol use disorders. Clinical trials with selective serotonin reuptake inhibitors for alcohol use disorders, however, have yielded mixed results. The goal of this project was to assess whether a single i.

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Rationale: Microglia are the main immune cells in the central nervous system and participate in neuroinflammation. When activated, microglia express increased levels of the translocator protein 18 kDa (TSPO), thereby making TSPO availability a marker for neuroinflammation. Using positron emission tomography (PET) scanning, our group recently demonstrated that smokers in the satiated state had 16.

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Patients with Alzheimer's Disease (AD) show difficulties with attention. Cognitive neuroscience models posit that attention can be broken down into alerting, orienting, and executive networks. We used the Stroop Color-Word test to interrogate the neural correlates of attention deficits in AD.

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Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted only on post-mortem material, with no differences in methamphetamine users from controls in the caudate nucleus and putamen and higher D1-receptor density in the nucleus accumbens. Released from neurons when methamphetamine is self-administered, dopamine binds to both D1- and D2-type receptors in the striatum, with downstream effects on cortical activity.

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Individuals with drug use disorders seek drugs over other rewarding activities, and exhibit neurochemical deficits related to dopamine, which is involved in value-based learning and decision-making. Thus, a dopaminergic disturbance may underpin drug-biased choice in addiction. Classical drug-choice assessments, which offer drug-consumption opportunities, are inappropriate for addicted individuals seeking treatment or abstaining.

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In the brain, microglia continuously scan the surrounding extracellular space in order to respond to damage or infection by becoming activated and participating in neuroinflammation. When activated, microglia increase the expression of translocator protein (TSPO) 18 kDa, thereby making the TSPO expression a marker for neuroinflammation. We used the radiotracer [C]DAA1106 (a ligand for TSPO) and positron emission tomography (PET) to determine the effect of smoking on availability of this marker for neuroinflammation.

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Deep brain stimulation has been successful in treating Parkinson disease and essential tremor and is now reducing PTSD symptoms in the first patient enrolled in an early-phase safety trial.

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Objective: This study aimed to investigate the neurobiologic correlates of two distinct clusters of agitation symptoms to identify the unique biologic substrates underlying agitated behaviors.

Methods: Eighty-eight outpatients with mild to moderate Alzheimer disease (AD) were recruited from the VA Greater Los Angeles Healthcare System Geropsychiatry Outpatient Program. A cross-sectional investigation was conducted of the relationship between cerebral glucose metabolism measured via F-fluorodeoxyglucose positron emission tomography and agitated symptoms from the Neuropsychiatric Inventory (NPI) in patients with AD.

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Objective: To compare regional nicotinic cholinergic receptor binding in older adults with Alzheimer disease (AD) and healthy older adults in vivo and to assess relationships between receptor binding and clinical symptoms.

Methods: Using cross-sectional positron emission tomography (PET) neuroimaging and structured clinical assessment, outpatients with mild to moderate AD (N = 24) and healthy older adults without cognitive complaints (C group; N = 22) were studied. PET imaging of α4β2* nicotinic cholinergic receptor binding using 2-[F]fluoro-3-(2(S)azetidinylmethoxy)pyridine (2FA) and clinical measures of global cognition, attention/processing speed, verbal memory, visuospatial memory, and neuropsychiatric symptoms were used.

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Introduction: The objective of this study was to distinguish the functional neuroanatomy of verbal learning and recognition in Alzheimer's disease (AD) using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning task.

Method: In 81 Veterans diagnosed with dementia due to AD, we conducted a cluster-based correlation analysis to assess the relationships between recency and recognition memory scores from the CERAD Word Learning Task and cortical metabolic activity measured using [F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET).

Results: AD patients (Mini-Mental State Examination, MMSE mean = 20.

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Stimulant use disorders are associated with deficits in striatal dopamine receptor availability, abnormalities in mesocorticolimbic resting-state functional connectivity (RSFC) and impulsivity. In methamphetamine-dependent research participants, impulsivity is correlated negatively with striatal D2-type receptor availability, and mesocorticolimbic RSFC is stronger than that in controls. The extent to which these features of methamphetamine dependence are interrelated, however, is unknown.

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