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Background: Low-intensity transcranial focused ultrasound (tFUS) is a brain stimulation approach that holds promise for the treatment of brain-based disorders. Studies in humans have shown that tFUS can successfully modulate perfusion in focal sonication targets, including the amygdala; however, limited research has explored how tFUS impacts large-scale neural networks., Objective: The aim of the current study was to address this gap and examine changes in resting-state connectivity between large-scale network nodes using a randomized, double-blind, within-subjects crossover study design., Methods: Healthy adults ( n =  18) completed two tFUS sessions, 14 days apart. Each session included tFUS of either the right amygdala or the left entorhinal cortex (ErC). The inclusion of two active targets allowed for within-subjects comparisons as a function of the locus of sonication. Resting-state functional magnetic resonance imaging was collected before and after each tFUS session., Results: tFUS altered resting-state functional connectivity (rsFC) within and between rs-network nodes. Pre-to-post sonication of the right amygdala modulated connectivity within nodes of the salience network (SAN) and between nodes of the SAN and the default mode network (DMN) and frontoparietal network (FRP). A decrease in SAN to FPN connectivity was specific to the amygdala target. Pre-to-post sonication of the left ErC modulated connectivity between the dorsal attention network (DAN) and FPN and DMN. An increase in DAN to DMN connectivity was specific to the ErC target., Conclusion: These preliminary findings may suggest that tFUS induces neuroplastic changes beyond the immediate sonication target. Additional studies are needed to determine the long-term stability of these effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gorka, Jimmy, Koning, Phan, Rotstein, Hoang-Dang, Halavi, Spivak, Monti, Reggente, Bookheimer and Kuhn.)

Transcranial Focused Ultrasound Stimulation (tFUS) is a new, rapidly growing field related to the study and treatment of brain circuits. Establishing safety cutoffs for focused ultrasound is crucial for non-ablative neurological ultrasound experiments. In addition to potential focal heating, there is concern about temperature elevation at the skin surface. Much work has been performed at or near the FDA guideline of I SPTA.3 = 720 mW/cm 2 , which technically only applies to diagnostic, not therapeutic, ultrasound. Furthermore, evidence of brain tissue damage on histology in the focal region has been shown not to occur until I SPTA.3 > 14 W/cm 2 . Therefore, this study was conducted across a range of intensities between these two values, evaluating both subjective and objective side effects. Subjective side effects encompassed any discomfort experienced during and after focused ultrasound stimulation, while objective side effects included clinical findings of skin irritation, such as erythema, edema, or burns. This study also examined how the skin temperature at the skin-transducer interface would change in order to assess whether there would be significant heating. The subjects did not experience any unpleasant sensation at the point of stimulation, including heat or pain, and no objective findings of skin irritation were observed following stimulation and the removal of the transducer. In addition, there was no intensity-dependent effect on temperature, and the maximal rise in temperature was 1.45 °C, suggesting that these parameters do not result in the heating of the skin at the interface in such a way that poses a risk to subjects when operating at or below the intensities tested in this experiment.

Background: The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively., Methods: We studied healthy older adult participants ( N  = 21, ages 48-79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task., Results: Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation., Conclusions: The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way.

Objective: This study intended to evaluate a possible therapeutic effect among patients with treatment-refractory generalized anxiety disorder (trGAD) by using transcranial focused ultrasound (tfUS) to modulate amygdalar activity., Methods: Twenty-five participants with severe trGAD as outlined in the DSM-V were recruited from Los Angeles neurology and psychiatry clinics. All participants completed eight weekly 10-min tfUS sessions targeting the right amygdala. Functional and structural neuroimaging were used to navigate individual targets. Outcome measures including the Hamilton Anxiety Inventory (HAM-A, primary outcome) and Beck Anxiety Inventory (BAI) were collected at baseline and protocol completion. Upon study completion, participants were asked to report perceived change in clinical status using the Patient Global Impression - Improvement (PGI-I) scale. Data was collected from May 2020 through January 2023., Results: All participants were able to tolerate treatment without notable side effects. No adverse events were reported. A Wilcoxon Signed-Rank Test was conducted to compare pre- and post-tfUS measures of anxiety. tfUS resulted in a significant decrease in anxiety as measured by the HAM-A (W = -3.69, p < 0.001, pre-post-Δ = -12.64 ± 12.51) and the BAI (W = -3.94, p < 0.001, pre-post-Δ = -12.88 ± 10.42). Sixteen (16) of twenty-five (25) total participants indicated clinically significant benefit on PGI-I scores at completion., Conclusion: This study provides preliminary evidence supporting the safety and efficacy of tfUS as a clinical intervention. These results warrant further investigation of tfUS as a therapeutic intervention for anxiety and other psychiatric and neurological disorders., Gov Identifier: NCT04250441., Competing Interests: Declaration of competing interest Author Alexander Bystritsky, MD, PhD, is the CEO of Brainsonix Corp., the manufacturer of the Brainsonix Pulsar 1002 device. Author Norman Spivak is a consultant for the BrainSonix Corp. Taylor Kuhn, PhD, is a consultant and is a shareholder of Sanmai Technologies, PBC. The remaining authors report no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Understanding the structural connectivity of key brainstem nuclei with limbic cortical regions is essential to the development of therapeutic neuromodulation for depression, chronic pain, addiction, anxiety and movement disorders. Several brainstem nuclei have been identified as the primary central nervous system (CNS) source of important monoaminergic ascending fibers including the noradrenergic locus coeruleus, serotonergic dorsal raphe nucleus, and dopaminergic ventral tegmental area. However, due to practical challenges to their study, there is limited data regarding their in vivo anatomic connectivity in humans., Objective: To evaluate the structural connectivity of the following brainstem nuclei with limbic cortical areas: locus coeruleus, ventral tegmental area, periaqueductal grey, dorsal raphe nucleus, and nucleus tractus solitarius. Additionally, to develop a group average atlas of these limbic brainstem structures to facilitate future analyses., Methods: Each nucleus was manually masked from 197 Human Connectome Project (HCP) structural MRI images using FSL software. Probabilistic tractography was performed using FSL's FMRIB Diffusion Toolbox. Connectivity with limbic cortical regions was calculated and compared between brainstem nuclei. Results were aggregated to produce a freely available MNI structural atlas of limbic brainstem structures., Results: A general trend was observed for a high probability of connectivity to the amygdala, hippocampus and DLPFC with relatively lower connectivity to the orbitofrontal cortex, NAc, hippocampus and insula. The locus coeruleus and nucleus tractus solitarius demonstrated significantly greater connectivity to the DLPFC than amygdala while the periaqueductal grey, dorsal raphe nucleus, and ventral tegmental area did not demonstrate a significant difference between these two structures., Conclusion: Monoaminergic and other modulatory nuclei in the brainstem project widely to cortical limbic regions. We describe the structural connectivity across the several key brainstem nuclei theorized to influence emotion, reward, and cognitive functions. An increased understanding of the anatomic basis of the brainstem's role in emotion and other reward-related processing will support targeted neuromodulatary therapies aimed at alleviating the symptoms of neuropsychiatric disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Levinson, Miller, Iftekhar, Justo, Arriola, Wei, Hazany, Avecillas-Chasin, Kuhn, Horn and Bari.)

Introduction: This study intended to evaluate the safety and possible therapeutic effect of transcranial infrared laser stimulation (TILS) based on photobiomodulation (PBM) among patients with traumatic brain injury (TBI). Methods: Eleven participants who were diagnosed with TBI after full neurological examination and MRI evaluation by a board-certified neurologist completed five to eight 20-minute TILS sessions using the Cytonsys CytonPro-5000 apparatus (pilot laser control, focused wavelength of 1064 nm, maximum output power of 10W, maximum optical power density of 500 mW/cm 2 , effective area 4.5 cm 2 in diameter). Per TILS session, participants underwent a laser dose of 250 mW/cm 2 continuous laser wave to each hemisphere using predetermined patient-specific coordinates. Structural imaging was used to neuronavigate individual treatment targets in the frontal cortex (Brodmann area 10). The primary safety measure for this study was the occurrence of adverse events (AEs) or serious adverse events (SAEs). The primary efficacy outcome measure was the participant-rated global rating of change (GRC) post-intervention. Secondary outcome measures included a battery of neuropsychological testing and mood questionnaires done both pre- and post-intervention. Results: All patients enrolled in this study protocol were able to tolerate the study procedures without any AEs or SAEs. Nine out of eleven participants had clinically significant improvements in GRC score (≥ +2). Neuropsychological testing and mood questionnaire outcomes also suggested a positive therapeutic effect. Conclusion: This study provides preliminary evidence supporting the safety and potential efficacy of TILS as a non-invasive clinical intervention for individuals with TBI., Competing Interests: We have no conflict of interest to disclose., (Copyright © 2022 J Lasers Med Sci.)

Objective: Cognitive impairment is common among individuals with Parkinson's disease (PD). Intraindividual variability (IIV) is a measure of variability across multiple tasks of cognitive functioning. Due to the limited amount of research, particularly among individuals with PD, IIV has been an underutilized metric of cognitive functioning both in research and clinical practice. Previous research demonstrated that individuals with PD have greater variability in cognitive performance relative to controls, and that IIV is predictive of future cognitive impairments. The aim of this study is to investigate the association between baseline IIV and change in cortical and subcortical volumes among individuals with PD., Method: The present study used data from 80 newly diagnosed PD patients who were part of a longitudinal cohort study (Parkinson progression marker initiative [PPMI]). Participants completed neuropsychological measures and underwent T1 structural magnetic resonance imaging (MRI) at baseline and the first annual follow-up. Neuropsychological tests assessed attention, processing speed, visuospatial functioning, verbal fluency learning, and memory. T1 scans were processed using standard Freesurfer protocols for extraction of regional volumes., Results: Greater IIV at baseline was predictive of change in cortical volume in posterior temporal/parietal regions over the 1-year period. Baseline IIV predicted cortical volume changes above and beyond the main effect of motor severity and the baseline statistical mean/global cognition score., Conclusion: Our results provide initial evidence that IIV is a marker of longitudinal cortical volume loss. Evidence is building that IIV is a sensitive marker of cognitive impairment and the underlying neurodegeneration among individuals with PD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Interventions for chronic discogenic spine pain are currently insufficient in lowering individual patient suffering and global disease burden. A 2016 study of platelet rich plasma (PRP) for chronic discogenic pain previously demonstrated clinically significant response among active group patients compared with controls., Objectives: To replicate the previous research to move this intervention forward as a viable option for patient care., Study Design: A double-blind, randomized, placebo-controlled study., Setting: Multicenter private practices., Methods: Twenty-six (12 men, 14 women) human patients, ages 25 to 71 with a diagnosis of chronic lumbar discogenic pain, were randomly assigned to active (PRP) or control (saline) groups in a ratio of 2 active to 1 control. Baseline and follow-up Oswestry Disability Index and Numeric Pain Rating Scale questionnaires were obtained to track patient outcomes at 8 weeks postoperatively., Results: Within group assessment showed clinically significant improvement in 17% of PRP patients and clinically significant decline in 5% (1 patient) of the active group. Clinically significant improvement was seen in 13% of placebo group patients and no placebo patients had clinically significant decline secondary to the procedure., Limitations: Possible explanations may include a range of factors including differences in patient demographics, outcome-measure sensitivity, or misalignment of statistical analyses., Conclusions: These findings are markedly different than the highly promising results of the 2016 PRP study. This study posits necessary caution for researchers who wish to administer PRP for therapeutic benefit and may ultimately point to necessary redirection of interventional research for discogenic pain populations.

Focused ultrasound is a novel brain stimulation modality that combines the noninvasiveness of repetitive transcranial magnetic stimulation and the precision of deep brain stimulation. In this review, the authors examine low-intensity focused ultrasound for brain mapping and neuromodulation. They also discuss high-intensity focused ultrasound, which is used for incisionless surgeries, such as capsulotomies for obsessive-compulsive disorder. Future potential applications of focused ultrasound are also presented., Competing Interests: Dr. Tyler reports being a cofounder of ISenseTec, LLC, and an inventor on issued and pending patents covering noninvasive neuromodulation methods and devices. The other authors report no financial relationships with commercial interests., (Copyright © 2022 by the American Psychiatric Association.)

Objective: Transcranial Focused Ultrasound (tFUS) is a promising new potential neuromodulation tool. However, the safety of tFUS neuromodulation has not yet been assessed adequately. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of tFUS neuromodulation. Histological changes in tissue after tFUS can be examined after surgical resection, while further potential safety concerns can be assessed using neuropsychological testing., Methods: Neuropsychological functions were assessed in eight patients before and after focused ultrasound sonication of the temporal lobe at intensities up to 5760 mW/cm 2 . Using the BrainSonix Pulsar 1002, tFUS was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed using various batteries. Histological changes were assessed using hematoxylin and eosin staining, among others., Results: With respect to safety, the histological analysis did not reveal any detectable damage to the tissue, except for one subject for whom the histology findings were inconclusive. In addition, neuropsychological testing did not show any statistically significant changes in any test, except for a slight decrease in performance on one of the tests after tFUS., Significance: This study supports the hypothesis that low-intensity Transcranial Focused Ultrasound (tFUS) used for neuromodulation of brain circuits at intensities up to 5760 mW/cm 2 may be safe for use in human research. However, due to methodological limitations in this study and inconclusive findings, more work is warranted to establish the safety. Future directions include greater number of sonications as well as longer exposure at higher intensity levels to further assess the safety of tFUS for modulation of neuronal circuits., Competing Interests: Declaration of competing interest Dr. Korb is a Vice-President of BrainSonix Inc. Dr. Schafer is the Chief Technology Officer of BrainSonix Inc. Dr. Bystritsky is the Founder and Chief Executive Officer of BrainSonix Inc. Drs. Korb, Schafer, Bystritsky also own shares in the company. Other authors report no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Anxiety Disorders are prevalent and often chronic, recurrent conditions that reduce quality of life. The first-line treatments, such as serotonin reuptake inhibitors and cognitive behavioral therapy, leave a significant proportion of patients symptomatic. As psychiatry moves toward targeted circuit-based treatments, there is a need for a theory that unites the phenomenology of anxiety with its underlying neural circuits. The Alarm, Belief, Coping (ABC) theory of anxiety describes how the neural circuits associated with anxiety interact with each other and domains of the anxiety symptoms, both temporally and spatially. The latest advancements in neuroimaging techniques offer the ability to assess these circuits in vivo. Using Neurosynth, a large open-access meta-analytic imaging database, the association between terms related to specific neural circuits was explored within the ABC theory framework. Alarm-related terms were associated with the amygdala, anterior cingulum, insula, and bed nucleus of stria terminalis. Belief-related terms were associated with medial prefrontal cortex, precuneus, bilateral temporal poles, and hippocampus. Coping-related terms were associated with the ventrolateral and dorsolateral prefrontal cortices, basal ganglia, and anterior cingulate. Neural connections underlying the functional neuroanatomy of the ABC model were observed. Additionally, there was considerable interaction and overlap between circuits associated with the symptom domains. Further neuroimaging research is needed to explore the dynamic interaction between the functional domains of the ABC theory. This will pave the way for probing the neuroanatomical underpinnings of anxiety disorders and provide an evidence-based foundation for the development of targeted treatments, such as neuromodulation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Nonmotor symptoms, including depression, anxiety, apathy, and cognitive dysfunction, are common in Parkinson's disease (PD). Although a link between mood symptoms and cognitive impairment in PD has been theorized vis-à-vis striatal dopamine depletion, studies have been inconsistent regarding the relationship between mood symptoms and cognitive function. Inconsistencies may reflect the cross-sectional nature of previous studies. The current study examined the bidirectional longitudinal relationship between mood and cognition., Method: Data were obtained from 310 individuals newly diagnosed with PD, who were followed up to 4 years (baseline, 1st, 2nd, 3rd, and 4th annual follow-ups). Apathy, anxiety, depressive symptoms, motor severity, and neurocognitive functioning were assessed at each annual assessment. The longitudinal relationship between apathy, anxiety, depressive symptoms, and cognition was analyzed with multilevel models., Results: Over the 4-year period, more severe depressive symptoms were related to worse performance on tasks of processing speed, verbal learning, and verbal delayed recall. Additionally, there was a significant Depression × Time interaction, suggesting that individuals with more severe depressive symptoms experience more rapid declines in global cognitive functioning and verbal learning. Apathy and anxiety were not significantly related to performance in any cognitive test. Lagged models revealed that changes in depression precede declines in working memory, verbal learning, delayed verbal recall, and global cognition., Conclusion: Findings suggest depressive symptoms may be a harbinger for future cognitive decline among individuals with PD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Introduction: Preclinical studies support investigation of focused ultrasound for breakdown of cerebral pathologies in neurodegenerative conditions including Alzheimer's disease (AD) and Parkinson's disease (PD)., Methods: A focused transcranial Doppler device with probes (2 MHz, 520 mW/cm 2 ) affixed bilaterally was used to target the hippocampus (AD) or substantia nigra (PD) with functional magnetic resonance imaging navigation for enhanced plaque removal. A total of 22 patients (n = 11 AD, n = 11 PD) underwent 8 consecutive, weekly, 1-hour treatments wherein sleep was encouraged naturally or pharmacologically. Cognitive and motor functioning assessment was carried out using standardized evaluations at baseline and conclusion., Results: Of all, 62.5% of patients had one or more improved cognitive scores without data incongruence, 87% had stable or improved fine motor scores, and 87.5% had stable or improved gross motor scores. No adverse events were reported., Discussion: The safety of focused transcranial Doppler and possible enhancement in patient functioning were suggested by outcome data.

The original Human Connectome Project yielded a rich data set on structural and functional connectivity in a large sample of healthy young adults using improved methods of data acquisition, analysis, and sharing. More recent efforts are extending this approach to include infants, children, older adults, and brain disorders. This paper introduces and describes the Human Connectome Project in Aging (HCP-A), which is currently recruiting 1200 + healthy adults aged 36 to 100+, with a subset of 600 + participants returning for longitudinal assessment. Four acquisition sites using matched Siemens Prisma 3T MRI scanners with centralized quality control and data analysis are enrolling participants. Data are acquired across multimodal imaging and behavioral domains with a focus on factors known to be altered in advanced aging. MRI acquisitions include structural (whole brain and high resolution hippocampal) plus multiband resting state functional (rfMRI), task fMRI (tfMRI), diffusion MRI (dMRI), and arterial spin labeling (ASL). Behavioral characterization includes cognitive (such as processing speed and episodic memory), psychiatric, metabolic, and socioeconomic measures as well as assessment of systemic health (with a focus on menopause via hormonal assays). This dataset will provide a unique resource for examining how brain organization and connectivity changes across typical aging, and how these differences relate to key characteristics of aging including alterations in hormonal status and declining memory and general cognition. A primary goal of the HCP-A is to make these data freely available to the scientific community, supported by the Connectome Coordination Facility (CCF) platform for data quality assurance, preprocessing and basic analysis, and shared via the NIMH Data Archive (NDA). Here we provide the rationale for our study design and sufficient details of the resource for scientists to plan future analyses of these data. A companion paper describes the related Human Connectome Project in Development (HCP-D, Somerville et al., 2018), and the image acquisition protocol common to both studies (Harms et al., 2018)., (Copyright © 2018. Published by Elsevier Inc.)

Objective: HIV-associated neurocognitive disorder (HAND) occurs in a significant percentage of HIV-infected (HIV+) adults. Increased intraindividual variability (IIV) in cognitive function may be an early marker of emerging neurocognitive disorder, which suggests that IIV may be a sensitive measure of neurologic compromise in HIV. In the current study, we hypothesize that increased IIV may predict impending morbidity, including future cognitive decline and death., Method: In 708 HIV+ participants followed longitudinally for up to 14 years, we assessed the role of dispersion in forecasting death and cognitive decline. Incident neurocognitive impairment was predicted in a mixed-effects ordinal logistic regression model using age, gender, baseline mean cognitive functioning, CD4+, time followed, years of education, and dispersion at the previous visit. Death before the next visit was predicted in a binomial mixed-effects regression model using age, gender, baseline mean cognitive functioning, CD4+, time followed, years of education, and dispersion., Results: Point-in-time dispersion and change in dispersion between visits predict future cognitive decline and death in HIV+ individuals. Individuals with greater dispersion at a visit or who had larger changes in dispersion between visits were more likely to demonstrate greater neurocognitive impairment at the subsequent visit. Greater IIV was also associated with an increased risk of death prior to the subsequent visit, even after controlling for HAND severity and global cognitive functioning., Conclusions: We conclude that the IIV in cognitive functioning may be more predictive of future disease consequence than mean level of cognitive functioning. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The purpose of the current study was to examine the independent and interactive effects of social adversity (SA) and HIV infection on subcortical shape alterations and cognitive functions. Participants included HIV+ (n = 70) and HIV- (n = 23) individuals who underwent MRI, neurocognitive and clinical assessment, in addition to completing questionnaires from which responses were used to create an SA score. Bilateral amygdalae and hippocampi were extracted from T1-weighted images. Parametric statistical analyses were used to compare the radial distance of the structure surface to a median curve to determine the presence of localized shape differences as a function of HIV, SA and their interaction. Next, multiple regression was used to examine the interactive association between HIV and SA with cognitive performance data. An HIV*SA interactive effect was found on the shape of the right amygdala and left hippocampus. Specifically, HIV-infected participants (but not HIV-uninfected controls) who evidenced higher levels of SA displayed an inward deformation of the surface consistent with reduced volume of these structures. We found interactive effects of HIV and SA on learning/memory performance. These results suggest that HIV+ individuals may be more vulnerable to neurological and cognitive changes in the hippocampus and amygdala as a function of SA than HIV- individuals, and that SA indicators of childhood SES and perceived racial discrimination are important components of adversity that are associated with cognitive performance.

Introduction: Past studies have shown that a large portion of individuals with Parkinson's disease (PD) and mild cognitive impairment (MCI) will revert to a cognitively intact (CI) status in the future. Aging studies have shown that individuals who revert from MCI to CI are at increased risk for reconverting to MCI or dementia in the future. The current study examined if individuals who revert from PD-mild cognitive impairment (PD-MCI) to CI will be at increased risk for future PD-MCI and Parkinson's disease dementia (PDD)., Method: The study utilized data from the Parkinson's Progression Markers Initiative (PPMI). The sample included 364 newly diagnosed PD participants who were followed annually for up to 4 years. Based on the first and second assessments, we identified individuals who were CI at each assessment (CI-Stable) and individuals who were PD-MCI at baseline but then reverted to CI (Reversion). Analyses examined if participants in the Reversion group were at greater risk, relative to the CI-Stable group, for cognitive impairment at future assessments., Results: Participants in the Reversion group were at greater risk for future cognitive impairment (PD-MCI or PDD) at the 2nd, 3rd and 4th annual follow-up, relative to the CI-Stable group. The Reversion group continued to be at increased risk for future cognitive impairment when adjusting for age, gender, education, depressive symptoms, and motor severity., Conclusion: A large proportion of individuals with PD-MCI will not show evidence of cognitive impairment within a year. However, these "reverters" continue to be at risk for future development of cognitive impairment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Historically marginalized groups are likely to be exposed to social adversity, which predicts important mental health outcomes (e.g., depression). Despite the well-established relationship between adversity and poor health, few studies have examined how adversity differentially predicts mental health among people living with multiple, co-occurring marginalized identities or statuses. The current study fills this gap by examining whether relationships between social adversity and depressive symptoms differed between those living with or without a stigmatized disease (i.e., HIV) and/or marginalized racial/ethnic identity (i.e., African American)., Method: A community sample of men and women (N = 149) completed questionnaires assessing demographics and depressive symptoms. Additionally, a composite index of social adversity was derived from measures of perceived discrimination, socioeconomic status, financial restriction to receiving medical care, and perceived neighborhood characteristics. Multiple regression was used to test whether relationships between adversity and depressive symptoms differed as a function of HIV status and racial/ethnic identity., Results: A significant 3-way interaction between social adversity, HIV status, and racial/ethnic identity indicated that there was a direct relationship between adversity and depressive symptoms for HIV-positive (HIV+) African Americans but not for HIV-negative (HIV-) African Americans, HIV+ Caucasians, or HIV- Caucasians. Further, HIV+ African Americans evidenced a significantly greater relationship between adversity and depressive symptoms compared with HIV- African Americans, but not compared with other groups., Conclusions: The findings suggest that HIV+ African Americans may be at risk for higher depressive symptoms amid adversity, highlighting the importance of evaluating intersectional identities/statuses in the context of mental health. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Background: The current study examined the independent and interactive effects of HIV and marijuana (MJ) use on brain structure and cognitive function among a sample of HIV-positive (HIV+) and HIV-negative (HIV-) individuals., Methods: Participants (HIV+, n=48; HIV-, n=29) individuals underwent cognitive testing, questionnaires about substance use, and brain MRI. The HIV+ group was clinically stable based upon current plasma CD4 count, 50% had undetectable viral load (i.e.,<20 copies/mL), and all were on a stable regimen of cART., Results: For HIV+ and HIV- participants, higher levels of MJ use were associated with smaller volumes in the entorhinal cortex and fusiform gyrus. HIV status (but not MJ use) was associated with cingulate thickness, such that HIV+ participants evidenced smaller thickness of the cingulate, as compared to HIV- controls. Regarding neurocognitive functioning, there was a HIV*MJ interactive effect on global cognition, such that when the amount of MJ use was less than 1.43g per week, the HIV- group displayed significantly better neurocognitive performance than the HIV+ group (t=3.14, p=0.002). However, when MJ use reached 1.43g per week, there were no significant HIV group differences in global cognitive performance (t=1.39, p=0.168)., Conclusions: Our results show independent and interactive effects of HIV and MJ on brain structure and cognition. However, our results do not support that HIV+ MJ users are at greater risk for adverse brain or cognitive outcomes compared to HIV- MJ users., Competing Interests: The authors report no conflict of interest., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Degenerative brain changes in Alzheimer's disease may occur in reverse order of normal brain development based on the retrogenesis model. This study tested whether evidence of reverse myelination was observed in mild cognitive impairment (MCI) using a data-driven analytic approach based on life span developmental data. Whole-brain high-resolution diffusion tensor imaging scans were obtained for 31 patients with MCI and 79 demographically matched healthy older adults. Comparisons across corpus callosum (CC) regions of interest (ROIs) showed decreased fractional anisotropy (FA) in the body but not in the genu or splenium; early-, middle-, and late-myelinating ROIs restricted to the CC revealed decreased FA in late- but not early- or middle-myelinating ROIs. Voxelwise group differences revealed areas of lower FA in MCI, but whole-brain differences were equally distributed across early-, middle-, and late-myelinating regions. Overall, results within the CC support the retrogenesis model, although caution is needed when generalizing these results beyond the CC., (© The Author(s) 2015.)

We examined how two critical constructs, health beliefs and sensation seeking, influence combination antiretroviral therapy adherence in HIV+ African Americans, and whether these factors mediate the association between age and adherence. Two-hundred-and-eighty-six HIV+ African Americans participated in this observational study. Path analyses revealed that higher levels of a specific health belief, perceived utility of treatment, and lower levels of a sensation-seeking component, Thrill and Adventure Seeking, directly predicted optimal adherence. The influence of age on adherence was partially mediated by lower Thrill and Adventure Seeking levels. Depression predicted adherence via perceived utility of treatment and Thrill and Adventure Seeking, whereas current substance abuse and dependence did via Thrill and Adventure Seeking. Poorer neurocognitive function had a direct, adverse effect on adherence. Our findings suggest that supporting the development of more positive perceptions about HIV treatment utility may help increase medication adherence among African Americans. This may be particularly relevant for those with higher levels of depression symptoms, which was directly associated with negative perceptions about treatment. Additionally, clinicians can assess sensation-seeking tendencies to help identify HIV+ African Americans at risk for suboptimal adherence. Compensatory strategies for medication management may help improve adherence among HIV+ individuals with poorer neurocognitive function.

The current study examined the independent and combined effects of HIV and marijuana (MJ) use (no use, light use, and moderate-to-heavy use) on neurocognitive functioning among a convenience sample of HIV-positive (HIV+) and HIV-negative (HIV-) individuals recruited from HIV community care clinics and advertisements in the Greater Los Angeles area. MJ users consisted of individuals who reported regular use of MJ for at least 12 months, with last reported use within the past month. Participants included 89 HIV+ (n = 55) and HIV- (n = 34) individuals who were grouped into non-users, light users, and moderate-to-heavy users based on self-reported MJ use. Participants were administered a brief cognitive test battery and underwent laboratory testing for CD4 count and viral load. HIV+ individuals demonstrated lower performance on neurocognitive testing than controls, and moderate-to-heavy MJ users performed more poorly on neurocognitive testing than light users or non-users. Moderate-to-heavy HIV+ users performed significantly lower on learning/memory than HIV- moderate-to-heavy users (MD = -8.34; 95% CI: -16.11 to -0.56) as well as all other comparison groups. In the domain of verbal fluency, HIV+ light users outperformed HIV- light users (MD = 7.28; 95% CI: 1.62-12.39), but no HIV group differences were observed at other MJ use levels. HIV+ MJ users demonstrated lower viral load (MD = -0.58; 95% CI: -1.30 to 0.14) and higher CD4 count than non-users (MD = 137.67; 95% CI: 9.48-265.85). The current study findings extend the literature by demonstrating the complex relationship between HIV status and MJ use on neurocognitive and clinical outcomes.