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Degenerative cervical myelopathy (DCM) can lead to significant brain structural reorganization. The association between the cortical changes and specific motor symptoms in DCM has yet to be fully elucidated. We investigated the associations between cortical thickness changes with neurological symptoms, such as dexterity and gait abnormalities, in patients with DCM in a case-control study. A 3 Tesla MRI scanner was used to acquire high-resolution T1-weighted structural scans from 30 right-handed patients with DCM and 22 age-matched healthy controls. Pronounced cortical thinning was observed in DCM patients relative to healthy controls, particularly in the bilateral precentral and prefrontal gyri, left pars triangularis, left postcentral gyrus, right transverse temporal and visual cortices ( P ≤ 0.04). Notably, cortical thickness in these regions showed strong correlations with objective motor deficits ( P < 0.0001). Specifically, the prefrontal cortex, premotor area and supplementary motor area exhibited significant thickness reductions correlating with diminished dexterity (R 2 = 0.33, P < 0.0007; R 2 = 0.34, P = 0.005, respectively). Similarly, declines in gait function were associated with reduced cortical thickness in the visual motor and frontal eye field cortices (R 2 = 0.39, P = 0.029, R 2 = 0.33, P = 0.04, respectively). Interestingly, only the contralateral precuneus thickness was associated with the overall modified Japanese Orthopaedic Association (mJOA) scores (R 2 = 0.29, P = 0.003). However, the upper extremity subscore of mJOA indicated an association with the visual cortex and the anterior prefrontal (R 2 = 0.48, P = 0.002, R 2 = 0.33, P = 0.0034, respectively). In conclusion, our findings reveal patterns of cortical changes correlating with motor deficits, highlighting the significance of combining objective clinical and brain imaging assessments for understanding motor network dysfunction in DCM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: There is a paucity of data on the burden and factors associated with hypertension among the Nagas (collective term for tribal ethnic groups predominantly residing in Nagaland) living in an urban environment. Insights from this study will aid in mapping focused community-based and primary care interventions for hypertension., Objectives: To determine the prevalence and risk factors associated with hypertension among Nagas aged 30-50 years residing in urban Dimapur, Nagaland., Methods: A community-based cross-sectional study was conducted between January and July 2019. This study screened 660 participants for hypertension using a digital blood pressure apparatus. A semi-structured questionnaire was used to assess the risk factors, and anthropometric measurements were recorded using standard guidelines., Results: The prevalence of hypertension and pre-hypertension was 25.9% and 44.5%, respectively. Non-modifiable risk factors such as male gender (adjusted odds ratio [AOR]: 2.02; 95% confidence interval [CI]: 1.32-3.09), age > 40 years (AOR: 2.32; 95% CI: 1.57-3.41), family history of hypertension (AOR, 1.87, 95% CI: 1.19-2.92) and modifiable risk factors such as current alcohol consumption (AOR: 2.05; 95% CI: 1.27-3.31), high/very high perceived stress (AOR: 2.15; 95% CI: 1.28-3.62), lack of participation in stress relief activities (AOR: 2.08; 95% CI: 1.17-3.71) and overweight/obesity (AOR: 2.26; 95% CI: 1.55-3.30) were independently associated with hypertension in this study., Conclusion: To avert an impending health crisis in this community, a multipronged approach involving primary-care/family physicians, culturally appropriate awareness, and targeted community-based screening programs with an adept referral system must be implemented to curtail this emerging threat., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

Early detection of oral cancer in low-resource settings necessitates a Point-of-Care screening tool that empowers Frontline-Health-Workers (FHW). This study was conducted to validate the accuracy of Convolutional-Neural-Network (CNN) enabled m(mobile)-Health device deployed with FHWs for delineation of suspicious oral lesions (malignant/potentially-malignant disorders). The effectiveness of the device was tested in tertiary-care hospitals and low-resource settings in India. The subjects were screened independently, either by FHWs alone or along with specialists. All the subjects were also remotely evaluated by oral cancer specialist/s. The program screened 5025 subjects (Images: 32,128) with 95% (n = 4728) having telediagnosis. Among the 16% (n = 752) assessed by onsite specialists, 20% (n = 102) underwent biopsy. Simple and complex CNN were integrated into the mobile phone and cloud respectively. The onsite specialist diagnosis showed a high sensitivity (94%), when compared to histology, while telediagnosis showed high accuracy in comparison with onsite specialists (sensitivity: 95%; specificity: 84%). FHWs, however, when compared with telediagnosis, identified suspicious lesions with less sensitivity (60%). Phone integrated, CNN (MobileNet) accurately delineated lesions (n = 1416; sensitivity: 82%) and Cloud-based CNN (VGG19) had higher accuracy (sensitivity: 87%) with tele-diagnosis as reference standard. The results of the study suggest that an automated mHealth-enabled, dual-image system is a useful triaging tool and empowers FHWs for oral cancer screening in low-resource settings., (© 2022. The Author(s).)

Functional magnetic resonance imaging (fMRI) has been used to study the influence of opioids on neural circuitry implicated in opioid use disorder, such as the cortico-striatal-thalamo-cortical (CSTC) circuit. Given the increase in fentanyl-related deaths, this study was conducted to characterize the effects of fentanyl on patterns of brain activation in awake nonhuman primates. Four squirrel monkeys were acclimated to awake scanning procedures conducted at 9.4 Tesla. Subsequently, test sessions were conducted in which a dose of fentanyl that reliably maintains intravenous (IV) self-administration behavior in monkeys, 1 μg/kg, was administered and the effects on patterns of brain activity were assessed using: (1) a pharmacological regressor to elucidate fentanyl-induced patterns of neural activity, and (2) seed-based approaches targeting bilateral anterior cingulate, thalamus, or nucleus accumbens (NAc) to determine alterations in CSTC functional connectivity. Results showed a functional inhibition of BOLD signal in brain regions that mediate behavioral effects of opioid agonists, such as cingulate cortex, striatum and midbrain. Functional connectivity between each of the seed regions and areas involved in motoric, sensory and cognition-related behavior generally decreased. In contrast, NAc functional connectivity with other striatal regions increased. These results indicate that fentanyl produces changes within CSTC circuitry that may reflect key features of opioid use disorder (e.g. persistent drug-taking/seeking) and thereby contribute to long-term disruptions in behavior and addiction. They also indicate that fMRI in alert nonhuman primates can detect drug-induced changes in neural circuits and, in turn, may be useful for investigating the effectiveness of medications to reverse drug-induced dysregulation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We assessed the impact of the national lockdown on a rural and tribal population in Tamil Nadu, southern India. A mixed-methods approach with a pilot-tested, semi-structured questionnaire and focus group discussions were used. The impact of the lockdown on health, finances, and livelihood was studied using descriptive statistics. Multivariable logistic regression was carried out to identify factors associated with households that borrowed loans or sold assets during the lockdown, and unemployment during the lockdown. Of the 607 rural and tribal households surveyed, households from comparatively higher socioeconomic quintiles (adjusted odds ratio [aOR], 1.84; 95% CI, 1.01-3.34), with no financial savings (aOR, 2.91; 95% CI, 1.17-7.22), and with larger families (aOR, 1.76; 95% CI, 1.22-2.53), took loans or sold assets during the lockdown. Previously employed individuals from rural households (aOR, 5.07; 95% CI, 3.30-7.78), lower socioeconomic households (aOR, 3.08; 95% CI, 1.74, 5.45), and households with no savings (aOR, 1.78; 95% CI, 1.30-2.44) became predominantly unemployed during the lockdown. Existing government schemes for the elderly, differently abled, and widows were shown to be accessible to 89% of the individuals requiring these schemes in our survey. During the focus group discussions, the limited reach of online classes for schoolchildren was noted and attributed to the lack of smartphones and poor Internet connectivity. Although the sudden, unannounced national lockdown was imposed to flatten the COVID-19 curve, aspects related to livelihood and financial security were affected for both the rural and tribal populations.

Corpus callosum (CC) abnormalities have been observed in several psychiatric disorders. Maltreatment has also been associated with marked differences in CC anatomy and microstructure, though rarely controlled for in psychiatric neuroimaging studies. The aim of this study was to identify type and timing of maltreatment associated with alterations in CC microstructure and to ascertain if they differ by sex. T1 and diffusion-weighted MRIs were obtained from 345 (135 M/210 F) healthy 18-25-year-olds. The Maltreatment and Abuse Chronology of Exposure scale provided retrospective data on exposure to ten types of maltreatment across each year of childhood. AI predictive analytics were used to identify the most significant type and time risk factors. The most striking maltreatment-associated alterations in males were in axial diffusivity and were most specifically associated with exposure to emotional abuse or neglect during segment-specific sensitive periods. In contrast, maltreatment was associated with marked alteration in radial diffusivity and fractional anisotropy in females and was most specifically associated with early physical neglect during one common sensitive period involving all segments except the splenium. Overall sex differences, controlling for maltreatment, brain size, and sociodemographic factors were limited to the genu with greater fractional anisotropy in males and radial diffusivity in females. These findings suggest that maltreatment may target myelinization in females and axonal development in males and that these sex differences need to be taken into account in studies seeking to delineate the contribution of CC abnormalities and interhemispheric communication to psychiatric disorders., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Objectives: To study the household environmental risk factors and hazards associated with elevated blood lead levels (EBLLs) in preschool children in an urban setting of Vellore, South India., Methods: A case-control study within the MAL-ED (Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development) birth cohort was conducted between January 2014 and January 2015. The study included 153 pre-school children: 87 cases and 66 controls with elevated and normal BLLs, respectively. A structured questionnaire was used to assess the sociodemographic profile, household environment, breastfeeding practices, children's habits, and the use of cosmetics in them. Household environmental samples of wall and door paint, floor dust, drinking water, and cosmetics were estimated for lead levels using gas flame atomic absorption spectrometry (FAAS)., Results: Children born with low birth weight, those living in houses painted at least once in the last five years and those residing in houses older than ten years had a higher odds of EBLLs [OR (95% CI) = 3.79 (1.24-11.1); 4.84 (1.42-16.53); 5.07 (2.06-12.46), and 2.58 (0.99-6.69)], respectively. Drinking water samples from both cases (88%) and controls (95%) had lead levels more than the Environmental Protection Agency (EPA), USA recommendation of 0.015 ppm., Conclusions: Low birth weight and the household environment pose important risk factors/hazards for elevated blood lead levels in urban preschool children. Multipronged interventions that include government legislations, household environmental modification, safe water supply, and community education are pivotal in reducing lead exposure in young children., (© 2021. Dr. K C Chaudhuri Foundation.)

In a rural block in North East India, community health workers (CHW) empowered with a mobile phone-based application screened a total of 2,686 participants for Oral Potentially Malignant Lesions (OPMLs), and an oral medicine specialist recommended treatment remotely. Independent risk factors were determined using independent multiple logistic regression models. Nearly 700 (26%) participants were identified with OPMLs. The sensitivity, specificity, positive predictive values, negative predictive values and accuracy of the CHW was 70.3, 88.4, 66.8, 89.9% and 83.7% respectively. Male gender, married status, smokeless tobacco, paan, areca-nut and alcohol consumption were independent predictors of OPMLs, the burden of which in North East India can be attributed to the high consumption of tobacco and non-tobacco products. Such programmes, with the recommendations from remote specialists, will facilitate early detection in remote settings.

Preferences for novel environments (novelty-seeking) is a risk factor for addiction, with little known about its underlying circuitry. Exposure to drug cues facilitates addiction maintenance, leading us to hypothesize that exposure to a novel environment activates a shared neural circuitry. Stimulation of the D1 receptor in the prelimbic cortex increases responsivity to drug-associated environments. Here, we use D1 receptor overexpression in the prelimbic cortex to probe brain responses to novelty-preferences (in a free-choice paradigm) and cocaine-associated odors following place conditioning. These same cocaine-conditioned odors were used to study neural circuitry with Blood Oxygen Level Dependent (BOLD) activity. D1 overexpressing females had deactivated BOLD signals related to novelty-preferences within the insula cortex and amygdala and activation in the frontal cortex and dopamine cell bodies. BOLD responses to cocaine cues were also sensitive to D1. Control females demonstrated a place preference for cocaine environments with no significant BOLD response, while D1 overexpressing females demonstrated a place aversion and weak BOLD responses to cocaine-conditioned odor cues within the insula cortex. For comparison, we provide data from an earlier study with juvenile males overexpressing D1 that show a strong preference for cocaine and elevated BOLD responses. The results support the use of a pharmacological manipulation (e.g., D1 overexpression) to probe the neural circuitry downstream from the prelimbic cortex., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: (1) To explore the role of ethnicity in receiving cognitive-behavioural therapy (CBT) for people with psychosis or bipolar disorder while adjusting for differences in risk profiles and symptom severity. (2) To assess whether context of treatment (inpatient vs community) impacts on the relationship between ethnicity and access to CBT., Design: Cohort study of case register data from one catchment area (January 2007-July 2017)., Setting: A large secondary care provider serving an ethnically diverse population in London., Participants: Data extracted for 30 497 records of people who had diagnoses of bipolar disorder (International Classification of Diseases (ICD) code F30-1) or psychosis (F20-F29 excluding F21). Exclusion criteria were: <15 years old, missing data and not self-defining as belonging to one of the larger ethnic groups. The sample (n=20 010) comprised the following ethnic groups: white British: n=10 393; Black Caribbean: n=5481; Black African: n=2817; Irish: n=570; and 'South Asian' people (consisting of Indian, Pakistani and Bangladeshi people): n=749., Outcome Assessments: ORs for receipt of CBT (single session or full course) as determined via multivariable logistic regression analyses., Results: In models adjusted for risk and severity variables, in comparison with White British people; Black African people were less likely to receive a single session of CBT (OR 0.73, 95% CI 0.66 to 0.82, p<0.001); Black Caribbean people were less likely to receive a minimum of 16-sessions of CBT (OR 0.83, 95% CI 0.71 to 0.98, p=0.03); Black African and Black Caribbean people were significantly less likely to receive CBT while inpatients (respectively, OR 0.76, 95% CI 0.65 to 0.89, p=0.001; OR 0.83, 95% CI 0.73 to 0.94, p=0.003)., Conclusions: This study highlights disparity in receipt of CBT from a large provider of secondary care in London for Black African and Caribbean people and that the context of therapy (inpatient vs community settings) has a relationship with disparity in access to treatment., Competing Interests: Competing interests: SLaM and its services have had no role, in the study design, in the analysis and interpretation of the data, in the writing of the report, or in the decision to submit the paper for publication. Caroline Cupitt is employed by SLaM and works within one of SLaM’s services which has produced some of the clinical notes that form part of the data analysed herein. RS declares research funding within the last 5 years from Roche, GSK and Janssen., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Long-term cocaine use is associated with a variety of neural and behavioral deficits that impact daily function. This study was conducted to examine the effects of chronic cocaine self-administration on resting-state functional connectivity of the dorsal anterior cingulate (dACC) and putamen-two brain regions involved in cognitive function and motoric behavior-identified in a whole brain analysis. Six adult male squirrel monkeys self-administered cocaine (0.32 mg/kg/inj) over 140 sessions. Six additional monkeys that had not received any drug treatment for ~1.5 years served as drug-free controls. Resting-state fMRI imaging sessions at 9.4 Tesla were conducted under isoflurane anesthesia. Functional connectivity maps were derived using seed regions placed in the left dACC or putamen. Results show that cocaine maintained robust self-administration with an average total intake of 367 mg/kg (range: 299-424 mg/kg). In the cocaine group, functional connectivity between the dACC seed and regions primarily involved in motoric behavior was weaker, whereas connectivity between the dACC seed and areas implicated in reward and cognitive processing was stronger. In the putamen seed, weaker widespread connectivity was found between the putamen and other motor regions as well as with prefrontal areas that regulate higher-order executive function; stronger connectivity was found with reward-related regions. dACC connectivity was associated with total cocaine intake. These data indicate that functional connectivity between regions involved in motor, reward, and cognitive processing differed between subjects with recent histories of cocaine self-administration and controls; in dACC, connectivity appears to be related to cumulative cocaine dosage during chronic exposure.

Background: While many adolescents exhibit risky behavior, teenagers with a family history (FH+) of an alcohol use disorder (AUD) are at a heightened risk for earlier initiation of alcohol use, a more rapid escalation in frequency and quantity of alcohol consumption and developing a subsequent AUD in comparison with youth without such family history (FH-). Neuroanatomically, developmentally normative risk-taking behavior parallels an imbalance between more protracted development of the prefrontal cortex (PFC) and earlier development of limbic regions. Magnetic resonance imaging (MRI)-derived volumetric properties were obtained for these structures in FH+ and FH- adolescents., Methods: Forty-two substance-naïve adolescents (13- to 14-year-olds), stratified into FH+ (N = 19, 13 girls) and FH- (N = 23, 11 girls) age/handedness-matched groups, completed MRI scanning at 3.0T, as well as cognitive and clinical testing. T1 images were processed using FreeSurfer to measure PFC and hippocampi/amygdalae subfields/nuclei volumes., Results: FH+ status was associated with larger hippocampal/amygdala volumes (p < 0.05), relative to FH- adolescents, with right amygdala results appearing to be driven by FH+ boys. Volumetric differences also were positively associated with family history density (p < 0.05) of having an AUD. Larger subfields/nuclei volumes were associated with higher anxiety levels and worse auditory verbal learning performance (p < 0.05)., Conclusions: FH+ risk for AUD is detectable via neuromorphometric characteristics, which precede alcohol use onset and the potential onset of a later AUD, that are associated with emotional and cognitive measures. It is plausible that the development of limbic regions might be altered in FH+ youth, even prior to the onset of alcohol use, which could increase later risk. Thus, targeted preventative measures are warranted that serve to delay the onset of alcohol use in youth, particularly in those who are FH+ for an AUD., (© 2019 by the Research Society on Alcoholism.)

The frontal cortex undergoes substantial structural and functional changes during adolescence and significant developmental changes also occur in the hippocampus. Both of these regions are notably vulnerable to alcohol and other substance use, which is typically initiated during adolescence. Identifying measures of brain function during adolescence, particularly before initiation of drug or alcohol use, is critical to understanding how such behaviors may affect brain development, especially in these vulnerable brain regions. While there is a substantial developmental literature on adolescent working memory, less is known about spatial memory. Thus, a virtual Morris water task (vMWT) was applied to probe function of the adolescent hippocampus. Multiband blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) data were acquired at 3T during task performance. Participants included 32 healthy, alcohol- and drug-naïve adolescents, 13-14 years old, examined at baseline of a 3-year longitudinal MRI study. Significantly greater BOLD activation was observed in the hippocampus and surrounding areas, and in prefrontal regions involved in executive function, during retrieval relative to motor performance. In contrast, significantly greater BOLD activation was observed in components of the default mode network, including frontal medial cortex, during the motor condition (when task demands were minimal) relative to the retrieval condition. Worse performance (longer path length) during retrieval was associated with greater activation of angular gyrus/supramarginal gyrus, whereas worse performance (longer path length/latency) during motor control was associated with less activation of frontal pole. Furthermore, while latency (time to complete task) was greater in females than in males, there were no sex differences in path length (accuracy), suggesting that females required more time to navigate the virtual environment, but did so as effectively as males. These findings demonstrate that performance of the vMWT elicits hippocampal and prefrontal activation patterns in early adolescence, similar to activation observed during spatial memory retrieval in adults. Given that this task is sensitive to hippocampal function, and that the adolescent hippocampus is notably vulnerable to the effects of alcohol and other substances, data acquired using this task during healthy adolescent development may provide a framework for understanding neurobiological impact of later initiation of use.

The hippocampus is a highly stress susceptible structure and hippocampal abnormalities have been reported in a host of psychiatric disorders including major depression and post-traumatic stress disorder (PTSD). The hippocampus appears to be particularly susceptible to early life stress with a graded reduction in volume based on number of types (multiplicity) or severity of maltreatment. We assessed whether the most important predictors of adult hippocampal volume were multiplicity, severity or duration of exposure or timing of maltreatment during developmental sensitive periods. 3T MRIs were collected on 336 unmedicated, right-handed subjects (132M/204F, 18-25 years). Exposure to broad categories of abuse and neglect during each year of childhood were assessed using the Maltreatment and Abuse Chronology of Exposure scale and evaluated using artificial intelligence and predictive analytics. Male hippocampal volume was predicted by neglect, but not abuse, up through 7 years of age. Female hippocampal volume was predicted by abuse, but not neglect, at 10, 11, 15 and 16 years. Exposure at peak age had greater predictive importance than multiplicity, severity or duration. There were also marked gender differences in subfields and portions (head, body or tail) affected by exposure. History and symptoms of major depression, PTSD or anxiety disorders were not predictive of hippocampal volume once maltreatment was accounted for. Neglect appears to foster inadequate hippocampal development in males while abuse appears to produce a stress-related deficit in females. Studies assessing hippocampal volume in psychiatric disorders need to control for the gender-specific effects of abuse and neglect., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The transition to college is associated with an increase in heavy episodic alcohol use, or binge drinking, during a time when the prefrontal cortex and prefrontal-limbic circuitry continue to mature. Traits associated with this immaturity, including impulsivity in emotional contexts, may contribute to risky and heavy episodic alcohol consumption. The current study used blood oxygen level dependent (BOLD) multiband functional magnetic resonance imaging (fMRI) to assess brain activation during a task that required participants to ignore background images with positive, negative, or neutral emotional valence while performing an inhibitory control task (Go-NoGo). Subjects were 23 college freshmen (seven male, 18-20 years) who engaged in a range of drinking behavior (past 3 months' binge episodes range = 0-19, mean = 4.6, total drinks consumed range = 0-104, mean = 32.0). Brain activation on inhibitory trials (NoGo) was contrasted between negative and neutral conditions and between positive and neutral conditions using non-parametric testing (5000 permutations) and cluster-based thresholding ( z = 2.3), p ≤ 0.05 corrected. Results showed that a higher recent incidence of binge drinking was significantly associated with decreased activation of dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and anterior cingulate cortex (ACC), brain regions strongly implicated in executive functioning, during negative relative to neutral inhibitory trials. No significant associations between binge drinking and brain activation were observed for positive relative to neutral images. While task performance was not significantly associated with binge drinking in this sample, subjects with heavier recent binge drinking showed decreased recruitment of executive control regions under negative versus neutral distractor conditions. These findings suggest that in young adults with heavier recent binge drinking, processing of negative emotional images interferes more with inhibitory control neurocircuitry than in young adults who do not binge drink often. This pattern of altered frontal lobe activation associated with binge drinking may serve as an early marker of risk for future self-regulation deficits that could lead to problematic alcohol use. These findings underscore the importance of understanding the impact of emotion on cognitive control and associated brain functioning in binge drinking behaviors among young adults.

Adolescents are highly vulnerable to addiction and are four times more likely to become addicted at first exposure than at any other age. The dopamine D1 receptor, which is typically overexpressed in the normal adolescent prefrontal cortex, is involved in drug cue responses and is associated with relapse in animal models. In human drug addicts, imaging methods have detected increased activation in response to drug cues in reward- and habit-associated brain regions. These same methods can be applied more quantitatively to rodent models. Here, changes in neuronal activation in response to cocaine-conditioned cues were observed using functional magnetic resonance imaging in juvenile rats that were made to over-express either D1 receptors or green fluorescent protein by viral-mediated transduction. Reduced activation was observed in the amygdala and dopamine cell body regions in the low cue-preferring/control juvenile rats in response to cocaine cues. In contrast, increased activation was observed in the dorsal striatum, nucleus accumbens, prefrontal cortex, and dopamine cell bodies in high cue-preferring/D1 juveniles. The increase in cue salience that is mediated by increased D1 receptor density, rather than excessive cocaine experience, appears to underlie the transition from aversion to reward in cue-induced neural response and may form the basis for habit-forming vulnerability.

Background: We previously reported rapid mood elevation following an experimental magnetic resonance imaging procedure in depressed patients with bipolar disorder (BPD). This prompted the design, construction, and testing of a portable electromagnetic device that reproduces only the rapidly oscillating (1 kHz, <1 V/m) electromagnetic field of the experimental procedure, called low field magnetic stimulation (LFMS)., Methods: We used a randomized, double blind, sham controlled treatment protocol to study the effects of LFMS in a large group of stably medicated, depressed patients with either BPD (n = 41) or major depressive disorder (n = 22). Subjects received a single, 20-minute treatment. Change in mood was assessed immediately afterward using a visual analog scale (VAS), the 17-item Hamilton Depression Rating Scale (HDRS-17), and the Positive and Negative Affect Schedule scales., Results: Substantial improvement (>10% of baseline) in mood was observed following LFMS treatment relative to sham treatment for both diagnostic subgroups for our primary outcomes, the VAS and the HDRS-17. These differences were not statistically significant in primary analyses stratifying by diagnosis but were significant in secondary analyses combining data across the two diagnostic groups (p = .01 VAS, p = .02 HDRS-17). Rapid improvement in mood was also observed using the Positive and Negative Affect Schedule scales as secondary measures (positive affect scale p = .02 BPD, p = .002 combined group). A finite element method calculation indicates a broad penetration of the LFMS electric field throughout the cerebral cortex., Conclusions: Low field magnetic stimulation may produce rapid changes in mood using a previously unexplored range of electromagnetic fields., (© 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.)

Objective: In this study, we sought to explore brain activity in nicotine-dependent men in response to acute intravenous nicotine using pharmacological magnetic resonance imaging (phMRI)., Methods: phMRI was used to evaluate brain activity in response to 1.5 mg/70 kg intravenous nicotine or saline. The nicotine and saline were administered on different visits. The time courses of individual subjects' nicotine levels were used as regressors to assess neural activity relating to the infusions. The influence of smoking history and physiological measures on the response to nicotine were also investigated., Results: Greater lifetime exposure to cigarette smoking was significantly correlated with higher peak serum nicotine levels. PhMRI analysis of the differential response of nicotine compared to the saline condition showed distinctive activation patterns when analyzed with the (a) nicotine time course, (b) nicotine time course controlling for smoking history (pack years), and (c) pack years controlling for nicotine., Conclusions: These results suggest that smoking exposure history influences serum nicotine levels and the brain's response to nicotine. Alterations in brain activity may be a result of vascular and neuro-adaptations involved in drug exposure and addiction., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Witnessing domestic violence (WDV) is a traumatic childhood experience associated with increased risk for depression, posttraumatic stress disorder and reduced IQ scores. Specific affects of WDV on brain development have not been assessed. We sought to ascertain whether WDV was associated with abnormalities in white matter (WM) tract integrity using diffusion tensor imaging (DTI). Twenty subjects who witnessed domestic violence (16F/4M, mean age 22.4 ± 2.48 years) but were not physically or sexually abused were compared to 27 healthy controls (19F/8M, 21.9 ± 1.97 years) without exposure to trauma or Axis I and II disorders. DTI images were acquired with a 3T Siemens Trio scanner. Group differences in fractional anisotropy (FA), covaried by age, gender, parental education, perceived financial sufficiency, IQ and degree of exposure to parental verbal aggression were assessed using tract-based spatial statistics (TBSS), which projects FA values onto an alignment-invariant fiber tract representation. FA values in the inferior longitudinal fasciculus of left lateral occipital lobe were significantly lower (P<0.05 corrected for multiple comparison) in the WDV group. FA values correlated inversely with ratings of depression, anxiety, somatization, 'limbic irritability' and neuropsychological measures of processing speed. Measures of radial but not axial diffusivity were affected suggesting alterations in myelination. Degree of FA reduction was associated with duration of witnessing interparental verbal aggression and with exposure between ages 7 and 13 years. The inferior longitudinal fasciculus connects occipital and temporal cortex and is the main component of the visual-limbic pathway that subserves emotional, learning and memory functions that are modality specific to vision. This finding is consistent with the hypothesis that exposure to childhood maltreatment is associated with alterations in fiber pathways that convey the adverse experience to frontal, temporal or limbic regions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background Context: A recent study involving interbody fusion patients found that preoperative work status was significantly related to clinical outcome. In another study comparing the best and worst outcomes of total disc replacement, among a battery of variables analyzed, the only one that differentiated the best and worst outcome groups was the length of time off work before total disc replacement., Purpose: The purpose of this study was to determine if there was a relationship between the length of time off work and treatment outcome at 24-month follow-up. If such a relationship existed, a secondary study objective would be to determine if a duration of work could be identified beyond which would be associated with compromised clinical outcome., Study Design and Setting: Data were collected prospectively from randomized clinical trials comparing total disc replacement with lumbar fusion conducted at a single site., Patient Sample: A database of 232 patients enrolled in one of two Food and Drug Administration-regulated trials comparing total disc replacement with fusion for the treatment of symptomatic disc degeneration was the basis of the study group. Only patients who had reached 24-month follow-up were included. The 28 patients who were not employed by choice preoperatively were not included in the analysis., Outcome Measures: Primary outcome measures used were visual analog scales (VAS) assessing pain and Oswestry disability index., Methods: The length of time off work before surgery was recorded in weeks. The mean percentage improvement between preoperative and 24-month follow-up scores were analyzed., Results: There was a significant relationship between duration off work preoperatively and clinical outcome (p<.05). The length of time off work preoperatively was more strongly related to outcome than was surgery type, insurance type, job demand, or preoperative VAS and Oswestry scores. Further analysis of the data identified a window of approximately 0 to 13 weeks off work preoperatively that was related to significantly greater improvements on visual analog scales (VAS) and Oswestry scores after surgery compared with patients who were off work for more than 13 weeks preoperatively. Although the subgroup off work for more than 13 weeks improved significantly from their preoperative status, the improvement was not as great as in the subgroup off work for a shorter duration., Conclusions: The results of this study found that patients off work for a longer duration before surgery improved significantly postoperatively, but had less favorable clinical outcomes than patients off work for a lesser duration. This study suggests a window of approximately 13 weeks off work before surgery after which clinical improvement is reduced. Implications of this finding may be that once a patient becomes unable to work for an extended period, more rigorous psychological screening may be in order as well as perhaps engaging in more rigorous rehabilitation after surgery. Further investigation is needed to determine if the 13 weeks identified in this study is applicable to other populations.

Background: Psychiatric sequelae of exposure to parental verbal abuse (PVA) appear to be comparable with that of nonfamilial sexual abuse and witnessing domestic violence. Diffusion tensor imaging (DTI) was used to ascertain whether PVA was associated with abnormalities in white matter (WM) tract integrity., Methods: 1271 healthy young adults were screened for exposure to childhood adversity. Diffusion tensor imaging was collected on 16 unmedicated subjects with history of high-level exposure to PVA but no other form of maltreatment (4 male/12 female subjects, mean age 21.9 +/- 2.4 years) and 16 healthy control subjects (5 male/11 female subjects, 21.0 +/- 1.6 years). Group differences in fractional anisotropy (FA), covaried by parental education and income, were assessed using tract-based spatial statistics (TBSS)., Results: Three WM tract regions had significantly reduced FA: 1) arcuate fasciculus in left superior temporal gyrus, 2) cingulum bundle by the posterior tail of the left hippocampus, and 3) the left body of the fornix. Fractional anisotropy in these areas was strongly associated with average PVA scores (r(s) = -.701, -.801, -.524, respectively) and levels of maternal verbal abuse. Across groups, FA in region 1 correlated with verbal IQ and verbal comprehension index. Fractional anisotropy in region 2 was inversely associated with ratings of depression, dissociation, and limbic irritability. Fractional anisotropy in region 3 was inversely correlated with ratings of somatization and anxiety., Conclusions: Exposure to PVA may be associated with alteration in the integrity of neural pathways with implications for language development and psychopathology.

Objectives: Diffusion tensor magnetic resonance imaging (DT-MRI) assesses the integrity of white matter (WM) tracts in the brain. Children with bipolar disorder (BPD) may have WM abnormalities that precede illness onset. To more fully examine this possibility, we scanned children with DSM-IV BPD and compared them to healthy peers and children at risk for BPD (AR-BPD), defined as having a first-degree relative with the disorder., Methods: Ten children with BPD, eight healthy controls (HC), and seven AR-BPD, similar in age, had MRI scans on a 1.5 Tesla GE scanner, including a standard DT-MRI sequence (T2-EPI) with 25 axial slices. Fractional anisotropy (FA) values were compared between groups to determine regions of significant difference (p < 0.05)., Results: Compared to HC, children with BPD had decreased FA in right and left superior frontal tracts, including the superior longitudinal fasciculus I (SLF I) and the cingulate-paracingulate WM (CG-PAC(WM)). In addition, the BPD group had reduced FA in left orbital frontal WM and the right corpus callosum body. Compared to AR-BPD, children with BPD showed reduced FA in the right and left CG-PAC(WM). Both the BPD and AR-BPD groups showed reduced FA relative to HC in bilateral SLF I., Conclusions: The bilateral SLF I finding in both the BPD and AR-BPD groups may represent a trait-based marker or endophenotype of the disorder. The finding of decreased FA in the right and left CG-PAC(WM) in children with BPD compared to the other two groups may represent a disease-state related finding.

Objectives: An increased incidence in white matter abnormalities is among the most frequently reported brain change in patients with bipolar disorder. The objective of the present study was to examine white matter tract integrity, using diffusion tensor imaging (DTI), in bipolar patients and healthy comparison subjects., Methods: Eleven DSM-IV bipolar I patients and 10 healthy age- and sex-matched controls were studied. DTI data were acquired on a 1.5 Tesla scanner. Fractional anisotropy (FA) and diffusivity (trace) were determined from axial images using region of interest (ROI) analyses. The ROIs were manually placed in the midline and forward projecting arms of the genu (anterior) and the midline of the splenium (posterior) of the corpus callosum., Results: Bipolar patients had significantly higher FA in the midline of the genu compared with healthy controls. Regional white matter differences were also observed, with significantly lower FA in the genu than forward projecting regions in both groups and lower FA in the genu than the splenium in controls., Conclusions: Diffusion tensor imaging revealed significant microstructural differences in the genu, as measured by elevated FA in bipolar patients compared with healthy controls. These preliminary findings further support the hypothesis that anomalous frontal brain mechanisms may be associated with bipolar disorder.

Rapid maturational brain changes occur during adolescence--a time associated with risk-taking behaviors and improvements in cognition. The present study examined the relationship between white matter (WM) microstructure, impulsive behavior and response inhibition in female and male adolescents. Twenty-one healthy adolescents underwent diffusion tensor imaging using a 3.0-T magnetic resonance imaging system. Impulse control was assessed using the Bar-On Emotional Quotient Inventory, Youth Version. Response inhibition was assessed using the Stroop Color-Word Interference Test. Fractional anisotropy (FA), a measure of WM coherence, and trace, a measure of overall diffusivity, were determined from voxels manually placed in the midline and in the left and right forward-projecting arms of the genu and the splenium of the corpus callosum. Sex-specific differences were observed for the relationship between FA and impulsive behavior in the right anterior callosum for males and in the splenium for females. Males, compared to females, displayed significantly higher FA in the left WM region. Although trace was not associated with impulse control, trace in the genu (for females) and splenium (males and females) was associated with Stroop performance. Regional differences in trace also were evident, with lower values in the splenium observed than in all other regions. Although the latter significantly improved with age, no sex differences in impulse control or in Stroop performance were detected. The present findings provide supporting evidence for sex-related differences in the development of WM microstructure during adolescence. These data further suggest a neurobiological mechanism underlying some of the emotional and cognitive changes commonly observed in males versus females during the adolescent period.

Context: Memory deficits are common in schizophrenia. Recent studies have demonstrated that relational memory is particularly impaired., Objective: To study the neural correlates of relational memory in schizophrenia using functional magnetic resonance imaging., Design: Cross-sectional case-control study., Setting: Academic medical center. Subjects Twenty patients with schizophrenia and 17 control subjects., Main Outcome Measures: Behavioral performance and brain activity were assessed during the discrimination of previously seen and novel pairs of visual stimuli, which varied in the degree of relational memory load. We performed whole-brain and region-of-interest (hippocampus) analyses., Results: Schizophrenic subjects displayed normal activation of the presupplementary motor area and ventral prefrontal cortex, but significantly decreased recruitment of the right parietal cortex and anterior cingulate cortex when discriminating novel pairs derived from a sequence of stimuli. Discrimination accuracy was decreased in schizophrenia only when the flexible representation of a sequence was required. This selective deficit was associated with decreased activation of the right parietal cortex and left hippocampus., Conclusions: Schizophrenia is characterized by a specific deficit of relational memory, which is associated with impaired function of the parietal cortex and hippocampus. Abnormal relational memory may be at the core of 2 prominent features of schizophrenia, ie, cognitive deficits and psychosis.

Background: Evidence suggests that a novel type of magnetic resonance imaging (MRI) scan called echo planar magnetic resonance spectroscopic imaging (EP-MRSI) has mood-elevating actions in humans during the depressive phases of bipolar disorder. We examined whether a low-energy component of EP-MRSI (low-field magnetic stimulation [LFMS]) has antidepressant-like, locomotor-stimulating, or amnestic effects in rats., Methods: We examined the effects of LFMS on immobility in the forced swim test (FST) and activity within an open field in separate groups of rats. After exposure to forced swimming, rats received LFMS (three 20-min sessions at 1.5 G/cm and .75 V/m) before behavioral testing. We also examined the effects of LFMS on fear conditioning (FC), a learning paradigm that also involves exposure to stressful conditions., Results: Low-field magnetic stimulation reduced immobility in the FST, an antidepressant-like effect qualitatively similar to that of standard antidepressants. Low-field magnetic stimulation did not alter locomotor activity or FC., Conclusions: Low-field magnetic stimulation has antidepressant-like effects in rats that seem unrelated to locomotor-activating or amnestic effects. These findings raise the possibility that electromagnetic fields can affect the brain biology and might have physiologic consequences that offer novel approaches to therapy for psychiatric disorders. These same consequences might render MRI-based scans more invasive than previously appreciated.

Objective: The authors hypothesized that changes in brain membrane composition resulting from omega-3 fatty acid administration in patients with bipolar disorder would result in greater membrane fluidity, as detected by reductions in T(2) values., Method: Women with bipolar disorder (N=12) received omega-3 fatty acids for 4 weeks. A cohort of bipolar subjects (N=9) and a group without bipolar disorder (N=12) did not receive omega-3 fatty acids. T(2) values were acquired at baseline and after 4 weeks., Results: Bipolar subjects who received omega-3 fatty acids had significant decreases in T(2). There was a dose-dependent effect when the bipolar omega-3 fatty acid group was subdivided into high- and low-dose cohorts., Conclusions: Omega-3 fatty acids lowered T(2) values, consistent with the hypothesis that the fluidity of cell membranes was altered. Further studies are needed to clarify the significance of alterations in brain physiology induced by omega-3 fatty acids, as reflected in T(2) values.

We examined whether lateral visual field stimulation (LSTM) could activate contralateral extrastriate cortical areas as predicted by a large experimental literature. We asked seven unscreened, control subjects to wear glasses designed to allow vision out of either the left (LVF) or right lateral visual field (RVF) depending upon which side the subject looked toward. Each subject participated in a block design functional magnetic resonance imaging (fMRI) study with alternating 30-s epochs in which he was asked to look to one side and then the other for a total of five epochs. On each side of the bore of the scanner, we taped a photograph for the subject to view in the LVF and RVF. The data were analyzed with SPM99 using a fixed effect, box-car design with contrasts for the LVF and the RVF conditions. Both LVF and RVF conditions produced the strongest fMRI activation in the contralateral occipitotemporal and posterior parietal areas as well as the contralateral dorsolateral prefrontal cortex. LSTM appears to increase contralateral fMRI activation in striate and extrastriate cortical areas as predicted by earlier studies reporting differential cognitive and/or emotional effects from unilateral sensory or motor stimulation.

Objective: Anecdotal reports have suggested mood improvement in patients with bipolar disorder immediately after they underwent an echo-planar magnetic resonance spectroscopic imaging (EP-MRSI) procedure that can be performed within clinical MR system limits. This study evaluated possible mood improvement associated with this procedure., Method: The mood states of subjects in an ongoing EP-MRSI study of bipolar disorder were assessed by using the Brief Affect Scale, a structured mood rating scale, immediately before and after an EP-MRSI session. Sham EP-MRSI was administered to a comparison group of subjects with bipolar disorder, and actual EP-MRSI was administered to a comparison group of healthy subjects. The characteristics of the electric fields generated by the EP-MRSI scan were analyzed., Results: Mood improvement was reported by 23 of 30 bipolar disorder subjects who received the actual EP-MRSI examination, by three of 10 bipolar disorder subjects who received sham EP-MRSI, and by four of 14 healthy comparison subjects who received actual EP-MRSI. Significant differences in mood improvement were found between the bipolar disorder subjects who received actual EP-MRSI and those who received sham EP-MRSI, and, among subjects who received actual EP-MRSI, between the healthy subjects and the bipolar disorder subjects and to a lesser extent between the unmedicated bipolar disorder subjects and the bipolar disorder subjects who were taking medication. The electric fields generated by the EP-MRSI scan were smaller (0.7 V/m) than fields used in repetitive transcranial magnetic stimulation (rTMS) treatment of depression (1-500 V/m) and also extended uniformly throughout the head, unlike the highly nonuniform fields used in rTMS. The EP-MRSI waveform, a 1-kHz train of monophasic trapezoidal gradient pulses, differed from that used in rTMS., Conclusions: These preliminary data suggest that the EP-MRSI scan induces electric fields that are associated with reported mood improvement in subjects with bipolar disorder. The findings are similar to those for rTMS depression treatments, although the waveform used in EP-MRSI differs from that used in rTMS. Further investigation of the mechanism of EP-MRSI is warranted.