Genetic risk for schizophrenia is associated with increased proportion of indirect connections in brain networks revealed by a semi-metric analysis: evidence from population sample stratified for polygenic risk.

Research studies based on tractography have revealed a prominent reduction of asymmetry in some key white-matter tracts in schizophrenia (SCZ). However, we know little about the influence of common genetic risk factors for SCZ on the efficiency of routing on structural brain networks (SBNs). Here, we use a novel recall-by-genotype approach, where we sample young adults from a population-based cohort (ALSPAC:N genotyped = 8,365) based on their burden of common SCZ risk alleles as defined by polygenic risk score (PRS). We compared 181 individuals at extremes of low (N = 91) or high (N = 90) SCZ-PRS under a robust diffusion MRI-based graph theoretical SBN framework. We applied a semi-metric analysis revealing higher SMR values for the high SCZ-PRS group compared with the low SCZ-PRS group in the left hemisphere. Furthermore, a hemispheric asymmetry index showed a higher leftward preponderance of indirect connections for the high SCZ-PRS group compared with the low SCZ-PRS group (PFDR < 0.05). These findings might indicate less efficient structural connectivity in the higher genetic risk group. This is the first study in a population-based sample that reveals differences in the efficiency of SBNs associated with common genetic risk variants for SCZ.

A rare case of bullhorn-injury associated traumatic hernia of anterior abdominal wall managed by laparoscopic sutured tissue-only repair.

Traumatic abdominal wall hernias (TAWHs) are relatively uncommon entities. Common mechanisms that predispose to such hernias include motor vehicle accidents, seat belt injuries, fall from height, handlebar injuries, and bullfighting. Bullhorn injury leading to TAWHs is an uncommon mechanism. We report here one such patient who was managed by laparoscopic transperitoneal anatomical repair of the defect using polypropylene suture. The patient recovered well without any complication and is being followed up. Such small defects can be managed laparoscopically and tissue-only repair using a nonabsorbable suture is a feasible option. Our case is the first reported case of bullhorn-injury associated traumatic hernia managed laparoscopically and first reported case of TAWH in an adult which was managed by laparoscopic sutured tissue-only repair.

Neurophysiologically-informed markers of individual variability and pharmacological manipulation of human cortical gamma.

The ability to quantify synaptic function at the level of cortical microcircuits from non-invasive data would be enormously useful in the study of neuronal processing in humans and the pathophysiology that attends many neuropsychiatric disorders. Here, we provide proof of principle that one can estimate inter-and intra-laminar interactions among specific neuronal populations using induced gamma responses in the visual cortex of human subjects - using dynamic causal modelling based upon the canonical microcircuit (CMC; a simplistic model of a cortical column). Using variability in induced (spectral) responses over a large cohort of normal subjects, we find that the predominant determinants of gamma responses rest on recurrent and intrinsic connections between superficial pyramidal cells and inhibitory interneurons. Furthermore, variations in beta responses were mediated by inter-subject differences in the intrinsic connections between deep pyramidal cells and inhibitory interneurons. Interestingly, we also show that increasing the self-inhibition of superficial pyramidal cells suppresses the amplitude of gamma activity, while increasing its peak frequency. This systematic and nonlinear relationship was only disclosed by modelling the causes of induced responses. Crucially, we were able to validate this form of neurophysiological phenotyping by showing a selective effect of the GABA re-uptake inhibitor tiagabine on the rate constants of inhibitory interneurons. Remarkably, we were able to recover the pharmacodynamics of this effect over the course of several hours on a per subject basis. These findings speak to the possibility of measuring population specific synaptic function - and its response to pharmacological intervention - to provide subject-specific biomarkers of mesoscopic neuronal processes using non-invasive data. Finally, our results demonstrate that, using the CMC as a proxy, the synaptic mechanisms that underlie the gain control of neuronal message passing within and between different levels of cortical hierarchies may now be amenable to quantitative study using non-invasive (MEG) procedures.

Increased visual gamma power in schizoaffective bipolar disorder.

BACKGROUND: Electroencephalography and magnetoencephalography (MEG) studies have identified alterations in gamma-band (30-80 Hz) cortical activity in schizophrenia and mood disorders, consistent with neural models of disturbed glutamate (and GABA) neuron influence over cortical pyramidal cells. Genetic evidence suggests specific deficits in GABA-A receptor function in schizoaffective bipolar disorder (SABP), a clinical syndrome with features of both bipolar disorder and schizophrenia. This study investigated gamma oscillations in this under-researched disorder. METHOD: MEG was used to measure induced gamma and evoked responses to a visual grating stimulus, known to be a potent inducer of primary visual gamma oscillations, in 15 individuals with remitted SABP, defined using Research Diagnostic Criteria, and 22 age- and sex-matched healthy controls. RESULTS: Individuals with SABP demonstrated increased sustained visual cortical power in the gamma band (t 35 = -2.56, p = 0.015) compared to controls. There were no group differences in baseline gamma power, transient or sustained gamma frequency, alpha band responses or pattern onset visual-evoked responses. CONCLUSIONS: Gamma power is increased in remitted SABP, which reflects an abnormality in the cortical inhibitory-excitatory balance. Although an interaction between gamma power and medication can not be ruled out, there were no group differences in evoked responses or baseline measures. Further work is needed in other clinical populations and at-risk relatives. Pharmaco-magnetoencephalography studies will help to elucidate the specific GABA and glutamate pathways affected.

Visual gamma oscillations: the effects of stimulus type, visual field coverage and stimulus motion on MEG and EEG recordings.

Increases in the power of neural oscillations in the gamma (>40 Hz) band are a key signature of information processing in cortical neuronal networks. However, non-invasive detection of these very small oscillations is difficult due to the presence of potential artefacts (both muscular and ocular) in the same frequency band and requires highly optimised paradigms. Numerous studies have shown that the properties of visual gamma-band responses to simple pattern stimuli are highly tuned to the stimuli parameters used. The aim of this work was to compare gamma oscillation response properties across some of the more commonly used stimulus configurations. To do this, MEG and EEG recordings were made during the presentation of eight different stimulus types in a 2 × 2 × 2 design. For the first stimulus factor, "Type", the stimulus pattern was either an annulus grating or a square wave grating. For the second stimulus factor, "Field", stimuli were presented in either four visual field quadrants simultaneously or only in the lower left quadrant. Finally, for the "Move" factor, stimuli either drifted at 1.33°s(-1) or were stationary. For MEG gamma band responses, the following main effects were observed, a) gamma-band power was increased for annular stimuli compared to square wave stimuli, b) gamma-band power was increased for full field stimuli compared to single quadrant stimuli and c) gamma-band power was larger for drifting compared to stationary stimuli and were of significantly higher frequency. For the detectors used, the signal to noise ratio was substantially higher for MEG than EEG. The advantages and disadvantages of the different types of stimulus types are discussed.

The effects of elevated endogenous GABA levels on movement-related network oscillations.

The EEG/MEG signal is generated primarily by the summation of the post-synaptic potentials of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons and cortical oscillations are thought to be dependent on the balance of excitation and inhibition between these cell types. To investigate the dependence of movement-related cortical oscillations on excitation-inhibition balance, we pharmacologically manipulated the GABA system using tiagabine, which blocks GABA Transporter 1(GAT-1), the GABA uptake transporter and increases endogenous GABA activity. In a blinded, placebo-controlled, crossover design, in 15 healthy participants we administered either 15mg of tiagabine or a placebo. We recorded whole-head magnetoencephalograms, while the participants performed a movement task, prior to, one hour post, three hour post and five hour post tiagabine ingestion. Using time-frequency analysis of beamformer source reconstructions, we quantified the baseline level of beta activity (15-30Hz), the post-movement beta rebound (PMBR), beta event-related desynchronisation (beta-ERD) and movement-related gamma synchronisation (MRGS) (60-90Hz). Our results demonstrated that tiagabine, and hence elevated endogenous GABA levels causes, an elevation of baseline beta power, enhanced beta-ERD and reduced PMBR, but no modulation of MRGS. Comparing our results to recent literature (Hall et al., 2011) we suggest that beta-ERD may be a GABAA receptor mediated process while PMBR may be GABAB receptor mediated.

The cortical topography of human swallowing musculature in health and disease.

Because no detailed information exists regarding the topographic representation of swallowing musculature on the human cerebral cortex in health or disease, we used transcranial magnetic stimulation to study the cortical topography of human oral, pharyngeal and esophageal musculature in 20 healthy individuals and the topography of pharyngeal musculature in two stroke patients, one with and one without dysphagia. Our results demonstrate that swallowing musculature is discretely and somatotopically represented on the motor and premotor cortex of both hemispheres but displays interhemispheric asymmetry, independent of handedness. Following stroke, dysphagia appeared to be associated with smaller pharyngeal representation on the intact hemisphere, which increases in size with recovery of swallowing.

Evaluation and comparison of conjunctival swab polymerase chain reaction results in SARS-CoV-2 patients with and without ocular manifestations.

PURPOSE: The aim of this study was to evaluate and compare the presence of SARS-CoV-2 in tears of patients with and without ocular symptoms in SARS-CoV-2 positive patients. METHODS: The prospective observational study conducted on 60 consecutive SARS-CoV-2 positive patients with ocular complaints was compared with 60 controls who had no ocular manifestations. The tear samples were taken within 48 h of admission from both the eyes of the enrolled patients for evaluating the presence SARS-CoV-2 by reverse transcription-polymerase chain reaction. RESULTS: Eleven cases (18.33%) tested positive for SARS-CoV-2 in tears on RT-PCR from cojunctival swab compared to 10 (16.66%) controls. The difference was not statistical significant. The difference between mean age of patients who tested positive or negative was also without statistical significance (P = 0.652), but the difference between patients who tested positive or negative by conjunctival swab for SARS-CoV-2 was statistically significant in terms of severity of COVID-19 disease (P = 0.0011), presence of comorbidity (P = 0.0015), mean TLC (P = 0.00498), and mean d dimer (P = 0.00465). CONCLUSION: Though the percentage of patients with positive RT PCR from conjunctival secretions is significantly less than nasopharyngeal swabs, potential risk of transmission of SARS-Co-2 through tears cannot be ruled out. Moreover, SARS-CoV-2 can be present in tears irrespective of ocular involvement.

Genetic risk for schizophrenia is associated with altered visually-induced gamma band activity: evidence from a population sample stratified polygenic risk.

Gamma oscillations (30-90 Hz) have been proposed as a signature of cortical visual information processing, particularly the balance between excitation and inhibition, and as a biomarker of neuropsychiatric diseases. Magnetoencephalography (MEG) provides highly reliable visual-induced gamma oscillation estimates, both at sensor and source level. Recent studies have reported a deficit of visual gamma activity in schizophrenia patients, in medication naive subjects, and high-risk clinical participants, but the genetic contribution to such a deficit has remained unresolved. Here, for the first time, we use a genetic risk score approach to assess the relationship between genetic risk for schizophrenia and visual gamma activity in a population-based sample drawn from a birth cohort. We compared visual gamma activity in a group (N = 104) with a high genetic risk profile score for schizophrenia (SCZ-PRS) to a group with low SCZ-PRS (N = 99). Source-reconstructed V1 activity was extracted using beamformer analysis applied to MEG recordings using individual MRI scans. No group differences were found in the induced gamma peak amplitude or peak frequency. However, a non-parametric statistical contrast of the response spectrum revealed more robust group differences in the amplitude of high-beta/gamma power across the frequency range, suggesting that overall spectral shape carries important biological information beyond the individual frequency peak. Our findings show that changes in gamma band activity correlate with liability to schizophrenia and suggest that the index changes to synaptic function and neuronal firing patterns that are of pathophysiological relevance rather than consequences of the disorder.

Long-term reorganization of human motor cortex driven by short-term sensory stimulation.

Removal of sensory input can induce changes in cortical motor representation that reverse when sensation is restored. Here we ask whether manipulation of sensory input can induce long-term reorganization in human motor cortex that outlasts the initial conditioning. We report that for at least 30 minutes after pharyngeal stimulation, motor cortex excitability and area of representation for the pharynx increased, while esophagus representation decreased, without parallel changes in the excitability of brainstem-mediated reflexes. Therefore increased sensory input can drive long-term cross-system changes in motor areas of the cerebral cortex, which suggests that sensory stimulation might rehabilitate dysphagia, a frequent consequence of cerebral injury.

Semantic and phonological task-set priming and stimulus processing investigated using magnetoencephalography (MEG).

In this study the neural substrates of semantic and phonological task priming and task performance were investigated using single word task-primes. Magnetoencephalography (MEG) data were analysed using Synthetic Aperture Magnetometry (SAM) to determine the spatiotemporal and spectral characteristics of cortical responses. Comparisons were made between the task-prime conditions for evidence of differential effects as a function of the nature of the task being primed, and between the task-prime and the task performance responses for evidence of parallels in activation associated with preparation for and completion of a specific task. Differential priming effects were found. Left middle temporal and inferior frontal voxels showed a statistically significant power decrease associated with the semantic task-prime, and a power increase associated with the phonological task-prime, within beta and gamma frequency bands respectively. Similarities between the task-related differential effects associated with task-prime presentation and those associated with target stimulus presentation were also found. For example, within the semantic task condition, left superior frontal and middle temporal regions showed a significant power decrease within both task-prime and target epochs; within the phonological task condition there were significant parietal and cerebellar power decreases within both types of epoch. In addition there was evidence within the priming epochs of dissociable patterns of activity which could be interpreted as indices of de-activation of task-irrelevant networks. Following a phonological task-prime, significant power increases were observed in those inferior frontal and middle temporal regions in which significant power decreases were associated with semantic task priming and performance.

Microbial decolorization and bioremediation of melanoidin containing molasses spent wash.

Molasses spent wash from cane-molasses based distilleries contains a brown coloured recalcitrantpolymer melanoidin, which if disposed untreated poses a great threat to environment. Microbial decolorization and chemical oxygen demand (COD) reduction was found to be dependent on specific carbon and nitrogen source. Under optimal condition of pH, carbon and nitrogen concentration for each treatment, it was found that Bacillus sp isolated from soil was capable of removing COD (85. 35%) and colour (81.10%) from distillery waste to the maximum extent after 9 days atpH 7 in the medium containing 0.5% peptone, 2% glucose and 10% (v/v), followed by Phanerochaete chrysosporium and lowest reduction was obtained by using native microbial consortium.

Effect of different phases of menstrual cycle on brainstem auditory evoked response.

INTRODUCTION: The change in the hormonal levels during the three phases of menstrual cycle, namely, menstrual phase (hormonal withdrawal), proliferative phase (estrogen peak), and secretory phase (progesterone peak), influences the conduction velocities in the central auditory pathways. Variable findings of brainstem auditory evoked response (BAER) have been reported during different phases of menstrual cycle by different researchers. AIM: To study the effect of different phases of menstrual cycle on BAER. METHODOLOGY: A prospective observational study on 80 audiometrically normal, healthy, eumenorrheic female students in age group of 18-24 years was done at a medical college of northern India. BAER was recorded across the three phases of the menstrual cycle, i.e., menstrual phase (day 1-3), proliferative phase (day 10-12), and secretory phase (day 20-22). Recordings of peak latencies, interpeak latencies, and amplitude of waves of BAER were taken and statistically analyzed. RESULTS: In this study, significant decrease in the latencies of wave III, wave V, and interpeak latency I-III and a trend of decrease in latencies of wave I and interpeak latency I-V (which was statistically insignificant) were observed in proliferative (estrogen peak) phase as compared to menstrual and secretory phase. However, there was no statistically significant difference found in the amplitude of waves of BAER during all the three phases of menstrual cycle. CONCLUSION: The hormonal changes during different phases of menstrual cycle do seem to influence BAER.

Effect of Different Phases of Menstrual Cycle on Heart Rate Variability (HRV).

BACKGROUND: Heart Rate Variability (HRV), which is a measure of the cardiac autonomic tone, displays physiological changes throughout the menstrual cycle. The functions of the ANS in various phases of the menstrual cycle were examined in some studies. AIMS AND OBJECTIVES: The aim of our study was to observe the effect of menstrual cycle on cardiac autonomic function parameters in healthy females. MATERIALS AND METHODS: A cross-sectional (observational) study was conducted on 50 healthy females, in the age group of 18-25 years. Heart Rate Variability (HRV) was recorded by Physio Pac (PC-2004). The data consisted of Time Domain Analysis and Frequency Domain Analysis in menstrual, proliferative and secretory phase of menstrual cycle. Data collected was analysed statistically using student's pair t-test. RESULTS: The difference in mean heart rate, LF power%, LFnu and HFnu in menstrual and proliferative phase was found to be statistically significant. The difference in mean RR, Mean HR, RMSSD (the square root of the mean of the squares of the successive differences between adjacent NNs.), NN50 (the number of pairs of successive NNs that differ by more than 50 ms), pNN50 (the proportion of NN50 divided by total number of NNs.), VLF (very low frequency) power, LF (low frequency) power, LF power%, HF power %, LF/HF ratio, LFnu and HFnu was found to be statistically significant in proliferative and secretory phase. The difference in Mean RR, Mean HR, LFnu and HFnu was found to be statistically significant in secretory and menstrual phases. CONCLUSION: From the study it can be concluded that sympathetic nervous activity in secretory phase is greater than in the proliferative phase, whereas parasympathetic nervous activity is predominant in proliferative phase.

Visual Evoked Potentials: Normative Values and Gender Differences.

INTRODUCTION: Visual evoked potentials (VEP) are used to assess the visual pathways through the optic nerves and brain. A normal VEP response to a pattern-reversal stimulus is a positive mid occipital peak that occurs at a mean latency of 100 ms. VEP may be affected by variety of physiological factors including age, sex, visual acuity and pupillary size. AIMS AND OBJECTIVES: The present study was performed on healthy medical students to determine the normative values and to investigate the effect of sex and anthropometric parameters on visual evoked potentials. MATERIALS AND METHODS: The study was conducted on 100 healthy medical students of Government Medical College, Patiala in the age group of 17-20 years, in which there were 50 males and 50 females. The anthropometric parameters including age, height, weight, BMI, BSA and Head circumference were recorded in all the subjects. VEP was recorded with a PC based, 2 channel, RMS EMG EP mark II machine and standard silver-silver chloride disc electrodes. A VEP monitor displaying checker board was used to give the pattern reversal stimulus. The VEP parameters recorded were latencies to N70, P100 and N155 waves, and peak to peak amplitude of P100 wave. RESULTS: Our results showed that the latencies of N70, P100 and N155 waves were significantly longer in males as compared to females. The amplitude of P100 wave was higher in females in both left and right eye as compared to males. No significant correlation was found between VEP parameters and head circumference in both male and female subjects in our study. CONCLUSION: Gender is an important variable affecting the VEP. The exact reason of gender difference is not clear, but it may be related to anatomical or endocrinal differences in the two sexes.

A comparative study of visual and auditory reaction times on the basis of gender and physical activity levels of medical first year students.

BACKGROUND: Reaction time (RT) is a measure of the response to a stimulus. RT plays a very important role in our lives as its practical implications may be of great consequences. Factors that can affect the average human RT include age, sex, left or right hand, central versus peripheral vision, practice, fatigue, fasting, breathing cycle, personality types, exercise, and intelligence of the subject. AIM: The aim was to compare visual RTs (VRTs) and auditory RTs (ARTs) on the basis of gender and physical activity levels of medical 1(st) year students. MATERIALS AND METHODS: The present cross-sectional study was conducted on 120 healthy medical students in age group of 18-20 years. RT for target stimulus that is, for the beep tone for measuring ART, and red circle for measuring VRT was determined using Inquisit 4.0 (Computer Software) in the laptop. The task was to press the spacebar as soon as the stimulus is presented. Five readings of each stimulus were taken, and their respective fastest RT's for each stimuli were recorded. Statistical analysis was done. RESULTS: In both the sexes' RT to the auditory stimulus was significantly less (P < 0.001) as compared to the visual stimulus. Significant difference was found between RT of male and female medical students (P < 0.001) as well as between sedentary and regularly exercising healthy medical 1(st) year students. CONCLUSION: The ART is faster than the VRT in medical students. Furthermore, male medical students have faster RTs as compared to female medical students for both auditory as well as visual stimuli. Regularly exercising medical students have faster RTs when compared with medical students with sedentary lifestyles.

Efficacy of milk-based diets in persistent diarrhea: a randomized, controlled trial.

OBJECTIVE: Previous studies have shown increased stool output when children with persistent diarrhea (PD) received milk as the predominant source of nutrition. METHODS: We evaluated the efficacy of milk given in modest amounts as a part of a mixed diet in children with PD. One hundred sixteen children 3 to 24 months of age with diarrhea for between 14 days and 12 weeks were allocated to milk-based (n = 60) or milk-free (n = 56) cereal dietary regimens. The two diets were isocaloric (86.9 calories/100 g for < or = 9 months; 95.6 cal/100 g for > 9 months) consisting of puffed rice cereal, sugar, and oil differing in only their source of protein, which was either milk or egg white, respectively. An average of 30% of the calories were constituted by milk in the milk-cereal diet. Both diets were offered at the rate of 150 kcal/kg per day. Children receiving milk-cereal consumed an average of 1.9 g/kg lactose per day. RESULTS: The baseline characteristics in the two groups were similar. Comparable amounts of diet were consumed in both groups. The milk-cereal group did not have higher median (range) stool output (g/kg/h) compared with the milk-free group during a 0- to 48-hour (milk-cereal, 1.7 [0.2 to 8.7]; milk-free, 1.5 [0.1 to 6.6]) or 0- to 120-hour (milk-cereal, 1.6 [0.4 to 7.2]; milk-free, 1.3 [0.1 to 7.6]) period. The percentage of weight gain was similar in the two groups, and there were no significant differences in the duration of diarrhea. Overall, 23 children had treatment failures, 10 (17%) in the milk-cereal and 13 (23.6%) in the milk-free groups. CONCLUSIONS: Our findings suggest that modest intakes of milk are well tolerated as a part of mixed diet during PD.

Localization and functional analysis of human cortical area V5 using magneto-encephalography.

Using a multi-channel SQUID-based neuromagnetometer, we have determined the location, temporal dynamics and functional response properties of the human homologue of the primate cortical area V5 (MT). We provide evidence that area V5 in humans is located near the occipito-temporal border in a minor sulcus immediately below the superior temporal sulcus. this area is selective for low spatial frequencies ( < or = 4.0 c/deg), responds to a wide range of temporal frequencies ( < or = 35 Hz) and shows response saturation for stimulus contrasts greater than 10%. In addition, we find that this area is not responsive to purely chromatic patterns but is responsive to motion-contrast stimuli. Our results are consistent with the hypothesis that area V5 in humans represents a stage of processing within the magnocellular pathway. We discuss our results in relation to the widespread belief that area V5 in humans is specifically concerned with motion perception.

Attentional suppression of activity in the human visual cortex.

We have used fMRI to examine the nature of the changes that occur in the human visual cortex when an observer attends to a particular location in the visual image. Previous studies have shown that the magnitude of the response to a visual stimulus is increased when the observer attends to the stimulus. We show that, in addition, attention to a particular location results in a widespread suppression of activity levels at all other locations. This suggests that a key mechanism of attentional modulation may be that spontaneous (baseline) levels of neural activity are adjusted in a position-dependent manner across the entire visual field.

An fMRI study of stimulus equivalence.

In order to study brain activation during the formation of equivalence relations, 12 subjects underwent fMRI during matching-to-sample (MTS) tests of (1) previously trained arbitrary relationships between iconic stimuli and the untrained, emergent relations of (2) symmetry, (3) transitivity, and (4) symmetry with transitivity, plus a test of verbal fluency (VF). Brain activation was similar in all MTS tasks and in the VF task. In particular, both types of task activated dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex bilaterally. However VF, but not the MTS tasks, activated Broca's area. In three of the four MTS tasks, behavioural accuracy was significantly correlated with left lateralisation of DLPFC activity. Brain activation patterns during equivalence thus resembled those involved in semantic processing underlying language, without involving regions concerned with the simple sub-vocal articulation of stimulus names.