Ventromedial Prefrontal Volume in Adolescence Predicts Hyperactive/Inattentive Symptoms in Adulthood.

Youths with attention-deficit/hyperactivity disorder symptomatology often exhibit residual inattention and/or hyperactivity in adulthood; however, this is not true for all individuals. We recently reported that dimensional, multi-informant ratings of hyperactive/inattentive symptoms are associated with ventromedial prefrontal cortex (vmPFC) structure. Herein, we investigate the degree to which vmPFC structure during adolescence predicts hyperactive/inattentive symptomatology at 5-year follow-up. Structural equation modeling was used to test the extent to which adolescent vmPFC volume predicts hyperactive/inattentive symptomatology 5 years later in early adulthood. 1104 participants (M = 14.52 years, standard deviation = 0.42; 583 females) possessed hyperactive/inattentive symptom data at 5-year follow-up, as well as quality controlled neuroimaging data and complete psychometric data at baseline. Self-reports of hyperactive/inattentive symptomatology were obtained during adolescence and at 5-year follow-up using the Strengths and Difficulties Questionnaire (SDQ). At baseline and 5-year follow-up, a hyperactive/inattentive latent variable was derived from items on the SDQ. Baseline vmPFC volume predicted adult hyperactive/inattentive symptomatology (standardized coefficient = -0.274, P < 0.001) while controlling for baseline hyperactive/inattentive symptomatology. These results are the first to reveal relations between adolescent brain structure and adult hyperactive/inattentive symptomatology, and suggest that early structural development of the vmPFC may be consequential for the subsequent expression of hyperactive/inattentive symptoms.

Hyperactivity/restlessness is associated with increased functional connectivity in adults with ADHD: a dimensional analysis of resting state fMRI.

BACKGROUND: Adult attention-deficit/hyperactivity disorder (ADHD) is a serious and frequent psychiatric disorder of multifactorial pathogenesis. Several lines of evidence support the idea that ADHD is, in its core, a disorder of dysfunctional brain connectivity within and between several neurofunctional networks. The primary aim of this study was to investigate associations between the functional connectivity within resting state brain networks and the individual severity of core ADHD symptoms (inattention, hyperactivity, and impulsivity). METHODS: Resting state functional magnetic resonance imaging (rs-fMRI) data of 38 methylphenidate-naïve adults with childhood-onset ADHD (20 women, mean age 40.5 years) were analyzed using independent component analysis (FSL's MELODIC) and FSL's dual regression technique. For motion correction, standard volume-realignment followed by independent component analysis-based automatic removal of motion artifacts (FSL's ICA-AROMA) were employed. To identify well-established brain networks, the independent components found in the ADHD group were correlated with brain networks previously found in healthy participants (Smith et al. PNAS 2009;106:13040-5). To investigate associations between functional connectivity and individual symptom severity, sex, and age, linear regressions were performed. RESULTS: Decomposition of resting state brain activity of adults with ADHD resulted in similar resting state networks as previously described for healthy adults. No significant differences in functional connectivity were seen between women and men. Advanced age was associated with decreased functional connectivity in parts of the bilateral cingulate and paracingulate cortex within the executive control network. More severe hyperactivity was associated with increased functional connectivity in the left putamen, right caudate nucleus, right central operculum and a portion of the right postcentral gyrus within the auditory/sensorimotor network. CONCLUSIONS: The present study supports and extends our knowledge on the involvement of the striatum in the pathophysiology of ADHD, in particular, in the pathogenesis of hyperactivity. Our results emphasize the usefulness of dimensional analyses in the study of ADHD, a highly heterogeneous disorder. TRIAL REGISTRATION: ISRCTN12722296 ( https://doi.org/10.1186/ISRCTN12722296 ).

Location of Acute Infarcts and Agitation and Aggression in Stroke.

The role of the infarct location in the development of poststroke agitation (PSA) is largely unknown. This study examined the association between the locations of infarcts and PSA at 9 months following the index stroke in 213 patients with the Chinese version of the Neuropsychiatric Inventory. Compared with the non-PSA group, PSA patients had a higher number and volume of acute pontine infarcts. Ventral pontine and lateral cerebellar infarcts were independent predictors of PSA in the multivariate analysis.

Aggressiveness is associated with excitement on the five-factor model of the positive and negative syndrome scale and prefrontal function in patients with stable schizophrenia.

Aggressiveness is a clinical concern in the stable phase of schizophrenia, as well as in the acute phase. The factors that affect aggressiveness during the stable phase remain unclear. This study investigated factors associated with aggressiveness in patients with stable schizophrenia. Sixty-six patients with schizophrenia who were in the stable phase without acute exacerbation were assessed for aggressiveness using the Buss-Perry Aggression Questionnaire; impulsivity using the Barratt Impulsiveness Scale Version 11, psychotic symptoms using the five-factor model of the Positive and Negative Syndrome Scale (PANSS) including positive symptoms, negative symptoms, disorganization, excitement, and emotional distress; and prefrontal hemodynamic responses using near-infrared spectroscopy. Multivariate regression analyses showed that the excitement factor of the PANSS five-factor model, which comprised four PANSS items (poor impulse control, hyperactivity, hostility, and uncooperativeness), and delayed prefrontal hemodynamic responses were associated with elevated aggressiveness. These findings suggest that in patients with stable schizophrenia, excitement symptoms and prefrontal dysfunction are associated with elevated aggressiveness. Furthermore, the impact of impulsive traits on aggressiveness is less relevant. Our results shed light on a specific aspect of aggressiveness in patients with stable schizophrenia and may indicate factors to consider in the clinical setting.

Voxel-Based Morphometry Correlates of an Agitated-Aggressive Syndrome in the At-Risk Mental State for Psychosis and First Episode Psychosis.

There are mixed reports on structural neuroimaging correlates of aggression in schizophrenia with weak evidence due to cohort overlaps and lack of replications. To our knowledge, no study examined volumetric neuroimaging correlates of aggression in early stages of psychosis. An agitated-aggressive syndrome is present in at-risk mental state (ARMS) and in first-episode psychosis (FEP) - it is unclear whether this syndrome is associated with structural brain abnormalities in early stages of psychosis. Using three-dimensional magnetic resonance imaging and a whole brain voxel-based morphometry approach, we examined 56 ARMS patients, 55 FEP patients and 25 healthy controls. We operationalized aggression using the Excited Component of the Brief Psychiatric Rating Scale (BPRS-EC) and dichotomized our patient group by median split into "BPRS-EC high" (n = 49) and "BPRS-EC low" groups (n = 62). The "BPRS-EC high" group had significantly smaller left lingual gyrus volume than HC. This finding was not present in the "BPRS-EC low" group. In addition, grey matter volume in the left lingual gyrus showed a negative linear correlation with BPRS-EC over all subjects (ρ = -0.318; p = 0.0001) and in the patient group (ρ = -0.202; p = 0.033). These findings provide first hints on structural brain abnormalities associated with an agitated-aggressive syndrome in ARMS and FEP patients.

FDG-PET and Neuropsychiatric Symptoms among Cognitively Normal Elderly Persons: The Mayo Clinic Study of Aging.

One of the key research agenda of the field of aging is investigation of presymptomatic Alzheimer's disease (AD). Furthermore, abnormalities in brain glucose metabolism (as measured by FDG-PET) have been reported among cognitively normal elderly persons. However, little is known about the association of FDG-PET abnormalities with neuropsychiatric symptoms (NPS) in a population-based setting. Thus, we conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging in order to examine the association between brain glucose metabolism and NPS among cognitively normal (CN) persons aged > 70 years. Participants underwent FDG-PET and completed the Neuropsychiatric Inventory Questionnaire (NPI-Q), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Cognitive classification was made by an expert consensus panel. We conducted multivariable logistic regression analyses to compute odds ratios (OR) and 95% confidence intervals after adjusting for age, sex, and education. For continuous variables, we used linear regression and Spearman rank-order correlations. Of 668 CN participants (median 78.1 years, 55.4% males), 205 had an abnormal FDG-PET (i.e., standardized uptake value ratio < 1.32 in AD-related regions). Abnormal FDG-PET was associated with depression as measured by NPI-Q (OR = 2.12; 1.23-3.64); the point estimate was further elevated for APOE ɛ4 carriers (OR = 2.59; 1.00-6.69), though marginally significant. Additionally, we observed a significant association between abnormal FDG-PET and depressive and anxiety symptoms when treated as continuous measures. These findings indicate that NPS, even in community-based samples, can be an important additional tool to the biomarker-based investigation of presymptomatic AD.

Selective D1- and D2-dopamine receptor blockade both induces akathisia in humans--a PET study with [11C]SCH 23390 and [11C]raclopride.

Pharmacological effects were recorded and time course for receptor binding in brain was followed by positron emission tomography after IV injection of the selective D1-dopamine receptor antagonist SCH 23390 in four healthy subjects in doses of 310-810 micrograms. Akathisia, the syndrome of motor restlessness, appeared after the three highest doses. The akathisia was transient and occurred only when [11C]SCH 23390 binding in the basal ganglia was at a high level with a central D1-dopamine receptor occupancy of 45-59%. The D2-dopamine receptor antagonist [11C]raclopride was injected IV into 20 healthy subjects and 13 schizophrenic patients. Akathisia appeared in 14 healthy subjects and 7 patients and coincided with maximal [11C]raclopride binding in the basal ganglia. The findings for [11C]raclopride and [11C]SCH 23390 are the first demonstration of a relationship between time courses for radioligand binding in the human brain and simultaneously induced pharmacological effects.

Hemiballism-hemichorea induced by subcortical ischemia.

Four patients presented with hemiballism-hemichorea as a clinical manifestation of white matter ischemia. These patients illustrate "positive" motor phenomena rather than limb weakness as a consequence of cerebral ischemia. In each patient, the involuntary movements disappeared following worsening of paresis. Subcortical white matter infarction in three patients and hemodynamic hypo-perfusion in the cerebral hemisphere contralateral to dyskinetic movements were possible causes. Neuroradiologically, none had pathological changes in the vicinity of the subthalamic nucleus. We presume from these observations that ischemia of the subcortical white matter, without involvement of the basal ganglia or the subthalamic nucleus, may cause hemiballism-hemichorea.

Postoperative hyperperfusion syndrome in elderly patients with chronic subdural hematoma.

BACKGROUND: Temporary acute agitated delirium is a frequent complication after surgery for chronic subdural hematoma (CSH) in elderly patients. To clarify the pathogenic mechanism underlying this complication, we measured cerebral blood flow before and after surgery in elderly patients with CSHs. METHODS: Twenty-seven patients aged 75 years or older with unilateral CSH underwent treatment involving a single burr hole craniostomy with continuous catheter drainage. Cerebral blood flow was measured using single photon emission computed tomography 1 day before surgery, and at 1 hour and 24 hours after surgery. Acute agitated delirium was diagnosed by the characteristic behavioral abnormality. RESULTS: SPECT imaging 1 hour after surgery demonstrated hyperperfusion in the cerebral cortex beneath the CSH in 14 patients (51.9%). Of these 14 patients, five showed acute agitated delirium a few hours after surgery that persisted for 10 to 12 hours. A hematoma was detected in the right hemisphere in all five patients. Hyperperfusion was significantly more intense in patients with acute agitated delirium both 1 hour and 24 hours after surgery than in patients (n = 9) without acute agitated delirium. Moreover, mean arterial blood pressure during the first postoperative hour was significantly higher in patients with acute agitated delirium. CONCLUSION: In elderly patients with CSH, intense and prolonged hyperperfusion after surgery induces temporary acute agitated delirium. This postoperative hyperperfusion syndrome is exacerbated by hypertension.

A SPECT study of wandering behavior in Alzheimer's disease.

BACKGROUND: Among behavior disturbance during Alzheimer's disease (AD), wandering is one of the most common. Different psychological processes have been suggested to explain the wandering behavior. The aim of this study was to examine whether wandering during AD was associated with cerebral perfusion patterns measured by (99 m)Tc-labeled bicisate (ECD) brain SPECT. METHODS: We compared SPECT scans of 13 AD subjects with wandering behavior (sex ratio M/F, 4/9; age, 73.1 years, SD 7.4; Mini Mental Status Examination score, median 20 interquartile range [16-23]), 13 AD subjects without wandering behavior (matched for age [ +/- 2 years], sex and MMSE score [ +/- 2 points]) and 13 healthy controls (matched for age [ +/- 2 years] and sex) without cognitive impairment. Wandering was defined on the Neuro-Psychiatric Inventory. Score of leukoaraiosis, assessed with the scale of Blennow and number of lacuna infarction were compared on CT scan. SPECT imaging was compared using statistical parametric mapping (SPM 2). RESULTS: There were no significant differences between the groups in term of educational level and CT scan analysis. SPECT imaging was consistent with the diagnosis of AD in both wanderers and AD subjects without wandering behavior. Despite similar clinical dementia severity, wanderers had more severely reduced regional cerebral blood flow (rCBF) in the left parietal-temporal lobe than AD subjects without wandering behavior. CONCLUSION: Wandering behavior could be facilitated by a specific patterns of cerebral blood flow. Wandering, as a physical activity, could also enhance the recruitment of the cortical network.

Slow progressive bilateral posterior artery infarction presenting as agitated delirium, complicated with Anton's syndrome.

Three patients presented with an acute agitated delirium as the earliest sign of bilateral posterior cerebral artery infarction. All patients showed a unique slow progressive deterioration with a remarkably long interval between the first neuropsychological and subsequent visual and neurological symptoms, ranging from 3 to 30 days. Repeated CT scans demonstrated hypodensities in the posterior artery territory only after a long interval of 9-12 days, in case 3, and between 33 and 48 days in case 2. In the latter case MRI was still negative 33 days after onset. In 2 patients the cortical blindness was complicated with anosognosia for blindness. Clinical condition worsened progressively in all patients, leading to death, probably due to brainstem infarction. In all 3, the combination of clinical and radiological findings indicated a 'top of the basilar' distribution, which could be confirmed in two by autopsy.