Empirical evidence for discrete neurocognitive subgroups in patients with non-psychotic major depressive disorder: clinical implications.

BACKGROUND: Neuropsychological deficits are present across various cognitive domains in major depressive disorder (MDD). However, a consistent and specific profile of neuropsychological abnormalities has not yet been established. METHODS: We assessed cognition in 170 patients with non-psychotic MDD using the Brief Assessment of Cognition in Schizophrenia and the scores were compared with those of 42 patients with schizophrenia as a reference for severity of cognitive impairment. Hierarchical cluster analysis was conducted to determine whether there are discrete neurocognitive subgroups in MDD. We then compared the subgroups in terms of several clinical factors and social functioning. RESULTS: Three distinct neurocognitive subgroups were found: (1) a mild impairment subgroup with near-normative performance and mild dysfunction in motor speed; (2) a selective impairment subgroup, which exhibited preserved working memory and executive function, but moderate to severe deficits in verbal memory, motor speed, verbal fluency, and attention/information processing speed; and (3) a global impairment subgroup with moderate to severe deficits across all neurocognitive domains, comparable with deficits in schizophrenia. The global impairment subgroup was characterized by lower pre-morbid intelligence quotient (IQ). Moreover, a significant difference between groups was observed in premorbid IQ (p = 0.003), antidepressant dose (p = 0.043), antipsychotic dose (p = 0.013), or anxiolytic dose (p < 0.001). CONCLUSIONS: These results suggest the presence of multiple neurocognitive subgroups in non-psychotic MDD with unique profiles, one of which exhibits deficits comparable to those of schizophrenia. The results of the present study may help guide future efforts to target these disabling symptoms using different treatments.

Validation of brain-derived signals in near-infrared spectroscopy through multivoxel analysis of concurrent functional magnetic resonance imaging.

Near-infrared spectroscopy (NIRS) is a convenient and safe brain-mapping tool. However, its inevitable confounding with hemodynamic responses outside the brain, especially in the frontotemporal head, has questioned its validity. Some researchers attempted to validate NIRS signals through concurrent measurements with functional magnetic resonance imaging (fMRI), but, counterintuitively, NIRS signals rarely correlate with local fMRI signals in NIRS channels, although both mapping techniques should measure the same hemoglobin concentration. Here, we tested a novel hypothesis that different voxels within the scalp and the brain tissues might have substantially different hemoglobin absorption rates of near-infrared light, which might differentially contribute to NIRS signals across channels. Therefore, we newly applied a multivariate approach, a partial least squares regression, to explain NIRS signals with multivoxel information from fMRI within the brain and soft tissues in the head. We concurrently obtained fMRI and NIRS signals in 9 healthy human subjects engaging in an n-back task. The multivariate fMRI model was quite successfully able to predict the NIRS signals by cross-validation (interclass correlation coefficient = ∼0.85). This result confirmed that fMRI and NIRS surely measure the same hemoglobin concentration. Additional application of Monte-Carlo permutation tests confirmed that the model surely reflects temporal and spatial hemodynamic information, not random noise. After this thorough validation, we calculated the ratios of the contributions of the brain and soft-tissue hemodynamics to the NIRS signals, and found that the contribution ratios were quite different across different NIRS channels in reality, presumably because of the structural complexity of the frontotemporal regions. Hum Brain Mapp 38:5274-5291, 2017. © 2017 Wiley Periodicals, Inc.

Reduced brain activation during imitation and observation of others in children with pervasive developmental disorder: a pilot study.

BACKGROUND: Children with pervasive developmental disorder (PDD) are thought to have poor imitation abilities. Recently, this characteristic has been suggested to reflect impairments in mirror neuron systems (MNS). We used near-infrared spectroscopy (NIRS) to examine the brain activity of children with PDD during tasks involving imitation and observations of others. FINDINGS: The subjects were 6 male children with PDD (8-14 years old) and 6 age- and gender-matched normal subjects (9-13 years old). A video in which a woman was opening and closing a bottle cap was used as a stimulus. Hemoglobin concentration changes around the posterior part of the inferior frontal gyrus and the adjacent ventral premotor cortex were measured with a 24-channel NIRS machine during action observation and action imitation tasks. Regional oxygenated hemoglobin concentration changes were significantly smaller in the PDD group than in the control group. Moreover, these differences were clearer in the action observation task than in the action imitation task. CONCLUSIONS: Dysfunction in the MNS in children with PDD was suggested by the reduced activation in key MNS regions during tasks involving observations and imitations of others. These preliminary results suggest that further studies are needed to verify MNS dysfunction in children with PDD.

The use of diffusional kurtosis imaging and neurite orientation dispersion and density imaging of the brain in bipolar disorder.

BACKGROUND: Diffusional kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) are new diffusional magnetic resonance imaging (dMRI) techniques to clarify the characterization of neural tissues in the human brain. In this study, we evaluated the structural changes of the cerebrum in patients with bipolar disorder (BD) by these dMRI techniques. METHODS: Thirty-one Japanese patients with BD (male/female: 14/17; 29 out of 31 patients were right-handed; mean age: 39.5 ±â€¯9.3) and 28 healthy, right-handed Japanese subjects underwent 3-Tesla dMRI. We compared the dMRI metrics between the 2 groups and examined the relationships among the metrics. LIMITATION: The majority of the participants in this study were medicated with antidepressants and antipsychotics. Further studies with drug-free participants will be needed before any conclusions can be drawn regarding microstructural changes in BD. RESULTS: The BD patients showed significantly reduced mean kurtosis in right inferior front-occipital fasciculus and right posterior cingulate cortex (PCC), and neurite density indices in the right -PCC, compared with the controls. As for the orientation dispersion index, we detected significant decrease in the left hippocampal region of BD patients. CONCLUSIONS: Using the new dMRI techniques, we observed disease-related alterations in the inferior front-occipital fasciculus, PCC, and hippocampal regions which play important roles in BD. These results may indicate that NODDI and DKI are useful to detect changes in the microstructural tissue organization in BD. It is anticipated that these techniques will be adopted as the mainstream methods for neuroimaging study.

The effect of transcranial direct current stimulation on psychotic symptoms of schizophrenia is associated with oxy-hemoglobin concentrations in the brain as measured by near-infrared spectroscopy: A pilot study.

Transcranial direct current stimulation (tDCS) has been shown to be effective in treating some of the symptoms of schizophrenia. In the current study, we sought to determine whether oxy-hemoglobin ([oxy-Hb]), measured by near-infrared spectroscopy (NIRS), is associated with effects of transcranial direct current stimulation (tDCS) on psychotic symptoms of schizophrenia. Twenty-six patients underwent tDCS (2 mA × 20 min) two times per day for five consecutive days. The anodal electrode was placed over the left dorsolateral prefrontal cortex while the cathodal electrode was placed over the right supraorbital region. One month after the last administration of tDCS, positive, but not negative symptoms, evaluated by the Positive and Negative Syndrome Scale (PANSS), were significantly improved. At baseline, regional [oxy-Hb] concentrations in the brain were measured by a 52-channel NIRS instrument. Significant negative correlation was demonstrated between [oxy-Hb] concentrations of left temporoparietal regions throughout verbal fluency tasks vs. changes of PANSS Positive and Negative subscale scores. This is the first study to demonstrate the correlation between the response of neural activity to cognitive tasks at baseline and the ability of tDCS to improve positive and negative psychotic symptoms. Our observations suggest that NIRS provides a marker to predict the response to treatment with tDCS in schizophrenia.

The use of diffusional kurtosis imaging and neurite orientation dispersion and density imaging of the brain in major depressive disorder.

Diffusional kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) are new diffusional magnetic resonance imaging (dMRI) techniques for the characterization of neural tissues in human brain. In this study, we used these dMRI techniques to evaluate the whole-brain microstructural changes in patients with major depressive disorder (MDD). Twenty-three patients with MDD and 26 healthy subjects underwent dMRI. We compared the dMRI metrics between the 2 groups and examined the relationships between the metrics and the clinical symptoms of MDD. The MDD patients showed significant fractional anisotropy reduction in the bilateral parietal, right parieto-occipital, and right superior temporal corti, compared with the controls. Mean kurtosis values were significantly reduced in MDD patients in the right superior temporal cortex and bilateral posterior thalamic radiation. Neurite density index reductions were found in the right superior temporal cortex, bilateral insulae, right inferior frontal cortex, left parahippocampal region, left middle cerebellar peduncle, and right cerebellum. Regarding the orientation dispersion index (ODI), we detected significant decreases in the left thalamus and left occipital cortex, and significant increases in the bilateral superior longitudinal fasciculi and left posterior thalamic radiation tract. Further, there were significant positive correlations between the total Hamilton Depression Rating scale-21 scores and the ODI values in the right frontal gyri. These results suggest that the DKI and NODDI methods may provide more information about microstructural abnormalities in patients with MDD than the DTI method. It is thus expected that these techniques will be adopted as the informative methods for neuroimaging study.

Association between cognitive deficits and suicidal ideation in patients with major depressive disorder.

The role of cognitive function in suicidal ideation in patients with major depressive disorder (MDD) has not been adequately explored. This research sought to measure the relationship between suicidal ideation and cognitive function. Therefore, in this study, the association between cognitive function and suicidal ideation in patients with MDD was assessed. Cognitive function was evaluated in 233 patients with MDD using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS). Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale. Approximately 59.2% of the patients (138/233) expressed suicidal ideation. Among the BACS subtests, only the executive function scores were significantly lower in patients with MDD with than in those without (p < 0.005). In addition, the executive function, motor speed function, and composite scores correlated negatively with the severity of suicidal ideation in these patients. These results suggest that executive function, motor speed function, and global neuropsychological function are associated with suicidal ideation in patients with MDD and that the BACS neuropsychological battery is an efficient instrument for monitoring these characteristics. Moreover, specific BACS scores can potentially serve as cognitive biomarkers of suicide risk in patients with MDD.

Working memory and prefrontal/temporal hemodynamic responses during post-task period in patients with schizophrenia: A multi-channel near-infrared spectroscopy study.

The relationship between cognitive impairments and social dysfunction in schizophrenia is widely accepted. Neuroimaging studies in patients with schizophrenia have demonstrated abnormal function in the prefrontal region during various neurocognitive tasks. However, studies exploring the neural basis of these cognitive impairments are still limited. Multi-channel near-infrared spectroscopy (NIRS) is a non-invasive functional neuroimaging technique used to detect the spatiotemporal characteristics of brain activity. Previous NIRS studies indicated oxy-hemoglobin (oxy-Hb) increase in patients with schizophrenia during the verbal fluency task (VFT), but to a lesser extent than in healthy participants. Furthermore, aberrant re-increase in the prefrontal region was observed during the post-task period. We hypothesized that prefrontal/temporal oxy-Hb aberrant re-increase during the post-task period was associated with cognitive impairment because oxy-Hb aberrant re-increase represent inadequate suppression of neural activity in the post-task period. We recruited 30 patients with schizophrenia and 30 healthy participants in this study. All participants underwent 52-channel NIRS measurement using the VFT. The patients with schizophrenia showed oxy-Hb aberrant re-increase in prefrontal and temporal regions during the post-task period. Although there was no significant relationship between changes in the oxy-Hb during the task and the scores of the Brief Assessment of Cognition in Schizophrenia (BACS), a significant negative correlation was observed between the oxy-Hb during the post-task period and BACS working memory z-scores (in DLPFC and temporal regions). These results suggest that oxy-Hb re-increase during the post-task period in prefrontal and temporal regions is associated with WM deficits in patients with schizophrenia and NIRS may be a potential biomarker of working memory in chronic schizophrenia.