HONOLULU, HI, United States

Neurobehavioral Research, Inc.

HONOLULU, HI, United States
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Camchong J.,Neurobehavioral Research, Inc. | Stenger A.,University of Hawaii at Manoa | Fein G.,Neurobehavioral Research, Inc. | Fein G.,University of Hawaii at Manoa
Cerebral Cortex | Year: 2013

Short-term abstinent alcoholics have shown increased engagement of reward regions and reduced engagement of executive control regions. There is no report yet on whether these differences can predict relapse. This is the first study that investigates whether differences in resting-state networks can predict later relapse. Resting-state functional magnetic resonance imaging data were collected from 69 short-term abstinent alcoholics. Participants performed the affective go/no-go task outside of the scanner. At 6-month follow-up, participants were grouped as abstainers (N = 40; age: M = 46.70, standard deviation [SD] = 6.83) and relapsers (N = 29; age: M = 46.91, SD = 7.25). We examined baseline resting-state synchrony (RSS) using seed-based measures. Compared with abstainers, relapsers showed significantly decreased RSS within both the reward and executive control networks as well as within the visual network (P < 0.05). Lower RSS in relapsers could predict relapse (P < 0.05) and was significantly correlated with poor inhibitory control of emotional-laden stimuli (P < 0.017) and with alcohol use (P < 0.05). Results suggest that lower RSS during short-term abstinence may predict subsequent relapse. The association of lower RSS with poorer inhibitory control suggests that low RSS may constitute a faulty foundation for future responses to external cues, which can be manifested as the inability to inhibit behavior. © 2012 The Author.

Fein G.,Neurobehavioral Research, Inc. | Fein G.,University of Hawaii at Manoa
Alcoholism: Clinical and Experimental Research | Year: 2013

Background: A high prevalence of comorbid mood and anxiety disorders has been demonstrated in alcoholics. We examined lifetime and current mood and anxiety diagnoses and symptoms in long-term (mean 7.6 years; n = 110) and short-term (mean 10.1 weeks; n = 101) abstinent alcoholics (LTAA and STAA) and nonsubstance abusing controls (NSAC; n = 82). All alcoholics met DSM-IV lifetime alcohol dependence criteria. About half of each alcoholic group had lifetime drug dependence. Methods: Alcohol use was assessed using timeline follow-back methodology, and drug and alcohol use disorders were diagnosed using the AUDADIS-IV. Lifetime and current mood and anxiety disorder diagnoses and symptom counts were gathered using the computerized Diagnostic Interview Schedule. Results: Over 60% of STAA and LTAA had a lifetime internalizing diagnosis versus about 15% of NSAC, with no difference between STAA and LTAA. The group effect on lifetime diagnoses was independent of comorbid drug dependence or gender and was of comparable size for mood and anxiety disorders. Current diagnoses showed a similar pattern, except that STAA had more current mood diagnoses than LTAA. Excluding individuals with lifetime internalizing diagnoses, alcoholics still had more mood and anxiety symptoms than controls. Conclusions: (i) The presence of a lifetime mood or anxiety diagnosis or of a current anxiety diagnosis did not differ between STAA and LTAA, suggesting that such diagnoses do not impact one's ability to achieve or maintain abstinence. (ii) Prevalence of mood and anxiety diagnoses was unaffected by presence of a comorbid substance use disorder, and (iii) excluding individuals with a mood or anxiety diagnosis does not eliminate mood and anxiety symptom count differences between groups. © 2013 by the Research Society on Alcoholism.

Fein G.,Neurobehavioral Research, Inc. | Fein G.,University of Hawaii at Manoa | Greenstein D.,Neurobehavioral Research, Inc.
Alcoholism: Clinical and Experimental Research | Year: 2013

Background: Disturbed gait and balance are common and important sequelae of chronic alcoholism. We present longitudinal data on recovery of gait and balance in alcoholics 6 to 15 weeks abstinent at baseline assessment through follow-up assessment 4 to 16 months after baseline. Methods: We performed a follow-up assessment (4 to 16 months after baseline) of gait and balance functioning in 37 short-term (6 to 15 weeks) abstinent alcoholics (STAA), 25 of whom remained abstinent through the follow-up period. Fourteen non-substance-abusing controls (NSAC) were also brought back for a follow-up assessment to examine practice effects. Results: Alcoholics showed gait and balance impairment versus controls at both the initial and follow-up assessments, showing no improvement in gait and balance measures over the follow-up period. At follow-up, NSAC showed improvement on the Walk on Floor eyes closed measure, possibly representing a practice effect not present in STAA. Conclusions: This study finds no improvement from about 10 weeks to about 1 year of abstinence in chronic alcoholics. The study is silent with regard to gait and balance recovery that occurs prior to 10 weeks abstinence, and after the first year of abstinence. Other studies suggest some recovery of gait and balance prior to 10 weeks abstinence, and our recent cross-sectional study (Smith and Fein, 2011, Alcohol Clin Exp Res 35:2184-2192) suggests that significant additional recovery occurs in the ensuing years. © 2012 by the Research Society on Alcoholism.

Price M.,Neurobehavioral Research, Inc. | Cardenas V.A.,Neurobehavioral Research, Inc. | Fein G.,Neurobehavioral Research, Inc.
NeuroImage | Year: 2014

Although the human cerebellum has been increasingly identified as an important hub that shows potential for helping in the diagnosis of a large spectrum of disorders, such as alcoholism, autism, and fetal alcohol spectrum disorder, the high costs associated with manual segmentation, and low availability of reliable automated cerebellar segmentation tools, has resulted in a limited focus on cerebellar measurement in human neuroimaging studies.We present here the CATK (Cerebellar Analysis Toolkit), which is based on the Bayesian framework implemented in FMRIB's FIRST. This approach involves training Active Appearance Models (AAMs) using hand-delineated examples. CATK can currently delineate the cerebellar hemispheres and three vermal groups (lobules I-V, VI-VII, and VIII-X). Linear registration with the low-resolution MNI152 template is used to provide initial alignment, and Point Distribution Models (PDM) are parameterized using stellar sampling. The Bayesian approach models the relationship between shape and texture through computation of conditionals in the training set. Our method varies from the FIRST framework in that initial fitting is driven by 1D intensity profile matching, and the conditional likelihood function is subsequently used to refine fitting.The method was developed using T1-weighted images from 63 subjects that were imaged and manually labeled: 43 subjects were scanned once and were used for training models, and 20 subjects were imaged twice (with manual labeling applied to both runs) and used to assess reliability and validity. Intraclass correlation analysis shows that CATK is highly reliable (average test-retest ICCs of 0.96), and offers excellent agreement with the gold standard (average validity ICC of 0.87 against manual labels). Comparisons against an alternative atlas-based approach, SUIT (Spatially Unbiased Infratentorial Template), that registers images with a high-resolution template of the cerebellum, show that our AAM approach offers superior reliability and validity. Extensions of CATK to cerebellar hemisphere parcels are envisioned. © 2014.

Camchong J.,Neurobehavioral Research, Inc. | Stenger A.,University of Hawaii at Manoa | Fein G.,Neurobehavioral Research, Inc. | Fein G.,University of Hawaii at Manoa
Alcoholism: Clinical and Experimental Research | Year: 2013

Background: Alcohol dependence is a disorder with an impulsive and compulsive "drive" toward alcohol consumption and an inability to inhibit alcohol consumption. Neuroimaging studies suggest that these behavioral components correspond to an increased involvement of regions that mediate appetitive drive and reduced involvement of regions that mediate executive control within top-down networks. Little is known, however, about whether these characteristics are present after long periods of abstinence. Methods: Resting-state functional magnetic resonance imaging data were collected to examine resting-state synchrony (RSS) differences between 23 long-term abstinent alcoholics (LTAA; 8 women, age: M = 48.46, SD = 7.10), and 23 nonsubstance abusing controls (NSAC; 8 women, age: M = 47.99, SD = 6.70). Using seed-based measures, we examined RSS with the nucleus accumbens (NAcc) and the subgenual anterior cingulate cortex (sgACC). All participants were assessed with the intra/extradimensional set shift task outside of the scanner to explore the relationship between RSS and cognitive flexibility. Results: Compared to NSAC, LTAA showed (i) decreased synchrony of limbic reward regions (e.g., caudate and thalamus) with both the anterior cingulate cortex seed and the NAcc seed and (ii) increased synchrony of executive control regions (e.g., dorsolateral prefrontal cortex) with both the NAcc seed and the sgACC seed. RSS differences were significantly correlated with task performance. Conclusions: The results are consistent with an interpretation of an ongoing compensatory mechanism in LTAA evident during rest, in which decision-making networks show reduced synchrony with appetitive drive regions and increased synchrony with inhibitory control regions. In addition, RSS differences were associated with cognitive flexibility. These resting-state findings indicate an adaptive mechanism present in long-term abstinence that may facilitate the behavioral control required to maintain abstinence. © 2012 by the Research Society on Alcoholism.

Fein G.,Neurobehavioral Research, Inc. | Nip V.,Neurobehavioral Research, Inc.
Alcoholism: Clinical and Experimental Research | Year: 2012

Background: Comorbidity of borderline personality disorder (BPD) and substance and alcohol use disorders (SUDs and AUDs) is very high. The literature suggests a negative synergy between BPD and SUDs, which may impact an individual's ability to achieve and maintain remission of either disorder in the face of the other. Methods: We examined lifetime and current (past year) BPD symptom counts in 3 gender- and age-comparable groups: short-term abstinent alcoholics (STA, 6 to 15 weeks abstinent), long-term abstinent alcoholics (LTA, more than 18 months abstinent), and nonsubstance-abusing controls (NSAC). Abstinent individuals were recruited primarily from mutual-help recovery networks and about half had comorbid drug dependence. BPD symptoms were obtained using the Structured Clinical Interview for DSM-IV-TR Axis II Personality Disorders, followed up with questions regarding currency, but did not require that BPD symptoms represent persistent or pervasive behavior such as would meet criteria for BPD diagnosis. Thus, our study dealt only with BPD symptoms, not BPD diagnoses. Results: Alcoholics had more lifetime and current symptoms for most all BPD criteria than NSAC. In general, STA and LTA did not differ in BPD symptoms, except for a group-by-gender effect for both lifetime and current anger-associated symptoms and for lifetime abandonment avoidance symptoms. For these cases, there were much higher symptom counts for STA women versus men, with comparable symptom counts for LTA women versus men. Conclusions: Our results suggest for the most part that BPD symptoms do not prevent the maintenance of recovery in AUD and SUD individuals who have established at least 6 weeks abstinence within the mutual-help recovery network-in fact the presence of BPD symptoms is the norm. However, we did find difficulty in establishing longer-term abstinence in women with anger-associated symptoms and abandonment avoidance symptoms. © 2012 by the Research Society on Alcoholism.

Hamm J.P.,University of Georgia | Gilmore C.S.,Neurobehavioral Research, Inc. | Clementz B.A.,University of Georgia
Schizophrenia Research | Year: 2012

Individuals with schizophrenia (SZ) have deviations in auditory perception perhaps attributable to altered neural oscillatory response properties in thalamo-cortical and/or local cortico-cortical circuits. Previous EEG studies of auditory steady-state responses (aSSRs; a measure of sustained neuronal entrainment to repetitive stimulation) in SZ have indicated attenuated gamma range (≈ 40. Hz) neural entrainment. Stimuli in most such studies have been relatively brief (500-1000. ms) trains of 1. ms clicks or amplitude modulated pure tones (1000. Hz) with short, fixed interstimulus intervals (200-1000. ms). The current study used extended (1500. ms), more aurally dense broadband stimuli (500-4000. Hz noise; previously demonstrated to elicit larger aSSRs) with longer, variable interstimulus intervals (2700-3300. ms). Dense array EEG (256 sensor) was collected while 17 SZ and 16 healthy subjects passively listed to stimuli modulated at 15 different frequencies spanning beta and gamma ranges (16-44. Hz in 2. Hz steps). Results indicate that SZ have augmented aSSRs that were most extreme in the gamma range. Results also constructively replicate previous findings of attenuated low frequency auditory evoked responses (2-8. Hz) in SZ. These findings (i) highlight differential characteristics of low versus high frequency and induced versus entrained oscillatory auditory responses in both SZ and healthy stimulus processing, (ii) provide support for an NMDA-receptor hypofunction-based pharmacological model of SZ, and (iii) report a novel pattern of aSSR abnormalities suggesting that gamma band neural entrainment deviations among SZ may be more complex than previously supposed, including possibly being substantially influenced by physical stimulus properties. © 2012 Elsevier B.V.

Fein G.,Neurobehavioral Research, Inc.
Alcoholism, clinical and experimental research | Year: 2010

Background: We previously demonstrated, in a small sample, steeper age-related gray matter shrinkage in treatment naïve alcohol-dependent (TxN) men compared to nonalcoholic controls, but could not separate out the contributions of age and lifetime duration of alcohol use (which were highly correlated) to this effect. In the current study, we have quadrupled the sample size and expanded it to include both men and women to try to replicate and extend the previous findings and to separate the contributions of age and alcohol use to the phenomenon. Methods: In the current study, we examine cortical gray matter volumes in 18- to 50-year-old TxN (n = 84) versus age and gender comparable controls (n = 67). We used a new Region of Interest Analysis method which accounts for differences in sulcal and gyral enfolding between individuals (Fein et al., 2009a). Results: We found greater age-related gray matter shrinkage in TxN than in controls. Partial correlation analysis showed that the effect was a function of age and not lifetime alcohol burden. Conclusions: Implications of the findings are discussed in terms of their contribution toward our knowledge of differences between different subpopulations of alcoholics and in terms of their implications for the morbidity of alcohol dependence in an aging national population.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 257.20K | Year: 2012

DESCRIPTION (provided by applicant): Cerebellar involvement has been implicated in a large spectrum of disorders. Reduced cerebellar volumes have been reported in alcoholism, autism spectrum disorders, schizophrenia, mood disorders, and essential head tremors. As an example of the work demonstrating the more widespread role of the cerebellum in brain function, Sullivan and colleagues have demonstrated impairment in static upright balance with excessive sway in individuals with pathology of the anterior superior vermis, and have shown that alterations in nodes of the frontocerebellar circuitry can predict executive dysfunction in prefrontal regions. There has been an explosion of studies in the last decade examining functional brain networks using task-activated fMRI, and resting state functional connectivity MRI . For the most part, cerebellar morphometric studies and studies of the cerebellar components of brain networks have been ignored, largely as a consequence of lack of tools to support such investigations. The time is ripe for reliable and valid tools to support such studies. We believe that a cerebellar analysis toolkit (CATK) not only has a waiting audience and market, but its availability will act as a catalyst for the incorporation of the cerebellumin studies of brain structure and function, and thus will be of great significance. The goal of this SBIR project is to develop an integrated cerebellar segmentation / parcellation and analysis suite. The core component will be MR image delineation of the cerebellum and its subregions. The suite will include a comprehensive set of image and surface analysis tools, including the capability for shape analysis of cerebellar structures, and for visualization and surface editing. We will develop an integratedanalysis environment with high performance tools implementation on GPUs using CUDA. CATK will have three major components: 1) cerebellar delineation, 2) A CUDA-based surface and image processing toolbox, and 3) A CUDA/openGL based rendering/surface editing tool. The product will provide a low cost means for extracting valuable information from existing MR image databases as well as from new data. PUBLIC HEALTH RELEVANCE: Cerebellar involvement has been implicated in a large spectrum of disorders. Reduced cerebellar volumes have been reported in alcoholism, autism spectrum disorders, schizophrenia, mood disorders, and essential head tremors. The goal of this SBIR project is to develop an integrated cerebellar segmentation / parcellation and analysis suite. Which will help give further insight into the significance of this structure in a myriad of diseases, helping to deepen our understanding of the cerebellumlt s role in normal brain function as well as in pathology.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 149.87K | Year: 2012

The goal of this project is for NRI and UCLA to develop a National Network on Drugged Driving (NNODD) website. The website will have an epidemiology component consisting of point prevalence and continuous monitoring data.

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