Randomized Controlled Trial of a Brief Mindfulness-Based Intervention for Suicidal Ideation Among Veterans.

INTRODUCTION: This study was a preliminary evaluation of a manualized, brief mindfulness-based intervention (MB-SI) for veterans with suicidal ideation (SI), admitted into an inpatient psychiatric unit (IPU). MATERIALS AND METHODS: A randomized, controlled pilot study of 20 veterans aged 18-70 years with SI, admitted into a psychiatric unit, assigned to treatment as usual (TAU) or MB-SI groups. Outcome data were collected at three time points: preintervention (beginning of first session), postintervention (end of last session), and 1-month postintervention. Primary outcomes were safety and feasibility. Secondary outcome measures were SI and behavior, mindfulness state and trait, cognitive reappraisal, and emotion regulation. Additionally, psychiatric and emergency department admissions were examined. Data analysis included Generalized Linear Models, Wilcoxon Signed-Rank, Mann-Whitney U, and Fisher's exact tests for secondary outcomes. RESULTS: Mindfulness-based intervention for suicidal ideation was feasible to implement on an IPU, and there were no associated adverse effects. Mindfulness-based intervention for suicidal ideation participants experienced statistically significant increase in Toronto Mindfulness Scale curiosity scores 1-month postintervention compared to preintervention and greater Toronto Mindfulness Scale decentering scores 1-month postintervention compared to TAU. Emotion Regulation Questionnaire Reappraisal scores significantly increased for the MB-SI group and significantly decreased for TAU over time. IPU and emergency department admissions were not statistically different between groups or over time. Both TAU and MB-SI participants experienced a significant reduction in Columbia-Suicide Severity Rating Scale-SI scores after the intervention. MB-SI participants experienced a higher increase in Five-Facet Mindfulness Questionnaire scores postintervention compared to TAU. CONCLUSIONS: Mindfulness-based intervention for suicidal ideation is feasible and safe to implement among veterans during an inpatient psychiatric admission with SI, as it is not associated with increased SI or adverse effects. Preliminary evidence suggests that MB-SI increases veterans' propensity to view experiences with curiosity while disengaging from experience without emotional overreaction. Further, more rigorous research is warranted to determine efficacy of MB-SI. TRIAL REGISTRATION: The clinicaltrials.gov registration number is NCT04099173 and dates are July 16, 2019 (initial release) and February 24, 2022 (most recent update).

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Abnormal functional connectivity of the medial cortex in euthymic bipolar II disorder.

This project utilized functional MRI (fMRI) and a motor activation paradigm to investigate neural circuitry in euthymic bipolar II disorder. We hypothesized that circuitry involving the cortical midline structures (CMS) would demonstrate abnormal functional connectivity. Nineteen subjects with recurrent bipolar disorder and 18 controls were studied using fMRI and a motor activation paradigm. We used functional connectivity analyses to identify circuits with aberrant connectivity. We found increased functional connectivity among bipolar subjects compared to healthy controls in two CMS circuits. One circuit included the medial aspect of the left superior frontal gyrus and the dorsolateral region of the left superior frontal gyrus. The other included the medial aspect of the right superior frontal gyrus, the dorsolateral region of the left superior frontal gyrus and the right medial frontal gyrus and surrounding region. Our results indicate that CMS circuit dysfunction persists in the euthymic state and thus may represent trait pathology. Future studies should address whether these circuits contribute to relapse of illness. Our results also suggest the possibility that aberrations of superior frontal circuitry may impact default mode network and cognitive processes.

Striatal circuit function is associated with prior self-harm in remitted major depression.

The neural processes underlying suicide risk are incompletely characterized. This project utilized functional MRI (fMRI) to determine whether a history of self-harm was associated with striatal circuit function in recurrent major depression in remission. Twenty unmedicated subjects with recurrent major depression and 21 controls were studied using fMRI and a motor activation paradigm. We used functional connectivity analyses to identify circuits with aberrant connectivity. We also used correlational analyses to determine whether functional connectivity was associated with a history of self-harm. There was a significant association between history of self-harm and functional connectivity of a striatal-motor circuit. Additionally, striatal and cortical midline circuits exhibited decreased functional connectivity in remitted unipolar depression as compared to controls. Our previous study of individuals experiencing an episode of depression indicated an association between striatal circuitry and a history of self-harm. That study, along with the results reported herein suggests striatal circuit function may play a key role in the neurobiology of suicide and self-harm risk in recurrent major depression. Our results also indicate that both striatal and CMS circuit dysfunction persists in the euthymic state of recurrent major depression and thus may represent trait pathology.

Differences in functional connectivity in major depression versus bipolar II depression.

BACKGROUND: Objective methods of differentiating unipolar versus bipolar depression would enhance our ability to treat these disorders by providing more accurate diagnoses. One first step towards developing diagnostic methodology is determining whether brain function as assessed by functional MRI (fMRI) and functional connectivity analyses might differentiate the two disorders. METHODS: Fourteen subjects with bipolar II depression and 26 subjects with recurrent unipolar depression were studied using fMRI and functional connectivity analyses. RESULTS: The first key finding of this study was that functional connectivity of the right posterior cingulate cortex differentiates bipolar II and unipolar depression. Additionally, results suggest that functional connectivity of this region is associated with suicidal ideation and depression severity in unipolar but not bipolar II depression. LIMITATIONS: The primary limitation is the relatively small sample size, particularly for the correlational analyses. CONCLUSIONS: The functional connectivity of right posterior cingulate cortex may differential unipolar from bipolar II depression. Further, connectivity of this region may be associated with depression severity and suicide risk in unipolar but not bipolar depression.

Aberrant functional connectivity of cortico-basal ganglia circuits in major depression.

There is considerable evidence of functional abnormalities of the cortico-basal ganglia circuitry in affective disorders. However, it has been unknown whether this represented primary pathology within these circuits or altered activation as a result of aberrant input from other brain regions. The aim of this study was to test the hypothesis that cortico-basal ganglia circuit dysfunction represents primary pathology in unipolar depression. Eighteen male subjects with recurrent unipolar depression and eighteen controls without psychiatric illness were studied using functional MRI and functional connectivity analyses. All unipolar subjects were unmedicated and without current psychiatric comorbidity. Compared to controls, unipolar subjects exhibited altered connectivity between bilateral subcortical components of the circuitry (putamen-thalamus) and left hemisphere input and output components. Results provided evidence that functional abnormalities of these circuits represent primary pathology. Further, we found that age of onset but not duration of illness impacts circuit function. These findings suggest that the cortico-basal ganglia circuitry is likely one of several loci of primary pathology in major depression. Additionally, early age of onset is associated with greater circuit abnormality and as such may impact clinical characteristics and/or treatment response through a mechanism of decreasing functional connectivity of some circuit segments. Finally, altered cortico-basal ganglia circuit connectivity with cortical regions (anterior cingulate, inferior frontal gyrus and sensorimotor) may contribute to the emotional dysregulation, impaired emotional recognition and psychomotor symptoms associated with unipolar illness.

Striatal and cortical midline circuits in major depression: implications for suicide and symptom expression.

BACKGROUND: In major depression, the neural mechanisms underlying suicide related thoughts and behaviors as well as the expression of other depressive symptoms are incompletely characterized. Evidence indicates that both the striatum and cortical midline structures (CMS) may be involved with both suicide and emotional dysregulation in unipolar illness. The aim of this study was to identify striatal-CMS circuits associated with current depression severity and suicidal ideation (SI) as well as a history of self-harm. METHODS: Twenty-two male subjects with recurrent unipolar depression were studied using functional MRI. All subjects were unmedicated and without current psychiatric comorbidity. Correlational analyses were used to determine whether striatal-CMS functional connectivity was associated with any of the three clinical variables. RESULTS: A network involving the bilateral striatum and anterior CMS was found to be associated with depressive symptom severity. Current SI was associated with a similar but less extensive circuit in the left hemisphere. A distinct striatal motor/sensory network was associated with self-harm behaviors, but not current SI or depression severity. CONCLUSIONS: The striatal-anterior CMS circuit likely plays a significant role in the expression of depressive symptoms and SI. In contrast, a striatum-motor/sensory cortex network may be a trait marker of suicide-related behaviors. If replicated, this result might eventually lead to the development of a biomarker that would be useful for studies of pharmacologic and/or psychotherapeutic suicide prevention interventions.

Aberrant emotional processing in posterior cortical midline structures in bipolar II depression.

Bipolar II depression is a serious and disabling illness associated with significant impairment and high rates of suicide attempts. However, mechanisms underlying emotional dysregulation in this condition are poorly characterized. The goal of this work was to investigate one component of emotional processing in this disorder, brain activation associated with exposure to emotional faces. Functional MRI was used to study 16 unmedicated male subjects with bipolar II depression and 19 healthy male controls. The activation paradigm exposed subjects to happy, fearful and neutral faces. The two key findings of this study were as follows. First, bipolar subjects demonstrated significantly decreased activation in response to happy facial expression in the left posterior cortical midline structures (CMS) and frontal cortex. Second, depression severity was positively correlated with activation of the posterior CMS and other regions. Our results suggest that mechanisms involving CMS dysfunction may play a role in the neurobiology of bipolar II depression as has been demonstrated for unipolar illness. Further investigations of CMS function in bipolar spectrum disorders are warranted.

Striatal and cortical midline activation and connectivity associated with suicidal ideation and depression in bipolar II disorder.

BACKGROUND: Considerable evidence implicates dysfunction of striatal and cortical midline structure (CMS) circuitry in mood disorders. Whether such aberrations exist in bipolar II depression is unknown. METHODS: Sixteen unmedicated subjects with bipolar II depression and 19 healthy controls were studied using functional MRI and a motor activation paradigm. Analyses of both activation and functional connectivity were conducted. RESULTS: A history of suicidal ideation (SI) was negatively correlated with activation of the left putamen while depression severity was positively correlated with activation of the left thalamus. The superior bilateral putamen was simultaneously correlated with depression severity and anti-correlated with SI. Striatal functional connectivity was altered with the bilateral CMS and right inferior parietal lobule. Depression severity was correlated with strength of connectivity between the bilateral striatum and the right lingual gyrus and left cerebellum. LIMITATIONS: Only males experiencing an episode of major depression were studied. CONCLUSIONS: Striatal and CMS circuit abnormalities likely contribute to the neurobiology of bipolar II depression. Altered connectivity of the striatum may directly impact depression severity. Further, dissociable components of activation associated with depression severity and suicidal ideation may exist. Finally, the motor activation paradigm used in this study appears to be a useful probe of some neural processes underlying bipolar II depression.

Reliability of fMRI motor tasks in structures of the corticostriatal circuitry: implications for future studies and circuit function.

The corticostriatal circuits are important information processing networks. There is evidence that these circuits may be dysfunctional in a variety of neuropsychiatric conditions ranging from Parkinson's disease to bipolar disorder. Cross-sectional fMRI studies may clarify normal circuit function, and longitudinal studies may provide information on changes related to age in control subjects, as well as illness progression and treatment response in patient groups. In this paper, we report a comprehensive analysis of the utility of several motor tasks as cross-sectional and longitudinal probes of corticostriatal function in terms of their activation strength and reliability. Our findings suggest that the motor tasks studied can be useful probes of corticostriatal function for studies utilizing group comparisons. However, longitudinal clinical studies in which individual results are important will need to take into account wide variation in individual activation and reliability. For example, measures of activation strength and reliability based on percent signal change display a dichotomy between simple motor tasks, which have high reliability and low activation, and complex tasks, which have lower reliability and higher activation. Size and overlap ratios calculated from activation maps produced a different view of reliability than intraclass correlation coefficients (ICC) based on percent signal change. Finally, these results suggest that the corticostriatal circuitry exhibit individualized responses to motor adaptation.

An fMRI motor activation paradigm demonstrates abnormalities of putamen activation in females with panic disorder.

BACKGROUND: The neurobiology of panic disorder is incompletely understood. The aim of this study was to determine if functional abnormalities of the putamen occur in panic disorder. METHODS: Activation patterns of 12 female subjects with panic disorder were compared to 18 female healthy controls using functional MRI at 3 T. A motor activation paradigm was used to probe putamen function. RESULTS: A complex motor activation paradigm for the non-dominant hand revealed decreased activation of the bilateral putamen among subjects with panic disorder. LIMITATIONS: The sample size was a relatively small cohort of non-depressed females. Further, some panic disorder subjects were taking medications and/or had comorbid conditions. However, second-level regression analyses did not reveal any correlations between medication use or comorbidity and activation patterns demonstrated by the non-dominant hand complex task. Finally, we used a post-hoc approach to determine the magnitude of global fMRI signal as a surrogate index of the global cerebral blood flow as a means of controlling for possible confounds from reduction of BOLD signal secondary to cerebral vasoconstriction resulting from possible hyperventilation among panic subjects. A more compelling approach would have been to record the respiratory data from subjects during scanning. CONCLUSIONS: Our findings suggest that putamen dysfunction occurs in at least some cases of panic disorder. We also provide preliminary evidence that a complex motor task for the non-dominant hand is a useful probe of putamen function in this disorder.

Putamen coactivation during motor task execution.

Models of corticostriatal motor circuitry have focused on the role of the circuit in the hemisphere of the motor cortex providing primary control (contralateral to the movement). We used functional magnetic resonance imaging and functional connectivity analyses to study circuit function in both the controlling and noncontrolling hemispheres. During the completion of a unilateral motor task with either hand, each putamen nucleus demonstrated strong coactivation with structures in both hemispheres. The putamen in the noncontrolling hemisphere (ipsilateral to the movement) coactivated more strongly with the controlling motor cortex than with the noncontrolling cortex. These findings suggest that the two corticostriatal circuits are functionally integrated. New circuit models based on functional connectivity may need to be developed.

Motor deactivation in the human cortex and basal ganglia.

We used a functional magnetic resonance imaging motor activation paradigm for both hands and functional connectivity analyses to investigate motor deactivation. These analyses revealed ipsilateral (to the task) postcentral gyrus connectivity with the ipsilateral primary motor cortex as well as contralateral cerebellum for both hands. Analyses using default-mode network nodes as seed regions revealed connectivity patterns similar to previous studies of the default network and therefore provide evidence that this network is demonstrable using a synchronized motor activation paradigm. We did not find evidence suggesting that motor deactivation represents modulation of the default mode network. Therefore, motor deactivation is likely a motor-specific process. Finally, we found no evidence of basal ganglia circuit deactivation, which suggests that the two-pathway hypothesis of frontal-subcortical circuit function may be incomplete.

A functional MRI study of a paced motor activation task to evaluate frontal-subcortical circuit function in bipolar depression.

The primary aim of this functional magnetic resonance imaging (fMRI) study was to test the utility of a paced motor activation task to evaluate frontal-subcortical (FSC) circuit function in bipolar depression. A secondary aim was to determine if utilizing both a motor and cognitive activation paradigm (Stroop) would provide information about the potential role of FSC dysfunction in the cognitive symptoms of bipolar depression. Analysis of the control group (n=15) alone revealed that the motor task activated FSC structures. Comparison of the control to bipolar group (n=14) revealed significant differences between the groups in striatum as well as cortical areas with FSC connections in response to the non-dominant-hand motor task. In response to the Stroop, there were significant differences between the groups in portions of the bilateral posterior cingulate and occipital cortex, but not in FSC structures. While these results must be considered preliminary, this work supports further studies of paced motor tasks to probe FSC function. Further, it suggests that the use of both a cognitive and motor task in the same study provides useful information about brain function. Finally, it supports the literature implicating FSC circuit abnormalities in bipolar disorder.

Clinical characteristics and health service use of veterans with comorbid bipolar disorder and PTSD.

OBJECTIVE: This study aimed to increase the understanding of the clinical characteristics and utilization of health services among veterans with comorbid bipolar disorder and posttraumatic stress disorder (PTSD). METHODS: A retrospective chart review was conducted that examined the clinical and health service use data of 139 male veterans with bipolar disorder (N=49), PTSD (N=49), or comorbid bipolar disorder and PTSD (N=41) who obtained services over two years from the Department of Veterans Affairs Salt Lake City Health Care System. RESULTS: Compared with patients with bipolar disorder or those with PTSD alone, those with both conditions had significantly higher mean Clinical Global Impression-Severity scores and required more frequent inpatient psychiatric treatment. Patients with both conditions and those with bipolar disorder were significantly less likely to have received psychotherapy and antidepressant pharmacotherapy than patients with PTSD. CONCLUSIONS: Patients with both conditions have a more severe illness course than those with bipolar disorder alone. Psychotherapy and antidepressant pharmacotherapy may be underutilized among patients with comorbid bipolar disorder and PTSD.

A preliminary longitudinal fMRI study of frontal-subcortical circuits in bipolar disorder using a paced motor activation paradigm.

BACKGROUND: Compelling evidence suggests abnormal functioning of frontal-subcortical (FSC) circuits in bipolar disorder, but it is unknown whether these are state or trait abnormalities. Longitudinal functional neuroimaging studies may help clarify this issue. However, studies to date have not determined which activation paradigms may be most useful for this purpose. A paced motor task has the potential to be more reliable than cognitive or emotional activation paradigms. METHODS: To evaluate the utility of a paced motor activation task as a longitudinal probe of FSC function, we conducted fMRI scans of 10 subjects with bipolar I disorder when euthymic. We compared activation patterns to the same subjects who had been previously scanned during an episode of depression. RESULTS: The paced motor task resulted in activation in the bilateral striatum which was consistent across mood states as well as greater activation among the subjects when euthymic in the right anterior cingulate and medial frontal gyrus. LIMITATIONS: The study sample was small (10 subjects) which limits generalizability of findings. CONCLUSIONS: To our knowledge, this is the first longitudinal study of bipolar illness utilizing a paced motor task. These findings suggest that a paced motor task is useful as a longitudinal probe of both state and trait function in bipolar disorder. Further, this study provides preliminary evidence that striatal functional abnormalities may represent a trait characteristic.

Wide-field Fizeau imaging telescope: experimental results.

A nine-aperture, wide-field Fizeau imaging telescope has been built at the Lockheed-Martin Advanced Technology Center. The telescope consists of nine, 125 mm diameter collector telescopes coherently phased and combined to form a diffraction-limited image with a resolution that is consistent with the 610 mm diameter of the telescope. The phased field of view of the array is 1 murad. The measured rms wavefront error is 0.08 waves rms at 635 nm. The telescope is actively controlled to correct for tilt and phasing errors. The control sensing technique is the method known as phase diversity, which extracts wavefront information from a pair of focused and defocused images. The optical design of the telescope and typical performance results are described.