Brain-age prediction: Systematic evaluation of site effects, and sample age range and size.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

Preliminary guidelines for safe and effective use of repetitive transcranial magnetic stimulation in moderate to severe traumatic brain injury.

Transcranial magnetic stimulation has generated extensive interest within the traumatic brain injury (TBI) rehabilitation community, but little work has been done with repetitive protocols, which can produce prolonged changes in behavior. This is partly because of concerns about the safety of repetitive transcranial magnetic stimulation (rTMS) in subjects with TBI, particularly the risk of seizures. These risks can be minimized by careful selection of the rTMS protocol and exclusion criteria. In this article, we identify guidelines for safe use of rTMS in subjects with TBI based on a review of the literature and illustrate their application with a case study. Our subject is a 48-year-old man who sustained a severe TBI 5 years prior to beginning rTMS for the treatment of post-TBI depression. After a 4-week baseline period, we administered daily sessions of low-frequency stimulation to the right dorsolateral prefrontal cortex for 6 weeks. After stimulation, we performed monthly assessments for 3 months. The Hamilton Depression Rating Scale (HAMD) was our primary outcome measure. The stimulation was well tolerated and the patient reported no side effects. After 6 weeks of stimulation, the patient's depression was slightly improved, and these improvements continued through follow-up. At the end of follow-up, the patient's HAMD score was 49% of the average baseline score.

White matter abnormalities associated with disruptive behavior disorder in adolescents with and without attention-deficit/hyperactivity disorder.

Disruptive behavior disorders (DBD) are among the most commonly diagnosed mental disorders in children and adolescents. Some important characteristics of DBD vary based on the presence or absence of comorbid attention-deficit/hyperactivity disorder (ADHD), which may affect the understanding of and treatment decision-making related to the disorders. Thus, identifying neurobiological characteristics of DBD with comorbid ADHD (DBD+ADHD) can provide a basis to establish a better understanding of the condition. This study aimed to assess abnormal white matter microstructural alterations in DBD+ADHD as compared to DBD alone and healthy controls using diffusion tensor imaging (DTI). Thirty-three DBD (19 with comorbid ADHD) and 46 age-matched healthy adolescents were studied using DTI. Fractional anisotropy (FA), and mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were analyzed using tract-based spatial statistics (TBSS). Significantly lower FA and higher MD, RD and AD in many white matter fibers were found in adolescents with DBD+ADHD compared to controls. Moreover, lower FA and higher RD were also found in the DBD+ADHD versus the DBD alone group. Alterations of white matter integrity found in DBD patients were primarily associated with ADHD, suggesting that ADHD comorbidity in DBD is reflected in greater abnormality of microstructural connections.

The interacting role of media violence exposure and aggressive-disruptive behavior in adolescent brain activation during an emotional Stroop task.

Only recently have investigations of the relationship between media violence exposure (MVE) and aggressive behavior focused on brain functioning. In this study, we examined the relationship between brain activation and history of media violence exposure in adolescents, using functional magnetic resonance imaging (fMRI). Samples of adolescents with no psychiatric diagnosis or with disruptive behavior disorder (DBD) with aggression were compared to investigate whether the association of MVE history and brain activation is moderated by aggressive behavior/personality. Twenty-two adolescents with a history of aggressive behavior and diagnosis of either conduct disorder or oppositional-defiant disorder (DBD sample) and 22 controls completed an emotional Stroop task during fMRI. Primary imaging results indicated that controls with a history of low MVE demonstrated greater activity in the right inferior frontal gyrus and rostral anterior cingulate during the violent word condition. In contrast, in adolescents with DBD, those with high MVE exhibited decreased activation in the right amygdala, compared with those with low MVE. These findings are consistent with research demonstrating the importance of fronto-limbic structures for processing emotional stimuli, and with research suggesting that media violence may affect individuals in different ways depending on the presence of aggressive traits.

Magnetic resonance imaging findings in children with a first recognized seizure.

This study characterized structural abnormalities associated with onset of seizures in children, using magnetic resonance imaging and a standardized classification system in a large prospective cohort. Two hundred eighty-one children aged 6-14 years completed magnetic resonance imaging within 6 months of their first recognized seizure. Most examinations were performed with a standardized, dedicated seizure protocol; all were scored using a standard scoring system. At least one magnetic resonance imaging abnormality was identified in 87 of 281 (31%) children with a first recognized seizure. Two or more abnormalities were identified in 34 (12%). The commonest abnormalities were ventricular enlargement (51%), leukomalacia/gliosis (23%), gray-matter lesions such as heterotopias and cortical dysplasia (12%), volume loss (12%), other white-matter lesions (9%), and encephalomalacia (6%). Abnormalities defined as significant, or potentially related to seizures, occurred in 40 (14%). Temporal lobe and hippocampal abnormalities were detected at a higher frequency than in previous studies (13/87). Magnetic resonance imaging and a standardized, reliable, valid scoring system demonstrated a higher rate of abnormal findings than previously reported, including findings formerly considered incidental. Practice parameters may need revision, to expand the definition of significant abnormalities and support wider use of magnetic resonance imaging in children with newly diagnosed seizures.

Magnetic resonance imaging (MRI) and electroencephalographic (EEG) findings in a cohort of normal children with newly diagnosed seizures.

In the initial assessment of children with new-onset seizures, the suggestion that electroencephalography (EEG) should be standard and that magnetic resonance imaging (MRI) should be optional has been questioned. The purposes of this study were to (1) describe the frequency of EEG and MRI abnormalities and (2) explore relationships between MRI and EEG findings to determine their relevance in the assessment of children with new-onset seizures who are otherwise developing normally. As part of an ongoing, prospective study of children with new-onset seizures, we studied 181 children (90 girls and 91 boys). Children were entered into the study within 3 months of their first-recognized seizure. The association between EEG and MRI abnormalities was explored using a chi-square test. Abnormal MRI findings were found in 32.6% (n = 59) of the sample. The EEG and MRI results agreed with respect to classification into normal or abnormal in 37% (n = 67). Of the 50 children with a normal EEG, however, 21 (42%) were found to have an abnormal MRI. We found an unexpectedly high frequency of imaging abnormalities in our sample of otherwise normal children, although the significance of these findings is not clear. Follow-up of these patients will help us interpret the importance of the abnormalities. Despite our relatively small sample, however, our findings indicate that a normal EEG does not reliably predict a normal MRI in children with first seizures.

fMRI study of acupuncture-induced periaqueductal gray activity in humans.

BOLD fMRI was used to study acupuncture-induced activation (increase in the BOLD signal from undetectable) of the periaqueductal gray (PAG) and two somatosensory cortical areas in seven healthy human subjects. Mechanical stimulation (push-pull) was given to the LI4 (Hoku) acupoint or to a non-acupoint. The stimulation paradigm consisted of 5 runs, each consisting of four 30 s On/30 s OFF periods over 30 min. The scan for each ON period was analyzed individually. The PAG and cortical areas showed different activity patterns. PAG activity was episodic and reliably demonstrated after 20-25 min of stimulation; both cortical areas, however, were active > 90% of the time. Stimulation of a non-acupoint (leg) resulted in reduced levels of PAG and cortical activity.

Executive functioning characteristics associated with ADHD comorbidity in adolescents with disruptive behavior disorders.

The nature of executive dysfunction in youth with disruptive behavior disorders (DBD) remains unclear, despite extensive research in samples of children with attention-deficit hyperactivity disorder (ADHD). To determine the relationship between DBD, ADHD, and executive function deficits in aggressive teens, adolescents with DBD and comorbid ADHD (DBD + ADHD; n = 25), DBD without ADHD (DBD-ADHD; n = 23), and healthy controls (HC; n = 25) were compared on neurocognitive tests and questionnaires measuring executive functioning. Teens with DBD + ADHD performed worse on both neurocognitive and questionnaire measures of executive function than the DBD-ADHD and HC groups. Results suggest that subgroups of DBD may exist depending on the presence or absence of comorbid ADHD, which may have implications for the selection and efficacy of treatment strategies.

The effect of tumour type and distance on activation in the motor cortex.

Functional MRI has been widely used to identify the eloquent cortex in neurosurgical/radiosurgical planning and treatment of CNS neoplasms and malformations. In this study we examined the effect of CNS tumours on the blood oxygenation level-dependent (BOLD) activation maps in the primary and supplementary motor cortex. A total of 33 tumour patients and five healthy right-handed adults were enrolled in the study. Patients were divided into four groups based on tumour type and distance from primary motor cortex: (1) intra-axial, near, (2) extra-axial, near, (3) intra-axial, far and (4) extra-axial, far. The intra-axial groups consisted of patients with astrocytomas, glioblastomas and metastatic tumours of mixed histology; all the extra-axial tumours were meningiomas. The motor task was a bilateral, self-paced, finger-tapping paradigm. Anatomical and functional data were acquired with a 1.5 T GE Echospeed scanner. Maps of the motor areas were derived from the BOLD images, using SPM99 software. For each subject we first determined the activation volume in the primary motor area and the supplementary motor area (SMA) and then calculated the percentage difference between the hemispheres. Two factors influenced the activation volumes: tumour type (P<0.04) and distance from the eloquent cortex (P<0.06). Patients in group 1 (intra-axial, near) had the smallest activation area in the primary motor cortex, the greatest percentage difference in the activation volume between the hemispheres, and the largest activation volume in the SMA. Patients in group 4 (extra-axial, far) had the largest activation volume in the primary motor cortex, the least percentage difference in volume between the hemispheres, and the smallest activation volume in the SMA. There was no significant change in the volume of the SMA in any group, compared with controls, suggesting that, although there is a gradual decrease in SMA volume with distance from the primary motor area, the effect on motor reorganisation is minimal. All the tumour patients showed a net loss in total activation volumes (both hemispheres plus SMA) compared with controls. The effect of the tumours on interhemispheric volume differences was: group 1>group 3>group 2>group 4. Within the intra-axial tumours, there was no significant effect of tumour type on the results. We conclude that BOLD-imaged activation volume is affected at least by the interplay of two factors: tumour type and distance from the motor cortex. Further, all tumours may be expected to cause some loss of activation volumes in motor areas. We suggest that, with proper precautions and planning, BOLD functional magnetic resonance imaging (fMRI) maps can be useful in minimising damage to the functional areas.

Differential cerebellar activation on functional magnetic resonance imaging during working memory performance in persons with multiple sclerosis.

OBJECTIVE: To explore the potential role of the cerebellum in working memory dysfunction in multiple sclerosis (MS). DESIGN: Blood oxygen level dependent functional magnetic resonance imaging (fMRI) was used to examine cerebellar activation during a working memory task. SETTING: University-affiliated medical rehabilitation facility. PARTICIPANTS: Eight persons with MS and 5 healthy controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Change in hemodynamic response. fMRI data were acquired and subsequently analyzed by using Statistical Parametric Mapping. RESULTS: Both the control and MS groups showed significantly greater activations in the right cerebellar hemisphere as compared with the left side. Persons with MS, however, showed no detectable activations in 4 cerebellar substructures that were significantly active in controls (ie, right vermis, right dentate nucleus, right tonsil, cerebellar peduncle). CONCLUSIONS: The significantly decreased cerebellar activation in the MS group suggests that the cerebellum may play a role in the working memory impairment observed in MS.