Neural Dynamics of Autistic Behaviors: Cognitive, Emotional, and Timing Substrates

What brain mechanisms underlie autism and how do they give rise to autistic behavioral symptoms? This article describes a neural model, called the iSTART model, which proposes how cognitive, emotional, timing, and motor processes may interact together to create and perpetuate autistic symptoms. These model processes were originally developed to explain data concerning how the brain controls normal behaviors. The iSTART model shows how autistic behavioral symptoms may arise from prescribed breakdowns in these brain processes.Air Force Office of Scientific Research (F49620-01-1-0397); Office of Naval Research (N00014-01-1-0624

Impaired regulation of emotion: Neural correlates of reappraisal and distraction in bipolar disorder and unaffected relatives

Deficient emotion regulation has been proposed as a crucial pathological mechanism in bipolar disorder (BD). We therefore investigated emotion regulation impairments in BD, the related neural underpinnings and their etiological relevance for the disorder. Twenty-two euthymic patients with bipolar-I disorder and 17 unaffected first-degree relatives of BD-I patients, as well as two groups of healthy gender-, age- and education-matched controls (N=22/17, respectively) were included. Participants underwent functional magnetic resonance imaging while applying two different emotion regulation techniques, reappraisal and distraction, when presented with emotional images. BD patients and relatives showed impaired downregulation of amygdala activity during reappraisal, but not during distraction, when compared with controls. This deficit was correlated with the habitual use of reappraisal. The negative connectivity of amygdala and orbitofrontal cortex (OFC) observed during reappraisal in controls was reversed in BD patients and relatives. There were no significant differences between BD patients and relatives. As being observed in BD patients and unaffected relatives, deficits in emotion regulation through reappraisal may represent heritable neurobiological abnormalities underlying BD. The neural mechanisms include impaired control of amygdala reactivity to emotional stimuli and dysfunctional connectivity of the amygdala to regulatory control regions in the OFC. These are, thus, important aspects of the neurobiological basis of increased vulnerability for BD

Golden oldies and silver brains : Deficits, preservation, learning, and rehabilitation effects of music in ageing-related neurological disorders

During the last decades, there have been major advances in mapping the brain regions that underlie our ability to perceive, experience, and produce music and how musical training can shape the structure and function of the brain. This progress has fueled and renewed clinical interest towards uncovering the neural basis for the impaired or preserved processing of music in different neurological disorders and how music-based interventions can be used in their rehabilitation and care. This article reviews our contribution to and the state-of-the-art of this field. We will provide a short overview outlining the key brain networks that participate in the processing of music and singing in the healthy brain and then present recent findings on the following key music-related research topics in neurological disorders: (i) the neural architecture underlying deficient processing of music (amusia), (ii) the preservation of singing in aphasia and music-evoked emotions and memories in Alzheimer's disease, (iii) the mnemonic impact of songs as a verbal learning tool, and (iv) the cognitive, emotional, and neural efficacy of music-based interventions and activities in the rehabilitation and care of major ageing-related neurological illnesses (stroke, Alzheimer's disease, and Parkinson's disease). (C) 2018 Elsevier Ltd. All rights reserved.Peer reviewe

Brain structure and function in Huntington's disease gene carriers far from predicted disease onset

Whilst there are currently no available disease modifying therapies for Huntington’s Disease (HD), recent progress in huntingtin-lowering strategies hold great promise. Initiating therapies early in the disease course will be important and a complete characterisation of the premanifest period will help inform when to initiate disease modifying therapies and the biomarkers that may be useful in such trials. Previous research has characterised the premanifest period up to approximately 15 years from predicted onset, but even at this early stage the disease process is already underway as evidenced by striatal and white matter atrophy, reductions in structural connectivity within brain networks, rising biofluid biomarkers of neuronal dysfunction, elevations in psychiatric symptoms and emerging subtle cognitive impairments. In order to understand how early neurodegeneration can be detected and which measures are most sensitive to the early disease processes, we need to look even earlier in the disease course. This thesis documents the recruitment and analysis of the HD Young Adult Study: a premanifest cohort further from predicted clinical onset than previously studied with an average of 24 years prior to predicted onset. Differences between gene carriers and controls were examined across a range of imaging, cognitive, neuropsychiatric and biofluid measures. The structural and functional brain connectivity in this cohort is then investigated in further detail. By providing a detailed characterisation of brain structure and function in the early premanifest period along with the most sensitive biomarkers at this stage, this work will inform future treatment strategies that may seek to delay the onset of functional impairments in HD