Patricia D. Walshaw

Behavioral approach system (BAS)–relevant cognitive styles and bipolar spectrum disorders: Concurrent and prospective associations.

The authors examined concurrent and prospective associations of behavioral approach system (BAS)-relevant and non-BAS-relevant cognitive styles with bipolar spectrum disorders. Controlling for depressive and hypomanic/manic symptoms, 195 individuals with bipolar spectrum disorders scored higher than 194 demographically similar normal controls on BAS sensitivity and BAS-relevant cognitive dimensions of performance concerns, autonomy, and self-criticism, but not on behavioral inhibition system sensitivity and non-BAS-relevant dimensions of approval seeking, sociotropy, and dependency. Moreover, group differences on autonomy fully mediated the association between higher BAS sensitivity and bipolar status. In addition, only BAS-related cognitive dimensions predicted the likelihood of onset of depressive and hypomanic/manic episodes among the bipolar individuals over a 3.2-year follow-up, controlling for initial symptoms and past history of mood episodes. Higher autonomy and self-criticism predicted a greater likelihood of hypomanic/manic episodes, and higher autonomy predicted a lower likelihood of major depressive episodes. In addition, autonomy mediated the associations between BAS sensitivity and prospective hypomanic/manic episodes. These findings suggest that individuals with bipolar spectrum disorders may exhibit a unique profile of BAS-relevant cognitive styles that influence the course of their mood episodes.

Executive Function in Pediatric Bipolar Disorder and Attention-Deficit Hyperactivity Disorder: In Search of Distinct Phenotypic Profiles

Often, there is diagnostic confusion between bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD) in youth due to similar behavioral presentations. Both disorders have been implicated as having abnormal functioning in the prefrontal cortex; however, there may be subtle differences in the manner in which the prefrontal cortex functions in each disorder that could assist in their differentiation. Executive function is a construct thought to be a behavioral analogy to prefrontal cortex functioning. We provide a qualitative review of the literature on performance on executive function tasks for BD and ADHD in order to determine differences in task performance and neurocognitive profile. Our review found primary differences in executive function in the areas of interference control, working memory, planning, cognitive flexibility, and fluency. These differences may begin to establish a pediatric BD profile that provides a more objective means of differential diagnosis between BD and ADHD when they are not reliably distinguished by clinical diagnostic methods.

Electroencephalography Correlates of Spatial Working Memory Deficits in Attention-Deficit/Hyperactivity Disorder: Vigilance, Encoding, and Maintenance

In the current study we sought to dissociate the component processes of working memory (WM) (vigilance, encoding and maintenance) that may be differentially impaired in attention-deficit/ hyperactivity disorder (ADHD). We collected electroencephalographic (EEG) data from 52 children with ADHD and 47 typically developing (TD) children, ages 7–14 years, while they performed a spatial Sternberg working memory task. We used independent component analysis and time-frequency analysis to identify midoccipital alpha (8–12 Hz) to evaluate encoding processes and frontal midline theta (4–7 Hz) to evaluate maintenance processes. We tested for effects of task difficulty and cue processing to evaluate vigilance. Children with ADHD showed attenuated alpha band event-related desynchronization (ERD) during encoding. This effect was more pronounced when task difficulty was low (consistent with impaired vigilance) and was predictive of memory task performance and symptom severity. Correlated with alpha ERD during encoding were alpha power increases during the maintenance period (relative to baseline), suggesting a compensatory effort. Consistent with this interpretation, midfrontal theta power increases during maintenance were stronger in ADHD and in high-load memory conditions. Furthermore, children with ADHD exhibited a maturational lag in development of posterior alpha power whereas age-related changes in frontal theta power deviated from the TD pattern. Last, subjects with ADHD showed age-independent attenuation of evoked responses to warning cues, suggesting low vigilance. Combined, these three EEG measures predicted diagnosis with 70% accuracy. We conclude that the interplay of impaired vigilance and encoding in ADHD may compromise maintenance and lead to impaired WM performance in this group.

Atypical EEG beta asymmetry in adults with ADHD.

BACKGROUND Abnormal brain laterality (ABL) is well established in ADHD. However, its clinical specificity and association to cognitive and clinical symptoms is not yet understood. Previous studies indicate increased right hemisphere (RH) contribution in both ADHD and reading impaired samples. The current study investigates whether this ABL characteristic occurs in adults with ADHD absent comorbid language impairment. METHODS EEG beta asymmetry was compared in 35 adult ADHD subjects and 104 controls during rest and active cognition. Group differences in beta asymmetry were then further evaluated for association to linguistic and attentional abilities, as well as association to beta asymmetry measures across different brain regions. RESULTS Adults with ADHD showed pronounced rightward beta asymmetry (p=.00001) in inferior parietal regions (P8-P7) during a continuous performance task (CPT) that could not be attributed to linguistic ability. Among ADHD subjects only, greater rightward beta asymmetry at this measure was correlated with better CPT performance. Furthermore, this measure showed a lack of normal association (i.e., observed in controls) to left-biased processing in temporal-parietal (TP8-TP7) brain regions important for higher order language functions. CONCLUSION Adult ADHD involves abnormally increased right-biased contribution to CPT processing that could not be attributed to poor language ability. This appears to also involve abnormal recruitment of LH linguistic processing regions and represents an alternative, albeit less effective, CPT processing strategy. These findings suggest different pathophysiologic mechanisms likely underlie RH biased processing in ADHD and reading impaired samples.

Parental expressed emotion and suicidal ideation in adolescents with bipolar disorder.

Family environmental variables are risk factors for recurrent courses of mood disorder in adolescents. The present study examined the association between parental expressed emotion (EE)-critical, hostile and/or emotionally overinvolved attitudes toward a concurrently ill offspring-and suicidal ideation in adolescents with bipolar disorder. The sample consisted of 95 adolescents with a bipolar I or II diagnosis who had experienced a mood episode in the prior 3 months. Participants (mean age=15.54 years, S.D.=1.4) were interviewed and completed questionnaires regarding current and past suicidal ideation prior to their participation in a treatment trial. Parents completed five-minute speech samples from which levels of EE were assessed. High EE attitudes in parents were associated with current suicidal ideation in adolescents. This relationship was independent of the effects of age, gender, current depressive or manic symptoms, comorbid diagnoses, bipolar I/II subtypes, family adaptability, and family cohesion. These results underscore the importance of addressing the emotional reactivity of caregivers in treating adolescents with bipolar disorder who have suicidal ideation.

Frontostriatal neuroimaging findings differ in patients with bipolar disorder who have or do not have ADHD comorbidity

BACKGROUND The inferior frontal cortical (IFC)-striatal network plays an integral role in response inhibition and is compromised in patients with Bipolar Disorder (BP) or Attention-Deficit/Hyperactivity Disorder (ADHD). Prior BP functional neuroimaging studies have not accounted for ADHD comorbidity despite its high prevalence. METHODS The authors conducted an fMRI study using a response inhibition task (Go-NoGo) in 32 euthymic adults with BP, half with comorbid ADHD (BP/ADHD); 16 adults with ADHD alone; and 30 healthy controls. Within- and between-group whole-brain analyses were performed to assess for significant neural function differences. RESULTS All groups activated frontal and striatal regions involved in response inhibition. ANOVA results demonstrated significant interaction effects of BP and ADHD in the anterior and posterior cingulate, left superior and middle frontal gyri and left inferior parietal lobule. Follow-up comparisons showed significant differences between BP subjects with and without ADHD. Other regions demonstrated main effects of BP (left inferior frontal gyrus, left middle frontal gyrus, right superior frontal gyrus and left insula) and ADHD (left inferior frontal gyrus, left precentral gyrus and right anterior cingulate). LIMITATIONS This study, as the first of its kind, requires replication using large sample sizes and controlling for potential effects of medication. CONCLUSIONS Euthymic bipolar adults with comorbid ADHD have significantly different neural activation patterns from BP patients without this comorbidity. If understanding of the neurobiology of bipolar disorder is to be achieved, it is critical to control for this potential confound, something not done by most prior fMRI studies of adults with BP.

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 Brocas and Wernickes 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 Brocas Area, Wernickes Area (inferior, superior), Exners 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.

Effects of d-Methylphenidate, Guanfacine, and Their Combination on Electroencephalogram Resting State Spectral Power in Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE Psychostimulant medications are the gold standard of treatment for attention-deficit/hyperactivity disorder (ADHD); however, a significant minority (∼30%) of individuals with ADHD fail to respond favorably. Noradrenergic agents are increasingly used as ADHD monotherapies or adjuncts for suboptimal stimulant response, yet knowledge of their cortical effects is limited. This study is the first to examine comparative effects of guanfacine (an α adrenergic 2A agonist), psychostimulant, and their combination on resting state cortical activity in ADHD. METHOD The sample comprised 179 participants aged 7 to 14 years old with ADHD (113 boys, 55 girls). Participants were randomized to 1 of 3 blinded conditions: guanfacine (GUAN), d-methylphenidate (DMPH), or the combination (COMB). Electroencephalography (EEG) was performed pre-, mid-, and post-medication titration, with concomitant assessment of behavioral and cognitive functioning. RESULTS Analyses of spectral power measures during resting EEG suggested that each medication condition displayed a distinct profile of effects on cortical activity. Significant time effects suggested that GUAN decreased global alpha band (8-12 hertz [Hz]) power, DMPH and COMB increased centro-parietal beta band (13-21 Hz) power, and COMB resulted in decreased theta band (4-7 Hz) power. Relative to other medication groups, COMB was associated with significantly lower theta band power and DMPH with higher beta band power compared with those in the GUAN group. Medication-related changes in theta power were correlated with improvements in behavioral and cognitive functioning. CONCLUSION These data reveal distinct underlying medication-related effects on neural mechanisms. The COMB condition uniquely exhibited an EEG profile that was associated with improved behavioral and cognitive functioning. Clinical trial registration information-Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273.

Role of the Wada test and functional magnetic resonance imaging in preoperative mapping of language and memory: two atypical cases

The Wada test is an invasive procedure used to determine cerebral memory and language dominance as well as risk of cognitive deficits following neurosurgery. However, the potential risks of Wada testing have led some to consider foregoing Wada testing in candidates for resective epilepsy surgery with right hemispheric seizure onset. We present two atypical cases in which the Wada test showed unexpected memory and language lateralization. These cases underscore the importance of functional magnetic resonance in which imaging and Wada examination in right-handed individuals even when the lesion would not suggest atypical language representation.

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

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.