Publications by authors named "Anusha Mohan"

23 Publications

  • Page 1 of 1

Sex Differences in Locus Coeruleus: A Heuristic Approach That May Explain the Increased Risk of Alzheimer's Disease in Females.

J Alzheimers Dis 2021 ;83(2):505-522

Lab for Clinical & Integrative Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland.

This article aims to reevaluate our approach to female vulnerability to Alzheimer's disease (AD) and put forth a new hypothesis considering how sex differences in the locus coeruleus-noradrenaline (LC-NA) structure and function could account for why females are more likely to develop AD. We specifically focus our attention on locus coeruleus (LC) morphology, the paucity of estrogens, neuroinflammation, blood-brain barrier permeability, apolipoprotein ɛ4 polymorphism (APOEɛ4), and cognitive reserve. The role of the LC-NA system and sex differences are two of the most rapidly emerging topics in AD research. Current literature either investigates the LC due to it being one of the first brain areas to develop AD pathology or acknowledges the neuroprotective effects of estrogens and how the loss of these female hormones have the capacity to contribute to the sex differences seen in AD; however, existing research has neglected to concurrently examine these two rationales and therefore leaving our hypothesis undetermined. Collectively, this article should assist in alleviating current challenges surrounding female AD by providing thought-provoking connections into the interrelationship between the disruption of the female LC-NA system, the decline of estrogens, and AD vulnerability. It is therefore likely that treatment for this heterogeneous disease may need to be distinctly developed for females and males separately, and may require a precision medicine approach.
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http://dx.doi.org/10.3233/JAD-210404DOI Listing
January 2021

Impact of Pediatric Dentistry Residents Posted in Pediatrics Department: A Retrospective Assessment of 6 Years.

Int J Clin Pediatr Dent 2021 Jan-Feb;14(1):84-87

Department of Pedodontics and Preventive Dentistry, Pushpagiri College of Dental Sciences, Thiruvalla, Kerala, India.

Aim: To measure the influence of rotatory pediatrics postings for dental residents on the outpatient census of the pediatric dentistry department. The secondary aims were to assess the change in trend toward the number of preschool children visiting the department before and after the initiation of pediatrics posting and also to find the percentage of children affected with caries among children visiting the pediatricians.

Materials And Methods: Retrospectively, the census of the pediatric dentistry department was calculated from 2010 to 2016. The number of preschool children who visited the pediatric dentistry department during this period was determined. From the pediatrics posting records, the dental status of the children, the number screened, the number referred, and the number reported to dentistry following referral were tabulated. Descriptive statistics and Chi-square tests were performed.

Results: After the initiation of pediatrics postings for residents, the outpatient census has increased by 26%. There was a significant increase in the number of preschool children visiting the pediatric dentist. About 57.09% of children screened in the pediatrics department had dental disease.

Conclusion: There is an increase in the patient flow of the pediatric dentistry department with a greater number of preschool children visiting the pediatric dentist after initiation of the pediatrics postings for residents. More than half the children visiting pediatricians had dental disease requiring professional care.

Clinical Significance: Pediatrics postings for residents can be used in teaching centers as an opportunity to spread awareness and increase the number of preschool children visiting pediatric dentists, thereby increasing prevention and early intervention of early childhood caries.

How To Cite This Article: Mohan A, Muthu MS, Ramachandran P, Impact of Pediatric Dentistry Residents Posted in Pediatrics Department: A Retrospective Assessment of 6 Years. Int J Clin Pediatr Dent 2021;14(1):84-87.
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http://dx.doi.org/10.5005/jp-journals-10005-1890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311764PMC
July 2021

Effect of Sustained Interventions from Infancy to Toddlerhood in Children with Cleft Lip and Palate for Preventing Early Childhood Caries.

Caries Res 2021 Jul 22:1-9. Epub 2021 Jul 22.

Department of Pediatric and Preventive Dentistry, Pushpagiri College of Dental Sciences, Thiruvalla, India.

The study aimed to evaluate the effectiveness of sustained interventions in children with cleft lip and palate (CLP) for preventing early childhood caries (ECC). This prospective, nonrandomized interventional cohort study was conducted in infants aged 0-12 months with congenital CLP. Interventions were given to parents/primary caregivers in the form of combined oral health-care measures (sterile wet gauze piece, finger brush, toothbrush, and toothpaste) by a motivational interviewing approach. Education of primary caregivers on oral hygiene was provided by audiovisual aids and demonstration. Reinforcement of the prescribed regimen was done through daily short message services in caregivers' preferred language and bimonthly telephone calls. Participants were followed up for 9-32 months from the time of recruitment, with a mean period of 18.3 ± 5.1 months. Rates of dental caries were represented as prevalence rates, incidence density, and transitional probability. The distribution of the International Caries Detection and Assessment System (ICDAS) scores on different tooth surfaces affected in the intervention group was compared descriptively with that of the age- and sex-matched historical control groups. On analysis of surface-wise distribution of the ICDAS scores in the intervention group (n = 1,919), 1.2% (n = 24) had noncavitated lesions (ICDAS codes 1 and 2), 0.88% (n = 17) had cavitated lesions (ICDAS codes 3-6), and 0.26% (n = 5) had both cavitated and noncavitated lesions (ICDAS codes 1-6). The incidence density of caries-affected children observed at the first and last follow-ups was 1.2 persons/100 person-months and 1.3 persons/100 person-months of observation, respectively. The incidence density of new caries-affected tooth surfaces at the first and last follow-ups was 0.163 surfaces/100 surface-months and 0.062 surfaces/100 surface-months, respectively. Maxillary first molars had the maximum transition from sound to the cavitated lesion (11.5%), followed by maxillary incisors from sound to noncavitated (7.5%) at the last follow-up. Based on the newly developed assessment criteria in our study, sustained interventions proved to be significantly effective in preventing ECC in children with CLP.
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http://dx.doi.org/10.1159/000517210DOI Listing
July 2021

Polarity-specific high-definition transcranial direct current stimulation of the anterior and posterior default mode network improves remote memory retrieval.

Brain Stimul 2021 Jul-Aug;14(4):1005-1014. Epub 2021 Jun 23.

School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, USA; Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland; Trinity College Institute for Neuroscience, Trinity College Dublin, Dublin, Ireland; Lab for Clinical & Integrative Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland. Electronic address:

Background: Previous studies show that activity in the posterior default mode network (pDMN), including the posterior cingulate cortex and the precuneus, is correlated with the success of long-term episodic memory retrieval. However, the role of the anterior DMN (aDMN) including the medial prefrontal cortex is still unclear. Some studies show that activating the medial prefrontal cortex improves memory retrieval while other studies show deactivation of the medial prefrontal cortex in successful retrieval of episodic memories, suggesting a possible functional dissociation between the aDMN and pDMN.

Objective: In the current study, we aim to causally explore this probable dissociation using high-definition transcranial direct current stimulation (HD-tDCS).

Methods: We perform a randomised double-blinded two-visit placebo-controlled study with 84 healthy young adults. During Visit 1 they learn 75 Swahili-English word-associations. Seven days later, they randomly receive either anodal, cathodal or sham HD-tDCS targeting the pDMN or aDMN while they recall what they have previously learned.

Results: We demonstrate that anodal stimulation of the pDMN and cathodal stimulation of the aDMN, equally improve the percentage of Swahili-English word-associations recalled 7 days after learning.

Conclusions: Modulating the activity in the aDMN and pDMN causally affect memory retrieval performance. HD-tDCS of the aDMN and pDMN shows that anodal stimulation of the pDMN and cathodal stimulation of the aDMN increases memory retrieval performance one week after the learning phase. Given consistent evidence, it is highly likely that we are increasing the activity in the pDMN with anodal pDMN stimulation. However, it is not clear if cathodal HD-tDCS targetting aDMN works via decoupling from the pDMN or via indirectly disinhibit pDMN.
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http://dx.doi.org/10.1016/j.brs.2021.06.007DOI Listing
June 2021

Thalamocortical dysrhythmia underpin the log-dynamics in phantom sounds.

Prog Brain Res 2021 16;262:511-526. Epub 2021 Apr 16.

Global Brain Health Institute & Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. Electronic address:

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http://dx.doi.org/10.1016/bs.pbr.2021.04.001DOI Listing
April 2021

Structural correlates of the audiological and emotional components of chronic tinnitus.

Prog Brain Res 2021 19;262:487-509. Epub 2021 Mar 19.

Lab for Clinical and Integrative Neuroscience, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States; Global Brain Health Institute & Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. Electronic address:

The objective is to investigate white matter tracts, more specifically the arcuate fasciculus and acoustic radiation, in tinnitus and assess their relationship with distress, loudness and hearing loss. DTI images were acquired for 58 tinnitus patients and 65 control subjects. Deterministic tractography was first performed to visualize the arcuate fasciculus and acoustic radiation tracts bilaterally and to calculate tract density, fractional anisotropy, radial diffusivity, and axial diffusivity for tinnitus and control subjects. Tinnitus patients had a significantly reduced tract density compared to controls in both tracts of interest. They also exhibited increased axial diffusivity in the left acoustic radiation, as well as increased radial diffusivity in the left arcuate fasciculus, and both the left and right acoustic radiation. Furthermore, they exhibited decreased fractional anisotropy in the left arcuate fasciculus, as well as the left and right acoustic radiation tracts. Partial correlation analysis showed: (1) a negative correlation between arcuate fasciculus tract density and tinnitus distress, (2) a negative correlation between acoustic radiation tract density and hearing loss, (3) a negative correlation between acoustic radiation tract density and loudness, (4) a positive correlation between left arcuate fasciculus and tinnitus distress for radial diffusivity, (5) a negative correlation between left arcuate fasciculus and tinnitus distress for fractional anisotropy, (6) a positive correlation between left and right acoustic radiation and hearing loss for radial diffusivity, (7) No correlation between any of the white matter characteristics and tinnitus loudness. Structural alterations in the acoustic radiation and arcuate fasciculus correlate with hearing loss and distress in tinnitus but not tinnitus loudness showing that loudness is a more functional correlate of the disorder which does not manifest structurally.
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http://dx.doi.org/10.1016/bs.pbr.2021.01.030DOI Listing
March 2021

Paradoxical relationship between distress and functional network topology in phantom sound perception.

Prog Brain Res 2021 24;260:367-395. Epub 2020 Oct 24.

Lab for Clinical and Integrative Neuroscience, Global Brain Health Institute, Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland; Lab for Clinical and Integrative Neuroscience, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States. Electronic address:

Distress is a domain-general symptom that accompanies several disorders, including tinnitus. Based on previous studies, we know that distress is encoded by changes in functional connectivity between cortical and subcortical regions. However, how distress relates to large-scale brain networks is not yet clear. In the current study, we investigate the relationship between distress and the efficiency of a network by examining its topological properties using resting state fMRI collected from 90 chronic tinnitus patients. The present results indicate that distress negatively correlates with path length and positively correlates with clustering coefficient, small-worldness, and efficiency of information transfer. Specifically, path analysis showed that the relationship between distress and efficiency is significantly mediated by the resilience of the feeder connections and the centrality of the rich-club connections. In other words, the higher the network efficiency, the lower the resilience of the feeder connections and the centrality of the rich-club connections, which in turn reflects in higher distress in tinnitus patients. This indicates a reorganization of the network towards a paradoxically more efficient topology in patients with high distress, potentially explaining their increased rumination on the tinnitus percept itself.
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http://dx.doi.org/10.1016/bs.pbr.2020.08.007DOI Listing
October 2020

The BDNF ValMet polymorphism regulates vulnerability to chronic stress and phantom perception.

Prog Brain Res 2021 22;260:301-326. Epub 2021 Jan 22.

Lab for Clinical and Integrative Neuroscience, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States.

Auditory phantom percepts, such as tinnitus, are a heterogeneous condition with great interindividual variations regarding both the percept itself and its concomitants. Tinnitus causes a considerable amount of distress, with as many as 25% of affected people reporting that it interferes with their daily lives. Although previous research gives an idea about the neural correlates of tinnitus-related distress, it cannot explain why some tinnitus patients develop distress and while others are not bothered by their tinnitus. BDNF ValMet polymorphism (rs6265) is a known risk factor for affective disorders due to its common frequency and established functionality. To elucidate, we explore the neural activation pattern of tinnitus associated with the BDNF ValMet polymorphism using electrophysiological data to assess activity and connectivity changes. A total of 110 participants (55 tinnitus and 55 matched control subjects) were included. In this study, we validate that the BDNF ValMet polymorphism plays an important role in the susceptibility to the clinical manifestation of tinnitus-related distress. We demonstrate that Val/Met carriers have increased alpha power in the subgenual anterior cingulate cortex that correlates with distress levels. Furthermore, distress mediates the relationship between BDNF ValMet polymorphism and tinnitus loudness. In other words, for Val/Met carriers, the subgenual anterior cingulate cortex sends distress-related information to the parahippocampus, which likely integrates the loudness and distress of the tinnitus percept.
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http://dx.doi.org/10.1016/bs.pbr.2020.08.005DOI Listing
January 2021

The peripheral effect of direct current stimulation on brain circuits involving memory.

Sci Adv 2020 Nov 4;6(45). Epub 2020 Nov 4.

Lab for Clinical and Integrative Neuroscience, School for Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, USA.

An ongoing debate surrounding transcranial direct current stimulation (tDCS) of the scalp is whether it modulates brain activity both directly and in a regionally constrained manner enough to positively affect symptoms in patients with neurological disorders. One alternative explanation is that direct current stimulation affects neural circuits mainly indirectly, i.e., via peripheral nerves. Here, we report that noninvasive direct current stimulation indirectly affects neural circuits via peripheral nerves. In a series of studies, we show that direct current stimulation can cause activation of the greater occipital nerve (ON-tDCS) and augments memory via the ascending fibers of the occipital nerve to the locus coeruleus, promoting noradrenaline release. This noradrenergic pathway plays a key role in driving hippocampal activity by modifying functional connectivity supporting the consolidation of a memory event.
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http://dx.doi.org/10.1126/sciadv.aax9538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673706PMC
November 2020

Anterior Cingulate Cortex Implants for Alcohol Addiction: A Feasibility Study.

Neurotherapeutics 2020 07;17(3):1287-1299

Department of Surgical Sciences, University of Otago, Dunedin, New Zealand.

Abnormal neural activity, particularly in the rostrodorsal anterior cingulate cortex (rdACC), appears to be responsible for intense alcohol craving. Neuromodulation of the rdACC using cortical implants may be an option for individuals with treatment-resistant alcohol dependence. This study assessed the effectiveness and feasibility of suppressing alcohol craving using cortical implants of the rdACC using a controlled one-group pre- and post-test study design. Eight intractable alcohol-dependent participants (four males and four females) were implanted with two Lamitrode 44 electrodes over the rdACC bilaterally connected to an internal pulse generator (IPG). The primary endpoint, self-reported alcohol craving reduced by 60.7% (p = 0.004) post- compared to pre-stimulation. Adverse events occurred in four out of the eight participants. Electrophysiology findings showed that among responders, there was a post-stimulation decrease (p = 0.026) in current density at the rdACC for beta 1 band (13-18 Hz). Results suggest that rdACC stimulation using implanted electrodes may potentially be a feasible method for supressing alcohol craving in individuals with severe alcohol use disorder. However, to further establish safety and efficacy, larger controlled clinical trials are needed.
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http://dx.doi.org/10.1007/s13311-020-00851-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641294PMC
July 2020

Investigating functional changes in the brain to intermittently induced auditory illusions and its relevance to chronic tinnitus.

Hum Brain Mapp 2020 05 10;41(7):1819-1832. Epub 2020 Mar 10.

Global Brain Health Institute & Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.

Several studies have demonstrated the neural correlates of chronic tinnitus. However, we still do not understand what happens in the acute phase. Past studies have established Zwicker tone (ZT) illusions as a good human model for acute tinnitus. ZT illusions are perceived following the presentation of a notched noise stimulus, that is, broadband noise with a narrow band-stop filter (notch). In the current study, we compared the neural correlates of the reliable perception of a ZT illusion to that which is not. We observed changes in evoked and total theta power in wide-spread regions of the brain particularly in the temporal-parietal junction, pregenual anterior cingulate cortex/ventromedial prefrontal cortex (pgACC/vmPFC), parahippocampus during perception of the ZT illusion. Furthermore, we observe that increased theta power significantly predicts a gradual positive change in the intensity of the ZT illusion. Such changes may suggest a malfunction of the sensory gating system that enables habituation to redundant stimuli and suppresses hyperactivity. It could also suggest a successful retrieval of the memory of the missing frequencies, resulting in their conscious perception indicating the role of higher-order processing in the mechanism of action of ZT illusions. To establish a more concrete relationship between ZT illusion and chronic tinnitus, future longitudinal studies following up a much larger sample of participants who reliably perceive a ZT illusion to see if they develop tinnitus at a later stage is essential. This could inform us if the ZT illusion may be a precursor to chronic tinnitus.
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http://dx.doi.org/10.1002/hbm.24914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268029PMC
May 2020

Effective connectivity analysis of inter- and intramodular hubs in phantom sound perception - identifying the core distress network.

Brain Imaging Behav 2020 Feb;14(1):289-307

Lab for Clinical & Integrative Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, 800 W Campbell Rd, Richardson, TX, 75080, USA.

Tinnitus, the perception of a phantom sound, is accompanied by loudness and distress components. Distress however accompanies not just tinnitus, but several disorders. Several functional connectivity studies show that distress is characterized by disconnectivity of fronto-limbic circuits or hyperconnectivity of default mode/salience networks. The drawback, however, is that it considers only the magnitude of connectivity, not the direction. Thus, the current study aims to identify the core network of the domain-general distress component in tinnitus by comparing whole brain directed functional networks calculated from 5 min of resting state EEG data collected from 310 tinnitus patients and 256 non-tinnitus controls. We observe a reorganization of the overall tinnitus network, reflected by a decrease in strength and efficiency of information transfer between fronto-limbic and medial temporal regions, forming the main hubs of the tinnitus network. Further, a disconnection amongst a subset of these connections was observed to correlate with distress, forming a core distress network. The core distress network showed a decrease in strength of connections specifically going from the left hippocampus/parahippocampus to the subgenual anterior cingulate cortex. Such a disconnection suggests that the parahippocampal contextual memory has little influence on the (paradoxical) value that is attached to the phantom sound and that distress is the consequence of the absence of modulation of the phantom sound.
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http://dx.doi.org/10.1007/s11682-018-9989-7DOI Listing
February 2020

Prevalence of Early Childhood Caries in India - A Systematic Review.

Indian J Pediatr 2019 Mar 3;86(3):276-286. Epub 2018 Oct 3.

South Asian Cochrane Centre, Christian Medical College, Vellore, Tamil Nadu, India.

Early Childhood Caries (ECC) is a serious public health problem in developed as well as developing nations, with high prevalence among children around the world. This systematic review of the national literature was undertaken to document the prevalence of Early Childhood Caries. Studies evaluating the prevalence of Early Childhood Caries (ECC) in the Indian population were investigated. The method under evaluation was the use of a caries experience index to calculate the prevalence of ECC. An extensive literature search was done in the following databases: PubMed, IndMED and Cochrane upto June 2016. A modified version of the Newcastle-Ottawa Scale for cross-sectional studies was used for assessment of the quality of the studies. A systematic literature search yielded 503 publications from the various databases searched. Based on the inclusion and exclusion criteria, the final number of included studies were 54. Among the included studies, 19 studies were carried out in the state of Karnataka. Analysis of all the included studies revealed the overall prevalence of ECC in India to be 49.6%. Andhra Pradesh was found to have the highest prevalence of ECC at 63%, and the lowest prevalence was reported in Sikkim (41.92%). This review has reported a high prevalence of ECC in India. None of the states reported prevalence below 40%. The government should identify ECC as a national priority which requires significant attention.
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http://dx.doi.org/10.1007/s12098-018-2793-yDOI Listing
March 2019

Diagnostic ability of a smart phone app (injured tooth) in diagnosing traumatic injuries to the teeth - a multicentre analysis.

Int J Paediatr Dent 2018 Nov 11;28(6):561-569. Epub 2018 Jul 11.

Department of Pedodontics and Preventive Dentistry, Oxford Dental College and Hospital, Bengaluru, India.

Background: Dental trauma is not uncommon. The initial management provided at the time of injury is critical in predicting prognosis. However, initial management depends on correct diagnosis. Recently an App named 'Injured Tooth' was made available to diagnose traumatic injuries to the teeth and supporting structures.

Aim: To test the diagnostic ability of the Injured Tooth App compared with the conventional method of diagnosing traumatic injuries to the teeth.

Design: A cross-sectional study was conducted at three different centres with 176 patients aged 0-15 years, having 201 injured teeth. Diagnosis of the injured teeth in these children at every centre was done independently by one experienced faculty using the traditional method and by a student using the Injured Tooth App.

Results: Injured Tooth App gave a correct diagnosis for 197 teeth included in the study. Statistical analysis showed that there was good agreement (Kappa = 0.973) between the diagnosis given by the App and the experienced faculty.

Conclusions: The study found that the diagnosis given by the Injured Tooth App was in good agreement with the diagnosis given by an experienced faculty. Hence, the App can be successfully used by dental students to arrive at diagnosis.
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http://dx.doi.org/10.1111/ipd.12411DOI Listing
November 2018

Distress-dependent temporal variability of regions encoding domain-specific and domain-general behavioral manifestations of phantom percepts.

Eur J Neurosci 2018 07 29;48(2):1743-1764. Epub 2018 Jun 29.

Lab for Clinical & Integrative Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas.

Tinnitus is the perception of a phantom sound characterized behaviorally by a loudness and a distress component. Although a wealth of information is available about the relationship between these behavioral correlates and changes in static functional connectivity, its relationship with dynamic changes in network connectivity is yet unexplored. The aim of this study was thus to investigate changes in the flexibility and stability of temporal variability in tinnitus and its relation to loudness and distress using continuous resting-state EEG. We observe an increase in temporal variability at the whole-brain level in tinnitus, which is spatiotemporally distributed at the nodal level. Behaviorally, we observe changes in the relationship between temporal variability and loudness and distress depending on the amount of distress experienced. In patients with low distress, there is no relationship between temporal variability and loudness or distress, demonstrating a resilience in dynamic connectivity of the brain. However, patients with high distress exhibit a direct relationship with increasing loudness in the primary auditory cortex and parahippocampus, and an inverse relationship with increasing distress in the parahippocampus. In tinnitus, the specific sensory (loudness) component related to increased temporal variability possibly reflects a Bayesian search for updating deafferentation-based missing information. On the other hand, the decreased temporal variability related to the nonspecific distress component possibly reflects a more hard-wired or less adaptive contextual processing. Therefore, our findings may reveal a way to understand the changes in network dynamics not just in tinnitus, but also in other brain disorders.
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http://dx.doi.org/10.1111/ejn.13988DOI Listing
July 2018

Effect of distress on transient network dynamics and topological equilibrium in phantom sound perception.

Prog Neuropsychopharmacol Biol Psychiatry 2018 06 2;84(Pt A):79-92. Epub 2018 Feb 2.

Lab for Clinical & Integrative Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, USA. Electronic address:

Distress is a domain-general behavioral symptom whose neural correlates have been under investigation for a long time now. Although some studies suggest that distress is encoded by changes in alpha activity and functional connectivity between specific brain regions, no study that we know has delved into the whole brain temporal dynamics of the distress component. In the current study, we compare the changes in the mean and variance of functional connectivity and small-worldness parameter over 3 min of resting state EEG to analyze the fluctuation in transient stable states, and network structure. On comparing these measures between healthy controls and patients experiencing low and high levels of distress due to a continuous ringing in the ear (tinnitus), we observe an increase in fluctuation between transient stable states characterized by an increase in both variance of functional connectivity and the small-worldness parameter. This results in a possible increase in degrees of freedom leading to a paradoxical equilibrium of the network structure in highly distressed patients. This may also be interpreted as a maladaptive compensation to look for information in order to reduce the hyper-salience in highly distressed individuals. In addition, this is correlated with the amount of distress only in the high distress tinnitus group, suggesting a catastrophic breakdown of the brain's resilience. Distress not only accompanies tinnitus, but other disorders such as somatic disorders, fibromyalgia, post-traumatic stress disorder, etc. Since the current study focuses on a disorder-general distress symptom, the methods and results of the current study have a wide application in different neuropathologies.
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http://dx.doi.org/10.1016/j.pnpbp.2018.01.025DOI Listing
June 2018

The neural correlates of the unified percept of alcohol-related craving: a fMRI and EEG study.

Sci Rep 2018 01 17;8(1):923. Epub 2018 Jan 17.

Lab for Clinical & Integrative Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at, Dallas, USA.

Alcohol addiction is accompanied by aberrant neural activity. Previously, task-based fMRI and resting-state EEG studies have revealed that craving, a critical component of addiction, is linked to abnormal activity in cortical regions including the dorsal anterior cingulate cortex (dACC), nucleus accumbens (NAcc), posterior cingulate cortex (PCC) and pregenual anterior cingulate cortex (pgACC), etc. In this study, we combine these two imaging techniques to investigate a group of alcohol-addicted patients and provide convergent evidence for the neural correlates of craving not only in alcohol but substance abuse in general. We observe abnormal BOLD signal levels in the dACC, NAcc, pgACC, PCC, amygdala, and parahippocampus (PHC) in a cue-reactivity fMRI experiment. These findings are consistent with increased beta-band activity in the dACC and pgACC in resting-state EEG. We further observe desynchronization characterized by decreased functional connectivity in cue-based fMRI and hypersynchronization characterized by increased functional connectivity between these regions in the theta frequency band. The results of our study show a consistent pattern of alcohol craving elicited by external cues and internal desires. Given the advantage of superior spatial and temporal resolution, we hypothesize a "central craving network" that integrates the different aspects of alcohol addiction into a unified percept.
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http://dx.doi.org/10.1038/s41598-017-18471-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772563PMC
January 2018

Adaptive and maladaptive neural compensatory consequences of sensory deprivation-From a phantom percept perspective.

Prog Neurobiol 2017 06 11;153:1-17. Epub 2017 Apr 11.

Lab for Clinical & Integrative Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, USA. Electronic address:

It is suggested that the brain undergoes plastic changes in order to adapt to changing environmental needs. Sensory deprivation results in decreased input to the brain leading to adaptive or maladaptive changes. Although several theories hypothesize the mechanism of these adaptive and maladaptive changes, the course of action taken by the brain heavily depends on the age of incidence of damage. The growing body of literature on the topic proposes that maladaptive changes in the brain are instrumental in creating phantom percepts, defined as the perception of a sensory experience in the absence of a physical stimulus. The current article reviews the mechanisms of adaptive and maladaptive plasticity in the brain in congenital, early, and late-onset sensory deprivation in conjunction with the phantom percepts in the different sensory domains. We propose that the mechanisms of adaptive and maladaptive plasticity fall under a universal construct of updating hierarchical Bayesian prediction errors. This theory of the Bayesian brain hypothesizes that the brain constantly compares its internal milieu with changing environmental cues and either adjusts its predictions or discards the change, depending on the novelty or salience of the external stimulus. We propose that adaptive plasticity reflects both successful bottom-up compensation and top-down updating of the model while maladaptive plasticity reflects failure in one or both mechanisms, resulting in a constant prediction-error. Finally, we hypothesize that phantom percepts are generated by the brain as a solution to this prediction error and are thus a manifestation of unsuccessful adaptation to sensory deprivation.
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http://dx.doi.org/10.1016/j.pneurobio.2017.03.010DOI Listing
June 2017

Dentists' Knowledge, Attitude and Practice in Treating Patients Taking Oral Antithrombotic Medications - A Survey.

J Clin Diagn Res 2017 Jan 1;11(1):ZC88-ZC91. Epub 2017 Jan 1.

Senior Lecturer, Department of Oral and Maxillofacial Surgery, Sri Ramachandra University , Chennai, Tamil Nadu, India .

Introduction: India lists high on patients suffering from diabetes, hypertension, stroke and myocardial infarction. Hence, a large proportion of the population is on long term Oral Antithrombotic Medications (OAM). Though several guidelines exist on dental management of these patients, previous surveys have shown variation among the dentists.

Aim: The purpose of this study was to assess the knowledge, attitude and practice of dentists in Chennai, India, towards dental management of patients taking OAM using a questionnaire survey.

Materials And Methods: The survey was conducted among 256 dentists in Chennai, India using a printed questionnaire containing 16 questions, at their university location. Descriptive statistical analysis was used to analyze the data.

Results: Of the final population of dentists who were included in the survey (n =212), majority of them were aware about drugs such as warfarin and aspirin compared to other newer drugs (dabigatran, rivaroxaban). Most participants took physician's opinion before proceeding with any invasive dental procedure and thromboembolic events were their major concern while treating patients on OAM.

Conclusion: The survey revealed dentists are knowledgeable about management of patients on OAM. However, they tend to overestimate the bleeding risk, thus being cautious in their treatment approach. Based on the results of the study, the authors suggest that continuing dental education programs and further training on management of such medically complex patients will be beneficial in order to provide optimum dental care to people taking OAM.
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http://dx.doi.org/10.7860/JCDR/2017/23648.9236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324504PMC
January 2017

Evidence for Behaviorally Segregated, Spatiotemporally Overlapping Subnetworks in Phantom Sound Perception.

Brain Connect 2017 04;7(3):197-210

1 Laboratory for Clinical and Integrative Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas , Richardson, Texas.

One of the most intriguing questions in neuroscience is to understand the mechanism of information transfer between different brain areas. Recently, network theory has gained traction and is at the forefront of providing a possible explanation to not only the mechanism of information transfer but also in the identification of different neuropathologies. The perception of a phantom ringing in the ear called tinnitus, similar to other neuropathologies, has been shown to be accompanied by aberrant functional connectivity between different brain areas. Although, there have been independent studies showing that specific groups of areas encode individual symptoms of tinnitus, there has not been one study to show that tinnitus is the unified percept of distinguishable subnetworks encoding different behavioral aspects. This study combines resting-state functional connectivity obtained from the source-localized electroencephalography of 311 tinnitus patients and 264 controls, and a k-fold cross-validation machine learning algorithm to develop a predictive model that verifies the presence of behaviorally specific, spatiotemporally overlapping subnetworks in tinnitus. This reorganization is found to be exclusive to tinnitus, even when compared to physiologically similar disorders such as chronic pain, with each behavioral symptom having a unique oscillatory signature. This frequency-specific transmission of information, called multiplexing, enables different types of information to be carried between two brain regions through the same anatomical connection. In addition to understanding the efficient compensation mechanism of the brain in the presence of multisymptom disorders, the exclusivity of the prediction model presents an encouraging possibility for an objective neural marker for tinnitus.
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http://dx.doi.org/10.1089/brain.2016.0459DOI Listing
April 2017

Robustness and dynamicity of functional networks in phantom sound.

Neuroimage 2017 02 18;146:171-187. Epub 2016 Apr 18.

Lab for Clinical & Integrative Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, USA. Electronic address:

Phantom sound perception is the perception of a sound in the absence of a corresponding external sound source. It is a common symptom for which no treatment exists. Gaining a better understanding of its pathophysiology by applying network science might help in identifying targets in the brain for neuromodulatory approaches to treat this elusive symptom. Brain networks are commonly organized as functional modules which have a densely connected core network coupled to a communally-organized peripheral network. The core network is called the rich club network and the peripheral network is divided into the feeder and local networks. In current study, we investigate the effects of virtual lesions on the endogenous dynamics, complexity and robustness of the remaining brain. It is hypothesized that depending on whether nodes is functionally central to the network or not, the robustness and dynamics of the network change when a lesion in introduced. We therefore investigate the effect of introducing a virtual focal lesion randomly to different nodes is in the tinnitus network and contrast it to the effect of specifically targeting the nodes of the rich-club, feeder and local nodes in patients experiencing a phantom sound (i.e. tinnitus). The tinnitus and control networks were computed from the source-localized EEG of 311 tinnitus patients and 256 control subjects. The results of the current study indicate that both the tinnitus and control networks are robust to the attack on random and rich club nodes, but are drastically modified when attacked from the periphery, especially while targeting the feeder hubs. In both the tinnitus and control networks, feeder nodes were found to have a higher betweenness centrality value than the rich club nodes. This shows that the feeders have a larger influence on the information transmission through the brain than the rich club nodes, by transferring information from the peripheral communities to the core. Further, evidence for the theoretical model of a multimodal tinnitus network is also presented showing that the tinnitus network is divided into individual, separable modules each possibly encoding a different aspect of tinnitus. The current study alludes to the concept that the efficient modification of the tinnitus network is theoretically possible by disconnecting the individual communities from the core of the pathological network.
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http://dx.doi.org/10.1016/j.neuroimage.2016.04.033DOI Listing
February 2017

Emerging hubs in phantom perception connectomics.

Neuroimage Clin 2016 4;11:181-194. Epub 2016 Feb 4.

Lab for Clinical & Integrative Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, USA. Electronic address:

Brain networks are small-world networks typically characterized by the presence of hubs, i.e. nodes that have significantly greater number of links in comparison to other nodes in the network. These hubs act as short cuts in the network and promote long-distance connectivity. Long-distance connections increase the efficiency of information transfer but also increase the cost of the network. Brain disorders are associated with an altered brain connectome which reflects either as a complete change in the network topology, as in, the replacement of hubs or as an alteration in the connectivity between the hubs while retaining network structure. The current study compares the network topology of binary and weighted networks in tinnitus patients and healthy controls by studying the hubs of the two networks in different oscillatory bands. The EEG of 311 tinnitus patients and 256 control subjects are recorded, pre-processed and source-localized using sLORETA. The hubs of the different binary and weighted networks are identified using different measures of network centrality. The results suggest that the tinnitus and control networks are distinct in all the frequency bands but substantially overlap in the gamma frequency band. The differences in network topology in the tinnitus and control groups in the delta, theta and the higher beta bands are driven by a change in hubs as well as network connectivity; in the alpha band by changes in hubs alone and in the gamma band by changes in network connectivity. Thus the brain seems to employ different frequency band-dependent adaptive mechanisms trying to compensate for auditory deafferentation.
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http://dx.doi.org/10.1016/j.nicl.2016.01.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761655PMC
December 2016

Graph theoretical analysis of brain connectivity in phantom sound perception.

Sci Rep 2016 Feb 2;6:19683. Epub 2016 Feb 2.

Lab for Clinical &Integrative Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, USA.

Tinnitus is a phantom sound commonly thought of to be produced by the brain related to auditory deafferentation. The current study applies concepts from graph theory to investigate the differences in lagged phase functional connectivity using the average resting state EEG of 311 tinnitus patients and 256 healthy controls. The primary finding of the study was a significant increase in connectivity in beta and gamma oscillations and a significant reduction in connectivity in the lower frequencies for the tinnitus group. There also seems to be parallel processing of long-distance information between delta, theta, alpha1 and gamma frequency bands that is significantly stronger in the tinnitus group. While the network reorganizes into a more regular topology in the low frequency carrier oscillations, development of a more random topology is witnessed in the high frequency oscillations. In summary, tinnitus can be regarded as a maladaptive 'disconnection' syndrome, which tries to both stabilize into a regular topology and broadcast the presence of a deafferentation-based bottom-up prediction error as a result of a top-down prediction.
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http://dx.doi.org/10.1038/srep19683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735645PMC
February 2016
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