Verbal creativity and schizotypal personality in relation to prefrontal hemispheric laterality: a behavioral and near-infrared optical imaging study

Although anecdotal and correlational results have suggested a reliable relationship between creativity and psychosis, few studies have examined this relationship using empirical methods. In addition, little is known about the neural substrates of creative thinking. We investigated the creative thinking process in relation to schizotypal personality, schizophrenia and prefrontal hemispheric laterality using behavioral and near-infrared optical spectroscopy (NIRS) methods. Schizophrenic, psychometrically ascertained schizotypal, and healthy control subjects (all right-handed) participated in a novel “alternate uses” task designed to assess divergent thinking (DT) ability. The DT task required subjects to generate “uses” for conventional and ambiguous objects. Prefrontal activity was measured using NIRS while subjects were engaged in DT vs. a cognitive control task in a subset of the subjects. Behavioral data indicated that schizotypes had enhanced DT ability compared with schizophrenic and control subjects, who showed similar performance overall. NIRS data showed that DT was associated with bilateral prefrontal cortex (PFC) activation, but the right PFC particularly contributed to the enhanced creative thinking in psychometric schizotypes compared with the other two groups. Thus, creative thinking seems to robustly recruit bilateral PFC, but it is the right PFC that is preferentially activated in schizotypes in relation to their enhanced DT.     

Task dependent prefrontal dysfunction in persons with Asperger's disorder investigated with multi-channel near-infrared spectroscopy

Dysfunction of the prefrontal cortex has been previously reported in individuals with Asperger's disorder. In the present study, we used multi-channel near-infrared spectroscopy (NIRS) to detect changes in the oxygenated hemoglobin concentration ([oxy-Hb]) during two verbal fluency tasks. The subjects were 20 individuals with Asperger's disorder and 18 age- and IQ-matched healthy controls. The relative [oxy-Hb] in the prefrontal cortex was measured during the category and letter fluency tasks. The mean total [oxy-Hb] during the category fluency task did not differ significantly between the groups; however, during the letter fluency task, the mean [oxy-Hb] in persons with Asperger's disorder was significantly lower than that in controls. These results suggested task-relevant or task-specific prefrontal dysfunction in persons with Asperger's disorder.     

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.     

Distinct roles for lateral and medial rostral prefrontal cortex in source monitoring of perceived and imagined events

Rostral prefrontal cortex (PFC) is known to be involved in source memory, the ability to recollect contextual information about an event. However it is unclear whether subregions of rostral PFC may be differentially engaged during the recollection of different kinds of source detail. We used event related functional MRI to contrast two forms of source recollection: (1) recollection of whether stimuli had previously been perceived or imagined, and (2) recollection of which of two temporally distinct lists those stimuli had been presented in. Lateral regions of rostral PFC were activated in both tasks. However medial regions of rostral PFC were activated only when participants were required to recollect source information for self-generated, “imagined” stimuli, indicating a specific role in self-referential processing. In addition, reduced activity in a region of medial ventro-caudal PFC/basal forebrain was associated with making “imagined-to-perceived” confabulation errors. These results suggest that whilst the processing resources supported by some regions of lateral rostral PFC play a general role in source recollection, those supported by medial rostral PFC structures may be more specialised in their contributions.     

Prefrontal Dysfunction in Attention-Deficit/Hyperactivity Disorder as Measured by Near-Infrared Spectroscopy

Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders with measurement of hemoglobin concentrations as cerebral blood volume. Twenty medication-naïve children with attention-deficit/hyperactivity disorder (ADHD) and 20 age- and sex-matched healthy control subjects participated in the present study after giving consent. The relative concentrations of oxyhemoglobin (oxy-Hb) were measured with frontal probes every 0.1 s during the Stroop color-word task, using 24-channel NIRS machines. During the Stroop color-word task, the oxy-Hb changes in the control group were significantly larger than that in the ADHD group in the inferior prefrontal cortex, especially in the inferior lateral prefrontal cortex bilaterally. The Stroop color-word task used with NIRS may be one useful measurement to assess prefrontal brain dysfunction in ADHD children.     

Prefrontal activation predicts social functioning improvement after initial treatment in late-onset depression

The activation of oxygenated hemoglobin (oxy-Hb) has been shown to be lacking in the prefrontal cortex (PFC) of patients with late-onset depression (LOD), in verbal fluency task (VFT)-related near-infrared spectroscopy (NIRS). In our previous studies, we have emphasized the connection between the lack of activation in the frontopolar cortex and social functioning disorder in patients with LOD. In this study, we investigated whether the responsiveness to medical treatment of untreated patients with LOD, particularly social functioning improvements, could be predicted by NIRS findings at the initial examination. The subjects were 29 patients with LOD who were diagnosed with major depression at 65 years or older at the initial examination (mean age ± standard deviation, 72.4 ± 5.71 years). We measured the changes in hemoglobin concentration in the prefrontal and temporal cortex regions during a VFT by using 52-channel NIRS. In addition, depression status and social functioning were evaluated with the Hamilton Depression Rating Scale and the Social Adaptation Self-evaluation Scale, respectively, at the initial examination and 8 weeks after the treatment. A negative correlation was found between the NIRS activation in the right ventrolateral PFC region before treatment and the improvement in social functioning. These results suggested that the social functioning improvements were greater in LOD with initially lower NIRS activation in the right ventrolateral PFC region. NIRS is a simple technique that can be used before treatment to evaluate the social functioning levels of patients with LOD, and predict social functioning improvement after treatment.     

Reduced Prefrontal Hemodynamic Response in Pediatric Obsessive–Compulsive Disorder as Measured by Near-Infrared Spectroscopy

Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders. Functional neuroimaging studies of patients with obsessive–compulsive disorder (OCD) have suggested that the frontal cortex and subcortical structures may play a role in the pathophysiology of the disorder. Twelve treatment-naïve children with OCD and 12 age- and sex-matched healthy control subjects participated in the present study after giving consent. The relative concentrations of oxyhemoglobin (oxy-Hb) were measured with prefrontal probes every 0.1 s during the Stroop color-word task, using 24-channel NIRS machines. During the Stroop color-word task, the oxy-Hb changes in the OCD group were significantly smaller than those in the control group in the prefrontal cortex, especially in the frontopolar cortex. The present study suggests that children with OCD have reduced prefrontal hemodynamic response as measured by NIRS.     

Evaluation of cerebral activity in the prefrontal cortex in mood [affective] disorders during animal-assisted therapy (AAT) by near-infrared spectroscopy (NIRS): A pilot study

Objective. Previous studies have shown the possibility that animal-assisted therapy (AAT) is useful for promoting the recovery of a patient's psychological, social, and physiological aspect. As a pilot study, we measured the effect that AAT had on cerebral activity using near-infrared spectroscopy (NIRS), and examined whether or not NIRS be used to evaluate the effect of AAT biologically and objectively. Methods. Two patients with mood [affective] disorders and a healthy subject participated in this study. We performed two AAT and the verbal fluency task (VFT). Results. The NIRS signal during AAT showed great [oxy-Hb] increases in most of the prefrontal cortex (PFC) in the two patients. When the NIRS pattern during AAT was compared with that during VFT, greater or lesser differences were observed between them in all subjects. Conclusion. The present study suggested that AAT possibly causes biological and physiological changes in the PFC, and that AAT is useful for inducing the activity of the PFC in patients with depression who have generally been said to exhibit low cerebral activity in the PFC. In addition, the possibility was also suggested that the effect of AAT can be evaluated using NIRS physiologically and objectively.     

Frontal and temporal cortical functional recovery after electroconvulsive therapy for depression: A longitudinal functional near-infrared spectroscopy study

While the efficacy and tolerability of electroconvulsive therapy (ECT) for depression has been well established, the acute effects of ECT on brain function remain unclear. Particularly, although cognitive dysfunction has been consistently observed after ECT, little is known about the extent and time course of ECT-induced brain functional changes, as observed during cognitive tasks. Considering the acute antidepressant effects of ECT on depression, aberrant brain functional responses during cognitive tasks in patients with depression may improve immediately after this treatment. To clarify changes in cortical functional responses to cognitive tasks following ECT, we used task-related functional near-infrared spectroscopy (NIRS) to assess 30 patients with major depressive disorder or bipolar depression before and after an ECT series, as well as 108 healthy controls. Prior to ECT, patients exhibited significantly smaller [oxy-Hb] values in the bilateral frontal cortex during a letter verbal fluency task (VFT) compared with healthy controls. We found a significant increase in [oxy-Hb] values in the bilateral frontal cortex during the VFT after ECT in the patient group. A decrease in depression severity was significantly correlated with an increase in [oxy-Hb] values in the right ventrolateral prefrontal cortex following ECT. This is the first NIRS study to evaluate brain functional changes before vs. after ECT. Impaired functional responses, observed during the cognitive task in depressed patients, were normalized after ECT. Thus, recovery from abnormal functional responses to cognitive tasks in the frontal brain regions may be associated with the acute therapeutic effects of ECT for depression.     

Neural mechanisms underlying spatial judgements on seen and imagined visual stimuli in the left and right hemifields in men

We investigated the neural networks involved in spatial judgements on visual and imagined stimuli in the left and right hemifields. Twenty healthy male right-handers were scanned using fMRI. In an adaptation of the Mental Clock Test, subjects judged whether the angle between visually presented or to be imagined clock hands at a given time (e.g. “12:20”) was >90° or <90°. The angle formed by the clock hands was always located either on the left or right hemifield of the clock face, constituting a 2 × 2 factorial design with factors stimulus type (visual “V”, imagined “I”) and attention to spatial hemifield (left “L”, right “R”). The contrast I > V revealed a bilateral neural network which included the superior parietal, prefrontal and antero-dorsal cingulate cortex. While right superior parietal cortex was activated during both RV and LV, left superior parietal cortex was only active during RV. The contrast RI versus LI (and vice versa) did not reveal significant differences with respect to activation height. However, a masking procedure and the calculation of a laterality index showed that RI recruited larger areas in the left than in the right hemisphere, while LI led to symmetrical activations in both hemispheres. Our data thus confirm that there are hemifield-specific asymmetries in brain activity during spatial processing of both visual and imagined stimuli. Our data indicate, however, that these asymmetries are less clear and of a different nature in the latter. Overall, our findings converge with neuropsychological data showing that representational and visuospatial neglect do not always co-occur.     

Variations in “same”-“different” judgments in patients with unilateral cortical lesions

Five subject groups (normal controls, left anterior lesion patients, left posterior lesion patients, right anterior lesion patients, right posterior lesion patients) were tested on two perceptual matching tasks. All groups performed comparably accurately, although right hemisphere lesion patients demonstrated longer RT scores for “same” than for “different” judgments, whereas left hemisphere lesion patients demonstrated the reverse effect. Increased perceptual complexity of “same” target produced higher RT scores for “different” responses in right (but not left) hemisphere lesion groups. Finally, high-prototypicality “same” targets yielded lower RT scores than low-prototypicality “same” targets for all groups.     

The hemodynamics of cognitive control: the level of concentration of oxygenated hemoglobin in the superior prefrontal cortex varies as a function of performance in a modified Stroop task

The purpose of this study was to establish the relationship between the hemodynamic response of prefrontal cortex (PFC) and individual differences in cognitive control, as measured by a color-word interference task. Twenty-five healthy volunteers were observed through functional near infrared spectroscopy (fNIRS) while performing a modified Stroop paradigm. Mean concentration levels of oxygenated hemoglobin (oxy-Hb) were correlated with behavioral performance in the conflict task. Those with shorter reaction times had higher levels of oxy-Hb concentration in superior dorsolateral PFC. Our results are the first to show a positive correlation between behavioral performance and oxy-Hb levels in superior dorsolateral PFC in a cognitive conflict task. These results suggest that the availability of oxygen in the superior PFC, possibly linked to an increase in metabolism, may be related to attention level and effectiveness of cognitive control.     

Prefrontal brain function in children with anorexia nervosa: A near-infrared spectroscopy study

To investigate the prefrontal hemodynamic response during a cognitive task in childhood anorexia nervosa (AN), we measured regional cerebral blood volume changes in terms of changes in hemoglobin concentrations [Hb], using near-infrared spectroscopy (NIRS). Sixteen females with AN (mean age 14.2 years old) and 12 age-matched healthy female control subjects (mean age 14.3 years old) participated in this study. Waveform patterns for [Hb] during the word fluency task differed between the two groups, although their task performances showed no significant difference. In the control group, the [total-Hb] and [oxy-Hb] immediately increased and the [deoxy-Hb] immediately decreased after the beginning of the task and gradually reached the baseline level after the end of the task. The patients with AN were consistently characterized by an unchanged or less fluctuating response pattern of [total-Hb], [oxy-Hb] and [deoxy-Hb] during the task and rest periods. In the AN group, subjects with higher Eating Attitudes Test (EAT-26) scores showed higher [oxy-Hb] during the task. On the other hand, in the control group, subjects with higher EAT-26 scores showed lower [oxy-Hb] during the task. The grand waveforms of each [Hb] during a motor activation task, which was applied as a control task, did not differ significantly between two groups. The different prefrontal hemodynamic responses might indicate that AN subjects might apply fewer brain circuits or fewer neurons per circuit during cognitive tasks and might use different brain circuits in relation to their preoccupation with eating behaviors.     

Right prefrontal cortex specialization for visuospatial working memory and developmental alterations in prefrontal cortex recruitment in school-age children

Objective

The right prefrontal cortex (PFC) plays an essential role in active processing within visuospatial working memory (VSWM). The aim of this study was to examine developmental changes in the recruitment patterns of the PFC during visuospatial memory tasks in school-age participants.

Cognitive impairment in aged rhesus monkeys associated with monoamine receptors in the prefrontal cortex

The “frontal aging hypothesis” has been proposed by many researchers suggesting that the earliest and most severe age-related changes in the cortex occur in the frontal lobes. Two of these changes include decreases in cognitive functions mediated by the prefrontal cortex (PFC) and significant decreases in norepinephrine (NE) and dopamine (DA). To investigate whether the changes in these neurotransmitter systems are directly related to the cognitive decline seen in aging we utilized the rhesus monkey as a model of normal human aging. Our goal was to determine if age-related changes in cognition is associated with changes in norepinephrine and dopamine receptor binding density in the PFC. Eight young monkeys between five and ten years of age (six males and two female) and eight aged monkeys between 25 and 32 years of age (five males and three females) were behaviorally characterized. Subsequently on-the-slide in vitro binding assays were used to quantify the -1 adrenergic, -2 adrenergic and DA1 receptors as well as the NE and DA uptake receptors. Aged animals as a group demonstrated significant cognitive impairments and aging produced a significant decrease in -1 adrenergic and -2 adrenergic receptor binding in the PFC but no significant change in binding for the DA1 receptor or the NE or DA uptake receptors. Further analysis revealed a significant relationship between monoamine receptor binding and cognitive performance on three tasks: delayed non-matching to sample, delayed recognition span test and the conceptual set-shifting task.     

Brain areas activated by uncertain reward-based decision-making in healthy volunteers

Reward-based decision-making has been found to activate several brain areas, including the ven- trolateral prefronta~ lobe, orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mesolimbic dopaminergic system. In this study, we observed brain areas activated under three de- grees of uncertainty in a reward-based decision-making task （certain, risky, and ambiguous）. The tasks were presented using a brain function audiovisual stimulation system. We conducted brain scans of 15 healthy volunteers using a 3.0T magnetic resonance scanner. We used SPM8 to ana- lyze the location and intensity of activation during the reward-based decision-making task, with re- spect to the three conditions. We found that the orbitofrontal cortex was activated in the certain reward condition, while the prefrontal cortex, precentral gyrus, occipital visual cortex, inferior parietal lobe, cerebellar posterior lobe, middle temporal gyrus, inferior temporal gyrus, limbic lobe, and midbrain were activated during the ＇risk＇ condition. The prefrontal cortex, temporal pole, inferior temporal gyrus, occipital visual cortex, and cerebellar posterior lobe were activated during am- biguous decision-making. The ventrolateral prefrontal lobe, frontal pole of the prefrontal lobe, orbi- tofrontal cortex, precentral gyrus, inferior temporal gyrus, fusiform gyrus, supramarginal gyrus, infe- rior parietal Iobule, and cerebellar posterior lobe exhibited greater activation in the ＇risk＇ than in the ＇certain＇ condition （P 〈 0.05）. The frontal pole and dorsolateral region of the prefrontal lobe, as well as the cerebellar posterior lobe, showed significantly greater activation in the ＇ambiguous＇ condition compared to the ＇risk＇ condition （P 〈 0.05）. The prefrontal lobe, occipital lobe, parietal lobe, temporal lobe, limbic lobe, midbrain, and posterior lobe of the cerebellum were activated during deci- sion-making about uncertain rewards. Thus, we observed different levels and regions of activation for different types of reward processing during decision-making. Specifically, when the degree of reward uncertainty increased, the number of activated brain areas increased, including greater ac- tivation of brain areas associated with loss.     

A comparison of systematic desensitization and “vicarious extinction” in a case of frigidity

Systematic desensitization was compared to “vicarious extinction” therapy in treating frigidity in a 29-year-old married female. Films of heterosexual behavior were shown to S during “vicarious extinction”. In spite of expectations of therapeutic improvement under both treatment conditions, S showed improvement only during systematic desensitization. Greatest improvement was noted in her report of subjective anxiety related to sexual behavior. Improvement was also indicated by the husband's independent report of their sexual behavior and by the Willoughby Scale. Reasons for the lack of effect of “vicarious extinction” are considered.     

Near-infrared spectroscopy analysis of frontal lobe dysfunction in schizophrenia.

BACKGROUND: Previous studies have shown that near-infrared spectroscopy (NIRS) has high temporal resolution, requires little restraint, and is suitable for examining the effect of psychological tasks on brain circulation. In the present study, frontal function in schizophrenic patients was analyzed by NIRS during random number generation (RNG), ruler-catching (RC), and sequential finger-to-thumb (SFT) tasks. METHODS: Two sets of NIRS probes were attached to the foreheads of 13 schizophrenic patients and 10 control subjects approximately at Fp1-F7 and Fp2-F8. Near-infrared spectroscopy was conducted at a sampling rate of 1 Hz, with the pathlength being determined by time-resolved spectroscopy with differential pathlength factor measurements. The absolute changes in oxygenated (oxy-Hb) and deoxygenated (deoxy-Hb) hemoglobin concentrations in response to each task were measured, and total hemoglobin (total-Hb) concentration was calculated as the sum of the two. RESULTS: During RNG task, total- and oxy-Hb concentrations increased, and deoxy-Hb decreased, but the responses were significantly smaller in schizophrenic patients. During RC task, oxy-Hb in schizophrenic patients tended to decrease, in contrast to the mostly increasing response in control subjects. No group difference was observed during SFT task. CONCLUSIONS: Task-dependent profile of functional abnormalities was observed in schizophrenic frontal brain metabolism. These results support the usefulness of NIRS data in investigating frontal lobe dysfunction and evaluating psychopathologic condition in schizophrenic patients.     

Multi-channel near-infrared spectroscopy shows reduced activation in the prefrontal cortex during facial expression processing in pervasive developmental disorder

Aim: The purpose of the present study was to investigate whether individuals with pervasive developmental disorders (PDD) show differential activation during an emotional activation task compared with age‐ and sex‐matched controls, by measuring changes in the concentration of oxygenated (oxyHb) and deoxygenated (deoxyHb) hemoglobin, using near‐infrared spectroscopy (NIRS). Methods: Fourteen patients with PDD and 14 age‐ and sex‐matched healthy controls participated in the study. The relative changes of concentrations of oxyHb and deoxyHb were measured on NIRS during an implicit processing task of fearful expression using Japanese standard faces. Results: PDD patients had significantly reduced oxyHb changes in the prefrontal cortex (PFC) compared to healthy controls. Conclusion: PFC dysfunction may exist in PDD.     

Neurobehavioral and hemodynamic evaluation of Stroop and reverse Stroop interference in children with attention-deficit/hyperactivity disorder

Failure of executive function (EF) is a core symptom of attention-deficit/hyperactivity disorder (ADHD). However, various results have been reported and sufficient evidence is lacking. In the present study, we evaluated the characteristics of children with ADHD using the Stroop task (ST) and reverse Stroop task (RST) that reflects the inhibition function of EF. We compared children with ADHD, typically developing children (TDC), and children with autism spectrum disorder (ASD), which is more difficult to discriminate from ADHD. A total of 10 children diagnosed with ADHD, 15 TDC, and 11 children diagnosed with ASD, all matched by age, sex, language ability, and intelligence quotient, participated in this study. While each subject performed computer-based ST and RST with a touch panel, changes in oxygenated hemoglobin (oxy-Hb) were measured in the prefrontal cortex (PFC) by near-infrared spectroscopy (NIRS) to correlate test performance with neural activity. Behavioral performance significantly differed among 3 groups during RST but not during ST. The ADHD group showed greater color interference than the TDC group. In addition, there was a negative correlation between right lateral PFC (LPFC) activity and the severity of attention deficit. Children with ADHD exhibit several problems associated with inhibition of color, and this symptom is affected by low activities of the right LPFC. In addition, it is suggested that low hemodynamic activities in this area are correlated with ADHD.