Timothy J. Silk

Dissociation in performance of children with ADHD and high-functioning autism on a task of sustained attention.

Attention deficit hyperactivity disorder (ADHD) and autism are two neurodevelopmental disorders associated with prominent executive dysfunction, which may be underpinned by disruption within fronto-striatal and fronto-parietal circuits. We probed executive function in these disorders using a sustained attention task with a validated brain-behaviour basis. Twenty-three children with ADHD, 21 children with high-functioning autism (HFA) and 18 control children were tested on the Sustained Attention to Response Task (SART). In a fixed sequence version of the task, children were required to withhold their response to a predictably occurring no-go target (3) in a 1–9 digit sequence; in the random version the sequence was unpredictable. The ADHD group showed clear deficits in response inhibition and sustained attention, through higher errors of commission and omission on both SART versions. The HFA group showed no sustained attention deficits, through a normal number of omission errors on both SART versions. The HFA group showed dissociation in response inhibition performance, as indexed by commission errors. On the Fixed SART, a normal number of errors was made, however when the stimuli were randomised, the HFA group made as many commission errors as the ADHD group. Greater slow-frequency variability in response time and a slowing in mean response time by the ADHD group suggested impaired arousal processes. The ADHD group showed greater fast-frequency variability in response time, indicative of impaired top-down control, relative to the HFA and control groups. These data imply involvement of fronto-parietal attentional networks and sub-cortical arousal systems in the pathology of ADHD and prefrontal cortex dysfunction in children with HFA.

White‐matter abnormalities in attention deficit hyperactivity disorder: A diffusion tensor imaging study

Current evidence suggests that attention deficit hyperactivity disorder (ADHD) involves dysfunction in wide functional networks of brain areas associated with attention and cognition. This study examines the structural integrity of white‐matter neural pathways, which underpin these functional networks, connecting fronto‐striatal and fronto‐parietal circuits, in children with ADHD. Fifteen right‐handed 8 to 18‐year‐old males with ADHD‐combined type and 15 right‐handed, age, verbal, and performance IQ‐matched, healthy males underwent diffusion tensor imaging. A recent method of tract‐based spatial statistics was used to examine fractional anisotropy (FA) and mean diffusivity within major white‐matter pathways throughout the whole‐brain. White‐matter abnormalities were found in several distinct clusters within left fronto‐temporal regions and right parietal‐occipital regions. Specifically, participants with ADHD showed greater FA in white‐matter regions underlying inferior parietal, occipito‐parietal, inferior frontal, and inferior temporal cortex. Secondly, eigenvalue analysis suggests that the difference in FA in ADHD may relate to a lesser degree of neural branching within key white‐matter pathways. Tractography methods showed these regions to generally form part of white‐matter pathways connecting prefrontal and parieto‐occipital areas with the striatum and the cerebellum. Our findings demonstrate anomalous white‐matter development in ADHD in distinct cortical regions that have previously been shown to be dysfunctional or hypoactive in fMRI studies of ADHD. These data add to an emerging picture of abnormal development within fronto‐parietal cortical networks that may underpin the cognitive and attentional disturbances associated with ADHD. Hum Brain Mapp, 2009.

Right parietal dysfunction in children with attention deficit hyperactivity disorder, combined type : a functional MRI study

Attention deficit hyperactivity disorder, combined type (ADHD-CT) is associated with spatial working memory deficits. These deficits are known to be subserved by dysfunction of neural circuits involving right prefrontal, striatal and parietal brain regions. This study determines whether decreased right prefrontal, striatal and parietal activation with a mental rotation task shown in adolescents with ADHD-CT is also evident in children with ADHD-CT. A cross-sectional study of 12 pre-pubertal, right-handed, 8–12-year-old boys with ADHD-CT and 12 pre-pubertal, right-handed, performance IQ-matched, 8–12-year-old healthy boys, recruited from local primary schools, was completed. Participants underwent functional magnetic resonance imaging while performing a mental rotation task that requires spatial working memory. The two groups did not differ in their accuracy or response times for the mental rotation task. The ADHD-CT group showed significantly less activation in right parieto-occipital areas (cuneus and precuneus, BA 19), the right inferior parietal lobe (BA 40) and the right caudate nucleus. Our findings with a child cohort confirm previous reports of right striatal-parietal dysfunction in adolescents with ADHD-CT. This dysfunction suggests a widespread maturational deficit that may be developmental stage independent.

Neural correlates of the emergence of consciousness of thirst

Thirst was induced by rapid i.v. infusion of hypertonic saline (0.51 M at 13.4 ml/min). Ten humans were neuroimaged by positron-emission tomography (PET) and four by functional MRI (fMRI). PET images were made 25 min after beginning infusion, when the sensation of thirst began to enter the stream of consciousness. The fMRI images were made when the maximum rate of increase of thirst occurred. The PET results showed regional cerebral blood flow changes similar to those delineated when thirst was maximal. These loci involved the phylogenetically ancient areas of the brain. fMRI showed activation in the anterior wall of the third ventricle, an area that is key in the genesis of thirst but is not an area revealed by PET imaging. Thus, this region plays as major a role in thirst for humans as for animals. Strong activations in the brain with fMRI included the anterior cingulate, parahippocampal gyrus, inferior and middle frontal gyri, insula, and cerebellum. When the subjects drank water to satiation, thirst declined immediately to baseline. A precipitate decline in intensity of activation signal occurred in the anterior cingulate area (Brodmann area 32) putatively related to consciousness of thirst. The intensity of activation in the anterior wall of the third ventricle was essentially unchanged, which is consistent with the fact that a significant time (15–20 min) would be needed before plasma Na concentration changed as a result of water absorption from the gut.

Spatial working memory and spatial attention rely on common neural processes in the intraparietal sulcus.

Our ability to remember locations in space (spatial working memory) and our ability to direct attention to those locations (spatial attention) are two fundamental and closely related cognitive processes. A growing body of behavioural evidence suggests that spatial working memory and spatial attention share common resources, while neuroimaging studies show some overlap in the neural regions that mediate these two cognitive functions. The current study used fMRI to directly examine the extent to which spatial working memory and spatial attention rely on common underlying neural mechanisms. Twenty healthy participants underwent functional MRI while performing a dual task of spatial working memory incorporating a visual search task during the working memory retention interval. Working memory and visual search task loads were parametrically modulated. A wide network of prefrontal, premotor, and parietal regions showed increasing activity with increased spatial working memory load. Of these areas, part of the right supramarginal gyrus, lying along the intraparietal sulcus, showed a significant interaction such that the neural activity associated with spatial working memory load was significantly attenuated as visual search load in the dual task was increased. This interaction suggests that this part of the supramarginal gyrus, along the intraparietal sulcus, is critical for mediating both spatial working memory and shifts in spatial attention.

Structural development of the basal ganglia in attention deficit hyperactivity disorder : a diffusion tensor imaging study

One of the most consistently reported brain regions of structural and functional difference in attention deficit hyperactivity disorder (ADHD) is the basal ganglia, particularly the caudate nucleus. Examining the structural organization of the basal ganglia in ADHD is important because it is the center of wider fronto-striatal networks, reported to be dysfunctional in ADHD. Fifteen right-handed 8- to 18-year-old males with ADHD-combined type and 15 right-handed, age- and performance IQ-matched healthy males underwent diffusion tensor imaging. Caudate, putamen and thalamus were manually identified as regions of interest (ROIs) and tested for differences in fractional anisotropy and mean diffusivity. Measures of fractional anisotropy (FA) showed the expected increase with age within the whole-brain volume and within putamen and thalamus ROIs for both ADHD and control groups. In the caudate nucleus, however, developmental changes in FA with age were significantly different between ADHD and control groups. This study shows that the developmental trajectory of micro-structural organization within the caudate nucleus is different in children with ADHD compared with controls over ages 8-18 years. We suggest that the difference in developmental trajectories arises predominantly during mid-late adolescence and may reflect a developmental delay that begins to normalise over this critical late adolescent age.

Lessons About Neurodevelopment From Anatomical Magnetic Resonance Imaging

The arrival of magnetic resonance imaging (MRI) has offered major advances in our understanding of both normal and abnormal neurodevelopment. This review is a broad overview of the key findings that anatomical MRI research has provided in regard to the normal developing brain and presents key issues and consideration in pediatric imaging. Volumetric MRI studies, using various methods, have reliably found that gray-matter volume increases and peaks in late childhood, followed by a slow but continued loss, whereas white matter increases rapidly until age 10 years with continued development well beyond adolescence. The introduction of analysis techniques, such as voxel-based morphometry, cortical thickness measures, and cortical pattern mapping, have begun to answer more regionally specific questions. Pediatric neuroimaging studies carry specific requirements, given not only the high degree of variability between individuals, ages, and sexes but also issues of behavioral compliance, MR signal, and postprocessing methodologies such as appropriate normalization. Considerations in future pediatric imaging studies are presented. Ultimately, the promise of computational analysis of structural MRI data is to understand how changes in cerebral morphology relate to acquisition and enhancement of skills and behaviors in typical and atypical development.

Executive function and attention in children and adolescents with depressive disorders: a systematic review

Numerous studies have shown that Major Depressive Disorder (MDD) in adults is associated with deficits in cognitive control. Particularly, impairment on executive function (EF) tasks has been observed. Research into EF deficits in children and adolescents with MDD has reported mixed results and it is currently unclear whether paediatric MDD is characterised by impairments in EF and attention. PsycInfo, Scopus and Medline were systematically searched to identify all studies that have investigated EF and attention in paediatric depressive disorders between 1994 and 2014. 33 studies meeting inclusion/exclusion criteria were identified. While across different domains of EF some studies identified a deficit in the clinical group, the majority of studies failed to find deficits in response inhibition, attentional set shifting, selective attention, verbal working memory, and verbal fluency. More research is needed to clarify the relationship between depressive disorders in children and adolescents and spatial working memory processing, sustaining attention, planning, negative attentional bias and measures of ‘hot’ EF. There is little support for EF deficits in paediatric depression. However, there are numerous methodological problems that may account for null findings. Alternatively, chronicity and/or severity of symptoms may explain discrepancies between cognitive deficits in adult and paediatric MDD. Recommendations for future studies are discussed.

The emergence of age-dependent social cognitive deficits after generalized insult to the developing brain: A longitudinal prospective analysis using susceptibility-weighted imaging

Childhood and adolescence are critical periods for maturation of neurobiological processes that underlie complex social and emotional behavior including Theory of Mind (ToM). While structural correlates of ToM are well described in adults, less is known about the anatomical regions subsuming these skills in the developing brain or the impact of cerebral insult on the acquisition and establishment of high‐level social cognitive skills. This study aimed to examine the differential influence of age‐at‐insult and brain pathology on ToM in a sample of children and adolescents with traumatic brain injury (TBI). Children and adolescents with TBI (n = 112) were categorized according to timing of brain insult: (i) middle childhood (5–9 years; n = 41); (ii) late childhood (10–11 years; n = 39); and (iii) adolescence (12–15 years; n = 32) and group‐matched for age, gender, and socioeconomic status to a typically developing (TD) control group (n = 43). Participants underwent magnetic resonance imaging including a susceptibility‐weighted imaging (SWI) sequence 2–8 weeks postinjury and were assessed on a battery of ToM tasks at 6‐ and 24‐months after injury. Results showed that for adolescents with TBI, social cognitive dysfunction at 6‐ and 24‐months postinjury was associated with diffuse neuropathology and a greater number of lesions detected using SWI. In the late childhood TBI group, we found a time‐dependent emergence of social cognitive impairment, linked to diffuse neuropathology. The middle childhood TBI group demonstrated performance unrelated to SWI pathology and comparable to TD controls. Findings indicate that the full extent of social cognitive deficits may not be realized until the associated skills reach maturity. Evidence for brain structure–function relationships suggests that the integrity of an anatomically distributed network of brain regions and their connections is necessary for the acquisition and establishment of high‐level social cognitive skills. Hum Brain Mapp 36:1677–1691, 2015.

White matter abnormalities in pediatric obsessive-compulsive disorder

Diffusion tensor imaging (DTI) has been useful in allowing us to examine the nature and extent of neuronal disruption associated with obsessive-compulsive disorder (OCD). However, little is known about the underlying brain structure in OCD. Diffusion-weighted magnetic resonance imaging was performed in 16 children with OCD and 22 typically developing children. Tract-based spatial statistics (TBSS) was used to compare the microstructure of white-matter tracts of OCD children with those of typically developing children. Correlation/regression analyses were also performed on each diffusion measure in order to detect any correlation of white-matter microstructure with scales of symptom severity. Analysis revealed significantly greater axial diffusivity in both the genu and the splenium of the corpus callosum in the control compared to the OCD group; these regions consecutively connect bilateral medial frontal regions and bilateral parietal regions. Secondly, correlation and voxel-based regression analysis revealed that lower axial diffusion correlated with greater severity of symptoms within the OCD group, as measured by the Child Behaviour Checklist-Obsessive Compulsive Scale (CBCL-OCS). The findings demonstrated a correlation of axial diffusivity with severity of symptoms in children with OCD. DTI may provide novel ways to help reveal the relationships between clinical symptoms and altered brain regions.