Investigating the predictive value of whole-brain structural MR scans in autism: A pattern classification approach

Autistic spectrum disorder (ASD) is accompanied by subtle and spatially distributed differences in brain anatomy that are difficult to detect using conventional mass-univariate methods (e.g., VBM). These require correction for multiple comparisons and hence need relatively large samples to attain sufficient statistical power. Reports of neuroanatomical differences from relatively small studies are thus highly variable. Also, VBM does not provide predictive value, limiting its diagnostic value.Here, we examined neuroanatomical networks implicated in ASD using a whole-brain classification approach employing a support vector machine (SVM) and investigated the predictive value of structural MRI scans in adults with ASD. Subsequently, results were compared between SVM and VBM. We included 44 male adults; 22 diagnosed with ASD using “gold-standard” research interviews and 22 healthy matched controls.SVM identified spatially distributed networks discriminating between ASD and controls. These included the limbic, frontal-striatal, fronto-temporal, fronto-parietal and cerebellar systems. SVM applied to gray matter scans correctly classified ASD individuals at a specificity of 86.0% and a sensitivity of 88.0%. Cases (68.0%) were correctly classified using white matter anatomy. The distance from the separating hyperplane (i.e., the test margin) was significantly related to current symptom severity. In contrast, VBM revealed few significant between-group differences at conventional levels of statistical stringency.We therefore suggest that SVM can detect subtle and spatially distributed differences in brain networks between adults with ASD and controls. Also, these differences provide significant predictive power for group membership, which is related to symptom severity.     

Unsupervised analysis of fMRI data using kernel canonical correlation

We introduce a new unsupervised fMRI analysis method based on kernel canonical correlation analysis which differs from the class of supervised learning methods (e.g., the support vector machine) that are increasingly being employed in fMRI data analysis. Whereas SVM associates properties of the imaging data with simple specific categorical labels (e.g., -1, 1 indicating experimental conditions 1 and 2), KCCA replaces these simple labels with a label vector for each stimulus containing details of the features of that stimulus. We have compared KCCA and SVM analyses of an fMRI data set involving responses to emotionally salient stimuli. This involved first training the algorithm (SVM, KCCA) on a subset of fMRI data and the corresponding labels/label vectors (of pleasant and unpleasant), then testing the algorithms on data withheld from the original training phase. The classification accuracies of SVM and KCCA proved to be very similar. However, the most important result arising form this study is the KCCA is able to extract some regions that SVM also identifies as the most important in task discrimination and these are located manly in the visual cortex. The results of the KCCA were achieved blind to the categorical task labels. Instead, the stimulus category is effectively derived from the vector of image features.     

The role of multidisciplinary decision making in oropharyngeal cancer: do we follow guidelines and are treatment decisions being implemented?

European Archives of Oto-Rhino-Laryngology - A multidisciplinary team (MDT) approach to cancer management is gold-standard. With an increasing disease incidence and growing research into human...     

The structural and functional mechanisms of motor recovery: complementary use of diffusion tensor and functional magnetic resonance imaging in a traumatic injury of the internal capsule

OBJECTIVES—Recovery from focal motor pathwaylesions may be associated with a functional reorganisation of corticalmotor areas. Previous studies of the relation between structural braindamage and the functional consequences have employed MRI and CT, whichprovide limited structural information. The recent development ofdiffusion tensor imaging (DTI) now provides quantitative measures offibre tract integrity and orientation. The objective was to use DTI andfunctional MRI (fMRI) to determine the mechanisms underlying theexcellent recovery found after a penetrating injury to the rightcapsular region.
METHODS—DTI and fMRI were performed on the patientdescribed; DTI was performed on five normal controls.
RESULTS—The injury resulted in a left hemiplegiawhich resolved fully over several weeks. When studied 18 months laterthere was no pyramidal weakness, a mild hemidystonia, and sensorydisturbance. fMRI activation maps showed contralateral primary andsupplementary motor cortex activation during tapping of each hand;smaller ipsilateral primary motor areas were activated by the recoveredhand only. DTI disclosed preserved structural integrity and orientationin the posterior capsular limb by contrast with the disrupted structure in the anterior limb on the injured side.
CONCLUSIONS—The findings suggest that the mainrecovery mechanism was a preservation of the integrity and orientationof pyramidal tract fibres. The fMRI studies do not suggest substantialreorganisation of the motor cortex, although ipsilateral pathways mayhave contributed to the recovery. The initial deficit was probably dueto reversible local factors including oedema and mass effect; permanentdamage to fibre tracts in the anterior capsular limb may account for the persistent sensory deficit. This study shows for the first time thepotential value of combining fMRI and DTI together to investigatemechanisms of recovery and persistent deficit in an individual patient.

     

A comparison of single-dose oral fluconazole with 3-day intravaginal clotrimazole in the treatment of vaginal candidiasis

Summary. A total of 369 women with clinical and mycological evidence of vaginal candidiasis received treatment, after random allocation, with either a single oral 150-mg dose of fluconazole (188 women) or 200 mg of intravaginal clotrimazole given daily for 3 consecutive days (181 women). They were assessed at 5–16 days and again at 27–62 days after treatment. Candida species were completely eradicated from the vagina in 72% of the fluconazole group and in 62% of the clotrimazole group at the long-term assessment (P=0·07). Favourable clinical responses were obtained in 99% of the fluconazole group and in 97% of the clotrimazole group at the short-term assessment and in 93% and 84% respectively at the long-term assessment when there was a significant advantage for fluconazole treatment (P=0·02). Symptoms in patients receiving fluconazole were relieved more rapidly (P<0·001). Treatment-related side-effects were few and minor in both groups. It is concluded that treatment of vaginal candidiasis with fluconazole, as a single oral dose, was more effective in the long term, relieved symptoms more rapidly, and was as safe as treatment with intravaginal clotrimazole.     

Effects on serotonin in rat hypothalamus of D-fenfluramine,aminorex, phentermine and fluoxetine

Hypothalamic 5-HT (serotonin) regulates food intake, energy expenditure and bodyweight. Using in vivo microdialysis, we determined the effects of various anorectic drugs on hypothalamic extracellular 5-HT levels during the dark phase when rats predominantly feed. Phentermine and aminorex, which were originally considered to be catecholaminergic drugs, markedly increased 5-HT efflux in rat hypothalamus. Their actions were less profound than D-fenfluramine, but considerably greater than that of the selective 5-HT reuptake inhibitor, fluoxetine. This suggests that enhanced hypothalamic 5-HT function could be involved in their anorectic actions. Pharmacological characterization revealed that D-fenfluramine, aminorex and probably also phentermine potentiate synaptic 5-HT function predominantly by release, whereas fluoxetine acts exclusively by reuptake inhibition. The results also revealed that the combined actions of phentermine and D-fenfluramine on hypothalamic extracellular 5-HT levels were additive, but not synergistic. In contrast, there was a significant negative cooperative effect on extraneuronal 5-HT of combining phentermine with fluoxetine.     

Novelty-related activation within the medial temporal lobes

Functional magnetic resonance imaging (fMRI) was used to examine whether (1) verbal associative encoding activates the medial temporal lobes (MTL) and related regions more than non-associative encoding, (2) verbal associative novelty is related to enhanced MTL activation, and (3) verbal item novelty is related to enhanced MTL activation and, if so, whether these activations are in different or overlapping sites. No increase in MTL activation was found during verbal associative encoding relative to non-associative encoding, although associative encoding was related to a relative increase in activation in the posterior cingulate cortex. In contrast, verbal associative novelty was found to activate the MTL and posterior cingulate cortex. Verbal item novelty did not significantly activate any brain region. The verbal associative novelty-related effect occurred despite subjects having little awareness of associative novelty. The verbal associative novelty-related activation in the MTL may be related either to unconscious novelty detection or to a priming effect at encoding. We argue that if the priming explanation is correct then this may account for our failure to observe an associative encoding MTL activation.     

Neural correlates of formal thought disorder in schizophrenia: preliminary findings from a functional magnetic resonance imaging study

BACKGROUND: Formal thought disorder (FTD) is a core symptom of schizophrenia, but its pathophysiology is little understood. We examined the neural correlates of FTD using functional magnetic resonance imaging. METHODS: Blood oxygenation level-dependent contrast was measured using functional magnetic resonance imaging while 6 patients with schizophrenia and 6 control subjects spoke about 7 Rorschach inkblots for 3 minutes each. In patients, varying degrees of thought-disordered speech were elicited during each "run." In a within-subject design, the severity of positive FTD was correlated with the level of blood oxygenation level-dependent contrast in the 2 runs that showed the highest variance of FTD in each patient. RESULTS: The severity of positive FTD in patients was negatively correlated (P<.001) with signal changes in the left superior and middle temporal gyri. Positive correlations were evident in the cerebellar vermis, the right caudate body, and the precentral gyrus. CONCLUSIONS: The severity of positive FTD was inversely correlated with the level of activity in the Wernicke area, a region implicated in the production of coherent speech. Reduced activity in this area might contribute to the articulation of incoherent speech. Because of the small sample size, these findings should be considered preliminary.