Deep brain stimulation of the amygdala for treatment-resistant combat post-traumatic stress disorder: Long-term results.

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. Here, we report long-term data on two TR-PTSD participants from an investigation utilizing high-frequency amygdala DBS. The two combat veterans were implanted bilaterally with quadripolar electrodes targeting the basolateral amygdala. Following a randomized staggered onset, patients received stimulation with adjustments based on PTSD symptom severity for four years while psychiatric and neuropsychiatric symptoms, neuropsychological performance, and electroencephalography were systematically monitored. Evaluation of vmPFC-Amygdala network engagement was assessed with 18FDG positron emission tomography (PET). CAPS-IV scores varied over time, but improved 55% from 119 at baseline to 53 at 4-year study endpoint in participant 1; and 44%, from 68 to 38 in participant 2. Thereafter, during 5 and 1.5 years of subsequent clinical care respectively, long-term bilateral amygdala DBS was associated with additional, clinically significant symptomatic and functional improvement. There were no serious stimulation-related adverse psychiatric, neuropsychiatric, neuropsychological, neurological, or neurosurgical effects. In one subject, symptomatic improvement was associated with an intensity-dependent reduction in amygdala theta frequency power. In our two participants, FDG-PET findings were inconclusive regarding the hypothesized mechanism of suppression of amygdala hyperactivity. Our findings encourage further research to confirm and extend our preliminary observations.

Decomposing risky decision-making in methamphetamine use disorder: Behavioral updating and D2 dopamine receptors.

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. This research aimed to clarify whether impaired behavioral updating contributes to maladaptive performance on the BART. METHODS: Two groups (28 drug-abstinent participants with MUD and 16 healthy control participants) were compared on BART performance. Using a computational model, we deconstructed behavior into risk-taking and behavioral updating. A subset of participants (22 MUD, 15 healthy control) underwent [18F]fallypride positron emission tomography scans to measure dopamine D2-type receptor availability (BPND) in the striatum (caudate and accumbens nuclei and putamen) and the globus pallidus. RESULTS: Participants with MUD exhibited slower behavioral updating than the healthy controls (p = 0.0004, d=1.77). BPND in all four bilateral volumes of interest were higher in the healthy control group (ps < 0.005, ds < 2.16), and updating rate correlated positively with BPND in the caudate nucleus (p = 0.002), putamen (p = 0.002), and globus pallidus (p = 0.03). CONCLUSIONS: The findings indicate that behavioral updating contributes to maladaptive decision-making in MUD and suggest that dysregulation of D2-type receptor signaling in the striatum and globus pallidus contributes to this behavioral deficit.

The Effects of Citalopram and Thalamic Dopamine D2/3 Receptor Availability on Decision-Making and Loss Aversion in Alcohol Dependence.

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. A double-blind, placebo-controlled, within-subject, outpatient study was conducted with active alcohol-dependent (DSM-IV-TR criteria) participants (n = 12) and matched healthy controls (n = 13). Serial doses of both citalopram (40 mg) and saline were administered intravenously before laboratory tests of decision-making (Balloon Analogue Risk Task, delay discounting task, and Loss Aversion Gambling Task) and positron emission tomography with [18F]-fallypride to measure dopamine D2/3 receptor availability, separated by at least one week. Alcohol-dependent participants demonstrated greater loss aversion than healthy controls, but there were no group differences in risk taking on the Balloon Analogue Risk Task. Citalopram increased delay discounting across groups, with no group difference in the effect. There were no effects of citalopram on risk taking on the Balloon Analogue Risk Task. PET showed a negative correlation between thalamic dopamine D2/3 receptor availability and loss aversion across groups. The effect of citalopram to decrease the valuation of monetary reward as a function of delay raises the possibility that SSRIs can influence risky decision-making in clinical populations. In addition, these results suggest that altered thalamic dopamine signaling may play an important role in disproportionately valuing losses in patients with Alcohol Use Disorder. This trial is registered under ClinicalTrials.gov registration NCT01657760.

It's Not What You Take Up, It's What You Keep: How Discoveries from Diverse Disciplines Directed the Development of the FDG PET/CT Scan.

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 (18F), the accurate imaging derived from coincidence detection of positron annihilation radiation combined with computed tomography, and the metabolic trapping of 2-deoxy-2-[18F]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. This article is followed by a review of the many applications of FDG-PET/CT to the gastrointestinal tract and hepatobiliary system (Mandelkern in Dig Dis Sci 2022).

Information Transfer and Multifractal Analysis of EEG in Mild Blast-Induced TBI.

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., spectral analysis) have not been successful in detecting the degree of cognitive and functional impairment in mbTBI. We therefore collected resting state EEG (5 minutes, 64 leads) from twelve patients with a history of mbTBI, along with repeat neuropsychological testing (D-KEFS Tower test) to compare two new methods for analyzing EEG (multifractal detrended fluctuation analysis (MF-DFA) and information transfer modeling (ITM)) with spectral analysis. For MF-DFA, we extracted relevant parameters from the resultant multifractal spectrum from all leads and compared with traditional power by frequency band for spectral analysis. For ITM, because the number of parameters from each lead far exceeded the number of subjects, we utilized a reduced set of 10 leads which were compared with spectral analysis. We utilized separate 30 second EEG segments for training and testing statistical models based upon regression tree analysis. ITM and MF-DFA models both generally had improved accuracy at correlating with relevant measures of cognitive performance as compared to spectral analytic models ITM and MF-DFA both merit additional research as analytic tools for EEG and cognition in TBI.

The relationship between duration of abstinence and gray-matter brain structure in chronic methamphetamine users.

Background: Brain structural findings in chronic methamphetamine users have been inconsistent. Identifying contributing influences (e.g., sex, abstinence duration) can help clarify the clinical course of recovery.Objectives: We studied the effects of long-term methamphetamine abstinence on gray-matter volume. Our hypothesis was that smaller volume early in abstinence would precede long-term recovery.Methods: Individuals who used methamphetamine (≥100 g lifetime use, mandated to residential treatment for methamphetamine-positive urine; 40 men, 21 women), undergoing supervised abstinence (men: 12-400 days; women: 130-594 days), were compared to healthy controls (49 men, 36 women) using T1-weighted MRI. Volumes of orbitofrontal, anterior cingulate and parietal cortex, hippocampus, and striatum were measured using Freesurfer software. Associations of volumes with abstinence duration were tested in males and females separately because their abstinence times differed (121.5 ± 124.5 vs. 348.0 ± 128.6 days, p < 0.001); only males were studied in early abstinence. The General Linear Model was used to test effects of abstinence duration and group (methamphetamine users vs. controls).Results: In males, duration of abstinence was multivariate significant for gray-matter volumes (p = 0.017). Abstinence duration was associated with increases in volumes of the orbitofrontal and parietal cortices (ps = 0.031, 0.016) and hippocampi (ps = 0.044). Irrespective of abstinence, male methamphetamine users had smaller hippocampi than male controls (p = 0.008). Females showed no significant effects of group or abstinence.Conclusions: In males, abstinence from methamphetamine appears to result in volumetric increases in regions important for cognitive function, which may affect recovery during the course of treatment. Data from the period of early abstinence are required to evaluate volumetric changes in females.

Striatal dopamine D2-type receptor availability and peripheral 17ß-estradiol.

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 17ß-estradiol and dopamine signaling in the human brain by testing for a relationship between two proxies for these variables: peripheral 17ß-estradiol and striatal dopamine D2-type receptor availability, measured with [18F]fallypride and positron emission tomography (PET). Sixteen (23-45 years of age) women were tested on 2 days of the menstrual cycle estimated prospectively to occur during (a) the early follicular phase, when estrogen levels are near their nadir, and (b) the periovulatory phase, when estrogen levels peak. PET scans with [18F]fallypride were performed on these 2 days, and serum 17ß-estradiol was measured using radioimmunoassay. Dopamine D2-type receptor availability did not differ significantly in the whole striatum or the caudate, putamen, or accumbens subregions during the high-estrogen vs. the low-estrogen phases of the menstrual cycle. We conclude that circulating estrogen levels do not affect dopamine D2-type receptor availability in the human striatum although other indices of dopaminergic function may be affected.

No significant elevation of translocator protein binding in the brains of recently abstinent methamphetamine users.

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. METHODS: We used PET with [11C]DAA1106 to compare standardized uptake values (SUVs) as an index of TSPO binding in the brains of methamphetamine-dependent participants who were abstinent for < 6 months (n = 11) and healthy controls (n = 12). We also assayed other typical correlates of Methamphetamine Dependence (e.g., striatal D2-type dopamine receptor deficits, depressed mood, anxiety and impaired emotion regulation). RESULTS: Methamphetamine users exhibited depression (p < 0.0001), anxiety (p = 0.002), difficulties in emotional regulation (p = 0.01), and lower striatal dopamine D2-type receptor availability vs. controls (p = 0.02). SUVs for [11C]DAA1106 were larger in all brain regions of methamphetamine-dependent participants vs. controls, but the effect size was small to medium and not statistically significant. CONCLUSIONS: The discrepancy between the lack of significant difference in TSPO binding in early-abstinent methamphetamine users vs. controls in this study and a previous report of elevated binding in longer-abstinent methamphetamine users may reflect methodological differences or limitations of TSPO binding as an index of neuroinflammation. It also seems possible that gliosis increases over time during the first 6 months of abstinence; longitudinal studies could clarify this possibility.

EEG multifractal analysis correlates with cognitive testing scores and clinical staging in mild cognitive impairment.

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.g., spectral analysis). We utilized an existing database of a study of healthy elderly patients (N = 20) who were assessed with cognitive testing (Folstein Mini Mental Status Exam; MMSE) and resting state EEG (4 leads). Each subject's EEG was separated into two 30 s tracings for training and testing a statistical model against the MMSE scores. We compared multifractal detrended fluctuation analysis (MF-DFA) against Fourier Transform (FT) in the ability to produce an accurate classification and regression trees estimator for the testing EEG segments. The MF-DFA-based statistical model MMSE estimation strongly correlated with the actual MMSE when applied to the test EEG parameter dataset, whereas the corresponding FT-based model did not. Using a standardized cutoff value for MMSE-based clinical staging, the MF-DFA-based statistical model was both sensitive and specific for clinical staging of both mild Alzheimer's disease and mild cognitive impairment. MF-DFA shows promise as a method of quantitative EEG analysis to accurately estimate cognition in Alzheimer's disease.

Effects of Citalopram on Cue-Induced Alcohol Craving and Thalamic D2/3 Dopamine Receptor Availability.

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.v. dose of a selective serotonin reuptake inhibitor reduces craving for alcohol and/or simultaneously increases striatal dopamine concentration in individuals with alcohol dependence. METHODS: Alcohol-dependent (DSM-IV-TR criteria) volunteers and matched controls (n = 10/group) underwent a double-blind, placebo-controlled, within-subjects study. Participants received i.v. citalopram (40 mg) or saline (counter-balanced) followed by a cue-induced craving assessment and [18F]-fallypride positron emission tomography scanning. RESULTS: In the alcohol-dependent individuals, the citalopram (compared with saline) resulted in decreased cue-induced craving for alcohol. For the whole study group, cue-induced alcohol craving was inversely correlated with thalamic (but not striatal) dopamine D2/3 receptor availability. CONCLUSIONS: Acute serotonin reuptake inhibition reduces cue-induced alcohol craving. Furthermore, thalamic dopamine abnormalities and the striatal hyperdopaminergic hypothesis of alcohol use disorder are supported.

Effect of overnight smoking abstinence on a marker for microglial activation: a [11C]DAA1106 positron emission tomography study.

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 16.8% less binding of the radiotracer [11C]DAA1106 (a radioligand for TSPO) in the brain than nonsmokers. OBJECTIVES: We sought to determine the effect of overnight smoking abstinence on [11C]DAA1106 binding in the brain. METHODS: Forty participants (22 smokers and 18 nonsmokers) completed the study (at one of two sites) and had usable data, which included images from a dynamic [11C]DAA1106 PET scanning session (with smokers having been abstinent for 17.9 ± 2.3 h) and a blood sample for TSPO genotyping. Whole brain standardized uptake values (SUVs) were determined, and analysis of variance was performed, with group (overnight abstinent smoker vs. nonsmoker), site, and TSPO genotype as factors, thereby controlling for site and genotype. RESULTS: Overnight abstinent smokers had lower whole brain SUVs (by 15.5 and 17.0% for the two study sites) than nonsmokers (ANCOVA, P = 0.004). The groups did not significantly differ in injected radiotracer dose or body weight, which were used to calculate SUV. CONCLUSIONS: These results in overnight abstinent smokers are similar to those in satiated smokers, indicating that chronic cigarette smoking leads to global impairment of microglial activation which persists into early abstinence. Other explanations for study results, such as smoking leading to reduced numbers of microglia or smokers having more rapid metabolism of the radiotracer than nonsmokers, are also possible.

Effect of Cigarette Smoking on a Marker for Neuroinflammation: A [11C]DAA1106 Positron Emission Tomography Study.

This corrects the article DOI: 10.1038/npp.2017.48.

Low Striatal Dopamine D2-type Receptor Availability is Linked to Simulated Drug Choice in Methamphetamine Users.

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. Fifteen recently abstinent methamphetamine users and 15 healthy controls completed two laboratory paradigms of 'simulated' drug choice (choice for drug-related vs affectively pleasant, unpleasant, and neutral images), and underwent positron emission tomography measurements of dopamine D2-type receptor availability, indicated by binding potential (BPND) for [18F]fallypride. Thirteen of the methamphetamine users and 10 controls also underwent [11C]NNC112 PET scans to measure dopamine D1-type receptor availability. Group analyses showed that, compared with controls, methamphetamine users chose to view more methamphetamine-related images on one task, with a similar trend on the second task. Regression analyses showed that, on both tasks, the more methamphetamine users chose to view methamphetamine images, specifically vs pleasant images (the most frequently chosen images across all participants), the lower was their D2-type BPND in the lateral orbitofrontal cortex, an important region in value-based choice. No associations were observed with D2-type BPND in striatal regions, or with D1-type BPND in any region. These results identify a neurochemical correlate for a laboratory drug-seeking paradigm that can be administered to treatment-seeking and abstaining drug-addicted individuals. More broadly, these results refine the central hypothesis that dopamine-system deficits contribute to drug-biased decision-making in addiction, here showing a role for the orbitofrontal cortex.

Cerebral metabolic correlates of attention networks in Alzheimer's Disease: A study of the Stroop.

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. We hypothesized that the Word, Color, and Color-Word conditions of the Stroop would all tap into the alerting and orienting networks. The Color-Word condition would additionally tap into the executive network. A ratio of Color-Word to Color naming performance would isolate the executive network from the others. To identify the neural underpinnings of attention in AD we correlated performance on the Stroop with brain metabolic activity. Sixty-six patients with probable AD completed [18F] fluorodeoxyglucose PET scanning and neuropsychological testing. Analysis was conducted with SPM12 (p<0.001 uncorrected, extent threshold 50 voxels). Performance on the Word, Color, and Color-Word conditions directly correlated with metabolic rate in right inferior parietal lobules/intraparietal sulci. The Color-Word/Color ratio revealed associations with metabolic rate in right medial prefrontal cortex and insula/operculum. Overall findings were largely consistent with the hypothesized neuroanatomical substrates of the alerting, orienting, and executive networks. As such, attention deficits in AD reflect compromise to multiple large-scale networks.

Effect of Cigarette Smoking on a Marker for Neuroinflammation: A [11C]DAA1106 Positron Emission Tomography Study.

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 [11C]DAA1106 (a ligand for TSPO) and positron emission tomography (PET) to determine the effect of smoking on availability of this marker for neuroinflammation. Forty-five participants (30 smokers and 15 non-smokers) completed the study and had usable data. Participants underwent a dynamic PET scanning session with bolus injection of [11C]DAA1106 (with smokers in the satiated state) and blood draws during PET scanning to determine TSPO affinity genotype and plasma nicotine levels. Whole-brain standardized uptake values (SUVs) were determined, and analysis of variance was performed, with group (smoker vs non-smoker) and genotype as factors, thereby controlling for genotype. Smokers and non-smokers differed in whole-brain SUVs (P=0.006) owing to smokers having 16.8% lower values than non-smokers. The groups did not differ in injected radiotracer dose or body weight, which were used to calculate SUV. An inverse association was found between whole-brain SUV and reported cigarettes per day (P<0.05), but no significant relationship was found for plasma nicotine. Thus, smokers have less [11C]DAA1106 binding globally than non-smokers, indicating less microglial activation. Study findings are consistent with much prior research demonstrating that smokers have impaired inflammatory functioning compared with non-smokers and that constituents of tobacco smoke other than nicotine affect inflammatory processes.

Cholinergic Receptor Binding in Alzheimer Disease and Healthy Aging: Assessment In Vivo with Positron Emission Tomography Imaging.

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 α4ß2* nicotinic cholinergic receptor binding using 2-[18F]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. RESULTS: 2FA binding was lower in the AD group compared with the C group in the medial thalamus, medial temporal cortex, anterior cingulate, insula/opercula, inferior caudate, and brainstem (p < 0.05, corrected cluster), but binding was not associated with cognition. The C group had significant inverse correlations between 2FA binding in the thalamus (left: rs = -0.55, p = 0.008; right: rs = -0.50, p = 0.02; N = 22) and hippocampus (left: rs = -0.65, p = 0.001; right: rs = -0.55, p = 0.009; N = 22) and the Trails A score. The AD group had inverse correlation between 2FA binding in anterior cingulate (left: rs = -0.50, p = 0.01; right: rs = -0.50, p = 0.01; N = 24) and Neurobehavioral Rating Scale agitation/disinhibition factor score. CONCLUSION: Cholinergic receptor binding is reduced in specific brain regions in mild to moderate AD and is related to neuropsychiatric symptoms. Among healthy older adults, lower receptor binding may be associated with slower processing speed. Cholinergic receptor binding in vivo may reveal links to other key brain changes associated with aging and AD and may provide a potential molecular treatment target.

18F-Fluorodeoxyglucose Positron Emission Tomography Cortical Metabolic Activity Associated with Distinct Agitation Behaviors in Alzheimer Disease.

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 18F-fluorodeoxyglucose positron emission tomography and agitated symptoms from the Neuropsychiatric Inventory (NPI) in patients with AD. Two empirically derived clusters of agitation symptoms were investigated: an Agitation factor comprising agitation/aggression and irritability/lability items of the NPI, and a Behavioral Dyscontrol factor comprising elation/euphoria, disinhibition, aberrant motor behavior, sleep, and appetite items of the NPI. Mean cerebral metabolism for patients who scored positively on each of the two factors was compared with mean cerebral metabolism for those who did not. RESULTS: Patients with AD who scored positively on the Agitation factor showed reduced glucose metabolism of the right temporal, right frontal, and bilateral cingulate cortex. In contrast, the Behavioral Dyscontrol factor did not show specific neurobiologic correlates. CONCLUSION: Symptoms encompassed within the Agitation factor have distinct neurobiologic underpinnings. The precipitants, course, and outcomes related to these symptoms may be unique from other neuropsychiatric symptoms characteristic of AD. Special attention to treatment of agitated behaviors involving anger, aggressiveness, hostility, and irritability/emotional lability is warranted, because they appear to reflect a clinically relevant symptom cluster with unique underlying neurobiologic correlates.

Neuromodulation for Treatment-Refractory PTSD.

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.