Pitfalls in brain age analyses

Over the past decade, there has been an abundance of research on the difference between age and age predicted using brain features, which is commonly referred to as the “brain age gap.” Researchers have identified that the brain age gap, as a linear transformation of an out‐of‐sample residual, is dependent on age. As such, any group differences on the brain age gap could simply be due to group differences on age. To mitigate the brain age gap''s dependence on age, it has been proposed that age be regressed out of the brain age gap. If this modified brain age gap is treated as a corrected deviation from age, model accuracy statistics such as R ² will be artificially inflated to the extent that it is highly improbable that an R ² value below .85 will be obtained no matter the true model accuracy. Given the limitations of proposed brain age analyses, further theoretical work is warranted to determine the best way to quantify deviation from normality.     

A new scale for assessing patients with vertebrobasilar stroke-the Israeli Vertebrobasilar Stroke Scale (IVBSS): inter-rater reliability and concurrent validity

OBJECTIVES: Most of existing stroke scoring systems have limited ability to evaluate patients with cerebrovascular events in the vertebrobasilar territory. We devised a new scale, the Israeli Vertebrobasilar Stroke Scale (IVBSS) in order to directly and more accurately assess clinical deficits of patients with vertebrobasilar stroke. The present study measured the reliability and validity of the IVBSS. PATIENTS AND METHODS: Forty-three patients (mean age+/-S.D., 70.9+/-8.8 years, 27 males) with vertebrobasilar stroke were evaluated with the IVBSS (11 items), the NIH Stroke Scale (NIHSS) and the disability modified Rankin Scale (mRS) by independent examiners. Interobserver agreement was rated by weighted kappa statistics for each item and the total IVBSS score. Validity was examined with Spearman rank coefficients to compare the IVBSS with NIHSS and mRS. RESULTS: Excellent reliability was demonstrated between the examiners for almost each item and the total score of the IVBSS (kappa>0.75). The total IVBSS score was strongly associated with NIHSS and mRS results (r=0.80 and 0.76, respectively; P<0.0002). CONCLUSIONS: The IVBSS is a valid instrument that allows the assessment of patients with vertebrobasilar stroke with high reliability. Further observations are warranted to determine the predictive value of the IVBSS for stroke outcome.     

Visual attention circuitry in schizophrenia investigated with oddball event-related functional magnetic resonance imaging

OBJECTIVE: Schizophrenia patients have problems directing attention. Sustained attention requires ensuring that brain resources are focused on a selected target (top-down task) while ignoring irrelevant distractors (bottom-up interference). Whether patients have too little ability to focus or too much interference from distraction has not been clarified. The oddball paradigm embeds infrequent targets and distractors into the stimulus train, and schizophrenia deficits have been linked to diminished responses to both. Cerebral activity underlying abnormal attention can be examined with event-related functional magnetic resonance imaging. METHOD: A visual oddball task was presented to 22 patients with schizophrenia and 28 comparison subjects. Statistical probability maps reflecting blood-oxygenation-level-dependent changes were generated for infrequent targets and novel distractors relative to frequent standard stimuli. Activation was related to performance and symptoms. RESULTS: Activation specific to targets and distractors was associated with faster performance. For targets, patients had diminished activation in superior temporal and frontal gyri, cingulate, thalamus, and basal ganglia. They had increased activation in right insula, mid-frontal gyrus, posterior cingulate, and left inferior parietal lobule. For distractors, patients showed less activation in occipital regions and left inferior parietal lobule but increased activation in parietal-occipital, right mid-frontal, and left inferior frontal gyri. Abnormal activation correlated with positive and negative symptoms. CONCLUSIONS: Abnormal activation in schizophrenia in response to attentional demands reflects both insufficient recruitment of brain systems required for target detection and overcommitment of resources for processing irrelevant distractors. Schizophrenia patients appear to have an inability both to focus on targets and ignore distraction.     

Phenylthiocarbamide (PTC) perception in patients with schizophrenia and first-degree family members: relationship to clinical symptomatology and psychophysical olfactory performance

The inability to taste phenylthiocarbamide (PTC; “taste-blindness”) has been associated with a number of medical and neurological illnesses not typically related to taste. We examined PTC sensitivity in 67 schizophrenia patients, 30 healthy controls, and 30 first-degree relatives to determine whether taster status could represent a simple vulnerability marker. A higher prevalence of non-tasters was seen in patients and family members relative to healthy controls. Among patients, non-tasters exhibited increased levels of negative and first-rank symptoms as well as poorer right nostril odor identification skills relative to PTC tasters. These differences were not explained by age, sex, education, smoking, or intensity differences. Phenotypic variation in PTC sensitivity is thought to be genetic in origin and suggests greater illness risk for those subjects with recessive taster alleles.     

Facial emotion recognition in schizophrenia: when and why does it go awry?

OBJECTIVE: Schizophrenia patients demonstrate impaired emotional processing that may be due, in part, to impaired facial emotion recognition. This study examined event-related potential (ERP) responses to emotional faces in schizophrenia patients and controls to determine when, in the temporal processing stream, patient abnormalities occur. METHOD: 16 patients and 16 healthy control participants performed a facial emotion recognition task. Very sad, somewhat sad, neutral, somewhat happy, and very happy faces were each presented for 100 ms. Subjects indicated whether each face was "Happy", "Neutral", or "Sad". Evoked potential data were obtained using a 32-channel EEG system. RESULTS: Controls performed better than patients in recognizing facial emotions. In patients, better recognition of happy faces correlated with less severe negative symptoms. Four ERP components corresponding to the P100, N170, N250, and P300 were identified. Group differences were noted for the N170 "face processing" component that underlies the structural encoding of facial features, but not for the subsequent N250 "affect modulation" component. Higher amplitude of the N170 response to sad faces was correlated with less severe delusional symptoms. Although P300 abnormalities were found, the variance of this component was explained by the earlier N170 response. CONCLUSION: Patients with schizophrenia demonstrate abnormalities in early visual encoding of facial features that precedes the ERP response typically associated with facial affect recognition. This suggests that affect recognition deficits, at least for happy and sad discrimination, are secondary to faulty structural encoding of faces. The association of abnormal face encoding with delusions may denote the physiological basis for clinical misidentification syndromes.     

Abnormal superior temporal connectivity during fear perception in schizophrenia

Patients with schizophrenia have difficulty in decoding facial affect. A study using event-related functional neuroimaging indicated that errors in fear detection in schizophrenia are associated with paradoxically higher activation in the amygdala and an associated network implicated in threat detection. Furthermore, this exaggerated activation to fearful faces correlated with severity of flat affect. These findings suggest that abnormal threat detection processing may reflect disruptions between nodes that comprise the affective appraisal circuit. Here we examined connectivity within this network by determining the pattern of intercorrelations among brain regions (regions of interest) significantly activated during fear identification in both healthy controls and patients using a novel procedure CORANOVA. This analysis tests differences in the interregional correlation strength between schizophrenia and healthy controls. Healthy subjects' task activation was principally characterized by robust correlations between medial structures like thalamus (THA) and amygdala (AMY) and middle frontal (MF), inferior frontal (IF), and prefrontal cortical (PFC) regions. In contrast, schizophrenia patients displayed no significant correlations between the medial regions and either MF or IF. Further, patients had significantly higher correlations between occipital lingual gyrus and superior temporal gyrus than healthy subjects. These between-group connectivity differences suggest that schizophrenia threat detection impairment may stem from abnormal stimulus integration. Such abnormal integration may disrupt the evaluation of threat within fronto-cortical regions.