Functional brain plasticity following childhood maltreatment: A longitudinal fMRI investigation of autobiographical memory processing.

Altered autobiographical memory (ABM) processing characterizes some individuals with experiences of childhood maltreatment. This fMRI study of ABM processing evaluated potential developmental plasticity in neural functioning following maltreatment. Adolescents with (N = 19; MT group) and without (N = 18; Non-MT group) documented childhood maltreatment recalled specific ABMs in response to emotionally valenced cue words during fMRI at baseline (age 12.71 ± 1.48) and follow-up (14.88 ± 1.53 years). Psychological assessments were collected at both timepoints. Longitudinal analyses were carried out with BOLD signal changes during ABM recall and psychopathology to investigate change over time. In both groups there was relative stability of the ABM brain network, with some developmental maturational changes observed in cortical midline structures (ventromedial PFC (vmPFC), posterior cingulate cortex (pCC), and retrosplenial cortex (rSC). Significantly increased activation of the right rSC was observed only in the MT group, which was associated with improved psychological functioning. Baseline group differences in relation to hippocampal functioning, were not detected at follow-up. This study provides preliminary empirical evidence of functional developmental plasticity in children with documented maltreatment experience using fMRI. This suggests that altered patterns of brain function, associated with maltreatment experience, are not fixed and may reflect the potential to track a neural basis of resilience.

Understanding the development of psychopathy: progress and challenges.

Psychopathy is an adult condition that incurs substantial societal and individual costs. Here we review neurocognitive and genetically informative studies that shed light on how and why this condition emerges. Children cannot present with psychopathy. However, the presence of callous-unemotional (CU) traits can distinguish a group of children who are at elevated risk of psychopathy in adulthood. These children display diminished empathy and guilt and show attenuated brain activation to distress cues in others. Genetically informative studies indicate that individual differences in CU traits show moderate-to-strong heritability, but that protective environmental factors can counter heritable risk. On the basis of the extant research findings, we speculate on what might represent the priorities for research over the next decade. We also consider the clinical implications of these research findings. In particular, we consider the importance of delineating what precisely works for children with CU traits (and their parents) and the ways in which intervention and prevention programs may be optimized to improve engagement as well as clinical outcomes.

DNA methylation and substance-use risk: a prospective, genome-wide study spanning gestation to adolescence.

Epigenetic processes have been implicated in addiction; yet, it remains unclear whether these represent a risk factor and/or a consequence of substance use. Here, we believe we conducted the first genome-wide, longitudinal study to investigate whether DNA methylation patterns in early life prospectively associate with substance use in adolescence. The sample comprised of 244 youth (51% female) from the Avon Longitudinal Study of Parents and Children (ALSPAC), with repeated assessments of DNA methylation (Illumina 450k array; cord blood at birth, whole blood at age 7) and substance use (tobacco, alcohol and cannabis use; age 14-18). We found that, at birth, epigenetic variation across a tightly interconnected genetic network (n=65 loci; q<0.05) associated with greater levels of substance use during adolescence, as well as an earlier age of onset amongst users. Associations were specific to the neonatal period and not observed at age 7. Key annotated genes included PACSIN1, NEUROD4 and NTRK2, implicated in neurodevelopmental processes. Several of the identified loci were associated with known methylation quantitative trait loci, and consequently likely to be under significant genetic control. Collectively, these 65 loci were also found to partially mediate the effect of prenatal maternal tobacco smoking on adolescent substance use. Together, findings lend novel insights into epigenetic correlates of substance use, highlight birth as a potentially sensitive window of biological vulnerability and provide preliminary evidence of an indirect epigenetic pathway linking prenatal tobacco exposure and adolescent substance use.

Childhood maltreatment and attention deficit hyperactivity disorder symptoms in adults: a large twin study.

BACKGROUND: Childhood maltreatment (CM) has been associated with increased risk of attention deficit hyperactivity disorder (ADHD) in children and adults. It is, however, unclear whether this association is causal or due to familial confounding. METHOD: Data from 18 168 adult twins, aged 20-46 years, were drawn from the population-based Swedish twin registry. Retrospective self-ratings of CM (emotional and physical neglect, physical and sexual abuse and witnessing family violence), and self-ratings for DSM-IV ADHD symptoms in adulthood were analysed. Possible familial confounding was investigated using a within twin-pair design based on monozygotic (MZ) and dizygotic (DZ) twins. RESULTS: CM was significantly associated with increased levels of ADHD symptom scores in adults [regression coefficient: 0.40 standard deviations, 95% confidence interval (CI) 0.37-0.43]. Within twin-pair analyses showed attenuated but significant estimates within DZ (0.29, 95% CI 0.21-0.36) and MZ (0.18, 95% CI 0.10-0.25) twin pairs. Similar results emerged for hyperactive/impulsive and inattentive ADHD symptom scores separately in association with CM. We conducted sensitivity analyses for early maltreatment, before age 7, and for abuse and neglect separately, and found similarly reduced estimates in DZ and MZ pairs. Re-traumatization after age 7 did not significantly influence results. CONCLUSIONS: CM was significantly associated with increased ADHD symptoms in adults. Associations were partly due to familial confounding, but also consistent with a causal interpretation. Our findings support cognitive neuroscience studies investigating neural pathways through which exposure to CM may influence ADHD. Clinicians treating adults with ADHD should be aware of the association with maltreatment.

Understanding Addiction as a Developmental Disorder: An Argument for a Developmentally Informed Multilevel Approach.

Substance abuse and drug addiction are two of the most common psychopathologies among the general population. While a host of risk factors are associated with the onset of drug abuse and drug addiction, there is a growing body of evidence pointing to the powerful influence of early adverse experiences, both child neglect and maltreatment, as well as drug use and abuse in parents and/or primary caretakers. We consider the case for drug addiction as a developmental disorder, outlining the need to consider the role of genetic, epigenetic, and neurobiological factors alongside experiences of adversity at key stages of development. Such a multilevel approach within a developmental framework has the potential to reframe our understanding of how addiction emerges and is maintained, and is essential if we are to identify the mechanisms underlying this disorder to better inform effective treatment and prevention across the generations.

Neural responses to fearful eyes in children with conduct problems and varying levels of callous-unemotional traits.

BACKGROUND: Children with conduct problems (CP) are a heterogeneous group. Those with high levels of callous-unemotional traits (CP/HCU) appear emotionally under-reactive at behavioural and neural levels whereas those with low levels of CU traits (CP/LCU) appear emotionally over-reactive, compared with typically developing (TD) controls. Investigating the degree to which these patterns of emotional reactivity are malleable may have important translational implications. Instructing participants with CP/HCU to focus on the eyes of fearful faces (i.e. the most salient feature) can ameliorate their fear-recognition deficits, but it is unknown whether this is mediated by amygdala response. It is also unknown whether focusing on fearful eyes is associated with increased amygdala reactivity in CP/LCU. METHOD: Functional magnetic resonance imaging (fMRI) was used to measure neural responses to fearful and calm faces in children with CP/HCU, CP/LCU and TD controls (n = 17 per group). On half of trials participants looked for a blue dot anywhere within target faces; on the other half, participants were directed to focus on the eye region. RESULTS: Reaction time (RT) data showed that CP/LCU were selectively slowed in the fear/eyes condition. For the same condition, CP/LCU also showed increased amygdala and subgenual anterior cingulate cortex (sgACC)/orbitofrontal cortex (OFC) responses compared with TD controls. RT and amygdala response to fear/eyes were correlated in CP/LCU only. No effects of focusing on the eye region were observed in CP/HCU. CONCLUSIONS: These data extend the evidence base suggesting that CU traits index meaningful heterogeneity in conduct problems. Focusing on regulating reactive emotional responses may be a fruitful strategy for children with CP/LCU.

How reading differs from object naming at the neuronal level.

This paper uses whole brain functional neuroimaging in neurologically normal participants to explore how reading aloud differs from object naming in terms of neuronal implementation. In the first experiment, we directly compared brain activation during reading aloud and object naming. This revealed greater activation for reading in bilateral premotor, left posterior superior temporal and precuneus regions. In a second experiment, we segregated the object-naming system into object recognition and speech production areas by factorially manipulating the presence or absence of objects (pictures of objects or their meaningless scrambled counterparts) with the presence or absence of speech production (vocal vs. finger press responses). This demonstrated that the areas associated with speech production (object naming and repetitively saying "OK" to meaningless scrambled pictures) corresponded exactly to the areas where responses were higher for reading aloud than object naming in Experiment 1. Collectively the results suggest that, relative to object naming, reading increases the demands on shared speech production processes. At a cognitive level, enhanced activation for reading in speech production areas may reflect the multiple and competing phonological codes that are generated from the sublexical parts of written words. At a neuronal level, it may reflect differences in the speed with which different areas are activated and integrate with one another.

Voice therapy outcomes in vocal fold nodules: a retrospective audit.

Twenty-six speech and language therapy (SLT) clinical files, in which patients presented with a medical diagnosis of bilateral or unilateral vocal fold nodule(s), were audited retrospectively over a six year period (1992-1998). The objective of the study was to evaluate current practice within our trust in the management of patients with vocal fold nodules against what was considered 'best practice' and to take action for improvements where deficits were identified. Multidimensional outcome measurements were employed. This study lends support to experimental findings of treatment effectiveness. Results demonstrated elimination and/or reduction of vocal fold nodules in over 70% of clinical files audited. Post-therapy over 80% of patients presented with either a normal voice quality or a mild degree of dysphonia.

Dyslexia: cultural diversity and biological unity.

The recognition of dyslexia as a neurodevelopmental disorder has been hampered by the belief that it is not a specific diagnostic entity because it has variable and culture-specific manifestations. In line with this belief, we found that Italian dyslexics, using a shallow orthography which facilitates reading, performed better on reading tasks than did English and French dyslexics. However, all dyslexics were equally impaired relative to their controls on reading and phonological tasks. Positron emission tomography scans during explicit and implicit reading showed the same reduced activity in a region of the left hemisphere in dyslexics from all three countries, with the maximum peak in the middle temporal gyrus and additional peaks in the inferior and superior temporal gyri and middle occipital gyrus. We conclude that there is a universal neurocognitive basis for dyslexia and that differences in reading performance among dyslexics of different countries are due to different orthographies.

Abnormal functional activation during a simple word repetition task: A PET study of adult dyslexics.

Eight dyslexic subjects, impaired on a range of tasks requiring phonological processing, were matched for age and general ability with six control subjects. Participants were scanned using positron emission tomography (PET) during three conditions: repeating real words, repeating pseudowords, and rest. In both groups, speech repetition relative to rest elicited widespread bilateral activation in areas associated with auditory processing of speech; there were no significant differences between words and pseudowords. However, irrespective of word type, the dyslexic group showed less activation than the control group in the right superior temporal and right post-central gyri and also in the left cerebellum. Notably, the right anterior superior temporal cortex (Brodmann's area 22 [BA 22]) was less activated in each of the eight dyslexic subjects, compared to each of the six control subjects. This deficit appears to be specific to auditory repetition as it was not detected in a previous study of reading which used the same sets of stimuli (Brunswick, N., McCrory, E., Price, C., Frith, C.D., & Frith, U. [1999]. Explicit and implicit processing of words and pseudowords by adult developmental dyslexics: A search for Wernicke's Wortschatz? Brain, 122, 1901-1917). This implies that the observed neural manifestation of developmental dyslexia is task-specific (i.e., functional rather than structural). Other studies of normal subjects indicate that attending to the phonetic structure of speech leads to a decrease in right-hemisphere processing. Lower right hemisphere activation in the dyslexic group may therefore indicate less processing of non-phonetic aspects of speech, allowing greater salience to be accorded to phonological aspects of attended speech.

A cultural effect on brain function.

We present behavioral and anatomical evidence for a multi-component reading system in which different components are differentially weighted depending on culture-specific demands of orthography. Italian orthography is consistent, enabling reliable conversion of graphemes to phonemes to yield correct pronunciation of the word. English orthography is inconsistent, complicating mapping of letters to word sounds. In behavioral studies, Italian students showed faster word and non-word reading than English students. In two PET studies, Italians showed greater activation in left superior temporal regions associated with phoneme processing. In contrast, English readers showed greater activations, particularly for non-words, in left posterior inferior temporal gyrus and anterior inferior frontal gyrus, areas associated with word retrieval during both reading and naming tasks.

Explicit and implicit processing of words and pseudowords by adult developmental dyslexics: A search for Wernicke's Wortschatz?

Two groups of male university students who had been diagnosed as dyslexic when younger, and two groups of control subjects of similar age and IQ to the dyslexics, were scanned whilst reading aloud and during a task where reading was implicit. The dyslexics performed less well than their peers on a range of literacy tasks and were strikingly impaired on phonological tasks. In the reading aloud experiment, simple words and pseudowords were presented at a slow pace so that reading accuracy was equal for dyslexics and controls. Relative to rest, both normal and dyslexic groups activated the same peri- and extra-sylvian regions of the left hemisphere that are known to be involved in reading. However, the dyslexic readers showed less activation than controls in the left posterior inferior temporal cortex [Brodmann area (BA) 37, or Wernicke's Wortschatz], left cerebellum, left thalamus and medial extrastriate cortex. In the implicit reading experiment, word and pseudoword processing was contrasted to visually matched false fonts while subjects performed a feature detection paradigm. The dyslexic readers showed reduced activation in BA 37 relative to normals suggesting that this group difference, seen in both experiments, resides in highly automated aspects of the reading process. Since BA 37 has been implicated previously in modality-independent naming, the reduced activation may indicate a specific impairment in lexical retrieval. Interestingly, during the reading aloud experiment only, there was increased activation for the dyslexics relative to the controls in a pre-motor region of Broca's area (BA 6/44). We attribute this result to the enforced use of an effortful compensatory strategy involving sublexical assembly of articulatory routines. The results confirm previous findings that dyslexic readers process written stimuli atypically, based on abnormal functioning of the left hemisphere reading system. More specifically, we localize this deficit to the neural system underlying lexical retrieval.