Functional magnetic resonance imaging (fMRI) as adjunct for planning laser interstitial thermal therapy (LITT) near eloquent structures.

LITT is a minimally-invasive laser ablation technique used to treat a wide variety of intracranial lesions. Difficulties performing intraoperative mapping have limited its adoption for lesions in/near eloquent regions. In this institutional case series, we demonstrate the utility of fMRI-adjunct planning for LITT near language or motor areas. Six out of 7 patients proceeded with LITT after fMRI-based tractography determined adequate safety margins for ablation. All underwent successful ablation without new or worsening postoperative symptoms requiring adjuvant corticosteroids, including those with preexisting deficits. fMRI is an easily accessible adjunct which may potentially reduce chances of complications in LITT near eloquent structures.

A Randomized Clinical Trial of Technology-Enhanced Family-Focused Therapy for Youth in the Early Stages of Mood Disorders.

Objective: Family-focused therapy (FFT) is associated with enhanced outcomes in youth with bipolar and depressive disorders, but has not been evaluated in conjunction with mobile health tools. In symptomatic adolescents whose parents had histories of mood disorders, we examined whether the effects of telehealth-based FFT were augmented by mobile health apps that emphasized mood tracking and family coping skills. Method: Participants (aged 13-19 years) had active mood symptoms and a parent with major depressive or bipolar disorder. Participants received 12 sessions in 18 weeks of telehealth FFT, with random assignment to (1) a mobile app (MyCoachConnect, MCC) that enabled mood tracking, reviews of session content, and text reminders to practice mood management and family communication skills (FFT-MCC); or (2) a mobile app that enabled mood tracking only (FFT-Track). Independent evaluators assessed youth every 9 weeks over 6 months on depressive symptoms (primary outcome), anxiety, and psychosocial functioning. Results: Participants (N = 65; mean age 15.8 ± 1.6 years) significantly improved in depressive symptoms over 6 months (F1,170 = 45.02, p < .0001; ή2 = 0.21, 95% CI = 0.11-0.31), but there were no effects of treatment condition or treatment by time interactions on depression scores. When secondary outcome measures were considered, the subgroup of youth with bipolar spectrum disorders showed greater improvements in anxiety and global functioning in FFT-MCC compared with FFT-Track. Conclusion: Youth in the early stages of mood disorder may benefit from FFT enhanced by mobile health apps. Collaborations between researchers and information technologists on mobile app design and user experience may lead to increases in engagement among adolescents. Clinical trial registration information: Technology Enhanced Family Treatment; https://clinicaltrials.gov/; NCT03913013.

Early Family Intervention for Youth at Risk for Bipolar Disorder: Psychosocial and Neural Mediators of Outcome.

BACKGROUND: The impairing neurodevelopmental course of bipolar disorder (BD) suggests the importance of early intervention for youth in the beginning phases of the illness. OBJECTIVE: We report the results of a 3-site randomized trial of family-focused therapy for youth at high-risk (FFT-HR) for BD, and explore psychosocial and neuroimaging variables as mediators of treatment effects. METHODS: High-risk youth (<18 years) with major depressive disorder or other specified BD, active mood symptoms, and a family history of BD were randomly assigned to 4 months of FFT-HR (psychoeducation, communication and problem-solving skills training) or 4 months of enhanced care psychoeducation. Adjunctive pharmacotherapy was provided by study psychiatrists. Neuroimaging scans were conducted before and after psychosocial treatments in eligible participants. Independent evaluators interviewed participants every 4-6 months over 1-4 years regarding symptomatic outcomes. RESULTS: Among 127 youth (mean 13.2 ± 2.6 years) over a median of 98 weeks, FFT-HR was associated with longer intervals prior to new mood episodes and lower levels of suicidal ideation than enhanced care. Reductions in perceived family conflict mediated the effects of psychosocial interventions on the course of mood symptoms. Among 34 participants with pre-/post-treatment fMRI scans, youth in FFT-HR had (a) stronger resting state connectivity between ventrolateral PFC and anterior default mode network, and (b) increased activity of dorsolateral and medial PFC in emotion processing and problem-solving tasks, compared to youth in enhanced care. CONCLUSION: FFT-HR may delay new mood episodes in symptomatic youth with familial liability to BD. Putative treatment mechanisms include neural adaptations suggestive of improved emotion regulation.

Characterizing physiological high-frequency oscillations using deep learning.

Objective.Intracranially-recorded interictal high-frequency oscillations (HFOs) have been proposed as a promising spatial biomarker of the epileptogenic zone. However, HFOs can also be recorded in the healthy brain regions, which complicates the interpretation of HFOs. The present study aimed to characterize salient features of physiological HFOs using deep learning (DL).Approach.We studied children with neocortical epilepsy who underwent intracranial strip/grid evaluation. Time-series EEG data were transformed into DL training inputs. The eloquent cortex (EC) was defined by functional cortical mapping and used as a DL label. Morphological characteristics of HFOs obtained from EC (ecHFOs) were distilled and interpreted through a novel weakly supervised DL model.Main results.A total of 63 379 interictal intracranially-recorded HFOs from 18 children were analyzed. The ecHFOs had lower amplitude throughout the 80-500 Hz frequency band around the HFO onset and also had a lower signal amplitude in the low frequency band throughout a one-second time window than non-ecHFOs, resembling a bell-shaped template in the time-frequency map. A minority of ecHFOs were HFOs with spikes (22.9%). Such morphological characteristics were confirmed to influence DL model prediction via perturbation analyses. Using the resection ratio (removed HFOs/detected HFOs) of non-ecHFOs, the prediction of postoperative seizure outcomes improved compared to using uncorrected HFOs (area under the ROC curve of 0.82, increased from 0.76).Significance.We characterized salient features of physiological HFOs using a DL algorithm. Our results suggested that this DL-based HFO classification, once trained, might help separate physiological from pathological HFOs, and efficiently guide surgical resection using HFOs.

Mood Instability in Youth at High Risk for Bipolar Disorder.

OBJECTIVE: Mood instability is associated with the onset of bipolar disorder (BD) in youth with a family history of the illness. In a clinical trial with youth at high risk for BD, we examined the association between mood instability and symptomatic, psychosocial, and familial functioning over an average of 2 years. METHOD: Youth (aged 9-17 years) with major depressive disorder or other specified BD, current mood symptoms, and a family history of BD were rated by parents on a mood instability scale. Participants were randomly assigned to 4 months of family-focused therapy or enhanced care psychoeducation, both with medication management as needed. Independent evaluators rated youth every 4-6 months for up to 4 years on symptom severity and psychosocial functioning, whereas parents rated mood instability of the youth and levels of family conflict. RESULTS: High-risk youth (N = 114; mean age 13.3 ± 2.6 years; 72 female) were followed for an average of 104.3 ± 65.8 weeks (range, 0-255 weeks) after randomization. Youth with other specified BD (vs major depressive disorder), younger age, earlier symptom onset, more severe mood symptoms, lower psychosocial functioning, and more familial conflict over time had higher mood instability ratings throughout the study period. Mood instability mediated the association between baseline diagnosis and mother/offspring conflict at follow-up (Z = 2.88, p = .004, αß = 0.19, 95% CI = 0.06-0.32). Psychosocial interventions did not moderate these associations. CONCLUSION: A questionnaire measure of mood instability tracked closely with symptomatic, psychosocial, and family functioning in youth at high risk for BD. Interventions that are successful in reducing mood instability may enhance long-term outcomes among high-risk youth. CLINICAL TRIAL REGISTRATION INFORMATION: Early Intervention for Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/; NCT01483391.

Longitudinal relationship between maternal distress and pediatric mood symptoms in youth with mood disorders.

Parents of a child with a mood disorder report significant levels of distress and burden from caregiving. This study examined whether maternal distress varies over time with levels of mood symptoms in youth with mood disorders, and whether expressed emotion (EE) and family functioning moderate these associations. We recruited youth (ages 9-17 years) with mood disorders and familial risk for bipolar disorder (BD) for a randomized trial of family-focused therapy compared to standard psychoeducation. Participants were assessed every 4-6 months for up to 4 years. Using repeated-measures mixed effects modeling, we examined the longitudinal effects of youths' mood symptoms and maternal distress concurrently, as well as whether each variable predicted the other in successive study intervals. Secondary analyses examined the moderating effects of EE and ratings of family cohesion and adaptability on maternal distress. In sample of 118 youth-mother dyads, levels of self-reported parental distress decreased over time, with no differences between treatment conditions. Youths' depressive symptoms and, most strongly, mood lability were associated with greater maternal distress longitudinally; however, maternal distress did not predict youths' mood symptoms or lability. The effect of youth symptoms on maternal distress was greater among mothers who were high EE. Family cohesion was associated with reduced concurrent ratings of maternal distress, whereas family adaptability was associated with reduced maternal distress at successive follow-ups. While maternal distress decreases over time as youths' symptoms decrease, mothers of youth with mood disorders experience significant distress that is directly linked to the youths' depressive symptom severity and lability. Improved family functioning appears to be an important mechanism by which to intervene.

Neural changes in youth at high risk for bipolar disorder undergoing family-focused therapy or psychoeducation.

BACKGROUND: Patients with mood disorders may benefit from psychosocial interventions through changes in brain networks underlying emotion processing. In this study, we used functional magnetic resonance imaging (fMRI) to investigate treatment-related changes in emotion processing networks in youth at familial high risk for bipolar disorder (BD). METHODS: Youth, ages 9-17, were randomly assigned to family-focused therapy for high-risk youth (FFT-HR) or an active comparison treatment, Enhanced Care (EC). Before and after these 4-month treatments, participants underwent fMRI while viewing happy, fearful, and calm facial expressions. Twenty youth in FFT-HR and 20 in EC were included in analyses of pre- to post-treatment changes in activation across the whole brain. Significant clusters were assessed for correlation with mood symptom improvement. RESULTS: In the dorsolateral prefrontal cortex (DLPFC), activation increased from pre- to post-treatment in the FFT-HR group and decreased in the EC group. Insula activation decreased in the FFT-HR group and did not change in the EC group. Across both treatments, decreasing activation in the hippocampus and amygdala was correlated with pre- to post-treatment improvement in hypomania, while increasing activation in the DLPFC was correlated with pre- to post-treatment improvement in depression. DISCUSSION: Psychosocial treatment addresses abnormalities in emotion regulation networks in youth at high risk for BD. Increased prefrontal cortex activation suggests enhanced emotion regulation from pre- to post-treatment with FFT-HR. Improvements in family interactions may facilitate the development of prefrontal resources that provide protection against future mood episodes.

Development and Open Trial of a Technology-Enhanced Family Intervention for Adolescents at Risk for Mood Disorders.

AIM: Integrating psychosocial interventions with mobile apps may increase treatment engagement among adolescents. We examined the user experience, uptake, and clinical effects of a mobile-enhanced family-focused therapy (FFT) among adolescents at risk for mood disorders. METHOD: We created a mobile app containing 12 lesson plans corresponding to content of weekly FFT sessions, with modules concerning mood management, family communication and problem-solving. We pilot tested the app in an open trial of FFT (12 sessions in 18 weeks) for adolescents who had active depressive or hypomanic symptoms, a parent with mood disorder, and at least one parent who expressed high levels of criticism. Teens and parents made daily and weekly ratings of youths' moods, amount of parent/offspring criticism, and practice of FFT psychoeducational, communication or problem-solving skills. Independent evaluators interviewed adolescents at baseline and every 9 weeks over 27 weeks to measure symptom trajectories. RESULTS: Participants were adolescents (n=22; mean age 15.4 ± 1.8 years; 45.5% female) and their 34 parents. Completion of requested app assessment and skill practices averaged 46%-65% among adolescents and parents over 18 weeks of treatment. Adolescents showed significant improvement in clinician-rated depression scores over 27 weeks (Cohen's d=1.58, 95% CI, 0.83 to 2.32) and reported reductions in the amount of perceived criticism expressed by parents. LIMITATIONS: The uncontrolled design limits inferences about whether the mobile app augmented the effects of FFT on moods or family relationships. CONCLUSIONS: Mobile applications may enhance users' responses to family therapy and provide clinicians with information regarding clinical status. Clinicaltrials.gov NCT03913013.

Changes in Intrinsic Brain Connectivity in Family-Focused Therapy Versus Standard Psychoeducation Among Youths at High Risk for Bipolar Disorder.

OBJECTIVE: We compared intrinsic network connectivity in symptomatic youths at high risk (HR) for bipolar disorder (BD) and healthy comparison (HC) youths. In HR youths, we also investigated treatment-related changes in intrinsic connectivity after family-focused therapy for high-risk youths (FFT-HR) vs standardized family psychoeducation. METHOD: HR youths (N = 34; age 9-17 years; mean 14 years, 56% girls and 44% boys) with depressive and/or hypomanic symptoms and at least 1 first- or second-degree relative with BD I or II were randomly assigned to 4 months of FFT-HR (12 sessions of psychoeducation, communication, and problem-solving skills training) or enhanced care (EC; 3 family and 3 individual psychoeducation sessions). Before and after 4 months of treatment, participants underwent resting state functional magnetic resonance imaging (rs-fMRI). A whole-brain independent component analysis compared rs-fMRI networks in HR youths and 30 age-matched HC youths at a pretreatment baseline. Then we identified pretreatment to posttreatment (4-month) changes in network connectivity in HR youths receiving FFT-HR (n = 16) or EC (n = 18) and correlated these changes with depression improvement. RESULTS: At baseline, HR youths had greater connectivity between the ventrolateral prefrontal cortex (VLPFC) and the anterior default mode network (aDMN) than did HCs (p = .004). Over 4 months of treatment, FFT-HR-assigned HR youths had increased VLPFC-aDMN connectivity from pre- to posttreatment (p = .003), whereas HR youths in EC showed no significant change over time (p = .11) (treatment by time interaction, t31 = 3.33, 95% CI = 0.27-1.14, p = .002]. Reduction in depression severity over 4 months inversely correlated with enhanced anterior DMN (r = -0.71) connectivity in the FFT-HR but not in the EC (r = -0.07) group (z = -2.17, p = .015). CONCLUSION: Compared to standard psychoeducation, FFT-HR is associated with stronger connectivity between the VLPFC and aDMN, suggesting possible enhancements of self-awareness, illness awareness, and emotion regulation. CLINICAL TRIAL REGISTRATION INFORMATION: Early Intervention for Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/; NCT01483391.

Longitudinal trajectories of mood symptoms and global functioning in youth at high risk for bipolar disorder.

BACKGROUND: Little is known about the longitudinal course of mood symptoms and functioning in youth who are at high risk for bipolar disorder (BD). Identifying distinct course trajectories and predictors of those trajectories may help refine treatment approaches. METHODS: This study examined the longitudinal course of mood symptoms and functioning ratings in 126 youth at high risk for BD based on family history and early mood symptoms. Participants were enrolled in a randomized trial of family-focused therapy and followed longitudinally (mean 2.0 years, SD = 53.6 weeks). RESULTS: Using latent class growth analyses (LCGA), we observed three mood trajectories. All youth started the study with active mood symptoms. Following the index mood episode, participants were classified as having a "significantly improving course" (n = 41, 32.5% of sample), a "moderately symptomatic course" (n = 21, 16.7%), or a "predominantly symptomatic course" (n = 64, 50.8%) at follow-up. More severe depression, anxiety, and suicidality at the study's baseline were associated with a poorer course of illness. LCGA also revealed three trajectories of global functioning that closely corresponded to symptom trajectories; however, fewer youth exhibited functional recovery than exhibited symptomatic recovery. LIMITATIONS: Mood trajectories were assessed within the context of a treatment trial. Ratings of mood and functioning were based on retrospective recall. CONCLUSIONS: This study suggests considerable heterogeneity in the course trajectories of youth at high risk for BD, with a significant proportion (32.5%) showing long-term remission of symptoms. Treatments that enhance psychosocial functioning may be just as important as those that ameliorate symptoms in youth at risk for BD.

Effects of family-focused therapy on suicidal ideation and behavior in youth at high risk for bipolar disorder.

BACKGROUND: Youth who are at clinical and familial risk for bipolar disorder (BD) often have significant suicidal ideation (SI). In a randomized trial, we examined whether family-focused therapy (FFT) is associated with reductions in SI and suicidal behaviors in high-risk youth. METHODS: Participants (ages 9-17 years) met diagnostic criteria for unspecified BD or major depressive disorder with active mood symptoms and had at least one relative with BD type I or II. Participants were randomly allocated to 12 sessions in 4 months of FFT or 6 sessions in 4 months of psychoeducation (enhanced care, EC), with pharmacotherapy as needed. Clinician- and child-rated assessments of mood, suicidal thoughts and behaviors, and family conflict were obtained at baseline and 4-6 month intervals over 1-4 years. RESULTS: Participants (N=127; mean 13.2±2.6 yrs., 82 female) were followed over an average of 105.9±64.0 weeks. Youth with high baseline levels of SI who received FFT had lower levels of (and fewer weeks with) SI at follow-up compared to youth with high baseline SI who received EC. Participants in FFT had longer intervals without suicidal behaviors than participants in EC. Youths' ratings of family conflict significantly mediated the effects of treatment on SI at follow-up. LIMITATIONS: Family conflict was based on questionnaires rather than observer ratings of family interactions. CONCLUSIONS: Family psychoeducation with skill training can be an effective deterrent to suicidal thoughts and behaviors in youth at high risk for BD. Reducing parent/offspring conflict should be a central objective of psychosocial interventions for high-risk youth with SI.

Characteristics of youth at high risk for bipolar disorder compared to youth with bipolar I or II disorder.

Significant efforts have been undertaken to characterize the phenomenology of the high-risk period for bipolar disorder (BD) through the examination of youth at familial risk (i.e., having a first- or second-degree relative with BD) or clinical high risk for the disorder (i.e., youth with BD Not Otherwise Specified [NOS] or major depressive disorder [MDD]). However, little is known about the phenomenology of youth at both familial and clinical high risk for BD. In this study, we examined the clinical and psychosocial characteristics of youth at familial and clinical high risk (HR) for BD, and compared these characteristics to those of youth with BD I and II. Both groups were recruited based on current, active mood symptoms from separate randomized trials of family therapy. A total of 127 HR youth were evaluated: 52 (40.9%) were diagnosed with BD-NOS and 75 (59.1%) were diagnosed with MDD. Compared to adolescents with BD I and II (n = 145), HR youth had higher rates of anxiety disorders, and comparable rates of attention-deficit/hyperactivity disorder and oppositional defiant disorder/conduct disorder. Manic symptom severity and psychosocial functioning were progressively more impaired consistent with diagnostic severity: BD I > BD II > BD-NOS > MDD. Nonetheless, HR youth exhibited depressive symptom severity that was comparable to adolescents with BD I. These results provide further support for the high rates of anxiety disorders and premorbid dysfunction in addition to active mood symptoms for youth at risk for BD, and suggest anxiety is an important phenomenological characteristic and treatment target in the high-risk period.

Effects of Family-Focused Therapy vs Enhanced Usual Care for Symptomatic Youths at High Risk for Bipolar Disorder: A Randomized Clinical Trial.

Importance: Behavioral high-risk phenotypes predict the onset of bipolar disorder among youths who have parents with bipolar disorder. Few studies have examined whether early intervention delays new mood episodes in high-risk youths. Objective: To determine whether family-focused therapy (FFT) for high-risk youths is more effective than standard psychoeducation in hastening recovery and delaying emergence of mood episodes during the 1 to 4 years after an active period of mood symptoms. Design, Settings, and Participants: This multisite randomized clinical trial included referred youths (aged 9-17 years) with major depressive disorder or unspecified (subthreshold) bipolar disorder, active mood symptoms, and at least 1 first- or second-degree relative with bipolar disorder I or II. Recruitment started from October 6, 2011, and ended on September 15, 2016. Independent evaluators interviewed participants every 4 to 6 months to measure symptoms for up to 4 years. Data analysis was performed from March 13 to November 3, 2019. Interventions: High-risk youths and parents were randomly allocated to FFT (12 sessions in 4 months of psychoeducation, communication training, and problem-solving skills training; n = 61) or enhanced care (6 sessions in 4 months of family and individual psychoeducation; n = 66). Youths could receive medication management in either condition. Main Outcomes and Measures: The coprimary outcomes, derived using weekly psychiatric status ratings, were time to recovery from prerandomization symptoms and time to a prospectively observed mood (depressive, manic, or hypomanic) episode after recovery. Secondary outcomes were time to conversion to bipolar disorder I or II and longitudinal symptom trajectories. Results: All 127 participants (82 [64.6%] female; mean [SD] age, 13.2 [2.6] years) were followed up for a median of 98 weeks (range, 0-255 weeks). No differences were detected between treatments in time to recovery from pretreatment symptoms. High-risk youths in the FFT group had longer intervals from recovery to the emergence of the next mood episode (χ2 = 5.44; P = .02; hazard ratio, 0.55; 95% CI, 0.48-0.92;), and from randomization to the next mood episode (χ2 = 4.44; P = .03; hazard ratio, 0.59; 95% CI, 0.35-0.97) than youths in enhanced care. Specifically, FFT was associated with longer intervals to depressive episodes (log-rank χ2 = 6.24; P = .01; hazard ratio, 0.53; 95% CI, 0.31-0.88) but did not differ from enhanced care in time to manic or hypomanic episodes, conversions to bipolar disorder, or symptom trajectories. Conclusions and Relevance: Family skills-training for youths at high risk for bipolar disorder is associated with longer times between mood episodes. Clarifying the relationship between changes in family functioning and changes in the course of high-risk syndromes merits future investigation. Trial Registration: ClinicalTrials.gov identifier: NCT01483391.

Early intervention for youth at high risk for bipolar disorder: A multisite randomized trial of family-focused treatment.

AIMS: Despite the considerable public health impact of bipolar disorder (BD), no psychosocial interventions have been systematically evaluated in its early prodromal stages. We describe the rationale, design and analytic methods for a 3-site randomized trial of family-focused treatment for youth at high risk (FFT-HR) for BD. METHODS: Participants (ages 9-17 years) have a diagnosis of unspecified BD or major depressive disorder, current mood symptoms and at least one first- or second-degree relative with a lifetime history of BD I or II. Participants are randomly assigned to FFT-HR (12 sessions in 4 months of family psychoeducation and skills training) or enhanced care (EC; 6 individual and family sessions over 4 months), with pharmacotherapy provided as needed. A subset of participants undergo pre- and post-treatment functional MRI (fMRI) scans while performing face-rating and family problem-solving tasks designed to activate corticolimbic circuitry. Independent evaluators assess participants' status every 4 to 6 months for up to 4 years. RESULTS: We hypothesize that FFT-HR will be more effective than EC in reducing the severity of mood symptoms (primary outcome) and the hazard of a first manic episode (secondary) over 4 years. Secondarily, we will explore whether FFT-HR is associated with greater decreases in amygdala activation and increases in dorsolateral, ventrolateral or anterior medial prefrontal cortex activation from pre- to post-treatment. Clinical characteristics of 133 subjects enrolled at baseline are described. CONCLUSIONS: This study will test a novel intervention to reduce the early symptoms of BD, and identify neural and behavioural mechanisms that may help refine future treatments.

Adjunctive thyroid hormone treatment in rapid cycling bipolar disorder: A double-blind placebo-controlled trial of levothyroxine (L-T4 ) and triiodothyronine (T3 ).

OBJECTIVES: This report describes the first comparative double-blind, placebo-controlled trial of levothyroxine (L-T4 ) and triiodothyronine (T3 ) as adjunctive treatments in rapid cycling bipolar disorder. METHODS: Thirty-two treatment-resistant, rapid cycling patients who had failed a trial of lithium were randomized into three treatment arms: L-T4 , T3 , or placebo. They were followed for ≥4 months with weekly clinical and endocrine assessments. RESULTS: There were no statistically significant differences between the groups in age, gender, duration of illness, or thyroid status. Markov chain analyses were employed to assess treatment effects on cycling patterns among mood states (euthymia, depression, mania, and mixed). Within groups, post-treatment the L-T4 group spent significantly less time depressed or in a mixed state and greater time euthymic. The T3 and placebo groups did not differ significantly pre- and post-treatment in any mood state, although the pattern of effects was the same for the T3 group as for the L-T4 group. Between groups, the L-T4 group had a significantly greater increase in time euthymic and decrease in time in the mixed state than the placebo group. Other group differences were not significant, although they were in the expected direction. CONCLUSIONS: The findings in this first double-blind study directly comparing the effects of L-T4 and T3 therapy against placebo provide evidence for the benefit of adjunctive L-T4 in alleviating resistant depression, reducing time in mixed states and increasing time euthymic. Adjunctive T3 did not show statistically significant evidence of benefit over placebo in reducing the time spent in disturbed mood states.

Presurgical language fMRI: Mapping of six critical regions.

Language mapping is a key goal in neurosurgical planning. fMRI mapping typically proceeds with a focus on Broca's and Wernicke's areas, although multiple other language-critical areas are now well-known. We evaluated whether clinicians could use a novel approach, including clinician-driven individualized thresholding, to reliably identify six language regions, including Broca's Area, Wernicke's Area (inferior, superior), Exner's Area, Supplementary Speech Area, Angular Gyrus, and Basal Temporal Language Area. We studied 22 epilepsy and tumor patients who received Wada and fMRI (age 36.4[12.5]; Wada language left/right/mixed in 18/3/1). fMRI tasks (two × three tasks) were analyzed by two clinical neuropsychologists who flexibly thresholded and combined these to identify the six regions. The resulting maps were compared to fixed threshold maps. Clinicians generated maps that overlapped significantly, and were highly consistent, when at least one task came from the same set. Cases diverged when clinicians prioritized different language regions or addressed noise differently. Language laterality closely mirrored Wada data (85% accuracy). Activation consistent with all six language regions was consistently identified. In blind review, three external, independent clinicians rated the individualized fMRI language maps as superior to fixed threshold maps; identified the majority of regions significantly more frequently; and judged language laterality to mirror Wada lateralization more often. These data provide initial validation of a novel, clinician-based approach to localizing language cortex. They also demonstrate clinical fMRI is superior when analyzed by an experienced clinician and that when fMRI data is of low quality judgments of laterality are unreliable and should be withheld. Hum Brain Mapp 38:4239-4255, 2017. © 2017 Wiley Periodicals, Inc.

Personality disorder symptom severity predicts onset of mood episodes and conversion to bipolar I disorder in individuals with bipolar spectrum disorder.

Although personality disorders (PDs) are highly comorbid with bipolar spectrum disorders (BSDs), little longitudinal research has been conducted to examine the prospective impact of PD symptoms on the course of BSDs. The aim of this study is to examine whether PD symptom severity predicts shorter time to onset of bipolar mood episodes and conversion to bipolar I disorder over time among individuals with less severe BSDs. Participants (n = 166) with bipolar II disorder, cyclothymia, or bipolar disorder not otherwise specified completed diagnostic interview assessments of PD symptoms and self-report measures of mood symptoms at baseline. They were followed prospectively with diagnostic interviews every 4 months for an average of 3.02 years. Cox proportional hazard regression analyses indicated that overall PD symptom severity significantly predicted shorter time to onset of hypomanic (hazard ratio [HR] = 1.42; p < .001) and major depressive episodes (HR = 1.51; p < .001) and conversion to bipolar I disorder (HR = 2.51; p < .001), after controlling for mood symptoms. Results also suggested that cluster B severity predicted shorter time to onset of hypomanic episodes (HR = 1.38; p = .002) and major depressive episodes (HR = 1.35; p = .01) and conversion to bipolar I disorder (HR = 2.77; p < .001), whereas cluster C severity (HR = 1.56; p < .001) predicted shorter time to onset of major depressive episodes. These results support predisposition models in suggesting that PD symptoms may act as a risk factor for a more severe course of BSDs. (PsycINFO Database Record

Alpha desynchronization and fronto-parietal connectivity during spatial working memory encoding deficits in ADHD: A simultaneous EEG-fMRI study.

The underlying mechanisms of alpha band (8-12 Hz) neural oscillations are of importance to the functioning of attention control systems as well as to neuropsychiatric conditions that are characterized by deficits of that system, such as attention deficit hyperactivity disorder (ADHD). The objectives of the present study were to test if visual encoding-related alpha event-related desynchronization (ERD) correlates with fronto-parieto-occipital connectivity, and whether this is disrupted in ADHD during spatial working memory (SWM) performance. We acquired EEG concurrently with fMRI in thirty boys (12-16 yrs. old, 15 with ADHD), during SWM encoding. Psychophysiological connectivity analyses indicated that alpha ERD during SWM encoding was associated with both occipital activation and fronto-parieto-occipital functional connectivity, a finding that expands on prior associations between alpha ERD and occipital activation. This finding provides novel support for the interpretation of alpha ERD (and the associated changes in occipital activation) as a phenomenon that involves, and perhaps arises as a result of, top-down network interactions. Alpha ERD was associated less strongly with occipital activity, but associated more strongly with fronto-parieto-occipital connectivity in ADHD, consistent with a compensatory attentional response. Additionally, we illustrate that degradation of EEG data quality by MRI-amplified motion artifacts is robust to existing cleaning algorithms and is significantly correlated with hyperactivity symptoms and the ADHD Combined Type diagnosis. We conclude that persistent motion-related MR artifacts in EEG data can increase variance and introduce bias in interpretation of group differences in populations characterized by hypermobility--a clear limitation of current-state EEG-fMRI methodology.

Safety, efficacy, and life satisfaction following epilepsy surgery in patients aged 60 years and older.

OBJECTIVE: Despite its potential to offer seizure freedom, resective epilepsy surgery (RES) is seldom performed in patients 60 years of age or older. Demonstrating successful outcomes including an improved quality of life may raise awareness about the advantages of referring this underrepresented population for specialized evaluation. Accordingly, the authors investigated outcomes and life fulfillment in patients with an age ≥ 60 years who had undergone RES. METHODS: All patients who, at the age of 60 years or older, had undergone RES for medically refractory focal onset seizures at the authors' center were evaluated. A modified Liverpool Life Fulfillment (LLF) tool was administered postoperatively (maximum score 32). Seizure outcomes were classified according to the Engel classification system. RESULTS: Twelve patients underwent RES. The majority of patients (9 [75%] of 12) had at least 1 medical comorbidity in addition to seizures. The mean follow-up was 3.1 ± 2.1 years. At the time of the final follow-up, 11 (91.7%) of 12 patients were documented as having a good postsurgical outcome (Engel Class I-II). Half (6 of 12 patients) were completely seizure free (Engel Class IA). Liverpool Life Fulfillment (LLF) data were available for 11 patients. Following surgery, the mean LLF score was 26.7 ± 6. Eight patients (72.7%) noted excellent satisfaction with their RES, with 5 (45.5%) noting postoperative improvements in overall health. CONCLUSIONS: Resective epilepsy surgery is safe and effective in patients with an age ≥ 60 years. Over 90% had a good surgical outcome, with 50% becoming completely seizure free despite 1 or more medical comorbidities in the majority. The study data indicated that an advancing age should not negatively influence consideration for RES.

Extreme cognitions in bipolar spectrum disorders: associations with personality disorder characteristics and risk for episode recurrence.

Bipolar spectrum disorders (BSDs) are often characterized by cognitive inflexibility and affective extremities, including "extreme" or polarized thoughts and beliefs, which have been shown to predict a more severe course of illness. However, little research has evaluated factors that may be associated with extreme cognitions, such as personality disorders, which are often characterized by extreme, inflexible beliefs and are also associated with poor illness course in BSDs. The present study evaluated associations among BSDs, personality disorder characteristics, and extreme cognitions (polarized responses made on measures of attributional style and dysfunctional attitudes), as well as links between extreme cognitions and the occurrence of mood episodes, among euthymic young adults with BSDs (n=83) and demographically matched healthy controls (n=89) followed prospectively for 3years. The relationship between personality disorder characteristics and negative and positive extreme cognitions was stronger among BSD participants than among healthy controls, even after statistically accounting for general cognitive styles. Furthermore, extreme negative cognitions predicted the prospective onset of major depressive and hypomanic episodes. These results suggest that extreme cognitive styles are most common in individuals with BSDs and personality disorder characteristics, and they provide further evidence that extreme negative cognitions may confer risk for mood dysregulation.