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Background. This proof-of-concept study investigated a method of multisensory perceptual training for tinnitus, and whether a short, low-dose administration of fluoxetine enhanced training effects and changed neural connectivity. Methods. A double-blind, randomized placebo controlled design with 20 participants (17 male, 3 female, mean age = 57.1 years) involved 30 min daily computer-based, multisensory training (matching visual, auditory and tactile stimuli to perception of tinnitus) for 20 days, and random allocation to take 20 mg fluoxetine or placebo daily. Behavioral measures of tinnitus and correlations between pairs of a priori regions of interest (ROIs), obtained using resting-state functional magnetic resonance imaging (rs-fMRI), were performed before and after the training. Results. Significant changes in ratings of tinnitus loudness, annoyance, and problem were observed with training. No statistically significant changes in Tinnitus Functional Index, Tinnitus Handicap Inventory or Depression Anxiety Stress Scales were found with training. Fluoxetine did not alter any of the behavioural outcomes of training compared to placebo. Significant changes in connectivity between ROIs were identified with training; sensory and attention neural network ROI changes correlated with significant tinnitus rating changes. Rs-fMRI results suggested that the direction of functional connectivity changes between auditory and non-auditory networks, with training and fluoxetine, were opposite to the direction of those changes with multisensory training and placebo. Conclusions. Improvements in tinnitus measures were correlated with changes in sensory and attention networks. The results provide preliminary evidence for changes in rs-fMRI accompanying a multisensory training method in persons with tinnitus.

Antisocial personality disorder (ASPD) and psychopathy involve significant interpersonal and behavioural impairments. However, little is known about their underlying neurobiology and in particular, abnormalities in white matter (WM) microstructure. Apreliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of adult psychopaths employing tractography revealed abnormalities in the right uncinate fasciculus (UF) (Craig et al., 2009), indicating fronto-limbic disconnectivity. However, it is not clear whether WM abnormalities are restricted to this tract or are or more widespread, including other tracts which are involved in connectivity with the frontal lobe.We performed whole brain voxel-based analyses on WM fractional anisotropy (FA) and mean diffusivity (MD) maps acquired with DT-MRI to compare 15 adults with ASPD and healthy age, handedness and IQ-matched controls. Also, within ASPD subjects we related differences in FA and MD to measures of psychopathy.Significant WM FA reduction and MD increases were found respectively in ASPD subjects relative to controls. FA was bilaterally reduced in the genu of corpus callosum while in the right frontal lobe FA reduction was found in the UF, inferior fronto-occipital fasciculus (IFOF), anterior corona radiata and anterior limb and genu of the internal capsule. These differences negatively correlated with measures of psychopathy. Also in the right frontal lobe, increased MD was found in the IFOF and UF, and the corpus callosum and anterior corona radiata. There was a significant positive correlation between MD and psychopathy scores. Conclusions: The present study confirms a previous report of reduced FA in the UF. Additionally, we report for the first time, FA deficits in tracts involved in interhemispheric as well as frontal lobe connectivity in conjunction with MD increases in the frontal lobe. Hence, we provide evidence of significant WM microstructural abnormalities in frontal brain regions in ASPD and psychopathy. © 2011 Elsevier Srl. 48 2 216 229 Cited By :51; Export Date: 17 July 2017

A 12-year-old boy currently is followed by multiple sub-specialists for problems caused by the chromosome 22q11.2 deletion syndrome (22q11DS) (Figure). He was born via spontaneous vaginal delivery, weighing 3033 g, to a 31-year-old G3P3 mother after a full-term pregnancy complicated only by mild polyhydramnios. Family history was non-contributory. Apgar scores were 8 at 1 minute and 9 at 5 minutes. With the exception of a weak cry, the results of the infant’s initial examination were unremarkable, and he was moved to the well-baby nursery. Shortly thereafter, a cardiac murmur was noted, the cardiology department was consulted, and the child was transferred to a local tertiary care facility with a diagnosis of tetralogy of Fallot. Stable, he was discharged home at 3 days of life. Figure Mild dysmorphic facial features of a boy aged 11 years with 22q11.2DS, including a short forehead, hooded eyelids with upslanting palpebral fissures, malar flatness, bulbous nasal tip with hypoplastic alae nasi, and protuberant ears. At 5 days of life, he had jerky movements. On presentation to the local emergency department, his total calcium level was 4.7 mg/dL, and later partial hypoparathyroidism was diagnosed. At that time, a consulting geneticist suggested the diagnosis of chromosome 22q11DS. Weeks later, the family received a telephone call confirming the diagnosis with fluorescence in situ hybridization (FISH). No additional information about the diagnosis, prognosis, etiology, or recurrence risk was provided until the child was 5 months of age, when he underwent cardiac repair at a third hospital, where a comprehensive 22q11DS program was in operation. In the interim, the child had feeding difficulties requiring supplemental nasogastric tube feeds, nasal regurgitation, and gastroesophageal reflux, while the parents searched the internet for reliable information about their son’s diagnosis. Subsequent notable abnormalities and interventions included: recurrent otitis media with bilateral myringotomy tube placement at 6 months; angioplasty with left pulmonary artery stent placement after the identification of pulmonary artery stenosis with bilateral pleural effusions at age 6 years; chronic upper respiratory infections with significant T cell dysfunction requiring live viral vaccines to be held until age 7 years; velopharyngeal incompetence necessitating posterior pharyngeal flap surgery at 7 years; enamel hypoplasia and numerous caries resulting in 3 separate dental procedures under general cardiac anesthesia beginning at age 7 years; multiple cervical and thoracic vertebral anomalies with thoracic levoconvex scoliosis and upper lumbar dextroscoliosis requiring growing rod placement at age 11 years with subsequent rod extension at ages 11.5 and 12 years; postoperative hypocalcemia; short stature; constipation; and persistent idiopathic thrombocytopenia. Pertinent negative test results included normal renal ultrasound scanning and parental 22q11.2 deletion studies. On physical examination, the boy’s height and weight have consistently tracked just below the fifth percentile, with no evidence of growth hormone deficiency. His head circumference is within reference range at the 25th percentile. Dysmorphic features include: a low anterior hairline; hooded eyelids; malar flatness; normally formed but protuberant ears with attached lobes; a mildly deviated nose with a bulbous nasal tip and hypoplastic alae nasi; asymmetric crying facies with a thin upper lip; mild micrognathia; a sacral dimple; and soft tissue syndactyly of the second and third toes. Developmentally, the boy had mild delays in achieving motor milestones, sitting at 11 months and walking at 18 months. However, he exhibited significant delays in the emergence of language: he never babbled, spoke his first words at age 3 years, and only achieved full conversational speech at 7 years. However, he had relative strengths in receptive language and communicated appropriately by the use of sign language. Now quite conversant, he is mainstreamed in the seventh grade with resource room supports. Moreover, he is affable, but exhibits anxiety and perseverations. Lastly, despite numerous medical, academic, and social challenges, he participates in assisted athletics, is an avid wrestling fan, and enjoys travel. However, his exceptionally supportive parents, siblings, and extended family continue to worry about his long-term outcome and transition of care as he approaches adulthood. As demonstrated by this boy’s complicated course, practical multi-system guidelines are needed to assist the general practitioner and specialists in caring for patients with 22q11DS. Although still under-recognized, detection, including in the prenatal setting, is increasing. Moreover, the phenotypic spectrum is highly variable, and patients may present at any age. Thus, initial guidelines developed by an international panel of experts present the best practice recommendations currently available across the lifespan, with a major focus on the changing issues through childhood development.