Ariel Brown

Gray Matter Alterations in Adults with Attention-Deficit/Hyperactivity Disorder Identified by Voxel Based Morphometry

BACKGROUND Gray and white matter volume deficits have been reported in many structural magnetic resonance imaging (MRI) studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural MRI studies of adults with ADHD. This study used voxel based morphometry and applied an a priori region of interest approach based on our previous work, as well as from well-developed neuroanatomical theories of ADHD. METHODS Seventy-four adults with DSM-IV ADHD and 54 healthy control subjects comparable on age, sex, race, handedness, IQ, reading achievement, frequency of learning disabilities, and whole brain volume had an MRI on a 1.5T Siemens scanner. A priori region of interest hypotheses focused on reduced volumes in ADHD in dorsolateral prefrontal cortex, anterior cingulate cortex, caudate, putamen, inferior parietal lobule, and cerebellum. Analyses were carried out by FSL-VBM 1.1. RESULTS Relative to control subjects, ADHD adults had significantly smaller gray matter volumes in parts of six of these regions at p ≤ .01, whereas parts of the dorsolateral prefrontal cortex and inferior parietal lobule were significantly larger in ADHD at this threshold. However, a number of other regions were smaller and larger in ADHD (especially fronto-orbital cortex) at this threshold. Only the caudate remained significantly smaller at the family-wise error rate. CONCLUSIONS Adults with ADHD have subtle volume reductions in the caudate and possibly other brain regions involved in attention and executive control supporting frontostriatal models of ADHD. Modest group brain volume differences are discussed in the context of the nature of the samples studied and voxel based morphometry methodology.

Sex Differences in the Functional Neuroanatomy of Working Memory in Adults With ADHD

OBJECTIVE Although attention deficit hyperactivity disorder (ADHD) in adults is associated with significant morbidity and dysfunction and afflicts both sexes, relatively few imaging studies have examined female subjects and none have had sufficient power to adequately examine sex differences. The authors examined sex differences in the neural functioning of adults with ADHD during performance of a verbal working memory task. METHOD The participants were 44 adults with ADHD matched on age, sex, and estimated IQ to 49 comparison subjects. Accuracy and reaction time on an N-back task were measured to assess working memory. The blood-oxygen-level-dependent functional MRI response was used as a measure of neural activity. RESULTS A group-by-sex analysis of variance showed no between-group differences in either reaction time or percent correct for the working memory task. For both sexes combined, the adults with ADHD showed less activity than comparison subjects in prefrontal regions. However, sex-by-group analyses revealed an interaction, such that male ADHD subjects showed significantly less activity in right frontal, temporal, and subcortical regions and left occipital and cerebellar regions relative to male comparison subjects, whereas female ADHD subjects showed no differences from female comparison subjects. Exploratory correlation analyses revealed negative associations between working-memory-related activation and number of hyperactive symptoms for men and number of inattentive symptoms for women. CONCLUSIONS Male but not female adults with ADHD showed significantly altered patterns of neural activity during a verbal working memory task. Men and women showed different associations between neural activity and ADHD symptoms.

A “Jekyll and Hyde” Within: Aggressive Versus Friendly Interactions in REM and Non-REM Dreams

We hypothesized that representations of social interactions in REM and non-REM (NREM) dreams would reflect differing regional brain activation patterns associated with the two sleep states, and that levels of aggressive interactions would be higher in REM than in NREM dreams. One hundred REM, 100 NREM, and 100 wake reports were collected in the home from 8 men and 7 women using the Nightcap sleep-wake mentation-monitoring system and scored for number and variety of social interactions. We found that (a) social interactions were more likely to be depicted in dream than in wake reports, (b) aggressive social interactions were more characteristic of REM than NREM or wake reports, and (c) dreamer-initiated friendliness was more characteristic of NREM than REM reports. We conclude that processing of, or simulations about, selected social interactions is preferentially performed while “off-line” during the dream state, with the REM state specializing in simulation of aggressive interactions and the NREM state specializing in simulation of friendly interactions.

Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies.

OBJECTIVE To evaluate the impact of therapeutic oral doses of stimulants on the brains of ADHD subjects as measured by magnetic resonance imaging (MRI)-based neuroimaging studies (morphometric, functional, spectroscopy). DATA SOURCES We searched PubMed and ScienceDirect through the end of calendar year 2011 using the keywords (1) psychostimulants or methylphenidate or amphetamine, and (2) neuroimaging or MRI or fMRI, and (3) ADHD or ADD or attention-deficit/hyperactivity disorder or attention deficit hyperactivity disorder. STUDY SELECTION We included only English language articles with new data from case-control or placebo controlled studies that examined attention-deficit/hyperactivity disorder (ADHD) subjects on and off psychostimulants (as well as 5 relevant review articles). DATA EXTRACTION We combined details of study design and medication effects in each imaging modality. RESULTS We found 29 published studies that met our criteria. These included 6 structural MRI, 20 functional MRI studies, and 3 spectroscopy studies. Methods varied widely in terms of design, analytic technique, and regions of the brain investigated. Despite heterogeneity in methods, however, results were consistent. With only a few exceptions, the data on the effect of therapeutic oral doses of stimulant medication suggest attenuation of structural and functional alterations found in unmedicated ADHD subjects relative to findings in controls. CONCLUSIONS Despite the inherent limitations and heterogeneity of the extant MRI literature, our review suggests that therapeutic oral doses of stimulants decrease alterations in brain structure and function in subjects with ADHD relative to unmedicated subjects and controls. These medication-associated brain effects parallel, and may underlie, the well-established clinical benefits.

Autonomy and control motivation and self-esteem

Two studies examined the hypothesis that primed autonomy and control motivations would influence self-esteem (SE) in the direction of autonomy increasing and control decreasing SE. Explicit, implicit, and defensive (i.e., the discrepancy between implicit and explicit) SE were measured. Results confirmed the hypothesis for implicit and for defensive SE. There were substantial sex differences, with men showing greater reactivity to motivation priming and threat than women. Results are interpreted in terms of a self-determination theory view of motivation and SE (Deci & Ryan, 2000).

Regional Prefrontal Cortex Gray Matter Volumes in Youth at Familial Risk for Schizophrenia from the Harvard Adolescent High Risk Study

BACKGROUND Regional prefrontal cortex gray matter reductions have been identified in schizophrenia, likely reflecting a combination of genetic vulnerability and disease effects. Few morphometric studies to date have examined regional prefrontal abnormalities in non-psychotic biological relatives who have not passed through the age range of peak risk for onset of psychosis. We conducted a region-of-interest morphometric study of prefrontal subregions in adolescent and young adult relatives of schizophrenia patients. METHODS Twenty-seven familial high-risk (FHR) first-degree relatives of schizophrenia patients and forty-eight control subjects without a family history of psychosis (ages 13-28) underwent high-resolution magnetic resonance imaging at 1.5Tesla. The prefrontal cortex was parcellated into polar, dorsolateral, ventrolateral, ventromedial and orbital subregions. The Chapman scales measured subpsychotic symptoms. General linear models examined associations of prefrontal subregion volumes with familial risk and subpsychotic symptoms. RESULTS FHR subjects had significantly reduced bilateral ventromedial prefrontal and frontal pole gray matter volumes compared with controls. Ventromedial volume was significantly negatively correlated with magical ideation and anhedonia scores in FHR subjects. CONCLUSIONS Selective, regional prefrontal gray matter reductions may differentially mark genetic vulnerability and early symptom processes among non-psychotic young adults at familial risk for schizophrenia.

Counterfactual cognitive deficit in persons with Parkinson’s disease

Background: Counterfactuals are mental representations of alternatives to past events. Recent research has shown them to be important for other cognitive processes, such as planning, causal reasoning, problem solving, and decision making—all processes independently linked to the frontal lobes. Objective: To test the hypothesis that counterfactual thinking is impaired in some patients with Parkinson’s disease and is linked to frontal dysfunction in these patients. Methods. Measures of counterfactual processing and frontal lobe functioning were administered to 24 persons with Parkinson’s disease and 15 age matched healthy controls. Results. Patients with Parkinson’s disease spontaneously generated significantly fewer counterfactuals than controls despite showing no differences from controls on a semantic fluency test; they also performed at chance levels on a counterfactual inference test, while age matched controls performed above chance levels on this test. Performance on both the counterfactual generation and inference tests correlated significantly with performance on two tests traditionally linked to frontal lobe functioning (Stroop colour–word interference and Tower of London planning tasks) and one test of pragmatic social communication skills. Conclusions: Counterfactual thinking is impaired in Parkinson’s disease. This impairment may be related to frontal lobe dysfunction.

Anterior Cingulate Volumetric Alterations in Treatment-Naïve Adults With ADHD: A Pilot Study

Objective: We sought to examine preliminary results of brain alterations in anterior cingulate cortex (ACC) in treatment-naïve adults with ADHD. The ACC is a central brain node for the integration of cognitive control and allocation of attention, affect and drive. Thus its anatomical alteration may give rise to impulsivity, hyperactivity and inattention, which are cardinal behavioral manifestations of ADHD. Method: Segmentation and parcellation of the ACC was performed on controls (n = 22), treated (n = 13) and treatment-naïve adults with ADHD (n = 13). Results: There was a 21% volume reduction in the left ACC of the treatment-naïve group relative to the control group. Also, there was a 23% volume reduction in the right ACC of the treated group relative to the control group. Conclusion: These results raise the possibility that in ADHD there are volumetric deficits persistent into adulthood, that are independent of medical treatment. (J. of Att. Dis. 2010; 13(4) 407-413)

A preliminary study of dopamine D4 receptor genotype and structural brain alterations in adults with ADHD

An emerging literature has demonstrated an association between the dopamine D4 receptor (DRD4) gene and volumetric brain abnormalities in children with ADHD. However, these results have not been extended to adults and have not addressed the impact of comorbidity. Our objective was to examine the DRD4 7R gene and volumetric brain abnormalities in adults with ADHD while accounting for comorbidity with bipolar disorder (BPD). Subjects were male and female adult outpatient referrals stratified into two diagnostic groups: 24 with ADHD, 19 with ADHD and BPD, as well as 20 male and female adult community controls without ADHD or BPD. We measured volumes (cm3) of a priori selected brain regions (superior frontal, middle frontal, anterior cingulate, and cerebellum cortices) by structural magnetic resonance imaging. Among adults with ADHD, subjects with the 7‐repeat allele of the DRD4 gene had a significantly smaller mean volume in the superior frontal cortex and cerebellum cortex compared to subjects without this allele. In contrast, no such effects were detected in the adults with ADHD + BPD or controls. Our findings suggest that volumetric abnormalities in the dorsolateral prefrontal cortex and cerebellum may represent an intermediate neuroanatomical phenotype between DRD4 genotype and the clinical expression of ADHD in adults, but only in ADHD subjects without comorbid BPD. These result support the heterogeneity of ADHD and provides insights as to its underlying pathophysiology.

Brain differences between persistent and remitted attention deficit hyperactivity disorder

Previous resting state studies examining the brain basis of attention deficit hyperactivity disorder have not distinguished between patients who persist versus those who remit from the diagnosis as adults. To characterize the neurobiological differences and similarities of persistence and remittance, we performed resting state functional magnetic resonance imaging in individuals who had been longitudinally and uniformly characterized as having or not having attention deficit hyperactivity disorder in childhood and again in adulthood (16 years after baseline assessment). Intrinsic functional brain organization was measured in patients who had a persistent diagnosis in childhood and adulthood (n = 13), in patients who met diagnosis in childhood but not in adulthood (n = 22), and in control participants who never had attention deficit hyperactivity disorder (n = 17). A positive functional correlation between posterior cingulate and medial prefrontal cortices, major components of the default-mode network, was reduced only in patients whose diagnosis persisted into adulthood. A negative functional correlation between medial and dorsolateral prefrontal cortices was reduced in both persistent and remitted patients. The neurobiological dissociation between the persistence and remittance of attention deficit hyperactivity disorder may provide a framework for the relation between the clinical diagnosis, which indicates the need for treatment, and additional deficits that are common, such as executive dysfunctions.