Cerebellar-limbic neurocircuit is the novel biosignature of physio-cognitive decline syndrome.

Both physical and cognitive deficits occur in the aging process. We operationally defined the phenomenon as physio-cognitive decline syndrome (PCDS) and aimed to decipher its corresponding neuroanatomy patterns and neurocircuit. High resolution 3T brain magnetic resonance imaging (MRI) images from a community-dwelling longitudinal aging cohort were analysed. PCDS was defined as weakness (handgrip strength) and/or slowness (gait speed) concomitant with impairment in any cognitive domain (defined by 1.5 standard deviation below age, sex-matched norms), but without dementia or disability. Among 1196 eligible ≥ 50-year-old (62±9 years, 47.6%men) subjects, 15.9% had PCDS. Compared to the other participants, individuals with PCDS had significantly lower gray-matter volume (GMV) in the bilateral amygdala and thalamus, right hippocampus, right temporo-occipital cortex, and left cerebellum VI and V regions. The regions of reduced GMV in people with PCDS were similar between the middle-aged and older adults; whereas larger clusters with more extensive GMV-depleted regions were observed in ≥65-year-olds with PCDS. Diffusion-weighted tractography showed disrupted hippocampus-amygdala-cerebellum connections in subjects with PCDS. The neuroanatomic characteristics revealed by this study provide evidence for pathophysiological processes associated with concomitant physio-cognitive decline in the elderly. This neurocircuit might constitute a target for future preventive interventions.

Audiovisual Multisensory Processing in Young Adults With Attention-Deficit/Hyperactivity Disorder.

Multisensory integration is a fundamental form of sensory processing that is involved in many everyday tasks. Those with Attention-Deficit/Hyperactivity Disorder (ADHD) have characteristic alterations to various brain regions that may influence multisensory processing. The overall aim of this work was to assess how adults with ADHD process audiovisual multisensory stimuli during a complex response time task. The paradigm used was a two-alternative forced-choice discrimination task paired with continuous 64-electrode electroencephalography, allowing for the measurement of response time and accuracy to auditory, visual, and audiovisual multisensory conditions. Analysis revealed that those with ADHD ( n = 10) respond faster than neurotypical controls ( n = 12) when presented with auditory, visual, and audiovisual multisensory conditions, while also having race model violation in early response latency quantiles. Adults with ADHD also had more prominent multisensory processing over parietal-occipital brain regions at early post-stimulus latencies, indicating that altered brain structure may have important outcomes for audiovisual multisensory processing. The present study is the first to assess how those with ADHD respond to multisensory conditions during a complex response time task, and demonstrates that adults with ADHD have unique multisensory processing when assessing both behavioral response time measures and neurological measures.

Influence of Motor Deficiency and Spatial Neglect on the Contralesional Posterior Parietal Cortex Functional and Structural Connectivity in Stroke Patients.

The posterior parietal cortex (PPC) is a key structure for visual attention and upper limb function, two features that could be impaired after stroke, and could be implied in their recovery. If it is well established that stroke is responsible for intra- and interhemispheric connectivity troubles, little is known about those existing for the contralesional PPC. In this study, we aimed at mapping the functional (using resting state fMRI) and structural (using diffusion tensor imagery) networks from 3 subparts of the PPC of the contralesional hemisphere (the anterior intraparietal sulcus), the posterior intraparietal sulcus and the superior parieto-occipital cortex to bilateral frontal areas and ipsilesional homologous PPC parts in 11 chronic stroke patients compared to 13 healthy controls. We also aimed at assessing the relationship between connectivity and the severity of visuospatial and motor deficiencies. We showed that interhemispheric functional and structural connectivity between PPCs was altered in stroke patients compared to controls, without any specificity among seeds. Alterations of parieto-frontal intra- and interhemispheric connectivity were less observed. Neglect severity was associated with several alterations in intra- and interhemispheric connectivity, whereas we did not find any behavioral/connectivity correlations for motor deficiency. The results of this exploratory study shed a new light on the influence of the contralesional PPC in post-stroke patients, they have to be confirmed and refined in further larger studies.

A thalamocortical pathway for fast rerouting of tactile information to occipital cortex in congenital blindness.

In congenitally blind individuals, the occipital cortex responds to various nonvisual inputs. Some animal studies raise the possibility that a subcortical pathway allows fast re-routing of tactile information to the occipital cortex, but this has not been shown in humans. Here we show using magnetoencephalography (MEG) that tactile stimulation produces occipital cortex activations, starting as early as 35 ms in congenitally blind individuals, but not in blindfolded sighted controls. Given our measured thalamic response latencies of 20 ms and a mean estimated lateral geniculate nucleus to primary visual cortex transfer time of 15 ms, we claim that this early occipital response is mediated by a direct thalamo-cortical pathway. We also observed stronger directed connectivity in the alpha band range from posterior thalamus to occipital cortex in congenitally blind participants. Our results strongly suggest the contribution of a fast thalamo-cortical pathway in the cross-modal activation of the occipital cortex in congenitally blind humans.

Median Nerve Electrical Stimulation-Induced Changes in Effective Connectivity in Patients With Stroke as Assessed With Functional Near-Infrared Spectroscopy.

Background. The cortical plastic changes in response to median nerve electrical stimulation (MNES) in stroke patients have not been entirely illustrated. Objective. This study aimed to investigate MNES-related changes in effective connectivity (EC) within a cortical network after stroke by using functional near-infrared spectroscopy (fNIRS). Methods. The cerebral oxygenation signals in the bilateral prefrontal cortex (LPFC/RPFC), motor cortex (LMC/RMC), and occipital lobe (LOL/ROL) of 20 stroke patients with right hemiplegia were measured by fNIRS in 2 conditions: (1) resting state and (2) MNES applied to the right wrist. Coupling function together with dynamical Bayesian inference was used to assess MNES-related changes in EC among the cerebral low-frequency fluctuations. Results. Compared with the resting state, EC from LPFC and RPFC to LOL was significantly increased during the MNES state in stroke patients. Additionally, MNES triggered significantly higher coupling strengths from LMC and LOL to RPFC. The interregional main coupling direction was observed from LPFC to bilateral motor and occipital areas in responding to MNES, suggesting that MNES could promote the regulation function of ipsilesional prefrontal areas in the functional network. MNES can induce muscle twitch of the stroke-affected hand involving a decreased neural coupling of the contralesional motor area on the ipsilesional MC. Conclusions. MNES can trigger sensorimotor stimulations of the affected hand that sequentially involved functional reorganization of distant cortical areas after stroke. Investigating MNES-related changes in EC after stroke may help further our understanding of the neural mechanisms underlying MNES.

Occipital nerve stimulation for non-migrainous chronic headaches: a systematic review protocol.

BACKGROUND: Defined as a headache lasting at least 15 days per month, chronic headache is reported by 3% of the general population, and a substantial proportion of them are refractory to current therapies. Occipital nerve stimulation (ONS) is a treatment option, but is still considered as a last resort treatment especially because of its invasive nature and the cost associated. Some reviews reported a limited efficacy of ONS for the treatment of migraines, with a high risk of complications. However, results reporting its efficacy and safety on other headache disorders are unclear. The aim of this review is to assess the efficacy and safety of ONS in regards to non-migrainous chronic headaches. METHODS: We will conduct a systematic review and meta-analysis of studies evaluating the use of ONS in comparison to sham stimulation or the best available treatment in patients with chronic headache. MEDLINE, CINHAL, EMBASE, PsycINFO, ECRI Institute Library, WIKISTIM, the Cochrane Library databases, and clinical trial registries will be searched for eligible studies. The review will include adult patients diagnosed with chronic headache excluding migraine. Two independent reviewers will process to the screening of studies according to titles, abstracts, and then full texts. The primary outcome is the overall reduction of head pain severity. The secondary outcomes are rates of reduction in the severity of head pain, headache frequency, and duration, use of medication, impairment, quality of life, healthcare utilization, return to work, and adverse events. Extracted data will include patients' and procedure characteristics, details on comparative treatment or sham, and clinical outcomes. The risk of bias of the studies will be also independently assessed using the Cochrane risk of bias tools. DISCUSSION: This systematic review will allow us to better evaluate the potential role of ONS for the treatment of patients with chronic headache that are refractory to less invasive therapies. It will help to determine the degree of safety of ONS. Moreover, it will help to design and conduct future randomized controlled trials focused on patients who may better respond to such treatment. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019121623.

Atypical Dorsolateral Prefrontal Activity in Female Adolescents With Conduct Disorder During Effortful Emotion Regulation.

BACKGROUND: Conduct disorder (CD), which is characterized by severe aggressive and antisocial behavior, is linked to emotion processing and regulation deficits. However, the neural correlates of emotion regulation are yet to be investigated in adolescents with CD. Furthermore, it remains unclear whether CD is associated with deficits in emotional reactivity, emotion regulation, or both. METHODS: We used functional magnetic resonance imaging to study effortful emotion regulation by cognitive reappraisal in 59 female adolescents 15 to 18 years of age (30 with a CD diagnosis and 29 typically developing (TD) control adolescents). RESULTS: Behaviorally, in-scanner self-report ratings confirmed successful emotion regulation within each group individually but significant group differences in emotional reactivity and reappraisal success when comparing the groups (CD < TD). Functional magnetic resonance imaging results revealed significantly lower activation in left dorsolateral prefrontal cortex and angular gyrus in CD compared with TD adolescents during emotion regulation, but no group differences for emotional reactivity. Furthermore, connectivity between left dorsolateral prefrontal cortex and the bilateral putamen, right prefrontal cortex, and amygdala was reduced in CD compared with TD adolescents during reappraisal. Callous-unemotional traits were unrelated to neural activation, but these traits correlated negatively with behavioral reports of emotional reactivity. CONCLUSIONS: Our results demonstrate reduced prefrontal brain activity and functional connectivity during effortful emotion regulation in female adolescents with CD. This sheds light on the neural basis of the behavioral deficits that have been reported previously. Future studies should investigate whether cognitive interventions are effective in enhancing emotion-regulation abilities and/or normalizing prefrontal and temporoparietal activity in female adolescents with CD.

Abnormal functional network of the thalamic subregions in adult patients with obsessive-compulsive disorder.

The thalamus plays an important role in pathological mechanisms underlying obsessive-compulsive disorder (OCD). As the thalamus is a heterogeneous brain region, functional connectivity (FC) between thalamic subregions and other brain regions is worth investigating in OCD. In addition, the relationship between abnormal FC and clinical symptoms is still unclear. In this study, we used resting-state functional magnetic resonance imaging to scan 45 OCD patients and 43 well-matched healthy controls (HCs). Thalamic subregions were defined according to the Human Brainnetome Atlas. The fractional amplitude of low-frequency fluctuations (fALFF) and FC seeding-based connectivity were compared using a two-sample t-test. Correlations between abnormal FC and clinical symptoms were analyzed in OCD patients. Compared with HCs, increased fALFF was found in the bilateral thalamus, and increased FC was observed between the right posterior parietal thalamus (PPtha) and left middle occipital gyrus (LMOG) and between the right occipital thalamus (Otha) and right middle occipital gyrus (RMOG) in OCD patients. In addition, OCD patients had reduced FC between the left sensory thalamus (Stha) and left orbital inferior frontal gyrus, right PPtha and left prefrontal cortex, and between the right Otha and left inferior parietal gyrus (LIPG), respectively. Within the OCD group, the FC between right PPtha-LMOG was correlated with severity of clinical symptoms. These results revealed that the FC between the thalamus and occipital lobe is related to obsessive-compulsive symptoms in OCD patients. This finding provides more accurate information about the involvement of the thalamus in the pathophysiology of OCD.

Altered thalamo­cortical and occipital­parietal­ temporal­frontal white matter connections in patients with anorexia and bulimia nervosa: a systematic review of diffusion tensor imaging studies

Background: Anorexia nervosa and bulimia nervosa are complex mental disorders, and their etiology is still not fully understood. This paper reviews the literature on diffusion tensor imaging studies in patients with anorexia nervosa and bulimia nervosa to explore the usefulness of white matter microstructural analysis in understanding the pathophysiology of eating disorders. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify diffusion tensor imaging studies that compared patients with an eating disorder to control groups. We searched relevant databases for studies published from database inception to August 2018, using combinations of select keywords. We categorized white matter tracts according to their 3 main classes: projection (i.e., thalamo­cortical), association (i.e., occipital­parietal­temporal­frontal) and commissural (e.g., corpus callosum). Results: We included 19 papers that investigated a total of 427 participants with current or previous eating disorders and 444 controls. Overall, the studies used different diffusion tensor imaging approaches and showed widespread white matter abnormalities in patients with eating disorders. Despite differences among the studies, patients with anorexia nervosa showed mainly white matter microstructural abnormalities of thalamo­cortical tracts (i.e., corona radiata, thalamic radiations) and occipital­parietal­temporal­frontal tracts (i.e., left superior longitudinal and inferior fronto-occipital fasciculi). It was less clear whether white matter alterations persist after recovery from anorexia nervosa. Available data on bulimia nervosa were partially similar to those for anorexia nervosa. Limitations: Study sample composition and diffusion tensor imaging analysis techniques were heterogeneous. The number of studies on bulimia nervosa was too limited to be conclusive. Conclusion: White matter microstructure appears to be affected in anorexia nervosa, and these alterations may play a role in the pathophysiology of this eating disorder. Although we found white matter alterations in bulimia nervosa that were similar to those in anorexia nervosa, white matter changes in bulimia nervosa remain poorly investigated, and these findings were less conclusive. Further studies with longitudinal designs and multi-approach analyses are needed to better understand the role of white matter changes in eating disorders.

Using real-time fMRI neurofeedback to restore right occipital cortex activity in patients with left visuo-spatial neglect: proof-of-principle and preliminary results.

Hemineglect is common after right parietal stroke, characterised by impaired awareness for stimuli in left visual space, with suppressed neural activity in the right visual cortex due to losses in top-down attention signals. Here we sought to assess whether hemineglect patients are able to up-regulate their right visual cortex activity using auditory real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback. We also examined any effect of this training procedure on neglect severity. Two different neurofeedback methods were used. A first group of six patients was trained to up-regulate their right visual cortex activity and a second group of three patients was trained to control interhemispheric balance between their right and left visual cortices. Over three sessions, we found that the first group successfully learned to control visual cortex activity and showed mild reduction in neglect severity, whereas the second group failed to control the feedback and showed no benefit. Whole brain analysis further indicated that successful up-regulation was associated with a recruitment of bilateral fronto-parietal areas. These findings provide a proof of concept that rt-fMRI neurofeedback may offer a new approach to the rehabilitation of hemineglect symptoms, but further studies are needed to identify effective regulation protocols and determine any reliable impact on clinical symptoms.

Trait anxiety and neural efficiency of abstract reasoning: An fMRI investigation.

Worries preoccupy the working memory capacity in anxious individuals, thereby affecting their performance during tasks that require efficient attention regulation. According to the attentional control theory (ACT), trait anxiety affects the processing efficiency, i.e. the effort required for task performance, more than the accuracy of task performance. We investigated the relation between trait anxiety and neural response for a reasoning task in healthy subjects. Functional magnetic resonance imaging (fMRI) was carried out on 22 healthy participants and blood oxygenation level dependent (BOLD) contrast estimates were extracted from a priori regions of interest (ROIs) that were earlier implicated in reasoning (i.e., bilaterally caudate head, globus pallidus, thalamus, prefrontal cortex [[ostral, dorsal and ventral regions]] inferior parietal lobule and middle occipital gyrus). Controlling for the effects of age, gender, state anxiety and depressive symptoms, for equivalent levels of task performance, trait anxiety of the participants was found to be associated with an increase in task related BOLD activation in right globus pallidus, left thalamus and left middle occipital gyrus. Our results suggest a reduced processing efficiency for reasoning in high trait anxiety subjects and provides important brain-behaviour relationships with respect to sub-clinical anxiety.

Treatment of refractory headache secondary to intracranial endovascular procedure by transcutaneous electrical nerve stimulation of the occipital nerve.

This pilot study aimed at assessing the effect of transcutaneous electrical nerve stimulation (TENS) of the occipital nerve (ON) to treat chronic refractory headache secondary to intracranial endovascular procedures (iEVP) in 4 patients. The duration of ON-TENS therapy was only 1 month (n=2) or longer than 4 months (n=2). Overall, pain intensity decreased from 7.8 (on a 0-10 scale) at baseline to 0.8 at 6 months after ON-TENS therapy initiation (-90%), while drug treatment was reduced from 34.3 to 0.8 (-98%) on the medication quantification scale. ON-TENS is a simple technique that may benefit patients with post-iEVP refractory headache.

Long-range gamma phase synchronization as a compensatory strategy during working memory in high-performing patients with schizophrenia.

Working memory deficits in schizophrenia may be associated with impairments in the integration of neural activity across a distributed network of cortical areas. However, evaluation of the contribution of this integration to working memory impairments in patients is severely confounded by behavioral performance. In the present multidimensional-neuroimaging study, measures of neural oscillations at baseline and during a working memory task, baseline gamma-aminobutyric acid (GABA) level in the left dorsolateral prefrontal cortex (DLPFC), and behavioral performance were obtained. Controlling behavioral performance by recruiting only "high-performing" patients with schizophrenia, we investigated whether the strength of cross-area communications differs between patients with schizophrenia and healthy participants under accurate and equivalent behavioral performance. Results of phase-locking value indicated that these high-performing patients recruited significantly more between frontal and occipital regions in the left hemisphere, t(13) = -2.16, p = .05, Cohen's d = -1.20, and between frontal and temporal regions in the right hemisphere, t(13) = -2.63, p = .02, Cohen's d = -1.46. These cross-area communication patterns may be associated with visuoverbal and visuospatial working memory networks of the left and right hemispheres, respectively. Moreover, correlations of patient's cross-area communication with in vivo GABA levels of the left DLPFC revealed a significant positive relationship (r = .77, p = .04), demonstrating that the critical role of GABA functions in gamma band oscillations may go beyond local neuronal assemblies in the left DLPFC. Altogether, these exploratory findings point to the heterogeneity among schizophrenia patients and highlight the notion that high-performing patients may engage in potential compensatory mechanisms and may represent a subgroup of patients that may be categorically or dimensionally divergent in psychopathology.

NREM sleep EEG activity and procedural memory: A comparison between young neurotypical and autistic adults without sleep complaints.

Delta EEG activity (0.75-3.75 Hz) during non-Rapid eye movement (NREM) sleep reflects the thalamo-cortical system contribution to memory consolidation. The functional integrity of this system is thought to be compromised in the Autism spectrum disorder (ASD). This lead us to investigate the topography of NREM sleep Delta EEG activity in young adults with ASD and typically-developed individuals (TYP). The relationship between Delta EEG activity and sensory-motor procedural information was also examined using a rotary pursuit task. Two dependent variables were computed: a learning index (performance increase across trials) and a performance index (average performance for all trials). The ASD group showed less Delta EEG activity during NREM sleep over the parieto-occipital recording sites compared to the TYP group. Delta EEG activity dropped more abruptly from frontal to posterior regions in the ASD group. Both groups of participants learned the task at a similar rate but the ASD group performed less well in terms of contact time with the target. Delta EEG activity during NREM sleep, especially during stage 2, correlated positively with the learning index for electrodes located all over the cortex in the TYP group, but only in the frontal region in the ASD group. Delta EEG activity, especially during stage 2, correlated positively with the performance index, but in the ASD group only. These results reveal an atypical thalamo-cortical functioning over the parieto-occipital region in ASD. They also point toward an atypical relationship between the frontal area and the encoding of sensory-motor procedural memory in ASD. Autism Res 2018, 11: 613-623. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Slow EEG waves recorded from the scalp during sleep are thought to facilitate learning and memory during daytime. We compared these EEG waves in young autistic adults to typically-developing young adults. We found less slow EEG waves in the ASD group and the pattern of relationship with memory differed between groups. This suggests atypicalities in the way sleep mechanisms are associated with learning and performance in a sensory-motor procedural memory task in ASD individuals.

Neuralgia occipital y su manejo en Atención Primaria / Occipital neuralgia and its management in Primary Care

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"Decoding versus comprehension": Brain responses underlying reading comprehension in children with autism.

Despite intact decoding ability, deficits in reading comprehension are relatively common in children with autism spectrum disorders (ASD). However, few neuroimaging studies have tested the neural bases of this specific profile of reading deficit in ASD. This fMRI study examined activation and synchronization of the brain's reading network in children with ASD with specific reading comprehension deficits during a word similarities task. Thirteen typically developing children and 18 children with ASD performed the task in the MRI scanner. No statistically significant group differences in functional activation were observed; however, children with ASD showed decreased functional connectivity between the left inferior frontal gyrus (LIFG) and the left inferior occipital gyrus (LIOG). In addition, reading comprehension ability significantly positively predicted functional connectivity between the LIFG and left thalamus (LTHAL) among all subjects. The results of this study provide evidence for altered recruitment of reading-related neural resources in ASD children and suggest specific weaknesses in top-down modulation of semantic processing.

Responsiveness of Myofascial Trigger Points to Single and Multiple Trigger Point Release Massages: A Randomized, Placebo Controlled Trial.

OBJECTIVE: This study aimed to assess the effects of single and multiple massage treatments on pressure-pain threshold (PPT) at myofascial trigger points (MTrPs) in people with myofascial pain syndrome expressed as tension-type headache. DESIGN: Individuals (n = 62) with episodic or chronic tension-type headache were randomized to receive 12 twice-weekly 45-min massage or sham ultrasound sessions or wait-list control. Massage focused on trigger point release (ischemic compression) of MTrPs in the bilateral upper trapezius and suboccipital muscles. PPT was measured at MTrPs with a pressure algometer pre and post the first and final (12th) treatments. RESULTS: PPT increased across the study timeframe in all four muscle sites tested for massage, but not sham ultrasound or wait-list groups (P < 0.0001 for suboccipital; P < 0.004 for upper trapezius). Post hoc analysis within the massage group showed (1) an initial, immediate increase in PPT (all P values < 0.05), (2) a cumulative and sustained increase in PPT over baseline (all P values < 0.05), and (3) an additional immediate increase in PPT at the final (12th) massage treatment (all P values < 0.05, except upper trapezius left, P = 0.17). CONCLUSIONS: Single and multiple massage applications increase PPT at MTrPs. The pain threshold of MTrPs have a great capacity to increase; even after multiple massage treatments additional gain in PPT was observed. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Understand the contribution of myofascial trigger points to myofascial pain; (2) Describe an effective treatment for decreasing tenderness of a myofascial trigger point; and (3) Discuss the relative values of single vs. multiple massage sessions on increasing pressure-pain thresholds at myofascial trigger points. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Light-Emitting Diode (LED) therapy improves occipital cortex damage by decreasing apoptosis and increasing BDNF-expressing cells in methanol-induced toxicity in rats.

Methanol-induced retinal toxicity, frequently associated with elevated free radicals and cell edema, is characterized by progressive retinal ganglion cell (RGC) death and vision loss. Previous studies investigated the effect of photomodulation on RGCs, but not the visual cortex. In this study, the effect of 670nm Light-Emitting Diode (LED) therapy on RGCs and visual cortex recovery was investigated in a seven-day methanol-induced retinal toxicity protocol in rats. Methanol administration showed a reduction in the number of RGCs, loss of neurons (neuronal nuclear antigen, NeuN+), activation of glial fibrillary acidic protein (GFAP+) expressing cells, suppression of brain-derived neurotrophic factor (BDNF+) positive cells, increase in apoptosis (caspase 3+) and enhancement of nitric oxide (NO) release in serum and brain. On the other hand, LED therapy significantly reduced RGC death, in comparison to the methanol group. In addition, the number of BDNF positive cells was significantly higher in the visual cortex of LED-treated group, in comparison to methanol-intoxicated and control groups. Moreover, LED therapy caused a significant decrease in cell death (caspase 3+ cells) and a significant reduction in the NO levels, both in serum and brain tissue, in comparison to methanol-intoxicated rats. Overall, LED therapy demonstrated a number of beneficial effects in decreasing oxidative stress and in functional recovery of RGCs and visual cortex. Our data suggest that LED therapy could be a potential condidate as a non-invasive approach for treatment of retinal damage, which needs further clinicl studies.

Involvement of the endocannabinoid system in the physiological response to transient common carotid artery occlusion and reperfusion.

BACKGROUND: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) may trigger a physiological response in an attempt to preserve tissue and function integrity. There are several candidate molecules among which the endocannabinoid system (ECS) and/or peroxisome-proliferator activated receptor-alpha (PPAR-alpha) may play a role in modulating oxidative stress and inflammation. The aims of the present study are to evaluate whether the ECS, the enzyme cyclooxygenase-2 (COX-2) and PPAR-alpha are involved during BCCAO/R in rat brain, and to identify possible markers of the ongoing BCCAO/R-induced challenge in plasma. METHODS: Adult Wistar rats underwent BCCAO/R with 30 min hypoperfusion followed by 60 min reperfusion. The frontal and temporal-occipital cortices and plasma were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS) to determine concentrations of endocannabinoids (eCBs) and related molecules behaving as ligands of PPAR-alpha, and of oxidative-stress markers such as lipoperoxides, while Western Blot and immunohistochemistry were used to study protein expression of cannabinoid receptors, COX-2 and PPAR-alpha. Unpaired Student's t-test was used to evaluate statistical differences between groups. RESULTS: The acute BCCAO/R procedure is followed by increased brain tissue levels of the eCBs 2-arachidonoylglycerol and anandamide, palmitoylethanolamide, an avid ligand of PPAR-alpha, lipoperoxides, type 1 (CB1) and type 2 (CB2) cannabinoid receptors, and COX-2, and decreased brain tissue concentrations of docosahexaenoic acid (DHA), one of the major targets of lipid peroxidation. In plasma, increased levels of anandamide and lipoperoxides were observed. CONCLUSIONS: The BCCAO/R stimulated early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The observed variations suggest that the positive modulation of the ECS and the increase of proinflammatory substances are directly correlated events. Increase of plasmatic levels of anandamide and lipoperoxides further suggests that dysregulation of these molecules may be taken as an indicator of an ongoing hypoperfusion/reperfusion challenge.

Switching between internally and externally focused attention in obsessive-compulsive disorder: Abnormal visual cortex activation and connectivity.

Obsessive-compulsive disorder (OCD) is characterized by excessive absorption with internally-generated distressing thoughts and urges, with difficulty incorporating external information running counter to their fears and concerns. In the present study, we experimentally probed this core feature of OCD through the use of a novel attention switching task that investigates transitions between internally focused (IF) and externally focused (EF) attentional states. Eighteen OCD patients and 18 controls imagined positive and negative personal event scenarios (IF state) or performed a color-word Stroop task (EF state). The IF/EF states were followed by a target detection (TD) task requiring responses to external stimuli. Compared to controls, OCD patients made significantly more errors and showed reduced activation of superior and inferior occipital cortex, thalamus, and putamen during TD following negative IF, with the inferior occipital hypoactivation being significantly greater for TD following negative IF compared to TD following the other conditions. Patients showed stronger functional connectivity between the inferior occipital region and dorsomedial prefrontal cortex. These findings point to an OCD-related impairment in the visual processing of external stimuli specifically when they follow a period of negative internal focus, and suggest that future treatments may wish to target the transition between attentional states.