Generalizability of machine learning for classification of schizophrenia based on resting‐state functional MRI data

Machine learning has increasingly been applied to classification of schizophrenia in neuroimaging research. However, direct replication studies and studies seeking to investigate generalizability are scarce. To address these issues, we assessed within‐site and between‐site generalizability of a machine learning classification framework which achieved excellent performance in a previous study using two independent resting‐state functional magnetic resonance imaging data sets collected from different sites and scanners. We established within‐site generalizability of the classification framework in the main data set using cross‐validation. Then, we trained a model in the main data set and investigated between‐site generalization in the validated data set using external validation. Finally, recognizing the poor between‐site generalization performance, we updated the unsupervised algorithm to investigate if transfer learning using additional unlabeled data were able to improve between‐site classification performance. Cross‐validation showed that the published classification procedure achieved an accuracy of 0.73 using majority voting across all selected components. External validation found a classification accuracy of 0.55 (not significant) and 0.70 (significant) using the direct and transfer learning procedures, respectively. The failure of direct generalization from one site to another demonstrates the limitation of within‐site cross‐validation and points toward the need to incorporate efforts to facilitate application of machine learning across multiple data sets. The improvement in performance with transfer learning highlights the importance of taking into account the properties of data when constructing predictive models across samples and sites. Our findings suggest that machine learning classification result based on a single study should be interpreted cautiously.     

Feeling addressed! The neural processing of social communicative cues in patients with major depression

The feeling of being addressed is the first step in a complex processing stream enabling successful social communication. Social impairments are a relevant characteristic of patients with major depressive disorder (MDD). Here, we investigated a mechanism which—if impaired—might contribute to withdrawal or isolation in MDD, namely, the neural processing of social cues such as body orientation and gesture. During funtional magnetic resonance imaging (fMRI) data acquisition, 33 patients with MDD and 43 healthy control subjects watched video clips of a speaking actor: one version with a gesture accompanying the speech and one without gesture. Videos were filmed simultaneously from two different viewpoints: one with the actor facing the viewer head‐on (frontal) and one side‐view (lateral). After every clip, the participants were instructed to evaluate whether they felt addressed or not. Despite overall comparable addressment ratings and a large overlap in activation patterns in MDD and healthy subjects for gesture processing, the anterior cingulate cortex, bilateral superior/middle frontal cortex, and right angular gyrus were more strongly activated in patients than in healthy subjects for the frontal conditions. Our analyses revealed that patients showed specifically higher activation than healthy subjects for the frontal condition without gesture in regions including the posterior cingulate cortex, left prefrontal cortex, and the left hippocampus. We conclude that MDD patients can recognize and interpret social cues such as gesture or body orientation; however, they seem to require more neural resources. This additional effort might affect successful communication and contribute to social isolation in MDD.     

Leukocyte depletion enhances cultured endothelial retention on vascular prostheses

Approximately 90% of endothelial cells that are seeded or cultured onto vascular prostheses are lost from the flow surface within 24 hours of implantation. To determine the contribution of leukocytes to endothelial cell loss, 111In-labeled, cultured canine jugular venous endothelial cells were grown to confluence on fibronectin-coated polyester elastomer tubes measuring 4 mm inner diameter and 30 mm in length. Autogenous cell-lined tubes were implanted as bilateral carotid replacement grafts in six dogs made leukopenic by cyclophosphamide. Similar unilateral grafts were placed in 12 control dogs. Grafts were removed and perfusion-fixed from six control animals after 2 hours of in vivo arterial perfusion and from the other six animals after 6 hours of perfusion. One graft was removed and perfusion-fixed from each leukopenic animal after 2 hours of implantation and the other after 6 hours. Attachment of endothelial cells to the grafts was measured by indium-labeling technique. Retention of endothelium on grafts removed after 2 hours was measured by planimetric counting with scanning electron microscopy and on those removed after 6 hours by radioisotope quantification. Endothelial cell retention after 2 hours was 37.6% +/- 27.0% in control dogs and 97.0% +/- 3.4% in leukopenic animals (p less than 0.0007). After 6 hours retention was 35.9% +/- 23.2% in control animals and 86.5% +/- 6.0% in leukopenic animals (p less than 0.0009). Leukocyte surface activity was present in less than 1% of the leukopenic dogs compared with 8.5% of the other in vivo midgrafts after 2 hours. These results suggest that leukocytes play a significant role in the loss of seeded endothelium from vascular prostheses.     

Computed tomography versus single-contrast arthrotomography in evaluation of the temporomandibular joint disc: A study of autopsy specimens

The lateral, central and medial parts of 15 right temporomandibular joint autopsy specimens were studied to compare the ability of computed tomography (CT) and single-contrast arthrotomography in diagnosing the disc position and configuration. The radiologic findings were compared with macroscopic findings in a blinded fashion. In the CT examination, the diagnostic accuracy was 40% in determining the disc position and 26.7% in determining the disc configuration. However, in many areas of the joints the disc was not possible to evaluate by CT. With arthrotomography the diagnostic accuracy in determining the disc position was 75.6% and the disc configuration 60%. The sensitivity of CT was 0.45 and of arthrotomography 0.95 for the diagnosis of the disc position. The specificity was 0.87 for CT and 0.76 for arthrotomography. From these results, we conclude that arthrotomography is a reliable aid to diagnosis of TMJ disc changes and that CT cannot replace it.     

Enamel microstructure and microstrain in the fracture of human and pig molar cusps

The role of microstructure in enamel strain and breakage was investigated in human molar cusps and those of the pig, Sus scrofa. Rosette strain gauges were affixed to cusp surfaces (buccal human M3, n=15, and lingual pig M1, n=13), and a compressive load was applied to individual cusps using an MTS materials testing machine. Load and strain data were recorded simultaneously until cusp fracture, and these data were used to estimate enamel stresses, principal strains, and stiffness. Fractured and polished enamel fragments were examined in multiple planes using scanning electron microscopy (SEM). Human cusp enamel showed greater stiffness than pig enamel (P=0.02), and tensile stress at yield was higher (17.9 N/mm2 in humans versus 8.9 N/mm2 in pigs, P=0.06). SEM revealed enamel rod decussation in both human and pig enamel; however, only pig enamel showed a decussation plane between rod and inter-rod crystallites. Human inter-rod enamel was densely packed between rods, whereas in pig enamel, inter-rod enamel formed partitions between rows of enamel rods. Overall, human enamel structure enabled molar cusps to withstand horizontal tensile stress during both elastic and plastic phases of compressive loading. In contrast, pig cusp enamel was less resistant to horizontal tensile stresses, but appeared to fortify the enamel against crack propagation in multiple directions. These structural and biomechanical differences in cusp enamel are likely to reflect species-level differences in occlusal function.     

Rash Impulsiveness and Negative Mood,but not Alexithymia or Reward Sensitivity,Differentiate Young to Middle-Aged Chronic Daily Smokers from Never-Smokers

Given the well-established associations of the personality traits alexithymia, impulsivity, and reward sensitivity with problematic use of a variety of substances, including alcohol and cannabis, the present study sought to determine whether daily tobacco smoking is similarly linked to these traits. Male and female adults aged 18 to 40 years were recruited from the local Australian community, allowing comparison of demographically similar samples of current daily smokers (n = 47) to never-smokers (n = 59) on the relevant self-report measures. Multivariate analysis of covariance revealed that current smokers scored significantly higher than never-smokers on indices of negative mood, impulsiveness, and risky alcohol use, after controlling for social desirability. No significant group differences were found on indices of alexithymia, reward sensitivity, or punishment sensitivity. Results suggest that chronic daily cigarette smoking may be an exception to the maladaptive behaviors associated with alexithymia, and is driven primarily by mood regulation and poor impulse control.