Response Inhibition Impairment in High Functioning Autism and Attention Deficit Hyperactivity Disorder: Evidence from Near-Infrared Spectroscopy Data

Background

Response inhibition, an important domain of executive function (EF), involves the ability to suppress irrelevant or interfering information and impulses. Previous studies have shown impairment of response inhibition in high functioning autism (HFA) and attention deficit hyperactivity disorder (ADHD), but more recent findings have been inconsistent. To date, almost no studies have been conducted using functional imaging techniques to directly compare inhibitory control between children with HFA and those with ADHD.

Method

Nineteen children with HFA, 16 age- and intelligence quotient (IQ)-matched children with ADHD, and 16 typically developing (TD) children were imaged using functional near-infrared spectroscopy (NIRS) while performing Go/No-go and Stroop tasks.

Results

Compared with the TD group, children in both the HFA and ADHD groups took more time to respond during the No-go blocks, with reaction time longest for HFA and shortest for TD. Children in the HFA and ADHD groups also made a greater number of reaction errors in the No-go blocks than those in the TD group. During the Stroop task, there were no significant differences between these three groups in reaction time and omission errors. Both the HFA and ADHD groups showed a higher level of inactivation in the right prefrontal cortex (PFC) during the No-go blocks, relative to the TD group. However, no significant differences were found between groups in the levels of oxyhemoglobin concentration in the PFC during the Stroop task.

Conclusion

Functional brain imaging using NIRS showed reduced activation in the right PFC in children with HFA or ADHD during an inhibition task, indicating that inhibitory dysfunction is a shared feature of both HFA and ADHD.     

Prefrontal Hemodynamic Functions during a Verbal Fluency Task in Blepharospasm Using Multi-Channel NIRS

Blepharospasm (BSP) has a morbidity of 16 to 133 per million and is characterized by orbicularis oculi spasms. BSP can severely impact daily life. However, to date, its pathophysiology has not been clearly demonstrated. Near-infrared spectroscopy (NIRS) is a portable, non-invasive, and high time resolution apparatus used to measure cerebral blood flow. This study aimed to investigate the hemodynamic response patterns of BSP patients and determine whether BSP alone can be an attributional factor to influence the function of the prefrontal area using a verbal fluency task (VFT) and NIRS. Twenty-three BSP patients (10 males and 13 females) and 13 healthy controls (HC; five males and eight females) matched by gender and education were examined using NIRS. BSP patients were divided into two groups based on the presence or absence of depression and anxiety symptoms. A covariance analysis was conducted to analyze differences between the three groups and reduce the influence of different ages and educational levels. Bonferroni was used to process the post hoc test. The bilateral orbitofrontal area (ch36, 39, and 41; P<0.01) exhibited a lower activation in BSP patients without psychiatric symptoms compared with HC. This study is the first report to identify the prefrontal function in BSP using NIRS. Our findings indicate that BSP alone may cause a hypoactive hemodynamic performance in the prefrontal cortex in the absence of psychiatric symptoms. These findings provide evidence to support novel pathophysiological mechanisms of BSP.     

Development, set-up and first results for a one-channel near-infrared spectroscopy system.

Abstract Near-infrared spectroscopy (NIRS) is a non-invasive optical technique that can be used to assess functional activity in the human brain. This work describes the set-up of a one-channel NIRS system designed for use as an optical brain-computer interface (BCI) and reports on first measurements of deoxyhemoglobin (Hb) and oxyhemoglobin (HbO(2)) changes during mental arithmetic tasks. We found relatively stable and reproducible hemodynamic responses in a group of 13 healthy subjects. Unexpected observations of a decrease in HbO(2) and increase in Hb concentrations measured over the prefrontal cortex were in contrast to the typical hemodynamic responses (increase in HbO(2), decrease in Hb) during cortical activation previously reported.     

Cortical Thickness Abnormalities in Late Adolescence with Online Gaming Addiction

Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction.     

Frontal GABA levels change during working memory

Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task. Further, only GABA increased significantly during the first working memory run and then decreased continuously across subsequent task runs. The decrease of GABA over time was paralleled by a trend towards decreased reaction times and higher task accuracy. These results demonstrate a link between neurotransmitter dynamics and hemodynamic activity during working memory, indicating that functional neuroimaging metrics depend on the balance of excitation and inhibition required for cognitive processing.     

Brain Structural Correlates of Reward Sensitivity and Impulsivity in Adolescents with Normal and Excess Weight

Introduction

Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups.

Methods

Fifty-two adolescents (16 with normal weight and 36 with excess weight) were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM) was used to assess possible between-group differences in regional gray matter (GM) and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI) and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices) and motivation/impulse control (hippocampus, prefrontal cortex).

Results

Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII) were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents.

Conclusion

Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation.     

Association between Catechol-O-Methyltrasferase Val108/158Met Genotype and Prefrontal Hemodynamic Response in Schizophrenia

Background

“Imaging genetics” studies have shown that brain function by neuroimaging is a sensitive intermediate phenotype that bridges the gap between genes and psychiatric conditions. Although the evidence of association between functional val108/158met polymorphism of the catechol-O-methyltransferase gene (COMT) and increasing risk for developing schizophrenia from genetic association studies remains to be elucidated, one of the most topical findings from imaging genetics studies is the association between COMT genotype and prefrontal function in schizophrenia. The next important step in the translational approach is to establish a useful neuroimaging tool in clinical settings that is sensitive to COMT variation, so that the clinician could use the index to predict clinical response such as improvement in cognitive dysfunction by medication. Here, we investigated spatiotemporal characteristics of the association between prefrontal hemodynamic activation and the COMT genotype using a noninvasive neuroimaging technique, near-infrared spectroscopy (NIRS).

Methodology/Principal Findings

Study participants included 45 patients with schizophrenia and 60 healthy controls matched for age and gender. Signals that are assumed to reflect regional cerebral blood volume were monitored over prefrontal regions from 52-channel NIRS and compared between two COMT genotype subgroups (Met carriers and Val/Val individuals) matched for age, gender, premorbid IQ, and task performance. The [oxy-Hb] increase in the Met carriers during the verbal fluency task was significantly greater than that in the Val/Val individuals in the frontopolar prefrontal cortex of patients with schizophrenia, although neither medication nor clinical symptoms differed significantly between the two subgroups. These differences were not found to be significant in healthy controls.

Conclusions/Significance

These data suggest that the prefrontal NIRS signals can noninvasively detect the impact of COMT variation in patients with schizophrenia. NIRS may be a promising candidate translational approach in psychiatric neuroimaging.     

Impulsivity, risk taking, and timing

This study examined the relations among measures of impulsivity and timing. Impulsivity was assessed using delay and probability discounting, and self-report impulsivity (as measured by the Barratt Impulsiveness Scale; BIS-11). Timing was assessed using temporal perception as measured on a temporal bisection task and time perspective (as measured by the Zimbardo Time Perspective Inventory). One hundred and forty three college students completed these measures in a computer laboratory. The degree of delay discounting was positively correlated with the mean and range of the temporal bisection procedure. The degree of delay and probability discounting were also positively correlated. Self-reported motor impulsiveness on the BIS-11 was positively correlated with present hedonism and negatively correlated with future orientation on the ZTPI. Self-reported non-planning on the BIS-11 was positively correlated with fatalism on the ZTPI. These results show that people who overestimate the passage of time (perceive time as passing more quickly) hold less value in delayed rewards. They also confirm previous results regarding the relation between delay and probability discounting, as well as highlight similarities in self-report measures of impulsivity and time perspective.     

Barratt Impulsivity and Neural Regulation of Physiological Arousal

Background

Theories of personality have posited an increased arousal response to external stimulation in impulsive individuals. However, there is a dearth of studies addressing the neural basis of this association.

Methods

We recorded skin conductance in 26 individuals who were assessed with Barratt Impulsivity Scale (BIS-11) and performed a stop signal task during functional magnetic resonance imaging. Imaging data were processed and modeled with Statistical Parametric Mapping. We used linear regressions to examine correlations between impulsivity and skin conductance response (SCR) to salient events, identify the neural substrates of arousal regulation, and examine the relationship between the regulatory mechanism and impulsivity.

Results

Across subjects, higher impulsivity is associated with greater SCR to stop trials. Activity of the ventromedial prefrontal cortex (vmPFC) negatively correlated to and Granger caused skin conductance time course. Furthermore, higher impulsivity is associated with a lesser strength of Granger causality of vmPFC activity on skin conductance, consistent with diminished control of physiological arousal to external stimulation. When men (n = 14) and women (n = 12) were examined separately, however, there was evidence suggesting association between impulsivity and vmPFC regulation of arousal only in women.

Conclusions

Together, these findings confirmed the link between Barratt impulsivity and heightened arousal to salient stimuli in both genders and suggested the neural bases of altered regulation of arousal in impulsive women. More research is needed to explore the neural processes of arousal regulation in impulsive individuals and in clinical conditions that implicate poor impulse control.     

Altered near‐infrared spectroscopy response to breath‐holding in patients with fibromyalgia

Fibromyalgia (FM) is a complex syndrome characterized by chronic widespread pain and a heightened response to pressure. Most medical researches pointed out that FM patients with endothelial dysfunction and arterial stiffness. A continuous‐wave near‐infrared spectroscopy (NIRS) system is used in present study to measure the hemodynamic changes elicited by breath‐holding task in patients with FM. Each patient completed a questionnaire survey including demographics, characteristics of body pain, associated symptoms, headache profiles and Hospital Anxiety and Depression Scale. A total of 27 FM patients and 26 health controls were enrolled. In comparison with healthy controls, patients with FM showed lower maximal and averaged change of oxyhemoglobin concentration in both the left (1.634 ±0.890 and 0.810 ±0.525 μM) and the right (1.576 ±0.897 and 0.811 ±0.601 μM) prefrontal cortex than healthy controls (P < .05 for both sides) during the breath‐holding task. In conclusion, FM is associated with altered cerebrovascular reactivity measured by NIRS and breath‐holding task, which may reflect endothelial dysfunction or arterial stiffness. Oxygenated hemoglobin concentration changes of healthy controls and FM patients.      

Suppressing Emotions Impairs Subsequent Stroop Performance and Reduces Prefrontal Brain Activation

Abundant behavioral evidence suggests that the ability to self-control is limited, and that any exertion of self-control will increase the likelihood of subsequent self-control failures. Here we investigated the neural correlates underlying the aftereffects of self-control on future control processes using functional magnetic resonance imaging (fMRI). An initial act of self-control (suppressing emotions) impaired subsequent performance in a second task requiring control (Stroop task). On the neural level, increased activity during emotion suppression was followed by a relative decrease in activity during the Stroop task in a cluster in the right lateral prefrontal cortex (PFC) including the dorsolateral prefrontal cortex (DLPFC), an area engaged in the effortful implementation of control. There was no reliable evidence for reduced activity in the medial frontal cortex (MFC) including the anterior cingulate cortex (ACC), which is involved in conflict detection processes and has previously also been implicated in self-control. Follow-up analyses showed that the detected cluster in the right lateral PFC and an area in the MFC were involved in both the emotion suppression task and the Stroop task, but only the cluster in the right lateral PFC showed reduced activation after emotion suppression during the Stroop task. Reduced activity in lateral prefrontal areas relevant for the implementation of control may be a critical consequence of prior self-control exertion if the respective areas are involved in both self-control tasks.     

The relationship between impulsive choice and impulsive action: a cross-species translational study

Maladaptive impulsivity is a core symptom in various psychiatric disorders. However, there is only limited evidence available on whether different measures of impulsivity represent largely unrelated aspects or a unitary construct. In a cross-species translational study, thirty rats were trained in impulsive choice (delayed reward task) and impulsive action (five-choice serial reaction time task) paradigms. The correlation between those measures was assessed during baseline performance and after pharmacological manipulations with the psychostimulant amphetamine and the norepinephrine reuptake inhibitor atomoxetine. In parallel, to validate the animal data, 101 human subjects performed analogous measures of impulsive choice (delay discounting task, DDT) and impulsive action (immediate and delayed memory task, IMT/DMT). Moreover, all subjects completed the Stop Signal Task (SST, as an additional measure of impulsive action) and filled out the Barratt impulsiveness scale (BIS-11). Correlations between DDT and IMT/DMT were determined and a principal component analysis was performed on all human measures of impulsivity. In both rats and humans measures of impulsive choice and impulsive action did not correlate. In rats the within-subject pharmacological effects of amphetamine and atomoxetine did not correlate between tasks, suggesting distinct underlying neural correlates. Furthermore, in humans, principal component analysis identified three independent factors: (1) self-reported impulsivity (BIS-11); (2) impulsive action (IMT/DMT and SST); (3) impulsive choice (DDT). This is the first study directly comparing aspects of impulsivity using a cross-species translational approach. The present data reveal the non-unitary nature of impulsivity on a behavioral and pharmacological level. Collectively, this warrants a stronger focus on the relative contribution of distinct forms of impulsivity in psychopathology.     

Multidimensional Measures of Impulsivity in Obsessive-Compulsive Disorder: Cannot Wait and Stop

Objective

Although the relationship between obsessive compulsive disorder (OCD) and impulsivity has long been debated, impulsivity has not been systematically examined in clinical samples of OCD. Meanwhile, recent findings suggest that impulsivity is multi-dimensional construct that can be examined through several constructs. Therefore, this study is aimed to evaluate multiple facets of impulsivity in OCD.

Method

The recruitment includes 80 OCD and 76 healthy control participants. Participants completed a test battery comprising three behavioral tasks of stop signal task (SST), delay discounting task (DDT) and balloon analog risk test (BART), and one self-report measure of the Barratt Impulsiveness scale (BIS-11).

Results

OCD subjects showed significantly lower stop signal reaction time of SST reflecting higher action impulsivity and higher delay discounting parameter of DDT suggesting increased choice impulsivity but significantly lower adjusted mean pump of BART implying lower risk taking propensity of BART than healthy control.

Conclusion

Increased Action and choice impulsivity, and decreased risk taking propensities were found in OCD. These findings seem to be consistent with clinical characteristics of OCD such as greater preference for or avoid risky situations (avoidance), inability to wait tension relief may provoke safety behaviors (compulsion) and inability to stop already started behaviors (repetition).     

Protective effects of omega-3 essential fatty acids against formaldehyde-induced neuronal damage in prefrontal cortex of rats

The aim of this study was to examine the neurotoxicity of formaldehyde on prefrontal cortex and the protective effects of omega-3 essential fatty acids against these toxic effects. For this purpose, 21 male Wistar rats were divided into three groups. The rats in group I comprised the controls, while the rats in group II were injected every other day with formaldehyde (FA). The rats in group III received omega-3 fatty acids daily while exposed to formaldehyde. At the end of the 14-day experimental period, all rats were killed by decapitation. The brains of the rats were removed and the prefrontal cortex tissues were obtained from all brain specimens. Some of the prefrontal cortex tissue specimens were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. The remaining prefrontal cortex tissue specimens were used for light microscopic and immunohistochemical evaluation. The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in rats treated with formaldehyde compared with those of the controls. Furthermore, in the microscopic examination of this group, formation of apoptotic bodies, pycnotic cells, and apoptotic cells including nuclear fragmentation and membrane budding were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered omega-3 fatty acids while exposed to formaldehyde. Additionally, cellular damage caused by formaldehyde was decreased, and structural appearance was similar to that of the control rats in this group. The biochemical and histological findings observed in all groups were also confirmed by immunohistochemical evaluation. It was determined that formaldehyde-induced neuronal damage in prefrontal cortex was prevented by administration of omega-3 essential fatty acids.     

Activity and impulsive action are controlled by different genetic and environmental factors

Both impulsivity in operant tasks and locomotor activity in a novel open field are known to predict the development of addiction-related behavior in rodents. In this study, we investigated to what extent impulsivity in the five-choice serial reaction time task and various measures of novelty exploration are controlled by shared genetic and environmental factors in 12 different inbred mouse strains. No genetic correlation was observed between the level of impulsivity and levels of activity, a low correlation was observed with traditional measures of anxiety-like behavior (impulsive strains tend to be less anxious) and a highly significant correlation was found between impulsivity and specific aspects of movement. Furthermore, we found that impulsivity and all measures of novelty exploration were under control of different environmental factors. Interestingly, in the dorsal medial prefrontal cortex, a brain region involved in impulsivity and activity in novelty exploration tests; these behavioral measures correlated with the expression of different genes (respectively, Frzb , Snx5, BC056474 and the previously identified Glo1 ). Taken together, our study shows that impulsivity and activity in novelty exploration tests are genetically and environmentally distinct, suggesting that mouse models of these behaviors provide complementary insights into the development of substance abuse disorder.     

Reading hidden intentions in the human brain

When humans are engaged in goal-related processing, activity in prefrontal cortex is increased. However, it has remained unclear whether this prefrontal activity encodes a subject's current intention. Instead, increased levels of activity could reflect preparation of motor responses, holding in mind a set of potential choices, tracking the memory of previous responses, or general processes related to establishing a new task set. Here we study subjects who freely decided which of two tasks to perform and covertly held onto an intention during a variable delay. Only after this delay did they perform the chosen task and indicate which task they had prepared. We demonstrate that during the delay, it is possible to decode from activity in medial and lateral regions of prefrontal cortex which of two tasks the subjects were covertly intending to perform. This suggests that covert goals can be represented by distributed patterns of activity in the prefrontal cortex, thereby providing a potential neural substrate for prospective memory. During task execution, most information could be decoded from a more posterior region of prefrontal cortex, suggesting that different brain regions encode goals during task preparation and task execution. Decoding of intentions was most robust from the medial prefrontal cortex, which is consistent with a specific role of this region when subjects reflect on their own mental states.     

Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects

The extracellular regulated kinases (ERK) 1 and ERK2 are members of mitogen-activated protein (MAP) kinase family that play an important role in transducing extracellular signals to the nucleus and have been implicated in a broad spectrum of biological responses. To test the hypothesis that MAP kinases may be involved in depression, we examined the activation of p44/42 MAP kinase and expression of ERK1 and ERK2 in the post-mortem brain tissue obtained from non-psychiatric control subjects (n = 11) and age- and the post-mortem interval-matched depressed suicide subjects (n = 11). We observed that p44/42 MAP kinase activity was significantly decreased in the prefrontal cortical areas (Brodmann's areas 8, 9 and 10) and the hippocampus of depressed suicide subjects without any change in the cerebellum. This decrease was associated with a decrease in mRNA and protein levels of ERK1 and ERK2. In addition, the expression of MAP kinase phosphatase (MKP)2, a 'dual function' ERK1/2 phosphatase, was increased in the prefrontal cortex and hippocampus. These studies suggest that p44/42 MAP kinases are less activated in the post-mortem brain of depressed suicide subjects and this may be because of reduced expression of ERK1/2 and increased expression of MKP2. Given the role of MAP kinases in various physiological functions and gene expression, alterations in p44/42 MAP kinase activation and expression of ERK1/2 may contribute significantly to the pathophysiology of depressive disorders.     

The counting Stroop: a cognitive interference task

The counting Stroop is a validated Stroop task variant. Initially designed as a functional magnetic resonance imaging (fMRI) task for identifying brain regions subserving cognition and attention (dorsal anterior midcingulate cortex (daMCC) and dorsolateral prefrontal cortex (DLPFC)), it has been used to study cognition in healthy volunteers and to identify functional brain abnormalities in neuropsychiatric disorders, such as attention deficit hyperactivity disorder (ADHD). During the counting Stroop, subjects report by button-press the number of words (one to four) appearing on the screen, regardless of word meaning. Neutral-word control trials contain single semantic category common animals (e.g., 'dog' written three times), while interference trials contain number words that are incongruent with the correct response (e.g., 'two' written four times). The counting Stroop can be completed in approximately 20 min per subject and can be used offline (behavioral performance) or with fMRI, positron emission tomography, event-related potentials, magnetoencephalography or intracranial recordings.     

Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism

Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus.     

Melatonin prevents formaldehyde-induced neurotoxicity in prefrontal cortex of rats: an immunohistochemical and biochemical study

This study was undertaken to investigate the protective effects of melatonin against formaldehyde-induced neurotoxicity in prefrontal cortex of rats. For this purpose, 21 male Wistar rats were divided into three groups. The rats in Group I were used as a control, while the rats in Group II were injected every other day with formaldehyde. The rats in Group III received melatonin daily while exposed to formaldehyde. At the end of 14-day experimental period, all rats were killed by decapitation. The brains of the rats were removed and the prefrontal cortex tissues were obtained from all brain specimens. Some of the prefrontal cortex tissue specimens were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) levels. The remaining prefrontal cortex tissue specimens were used for immunohistochemical evaluation. The levels of SOD and GSH-Px were significantly decreased, and MDA levels, were significantly increased in rats treated with formaldehyde compared with those of the controls. In the immunohistochemical evaluation of this group, apoptotic cells were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels, were detected in the rats administered melatonin while exposed to formaldehyde. Furthermore, apoptotic changes caused by formaldehyde were decreased in these rats. The results of our study suggest that melatonin treatment prevents formaldehyde-induced neuronal damage in prefrontal cortex.