Cortical excitation-inhibition ratio mediates the effect of pre-attentive auditory processing deficits on interpersonal difficulties.

Several lines of evidence identify aberrant excitatory-inhibitory neural processes across autism and schizophrenia spectrum disorders, particularly within the psychosocial domain. Such neural processes include increased excitatory glutamate and reduced inhibitory GABA concentrations, which may affect auditory pre-attentive processing as indexed by the mismatch negativity (MMN); thus, an excitation-inhibition imbalance might lead to aberrant MMN, which might in turn drive the relationship between the MMN and psychosocial difficulties. This research has the potential to enhance the neurochemical understanding of the relationship between electrophysiology (MMN) and behavioural/clinical measures (psychosocial difficulties). Thirty-eight adults (18 male, 18-40 years) completed the Schizotypal Personality Questionnaire (SPQ) and Autism-Spectrum Quotient (AQ). Glutamate and GABA concentrations in bilateral superior temporal cortex (STC) were quantified using proton magnetic resonance spectroscopy (1H-MRS) while auditory MMN to a duration deviant was measured with magnetoencephalography. Spearman correlations probed the relationships between STC glutamate/GABA ratios, MMN amplitude and latency, and AQ and SPQ dimensions. Mediation effects of glutamate/GABA ratios on the relationship between MMN and AQ-SPQ dimensions were probed using causal mediation analysis. Only SPQ-interpersonal and AQ-communication were significantly correlated with right hemisphere glutamate/GABA ratios and MMN latency (ps < 0.05), which were themselves correlated (p = .035). Two mediation models were investigated, with right MMN latency as predictor and SPQ-interpersonal and AQ-communication as outcome variables. Right STC glutamate/GABA ratios significantly mediated the relationship between MMN latency and SPQ-interpersonal scores, but only partially mediated the relationship between MMN latency and AQ-communication scores. These findings support the growing body of literature pointing toward an excitation-inhibition imbalance that is central to psychosocial functioning across multi-dimensional spectrum disorders, such as autism and schizophrenia, and provides neurochemical indicators of the processes that underlie psychosocial dysfunction.

Fish oil supplementation associated with decreased cellular degeneration and increased cellular proliferation 6 weeks after middle cerebral artery occlusion in the rat.

Anti-inflammatory long-chain omega-3 polyunsaturated fatty acids (n-3-LC-PUFAs) are both neuroprotective and have antidepressive effects. However the influence of dietary supplemented n-3-LC-PUFAs on inflammation-related cell death and proliferation after middle cerebral artery occlusion (MCAo)-induced stroke is unknown. We have previously demonstrated that anxiety-like and hyperactive locomotor behaviors are reduced in n-3-LC-PUFA-fed MCAo animals. Thus in the present study, male hooded Wistar rats were exposed to MCAo or sham surgeries and examined behaviorally 6 weeks later, prior to euthanasia and examination of lesion size, cell death and proliferation in the dentate gyrus, cornu ammonis region of the hippocampus of the ipsilesional hemispheres, and the thalamus of the ipsilesional and contralesional hemispheres. Markers of cell genesis and cell degeneration in the hippocampus or thalamus of the ipsilesional hemisphere did not differ between surgery and diet groups 6 weeks post MCAo. Dietary supplementation with n-3-LC-PUFA decreased cell degeneration and increased cell proliferation in the thalamic region of the contralesional hemisphere. MCAo-associated cell degeneration in the hippocampus and thalamus positively correlated with anxiety-like and hyperactive locomotor behaviors previously reported in these animals. These results suggest that anti-inflammatory n-3-LC-PUFA supplementation appears to have cellular protective effects after MCAo in the rat, which may affect behavioral outcomes.

Factor Analysis Demonstrates a Common Schizoidal Phenotype within Autistic and Schizotypal Tendency: Implications for Neuroscientific Studies.

Behavioral and cognitive dysfunction, particularly social and communication impairments, are shared between autism and schizophrenia spectrum disorders, while evidence for a diametric autism-positive schizophrenia symptom profile is inconsistent. We investigated the shared phenotype at a personality trait level, particularly its resemblance to schizoid personality disorder, as well as differential aspects of the autism-schizophrenia model. Items of the autism spectrum quotient (AQ) and schizotypal personality questionnaire (SPQ) were pseudo-randomly combined, and were completed by 449 (162 male, 287 female) non-clinical participants aged 18-40. A factor analysis revealed three factors; the first represented a shared social disorganization phenotype, the second reflected perceptual oddities specific to schizotypy while the third reflected social rigidity specific to autism. The AQ and SPQ were strongly correlated with Factor 1 (AQ: r = 0.75, p < 0.001; SPQ: r = 0.96, p < 0.001), SPQ score was correlated with Factor 2 (r = 0.51, p < 0.001), particularly in cognitive-perceptual features (r = 0.66, p < 0.001), and AQ score was strongly correlated with Factor 3 (r = 0.76, p < 0.001). Furthermore, there was no relationship between Factor 1 and Factor 2. Thus, there is robust evidence for a shared social disorganization phenotype in autistic and schizotypal tendency, which reflects the schizoid phenotype. Discriminating and independent dimensions of schizotypal and autistic tendency exist in Factors 2 and 3, respectively. Current diagnostic protocols could result in different diagnoses depending on the instrument used, suggesting the need for neuromarkers that objectively differentiate autistic and schizotypal traits and resolve the question of commonality versus co-morbidity.

Fish oil diet associated with acute reperfusion related hemorrhage, and with reduced stroke-related sickness behaviors and motor impairment.

Ischemic stroke is associated with motor impairment and increased incidence of affective disorders such as anxiety/clinical depression. In non-stroke populations, successful management of such disorders and symptoms has been reported following diet supplementation with long chain omega-3-polyunsaturated-fatty-acids (PUFAs). However, the potential protective effects of PUFA supplementation on affective behaviors after experimentally induced stroke and sham surgery have not been examined previously. This study investigated the behavioral effects of PUFA supplementation over a 6-week period following either middle cerebral artery occlusion or sham surgery in the hooded-Wistar rat. The PUFA diet supplied during the acclimation period prior to surgery was found to be associated with an increased risk of acute hemorrhage following the reperfusion component of the surgery. In surviving animals, PUFA supplementation did not influence infarct size as determined 6 weeks after surgery, but did decrease omega-6-fatty-acid levels, moderate sickness behaviors, acute motor impairment, and longer-term locomotor hyperactivity and depression/anxiety-like behavior.

Changes in ocular accommodation when shifting between global and local attention.

BACKGROUND: The link between cognitive changes in attentional focus and the physiological parameters of the eye is not well understood. The aim of the current work was to examine the role of ocular accommodation, that is, the process of changing the shape of the crystalline lens in order to focus an image onto the retina, in active shifts of visual attention between global and local information. METHOD: Ten adult participants (aged 19 to 27) viewed sequences of complex global/local figures presented at the same location. They were asked to identify either a global or local red target letter and to look for either a global or local letter x (probe) in the sequence following. Target and probe items were separated by a temporal gap of approximately one second. Refraction was measured using a Canon Autorefractor R1 at the time of target appearance and again at the time of probe presentation. Particular interest was paid to trials where participants were required to shift attention either from a local to global level or in the reverse direction. The difference between the two measurements of refraction gave a 'change score' which provided an indication of the change of accommodation. RESULTS: No significant change in refraction was observed when shifting from the local to the global condition. A mean change in refraction of -0.128 dioptres was observed for the global to local condition. The 95 per cent confidence interval for this difference did not overlap zero, indicating a significant change in refraction, which was attributed to an increase in accommodation. DISCUSSION: The results suggest that while a change in accommodation occurs in shifting attention from the global to the local aspect of the complex figures, a similar change is not observed in the reverse direction. These results are consistent with the hypothesis that it is more difficult to restrict attentional focus than it is to widen it.

Structural and elemental evidence for edema in the retina, retinal pigment epithelium, and choroid during recovery from experimentally induced myopia.

PURPOSE: The purpose of this study was to monitor temporal changes in the retina, retinal pigment epithelium (RPE), and choroid of chick eyes using biometric, ultrastructural, and elemental microanalysis techniques as a means of visualizing more detailed signs of the physiological processes underlying choroidal expansion and refractive normalization during recovery from form deprivation. METHODS: Axial dimensions and refractions were measured on form-deprived and fellow eyes of 117 experimental chickens reared with monocular translucent occlusion from days 1 to 15 and given different lengths of visual experience (T = 0-144 hours) before death. Tissue was analyzed ultrastructurally by electron microscopy and relative sodium (Na) and chloride (Cl) ion abundances, by using x-ray microanalysis to determine changes in the presence of these indicators of tissue hydration. RESULTS: Refractive error decreased from more than 20 D of myopia almost linearly over the first 144 hours after occlusion. Concurrent changes in thickness in the retina, RPE, and choroid were seen as a series of thickness increases and edema, which returned to normal thickness, first in the retina, and did not reach maximum until 3 days after occluder removal in the choroid. In freeze-dried tissue, Na and Cl ion concentrations were greatest in the RPE photoreceptor outer segments and extravascular choroid at T = 0, decreasing toward fellow eye levels by T = 48 in the RPE and choroid. Na and Cl ion abundances in the frozen lymph of choroidal lymphatics were nearly at control levels (T = 0) and increased later as the vessels became more distended after the extravascular edema became significant. CONCLUSIONS: The results suggest that occluder removal induces edema across the retina and choroid and that this fluid may be the vector eliciting choroidal expansion during recovery from form deprivation possibly driven by the hyperosmolarity in the choroid, RPE, and photoreceptor outer segments that accompanies deprivation.

Clinical application of the multifocal visual evoked potential.

BACKGROUND: Measures of visual function thresholds such as visual acuity and visual fields are generally dependent on subjective responses and assume maintenance of fixation, attention and motivation. In the young, elderly, cognitively impaired or malingering populations, such measures may be inaccurate or difficult to obtain. The Visual Evoked Response Imaging System (VERIS) has been claimed to give more objective topographic recordings of retinal and cortical function. This paper aims to explore the adequacy of this technique in four unusual, unrelated, clinically difficult cases. METHODS: Multifocal visual evoked potentials (mfVEPs) recorded on the VERIS System 3.01 are used to assess visual function in four cases with contradictory clinical findings or unreliable subjective responses. RESULTS: Patient 1 had sustained a head injury and had normal ocular and pupil examination but light perception in the right eye and 6/5 acuity in the left. Multifocal VEPs showed a marked depression of the right visual field with little macular response. Patient 2 had sustained a head injury, had a left field hemianopia, possible macular sparing and loss of much of the right field, reduced but variable visual acuities, good near vision and normal ocular fundi. Multifocal VEPs showed a severe depression in both visual fields (L more than R) with little macular response. Patient 3 had a left optic nerve meningioma and experienced great difficulty with visual field assessment. mfVEPs showed a bilateral depression in the superior field particularly the left field, with a larger deficit in the left eye. Patient 4 had unexplained visual acuity and peripheral field deficits. mfVEP results were inconclusive in this case. DISCUSSION: Where there is difficulty performing traditional techniques or conflicting clinical findings, mfVEPs may provide additional objective information to aid in the assessment of patients.