Mood Disorders in Young People With Acquired Brain Injury: An Integrated Model.

Purpose/Objective: Young people with paediatric acquired brain injury (pABI) are twice as likely to develop a mood disorder as their peers, frequently have significant unmet socio-emotional needs, and are at over double the risk of going on to use adult mental health services. Recent years have seen significant advances in the development of interventions for young people with mood disorders. However, evidence-based approaches to mood disorders in pABI are lacking and surprisingly little work has evaluated clinical and neuro-developmental models of mood disorders in this population. Method: We review the literature regarding key mechanisms hypothesised to account for the increased vulnerability to mood disorders in pABI: First, we summarise the direct neurocognitive consequences of pABI, considering the key areas of the brain implicated in vulnerability to mood disorders within a neurodevelopmental framework. Second, we outline five key factors that contribute to the heightened prevalence of mood disorders in young people following ABI. Finally, we synthesise these, integrating neuro-cognitive, developmental and systemic factors to guide clinical formulation. Results and Implications: We present a framework that synthesises the key mechanisms identified in our review, namely the direct effects of pABI, neurocognitive and neuroendocrine factors implicated in mood and anxiety disorders, maladaptive neuroplasticity and trauma, structural and systemic factors, and psychological adjustment and developmental context. This framework is the first attempt to provide integrated guidance on the multiple factors that contribute to elevated life-long risk of mood disorders following pABI.

The neural correlates of working memory training in typically developing children.

Working memory training improves children's cognitive performance on untrained tasks; however, little is known about the underlying neural mechanisms. This was investigated in 32 typically developing children aged 10-14 years (19 girls and 13 boys) using a randomized controlled design and multi-modal magnetic resonance imaging (Devon, UK; 2015-2016). Training improved working memory performance and increased intrinsic functional connectivity between the bilateral intraparietal sulci. Furthermore, improvements in working memory were associated with greater recruitment of the left middle frontal gyrus on a complex span task. Repeated engagement of fronto-parietal regions during training may increase their activity and functional connectivity over time, affording greater working memory performance. The plausibility of generalizable cognitive benefits from a neurobiological perspective and implications for neurodevelopmental theory are discussed.

Technology-assisted rehabilitation interventions following pediatric brain injury.

INTRODUCTION: Following traumatic brain injury (TBI), children experience a variety of physical, motor, speech, and cognitive deficits that can have a long-term detrimental impact. The emergence and popularity of new technologies has led to research into the development of various apps, gaming systems, websites, and robotics that might be applied to rehabilitation. The objective of this narrative review was to describe the current literature regarding technologically-assisted interventions for the rehabilitation of motor, neurocognitive, behavioral, and family impairments following pediatric TBI. EVIDENCE ACQUISITION: We conducted a series of searches for peer-reviewed manuscripts published between 2000 and 2017 that included a technology-assisted component in the domains of motor, language/communication, cognition, behavior, social competence/functioning, family, and academic/school-based functioning. EVIDENCE SYNTHESIS: Findings suggested several benefits of utilizing technology in TBI rehabilitation including facilitating engagement/adherence, increasing access to therapies, and improving generalizability across settings. There is fairly robust evidence regarding the efficacy of online family problem-solving therapy in improving behavior problems, executive functioning, and family functioning. There was less compelling, but still promising, evidence regarding the efficacy other technology for motor deficits, apps for social skills, and computerized programs for cognitive skills. Overall, many studies were limited in the rigor of their methodology due to small heterogeneous samples and lack of control groups. CONCLUSIONS: Technology-assisted interventions have the potential to enhance pediatric rehabilitation after TBI. Future research is needed to further support their efficacy with larger controlled trials and to identify characteristics of children who are most likely to benefit.

Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation.

Blueberries are rich in flavonoids, which possess antioxidant and anti-inflammatory properties. High flavonoid intakes attenuate age-related cognitive decline, but data from human intervention studies are sparse. We investigated whether 12 weeks of blueberry concentrate supplementation improved brain perfusion, task-related activation, and cognitive function in healthy older adults. Participants were randomised to consume either 30 mL blueberry concentrate providing 387 mg anthocyanidins (5 female, 7 male; age 67.5 ± 3.0 y; body mass index, 25.9 ± 3.3 kg·m-2) or isoenergetic placebo (8 female, 6 male; age 69.0 ± 3.3 y; body mass index, 27.1 ± 4.0 kg·m-2). Pre- and postsupplementation, participants undertook a battery of cognitive function tests and a numerical Stroop test within a 1.5T magnetic resonance imaging scanner while functional magnetic resonance images were continuously acquired. Quantitative resting brain perfusion was determined using an arterial spin labelling technique, and blood biomarkers of inflammation and oxidative stress were measured. Significant increases in brain activity were observed in response to blueberry supplementation relative to the placebo group within Brodmann areas 4/6/10/21/40/44/45, precuneus, anterior cingulate, and insula/thalamus (p < 0.001) as well as significant improvements in grey matter perfusion in the parietal (5.0 ± 1.8 vs -2.9 ± 2.4%, p = 0.013) and occipital (8.0 ± 2.6 vs -0.7 ± 3.2%, p = 0.031) lobes. There was also evidence suggesting improvement in working memory (2-back test) after blueberry versus placebo supplementation (p = 0.05). Supplementation with an anthocyanin-rich blueberry concentrate improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults.

Development and Validation of a Modified Multiple Errands Test for Adults with Intellectual Disabilities.

BACKGROUND: The aims of the current study were to adapt a version of the MET for people with intellectual disabilities and assess its ecological and construct validity. MATERIAL AND METHODS: Using a correlational design, 40 participants with intellectual disabilities were invited to complete a battery of neuropsychological assessments and the modified Multiple Errands Test for Intellectual Disabilities (mMET-IDs). RESULTS: The ability to successfully complete tasks on the mMET-IDs correlated significantly with measures of the Supervisory Attentional System, namely, the Tower of London Test and the Six Parts Test. However, performance on the mMET-IDs and the Six Parts Test could be accounted for by Verbal IQ and receptive vocabulary. The mMET-IDs failed to correlate with the DEX-IR. CONCLUSIONS: The mMET-IDs can be successfully used to assess some aspects of the Supervisory Attentional System in people with intellectual disabilities. Further development is needed, however, to improve the ecological validity of the mMET-IDs.

A meta-analysis of working memory impairments in survivors of moderate-to-severe traumatic brain injury.

OBJECTIVES: To establish the magnitude of deficits in working memory (WM) and short-term memory (STM) in those with moderate-to-severe traumatic brain injury (TBI) relative to age-matched, healthy controls and to explore the moderating effects of time since injury and age at injury on these impairments. METHOD: Twenty-one studies that compared the WM and/or STM abilities of individuals with at least a moderate TBI relative to healthy controls were included in a random effects meta-analysis. Measures used to examine memory performance were categorized by modality (visuospatial, verbal) and memory system (WM, STM). RESULTS: Individuals with TBI had significant deficits in verbal STM (Cohen's d = .41), visuospatial WM (Cohen's d = .69), and verbal WM (Cohen's d = .37) relative to controls. Greater decrements in verbal STM and verbal WM skills were associated with longer time postinjury. Larger deficits were observed in verbal WM abilities in individuals with older age at injury. CONCLUSION: Evidence for WM impairments following TBI is consistent with previous research. Larger verbal STM and verbal WM deficits were related to a longer time postinjury, suggesting that these aspects of memory do not "recover" over time and instead, individuals might show increased rates of cognitive decline. Age at injury was associated with the severity of verbal WM impairments, with larger deficits evident for injuries that occurred later in life. Further research needs to chart the long-term effects of TBI on WM and to compare the effects of injury on verbal relative to visuospatial memory. (PsycINFO Database Record

Memory for action sequences in semantic dementia.

Semantic dementia (SD) is associated with a progressive, relatively selective, degeneration of semantic memory (both verbal and nonverbal facts and knowledge). Episodic memory, however, is thought to be relatively preserved. This study aimed to further assess the nonverbal, incidental, episodic memory profile associated with SD using deferred imitation, which measures recall by the nonverbal imitation of novel action sequences after a 24-h delay. The performance of six individuals with SD was compared to that of 10 healthy age- and education-matched controls. After a baseline phase, where sets of objects were presented for manipulation to measure the spontaneous production of relevant action sequences, participants were shown eight novel three-step action sequences with the sets of objects. The component actions of the sequences were causally related in four of the eight series and arbitrarily related in the remaining four, to investigate the influence of sequence structure on memory performance. All participants produced more target actions and pairs in the arbitrary sequences 24-h after demonstration compared to baseline, indicating memory for the sequences, but only the control group showed significant memory for the order of the causal sequences (pairs). Furthermore, and perhaps more strikingly, only the control participants showed a recall advantage for the causal relative to the arbitrary sequences, indicating that they, but not the patients, could take advantage of the semantic nature of these sequences. Together these findings suggest that individuals with SD show some nonverbal episodic memory, even after a 24-h delay, and that new anterograde memory can to some extent be established without significant support from semantic memory.

The Cambridge Semantic Memory Test Battery: detection of semantic deficits in semantic dementia and Alzheimer's disease.

The aims of this study were (a) to explore the utility of, and make more widely available, an updated and extended version of the Cambridge Semantic Memory test battery, and (b) to use this battery in conjunction with other tests to characterise the profile of several different forms of progressive cognitive impairment: semantic dementia (SD, n = 15), mild cognitive impairment (MCI, n = 7), established Alzheimer's disease (AD) (n = 8), all in comparison to normal controls (n = 45). The semantic battery is useful in a variety of ways for exploring the nature of semantic deficits; on its own, however, it does not provide sensitive differentiation between patients with AD and SD. An assessment including measures of episodic memory and visuospatial abilities as well as the semantic battery is recommended for good characterisation of the cognitive profiles associated with SD and AD.

Dissociation between recognition and recall in developmental amnesia.

Developmental amnesia (DA) is a memory disorder due to hypoxia/ischaemia-induced damage to the hippocampus early in life. To test the hypothesis that this disorder is associated with a disproportionate impairment in recall vis-à-vis recognition, we examined a group of 10 patients with DA on the Doors and People test, which affords a quantitative comparison between measures of the two memory processes. The results supported the hypothesis in that the patients showed a sharp, though not complete, recall-recognition dissociation, exhibiting impairment on both measures relative to their matched controls, but with a far greater loss in recall than in recognition. Whether their relatively spared recognition ability is due to restriction of their medial temporal lobe damage to the hippocampus or whether it is due instead to their early age at injury is still uncertain.

Repeat and Point: differentiating semantic dementia from progressive non-fluent aphasia.

To determine whether a new, simple, quick measure, the Repeat and Point test, reliably differentiates between semantic dementia (SD) and progressive non-fluent aphasia (PNFA). Fifteen patients with SD, six patients with PNFA and 18 healthy controls were administered the Repeat and Point test. Participants were required to repeat 10 multi-syllabic concrete nouns and, following each repetition, to point to the word's pictorial referent amongst an array of six semantically and perceptually similar foils. Patients with SD were consistently impaired relative to PNFA patients and controls on the comprehension (pointing) component of the task, whereas patients with PNFA showed no significant deficit on pointing but were impaired at the production (repeating) component. Discriminant function analysis confirmed perfect classification of the individual patients into their respective groups: criteria involving a ratio of the two scores are provided. The Repeat and Point test is particularly appropriate for routine use in a clinical context: it is quick and easy to administer and score; it reliably discriminated between the two patient groups, SD and PNFA; and it offers a simple rule of thumb, i.e., the Repeat-to-Point ratio, to aid in the diagnosis of these two language variants of frontotemporal dementia (FTD).

Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene.

The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits food intake, and rodent models of BDNF disruption all exhibit increased food intake and obesity, as well as hyperactivity. We report an 8-year-old girl with hyperphagia and severe obesity, impaired cognitive function, and hyperactivity who harbored a de novo chromosomal inversion, 46,XX,inv(11)(p13p15.3), a region encompassing the BDNF gene. We have identified the proximal inversion breakpoint that lies 850 kb telomeric of the 5' end of the BDNF gene. The patient's genomic DNA was heterozygous for a common coding polymorphism in BDNF, but monoallelic expression was seen in peripheral lymphocytes. Serum concentration of BDNF protein was reduced compared with age- and BMI-matched subjects. Haploinsufficiency for BDNF was associated with increased ad libitum food intake, severe early-onset obesity, hyperactivity, and cognitive impairment. These findings provide direct evidence for the role of the neurotrophin BDNF in human energy homeostasis, as well as in cognitive function, memory, and behavior.

Semantic knowledge in mild cognitive impairment and mild Alzheimer's disease.

The aim of this study was to investigate memory in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Ten patients with MCI, 11 with AD and a group of age and education matched healthy control participants were assessed on a comprehensive battery of semantic memory tests, including traditional semantic memory measures and a non-verbal test of knowledge of object use. The MCI group was impaired on tests of category fluency and all three conditions of an object knowledge test (matching to recipient, function and action), plus a difficult object-naming test. The mild AD group showed additional impairments on traditional measures of semantic memory, including naming high frequency items, comprehension and semantic association. Together these findings suggest that semantic memory impairments occur early in the course of AD, more specifically in patients with "amnesic" MCI, and provide further evidence that impaired category fluency reflects semantic breakdown.

Deferred imitation of action sequences in developmental amnesia.

The aims of this study were to investigate whether patients with developmental amnesia (DA) associated with bilateral hippocampal volume reduction show an impairment in incidental nonverbal recall of action sequences, and whether the severity of this memory impairment is influenced by the sequence structure (causal vs. arbitrary). Like adult-onset cases of amnesia (McDonough, Mandler, McKee, & Squire, 1995), patients with DA did not differ significantly from their age-, sex-, and IQ-matched controls in spontaneous production of the sequences prior to modeling but recalled fewer target actions and action pairs than the control group after a 24-hour delay, independent of sequence structure. Unlike the patients with adult-onset amnesia, however, the patients with DA showed some memory for both types of sequences after a 24-hour delay. This difference in severity of memory impairment might reflect differences in extent of pathology and/or age at injury.