Felipe A. Jain

Subthalamic Nucleus Discharge Patterns during Movement in the Normal Monkey and Parkinsonian Patient

The pathophysiology of Parkinson disease (PD) is characterized by derangements in the discharge rates, bursting patterns, and oscillatory activity of basal ganglia (BG) neurons. In this study, subthalamic nucleus (STN) neuronal activity patterns in humans with PD were compared with that in the normal monkey during performance of similar volitional movements. Single-unit STN recordings were collected while PD patients and animals moved a joystick in the direction of targets presented on a monitor. When discharge rates in all PD human and normal monkey neurons were compared, no significant differences were observed. However, when neurons were classified by peri-movement response type (i.e., excited, inhibited, or unresponsive to movement) statistical differences were demonstrated - most significantly among PD excited neurons. Analysis of burst activity demonstrated inter- and intra-burst activities were greater in the PD human compared to the monkey irrespective of neuronal response type. Moreover, simultaneously recorded neurons in the human demonstrated consistent oscillatory synchronization at restricted frequency bands, whereas synchronized oscillatory neurons in the monkey were not restricted to distinct frequencies. During movement, discharge and burst rates were positively correlated, independent of subject or neuronal response type; however, rates and oscillatory activity were more strongly correlated in the PD human than the normal monkey. Interestingly, across all domains of analysis, STN neurons in PD demonstrated reduced response variability when compared to STN neurons in the normal monkey brain. Thus, the net effect of PD may be a reduction in the physiological degrees of freedom of BG neurons with diminished information carrying capacity.

Predictive socioeconomic and clinical profiles of antidepressant response and remission.

There are many prognostic factors for treatment outcome in major depressive disorder (MDD). The predictive power of any single factor, however, is limited. We aimed to develop profiles of antidepressant response and remission based upon hierarchical combinations of baseline clinical and demographic factors.

Critical Analysis of the Efficacy of Meditation Therapies for Acute and Subacute Phase Treatment of Depressive Disorders: A Systematic Review

BACKGROUND Recently, the application of meditative practices to the treatment of depressive disorders has met with increasing clinical and scientific interest, owing to a lower side-effect burden, potential reduction of polypharmacy, and theoretical considerations that such interventions may target some of the cognitive roots of depression. OBJECTIVE We aimed to determine the state of the evidence supporting this application. METHODS Randomized controlled trials of techniques meeting the Agency for Healthcare Research and Quality definition of meditation, for participants having clinically diagnosed depressive disorders, not currently in remission, were selected. Meditation therapies were separated into praxis (i.e., how they were applied) components, and trial outcomes were reviewed. RESULTS 18 studies meeting the inclusion criteria were identified, encompassing 7 distinct techniques and 1173 patients. Mindfulness-Based Cognitive Therapy comprised the largest proportion of studies. Studies including patients having acute major depressive episodes (n = 10 studies), and those with residual subacute clinical symptoms despite initial treatment (n = 8), demonstrated moderate to large reductions in depression symptoms within the group, and relative to control groups. There was significant heterogeneity of techniques and trial designs. CONCLUSIONS A substantial body of evidence indicates that meditation therapies may have salutary effects on patients having clinical depressive disorders during the acute and subacute phases of treatment. Owing to methodologic deficiencies and trial heterogeneity, large-scale, randomized controlled trials with well-described comparator interventions and measures of expectation are needed to clarify the role of meditation in the depression treatment armamentarium.

Heart rate variability and treatment outcome in major depression: a pilot study.

Variations in heart rate variability (HRV) have been associated with major depressive disorder (MDD), but the relationship of baseline HRV to treatment outcome in MDD is unclear. We conducted a pilot study to examine associations between resting baseline HRV and MDD treatment outcome. We retrospectively tested several parameters of HRV in an MDD treatment study with escitalopram (ESC, N=26) to generate a model of how baseline HRV related to treatment outcome, and cross-validated the model in a separate trial of MDD treatment with Iyengar yoga (IY, N=16). Lower relative power of very low frequency (rVLF) HRV at baseline predicted improvement in depressive symptoms when adjusted for age and gender (R2>.43 and p<0.05 for both trials). Although vagal parasympathetic measures were correlated with antidepressant treatment outcome, their predictive power was not significant after adjusting for age and gender. In conclusion, baseline resting rVLF was associated with depression treatment outcome in two independent MDD treatment studies. These results should be interpreted with caution due to limited sample size, but a strength of this study is its validation of the rVLF predictor in an independent sample. rVLF merits prospective confirmation as a candidate biomarker.

Individual risk profiles for postoperative delirium after joint replacement surgery.

BACKGROUND Delirium occurs in nearly half of older patients after joint replacement surgery. However, risk profiles for developing delirium have not been established. OBJECTIVE We sought to identify risk profiles for delirium in patients following joint replacement surgery. METHOD Based on data from a randomized, double-blind, placebo-controlled trial of olanzapine (10 mg) as delirium prophylaxis in 400 patients (67-81 years old) undergoing hip or knee replacement surgery, we performed a signal detection analysis to develop risk profiles for postsurgical delirium (using baseline patient characteristics, iatrogenic factors, and physiologic response parameters). RESULTS Olanzapine reduced the incidence of delirium by 63% relative to placebo. Among patients receiving placebo, those with an ASA class = 3 and age ≥ 74 years had a 64% risk of delirium. Those with ASA class < 3 still had a 67% risk of delirium if postoperative oxygen saturation was < 95%. Patients who received olanzapine had an 83% risk of developing delirium if they received ≥ 42.5 mg equivalents of intra-operative morphine, were ≥ 74 years old, and had a mean arterial pressure (MAP) < 90 mm Hg at the presurgical screening visit. Patients with the lowest risk (6%) of developing delirium received olanzapine had a hematocrit ≥ 28%, and a presurgical MAP ≥ 90. CONCLUSION Although use of prophylactic olanzapine reduced the incidence of delirium, subsets of patients remained likely to develop delirium. The risk of developing delirium may be reduced through prophylactic dispensation of olanzapine, maintaining optimal perfusion and oxygenation, and limiting intra-operative opioids.

Feasibility of Central Meditation and Imagery Therapy for dementia caregivers

Family dementia caregivers are at high risk of depression and burnout. We assessed the feasibility of Central Meditation and Imagery Therapy for Caregivers (CMIT‐C), a novel 8‐week group meditation and guided imagery group therapy program, for dementia caregivers reporting stress because of caregiving responsibilities.

Neurophysiologic Correlates of Headache Pain in Subjects With Major Depressive Disorder.

Background. Headache pain is often comorbid with major depressive disorder (MDD) and is associated with greater symptom burden, disability, and suicidality. The biological correlates of headache pain in MDD, however, remain obscure. The purpose of this study was to examine the association between brain oscillatory activity and headache pain in MDD subjects. Methods. A total of 64 subjects with MDD who were free of psychoactive medications were evaluated for severity of headache pain in the past week. Brain function was assessed using resting-state quantitative electroencephalography (qEEG). We derived cordance in the theta (4-8 Hz) and alpha (8-12 Hz) frequency bands at each electrode, and examined correlations with headache pain in regions of interest while controlling for depression severity. Frontal and posterior asymmetry in alpha power was calculated in regions of interest. Results. Headache pain severity was associated with depression severity (r = 0.447, P < .001). In bilateral frontal and right posterior regions, alpha cordance was significantly associated with headache intensity, including when controlling for depression severity. The direction of the correlation was positive anteriorly and negative posteriorly. Frontal left dominant alpha asymmetry correlated with severity of headache but not depression symptoms. Conclusion. Alterations in brain oscillations identified by alpha cordance and alpha asymmetry may be associated with the pathophysiology of headache pain in depression. These findings should be prospectively confirmed.

Cortisol Predicts Antidepressant Treatment Outcome, Memory Improvement, and Brain Response to Negative Emotions: The Importance of Aging

Background Studies testing the relationship between cortisol levels, depression, and antidepressant treatment response have yielded divergent results suggesting the possibility of moderators of a cortisol effect. Several studies indicate that age may moderate the relationship between cortisol and psychopathology. In patients with Major Depressive Disorder (MDD), we studied the interactive effects of age and cortisol on predicting diagnostic status, improvement in mood and memory function with antidepressant treatment, and brain response to negative emotional stimuli. Methods 66 unmedicated patients with MDD and 75 matched healthy controls had serum assayed at pre-treatment baseline for cortisol. Logistic regression was used to determine an association of age, cortisol and their interaction with MDD diagnosis. Thirty-four of the MDD participants (age range: 19-65 years; median: 36) underwent treatment with a selective serotonin reuptake inhibitor (SSRl) for 8 weeks. Clinician and self-ratings of depression symptoms, as well as tests of verbal and visual delayed recall were obtained at baseline and post treatment. Moderation analyses determined the effect of age on the relationship between baseline cortisol and treatment outcome. A separate sample of 8 MDD participants prospectively underwent fMRI neuroimaging and cortisol collection while viewing negative emotional faces. Results Age moderated the effects of cortisol on predicting MDD diagnosis (p<.05), treatment-associated reduction of depression symptoms (p<.001), improvement of delayed recall (p<.001), and baseline brain response to negative emotions (p<.05, whole brain corrected). Modeling the Age X Cortisol interaction suggested that for the participants below the median age of our sample, lower cortisol levels predicted a lower rate of MDD diagnosis, higher antidepressant effects and decreased brain reactivity in emotion regulation regions such as the anterior cingulate gyrus. On the contrary, in those above the median sample age, lower cortisol predicted a higher rate of MDD, less improvement in depression symptoms and memory performance, and more brain reactivity in the anterior cingulate. Conclusions Our results indicate that age moderates the relationship between peripheral cortisol levels and (1) MDD diagnosis, (2) brain reactivity to emotional stimuli, and (3) antidepressant-associated improvement in depression and memory symptoms. These results indicate that previous disparities in the literature linking peripheral cortisol levels with depression characteristics and treatment response may critically relate, at least in part, to the age of the patients studied.

Assessment of the Hispanic Cognitively Impaired Elderly Patient

Hispanics are the largest minority group in the United States, approximately 7% of the population older than 65. They often encounter challenges related to health care access and quality of care. The prevalence of dementia among Hispanics is higher than that of non-Hispanic whites and they frequently present at a more advanced stage of illness. Cognitive evaluation should take into account sociodemographic information and cultural factors to avoid misdiagnosis and guide management. A provider who has knowledge of Hispanic culture should conduct the neuropsychological assessment, and tests used to measure cognitive functioning should be developed for Hispanics in the United States.

NEURAL CIRCUITRY OF GRIEF IN DEMENTIA CAREGIVERS

Background:Microbleeds (MB) have been shown to occur in the brains of Alzheimer’s disease (AD). We aim to elucidate frequency or distribution of MB in the typical AD and the AD patients that present atypical clinical features. Methods:We examined amnestic dominantly deficit early onset Alzheimer’s disease (EOAD)(N1⁄420), late onset Alzheimer’s disease (LOAD)(N1⁄420), and two atypical variants of l-AD (language dominantly deficit AD)(N1⁄416) and v-AD (visuospatial dominantly deficit AD)(N1⁄48) on CSF biomarkers (Ab1-42 and ptau-181) and Neuroimaging markers (C PiB-PET, F FDG-PET, Tc ECDSPECT). Among four types of AD, we analyzed the number and localization of MB, the localization and extent of PiB, CBF (cerebral blood flow) and glucose metabolism. Results: Frequency of MB was observed most frequently in l-AD (63.5%), while less number of MB in v-AD (12.5%) compared with other subtypes of EOAD (35.0%) and LOAD (35.0%). Distributions of MB in l-AD were frequently observed in left frontal and temporal lobes compared with those in right side (p<0.01, respectively). l-AD showed CBF decrease significantly in left frontal, temporal and parietal lobes compared with those in right side (p<0.001, respectively). v-AD showed decrease of CBF in bilateral occipital and parietal lobes. Conclusions: MB are thought to be related to speech dysfunctions in v-AD, also may be involved CBF decrease in left temporo-parietal and frontal lobes, which might be partly due to cerebral Ab angiopathy. The number of MB was observed relatively to relatively less degree in v-AD, which might occur different pathogenic mechanisms from l-AD.