Graduate Program in Neuroscience - Master's degree

Permanent URI for this collection

https://hdl.handle.net/11693/13952

Browse

Now showing 1 - 20 of 56

Open Access
The activation of default mode and multiple demand networks: an fMRI study on intentional and unintentional mind wandering
(Bilkent University, 2023-08) Falahat, Shahrzad; Farooqui, Ausaf Ahmed
Mind wandering or task-unrelated, self-generated thoughts happen every day in life. These thoughts can either be Unintentional or Intentional. The brain’s Default Mode (DMN) and Multiple Demand (MD) networks integrate during Mind Wandering. In this study, we conducted a functional magnetic resonance imaging (fMRI) experiment where Mind Wandering was the task. During this task’s think part, an Intentional form of Mind Wandering occurred. Meanwhile, Unintentional Mind Wandering took place during the rest part where participants rested in the fMRI machine. We aimed to see the difference in the pattern of activity in both the Default Mode and Multiple Demand Networks during the Intentional and Unintentional Mind Wandering. Our results showed that, in the Posterior Cingulate Cortex (PCC) and the left Temporoparietal Junction (TPJ) regions of the Default Mode Network, the think part provokes a stronger response than the rest part. On the other hand, the Multiple Demand network regions responded differently to the different forms of Mind Wandering. Some Multiple Demand regions, such as the left Inferior Frontal Sulcus (IFS) and the pre-Supplementary Motor Area (pre-SMA), represented a more robust response in the think part than the rest part. Meanwhile, the bi-lateral Intraparietal Sulcus (IPS) regions showed stronger activation in response to the rest part. In addition, we showed that the Language regions have a more pronounced activation in the think part than the rest part. Consequently, the Default Mode Network’s regions, some of the Multiple Demand regions, and Language regions respond more robustly to the Intentional form of Mind Wandering than the Unintentional Mind Wandering.
Open Access
Impact of the inflammatory process in the aging brain: evidence from in Vitro and Ex Vivo models
(Bilkent University, 2023-08) Aktürk, Serena Sevdiye; Adams, Michelle Marie
Aging is a complex and dynamic process that is characterized by a gradual decline over time in the physiological integrity of organisms. Several cellular mechanisms contribute to aging, including telomere shortening, damage accumulation in DNA, disabled macroautophagy, mitochondrial dysfunction, and cellular senescence. These processes, consecutively, lead to impaired cellular function, declined tissue repair, and stem cell exhaustion and are seen in the development of neurodegenerative disorders and healthy aging. One of the hallmarks of brain aging is the altered chronic inflammatory status of the brain. The over-activation and polarization of microglia, increased secretion of pro-inflammatory cytokines and reactive oxygen species, inflammasome activation, and the upregulation of the NF- κB signaling pathway are among the markers of neuroinflammation. This mechanism's anticipated effects include dysregulated nutrition sensing via the mTOR (mammalian target of rapamycin) pathway, decreased neurogenesis, and synaptic integrity over time. Another element that contributes to vulnerability to inflammation is genetic predisposition. Hence, additional research endeavors are required to investigate the influence of dietary interventions and therapeutic modalities targeting inflammation on genetic pathways. Thus, this study aimed to understand how inflammation can be triggered on different models, investigate potential inflammation-related biomarkers with meta-analysis and observe the effect of inflammation for both zebrafish primary brain cells and murine microglial cells. We conducted short-term copper sulfate treatments on both models for this objective. Moreover, to examine the effects of intermittent fasting, an mTOR downregulator, and high-fat diet, an inflammation inducer, on the brain of zebrafish at the molecular level by primary cell culture method. Finally, we applied rapamycin+DMSO treatment to primary cells to assess the possibility of reversing the progression of inflammation. The results showed that copper sulfate is an efficient oxidative stress-induced inflammatory reagent for zebrafish; however, it did not cause a direct inflammatory response in murine microglial cells. For zebrafish, in the copper sulfate+DMSO treated group, age affected Nrf2a mRNA, altering oxidative stress in old animals. Regardless of diet and treatment group, inflammation markers were higher in old animals, which underscores the association between aging and chronic inflammation. Elevated Lc3b levels in young and old animals captured that high copper concentrations can trigger autophagy. Results for neurogenesis markers revealed that overfeeding or acute inflammation could contribute to compromised neurogenesis in advanced stages of life. On the contrary, the enhanced neurogenesis potential of intermittent fasting in old animals was revealed. In conclusion, this study has demonstrated that the modulation of neuroinflammatory responses, as well as oxidative stress, neurogenesis, and autophagy, occurs in an age-related manner. Moreover, dietary or pharmaceutical interventions could yield comprehensive outcomes in perceiving the brain's neuroinflammatory profile during aging.
Embargo
The interplay of prior information and motion cues in resolving visual ambiguity in agent perception
(Bilkent University, 2023-08-06) Elmas, Sena Er; Ürgen, Burcu Ayşen
Agent perception, a complex cognitive task that involves interpreting an agent’s actions to infer their internal states and adjust our behavior accordingly, is a fundamental aspect of human cognition. Despite its importance, a significant gap persists in our understanding of how low-level factors, such as motion and form information, interact with top-down factors, such as prior information about the agents. To address this gap, we conducted two electroencephalogram (EEG) experiments investigating the interplay of prior knowledge and motion information on the temporal dynamics of agent perception in the human brain. We used human, android and robot agents engaged in various actions. The chosen agents were designed to form a set wherein form information alone could not easily resolve the ambiguity in agent identities. In the first experiment, participants were informed about agent identities be-fore the experiment (Prior Experiment), while in the second experiment, participants remained uninformed (Naive Experiment). We controlled the availability of motion information by presenting stimuli in either video and image formats. We recorded scalp EEG and utilized event-related potential (ERP) analysis and model-based representational similarity analysis (RSA) to uncover the temporal course of agent representation in the human brain. Our results revealed that the processing of agents in EEG depends on the availability of motion information and prior information. Specifically, in the Naive Experiment, agent information was available longer during the still condition than in the moving condition. In contrast, agent information was present for similar durations in still and moving conditions of the Prior Experiment. These findings suggest that prior knowledge and motion information interactively modulate the duration of the processing of agent information. Our results underscore the critical role of prior knowledge and motion cues in shaping the processing of agent information, highlighting the complex interplay between top-down modulation and bottom-up cues in driving the perception of agents and their actions. This study contributes to our understanding of the temporal dynamics of agent perception and the role of top-down and bottom-up processes in this complex cognitive task.
Open Access
It’s not the rule! rule-decodability is not limited to cognitive control-related frontoparietal regions
(Bilkent University, 2023-07) Gezici, Tamer; Farooqui, Ausaf Ahmed
Performing tasks require us to abide and apply the relevant rules to the task (ie., do not wash white clothes with coloured clothes). As we perform tasks, these rules are maintained through cognitive control processes. Functional magnetic resonance imaging (fMRI) studies have shown that rule representations are decodable in a set of regions called the multiple demands (MD) network. Another set of regions called the default mode network (DMN) decorrelate with task-related networks. However, recent studies show that rule representations are decodable in tasknegative networks such as DMN as well. The present study investigated rule decodability using multivariate fMRI analysis methods. Subjects performed an event-related rule switch fMRI experiment in which there were two rules: categorizing numbers as even/odd (parity rule) or greater/smaller (value rule) than 10. In our first analysis, these two rules were modelled based on the switch or repeat status of the specific trial. We found that on switch trials, rules were decodable across the whole brain. In contrast, on repeat trials rules could not be decoded from any brain region. Curiously, repeat trials rule classification was significantly below chance, suggesting that training the classifier on one set of patterns made them worse than chance in classifying on the remaining set. This would happen if different instances of the same rule on repeat trials may have been accompanied by very different patterns of activity. In our second analysis we investigated if rule-related patterns changed with the number of consecutive repetitions or the number of consecutive switches, e.g., if the activity-pattern related to the parity rule on the first instance of a repeat trial was different from the pattern when this rule repeated again. We found that this was indeed the case. While the same rule could not be classified much across two consecutive switch trials, the same rule could be classified nearly everywhere across two consecutive repeat trials.
Embargo
Perception of built environments and its neural modulation by the behavioral goals of the perceiver
(Bilkent University, 2023-07) Koç, Aysu Nur; Afacan, Yasemin
A scene is a view of an environment with a spatial layout one can act within. Scene perception has been studied extensively in the neuroscience literature, examining changes in neural activity across the brain and scene-selective regions (PPA, RSC, OPA), in response to various low and high-level features and tasks. The focus of the field has been mostly on outdoor scenes based on broad categorical differences (e.g. natural/man-made) or basic differences between otherwise similar indoor environments (e.g. ceiling height) and behavioral components regarding scene perception have been overlooked. Interactions with fields such as environ-mental psychology or neuroarchitecture, which could inspire a more ecologically valid study of scenes, are rare. Hereby, we investigated the perception of built environments where we spend most of our time, drew our categorization method from the architecture literature, and employed multiple tasks. The categories were elements that (i) allow our access to and circulation within environments (entrances, exits, corridors, stairs); and that (ii) do not directly aid locomotion but rather serve human needs (restrooms, eating and seating areas). FMRI scans were obtained from 23 participants as they viewed scenes from built environments and performed two tasks: a categorization task based on the main afforded action differences between the defined categories, and an approach-avoidance task where participants decided to enter the scene or not, measuring the initial action regarding an environment. Scene-selective ROIs were defined with a localizer session. Univariate analyses did not reveal strong differences between the tasks. Searchlight MVPA revealed categories, but not tasks, are classified at the whole-brain level, at the lingual and parahippocampal gyri, the SMA, and the occipital cortex. Model-based RSA at the ROI level revealed that tasks modulate activation patterns to built environments in all three ROIs, but do not entirely explain them, whereas categorical and visual models did not correlate with the activation patterns in any of these regions. We utilize an interdisciplinary perspective to scene perception to expand the ecological validity of the stimuli and task con-tent, showing that neural responses to built environments are modulated by the behavioral goals of the observer at the ROI level, and stimulus category at the whole-brain level.
Open Access
Predictive processing during novel word learning: ERP measures of vowel harmony
(Bilkent University, 2023-06) Müftüoğlu, Berrak; Kafalıgönül, Hacı Hulusi
This project investigated the effect of Turkish vowel harmony (TVH) on the acquisition of multi-syllabic words via cross-situational word learning (CSWL). CSWL is an implicit learning paradigm requiring learners to statistically track word-referent pairs across ambiguous conditions. Although there are many studies have examined certain lexical conditions that span word boundaries, within-lexical unit characteristics, such as TVH, have not been examined. We conducted 2 experiments; Experiment 1 is an internet-based experiment with Native Turkish speakers and speakers of other languages, and Experiment 2 is an EEG experiment focusing on N400 and LPC ERPs with Native Turkish speakers. In experiment 1, participants received training and recognition test phases. During training, participants were presented with novel pseudowords, both harmonious and disharmonious for TVH, with multiple referent pictures. In the recognition test, participants heard a pseudoword and were asked to select the correct referent for it. The results of the first experiment did not show a significant difference. In experiment 2, learning was additionally measured by a semantic judgment task (SJT). In the SJT, participants were presented with either a learned pseudoword or a real Turkish word, then with another real Turkish word. Their task was to indicate whether the two presented words were from the same semantic category. The recognition test results showed high accuracy, implying successful learning, with no differences among TVH conditions. The SJT results were modulated by both the novelty of the words (pseudowords vs. real words) and the harmony conditions in both behavioral and ERP measures. Specifically, harmonious words lead to N400 responses similar to real words, with no such effect on the disharmonious words. These results suggest that the phonological rules of participants’ native language had an impact on semantic consolidation.
Embargo
Behavioral and neural investigation on the effects of prior information on biological motion perception
(Bilkent University, 2023-07) Elmas, Hüseyin Orkun; Ürgen, Burcu Ayşen
The capacity to understand the actions of others, a cognitive phenomenon known as biological motion perception, is crucial for humans. Recent research demonstrates that biological motion is processed distinctively compared to the motions of inanimate objects. A dedicated brain network for processing biological motion and actions has been uncovered through fMRI studies. M/EEG studies have revealed time windows within which biological motion processing occurs. Despite these findings, a comprehensive understanding of the fundamental mechanisms driving biological motion perception, especially the effects of top-down processes, and the temporal dimension of these effects still remain unexplored. Recent evidence in visual perception suggests that prior knowledge and expectations affect visual perception; however, the generalizability of these effects to socially important stimuli, such as biological motion, is still unknown. This study aims to illuminate the effects of prior information on the behavioral and neural mechanisms of biological motion perception. To this end, we conducted a series of behavioral experiments and an EEG experiment to investigate the effects of prior information on biological motion perception. Through our behavioral experiments, we found that prior information influences the individuation process of biological motion, albeit conditionally. Specifically, this influence is observed only when the cue carries information about the type of action in the biological motion stimuli, and the reliability of the cue is high, at 75%. Our EEG experiment demonstrated that correct and incorrect prior information affects the temporal dimension of biological motion perception, suggesting an early effect of prior information during biological motion processing. More-over, a comparison of the temporal generalization matrices suggested that correct prior information accelerates biological motion perception by accelerating the for-mation of related representations in the brain relative to the neutral condition. Additionally, the temporal generalization analysis results illustrate a sequence in representations within brain activity: the representation of location information precedes the representation of action type of biological motion. These results suggest that computational models, developed to model the underlying mechanisms of biological motion perception, should consider the implications of predictive processes and their temporal dimension. Furthermore, these findings support the applicability of predictive models to not only low-level stimuli but also to higher-level stimuli.
Open Access
Investigation of how task related programs affect activation of frontoparietal regions
(Bilkent University, 2023-01) Çiftçi, İpek; Farooqui, Ausaf Ahmed
We prepare breakfast, take a shower, do grocery shopping. While completing these daily goals we don’t individually execute many components. For instance, while preparing instant coffee we sequentially execute subtask such as ’take the coffee, boil water, put coffee and water to a mug, take a spoon, mix it with spoon’ under the goal of preparing the coffee but we don’t individually execute them. We execute this whole temporally extended task as one entity which is called ’preparing instant coffee’ in this example. We execute a temporally extended, goal-directed behavior as one entity. The construction of this extended behavior in cognition is hierarchical since it consists of subtasks that complete the subgoals in different levels. For example, the step ’put coffee and water to a mug’ completes the subgoal of putting necessary ingredients together. Mixing them completes the actual goal. In terms of goal completion, former one is in a lower level than latter one. Execution of extended behavior that subsumes the entire task occurs via programs. Programs are related to the entire task. These programs are constructed in the beginning of episode. A program of a longer task requires larger programs than same but shorter task. Executing a longer task as one entity is more demanding than a shorter task. So, the program load of the longer task higher than the shorter one. it has been shown that the reaction time of the first item in a longer task is greater than the same but a shorter task [1]. A set of fronto-parietal regions (also known as Multiple Demands (MD) regions) activates in response to goal-directed tasks that require cognitive control and attention. Activation in MD regions higher for more demanding tasks. Demanding task here can be the tasks that have more working memory load or requires more cognitive control demands. In other words, a higher cognitive load is associated with higher activity in MD regions. Can it be a different cognitive load processing differently than the defined above? If the program loads differently than the typical cognitive load defined in the literature, the activity pattern in MD regions should be different than the typical effect of cognitive load in MD regions. In this study, we investigated this issue. In the experiment, participants executed 3-back task in 2 conditions. One condition had high working memory load (high cognitive control demands) and high program load. The other condition had low working memory load (low cognitive control demands) and low program load. Results showed that activity in low working memory load conditions in MD regions was higher than the activity in high working memory load condition. This indicates that the program load has different construction from working memory load because, it reflects different pattern of activity in MD regions.
Open Access
Effects of genetic liability to psychosis proneness and psychosis proneness on functional connectivity of the salience network
(Bilkent University, 2022-12) Aydoğan, İlayda; Toulopoulou, Timothea
The effect of psychosis proneness, a psychometrically defined index of subclinical psychosis, has limited research on its effect on brain connectivity in healthy populations. In addition, functional connectivity research in psychosis proneness mainly focuses on brain networks such as the default-mode network (DMN) and the central executive network (CEN) but not on the salience network (SN). On a similar note, research on genetic susceptibility to psychosis in healthy populations and the combinatory analysis between brain connectivity and genetic liability have not been explored thoroughly. This thesis assessed the relationship between psychosis proneness and genetic liability to psychosis to functional connectivity of the salience network. Seventy-two pairs of twins, siblings, and triplets were included in the analysis for genetic liability and functional connectivity. Participants’ psychosis proneness was assessed via the Community Assessment of Psychic Experience (CAPE-42) questionnaire, and genetic liability scores (PRS-SCZ) were calculated through PLINK and PRSIce-2 software. Global patterns of connectivity, seed-based connectivity, and network topology of the salience network were examined. The findings have revealed that the connectivity levels within the salience network differed in individuals with high psychosis proneness com- pared to individuals with low psychosis proneness. Further analysis has shown that PRS-SCZ did not show a significant difference between high and low psy- chosis proneness groups. The results show that connectivity levels in the salience network differ in individuals with psychometrically defined psychosis proneness. These results were not explained by differences in genetic loading among the participants.
Open Access
Working memory capacity: concurrent subtasks need not interfere
(Bilkent University, 2022-10) Şengil, Gülsüm Özge; Farooqui, Ausaf Ahmed
Any extended task episode is subsumed by goal-directed programs that hierar- chically control its execution. We investigated the relationship between working memory capacity and the control instantiated by such hierarchical task entities across four experiments. In a new extended task consisting of subtask A and subtask B, participants first memorized the orientation of subtask A lines (let’s call this event mA), then memorized subtask B lines (mB), then recalled these B lines (rB), and finally recalled A lines (rA). The task structure was: mA-mB-rB- rA. Subtask A lines were thus held in mind during the execution of subtask B. Even though participants had to remember the orientation of lines in both cases, increased WM load of lines A only affected performance on subtask A and did not affect the performance on subtask B. In Experiment 2, four trials of Exp1 were organized into a complex 4-part task with the added condition that A lines of a part be recalled not in that part but in the next part. The task structure was: mA1-mB1-rB1—mA2-mB2-rB2-rA1—mA3-mB3-rB3-rA2—mB3-rB3-rA3. Load of A lines again did not affect B lines. Crucially, load of A2 and A3 lines did not affect the recall of A1 and A2 lines, respectively. In Experiment 3, in a design similar to Exp1, time constraint on mA and mB increased the interference across concurrent subtasks. Experiment 4 showed that increasing the similarity between subtask A and subtask B of Exp1 may increase the across-subtask in terference. We show that WM information of different concurrent subtasks can be maintained separately, perhaps as part of their goal-directed programs. And, encoding to these non-interfering stores, as well as retrieval from them, might depend on attentional and time-based mechanisms.
Open Access
Peptide therapeutics to prevent protein aggregation in Huntington’s disease
(Bilkent University, 2022-09) Khan, Anooshay; Şeker, Urartu Özgür Şafak
Huntington’s disease is a progressive, autosomal dominant neurodegenerative disease caused by dramatic CAG repeat expansion in exon 1 of the Huntington (HTT) gene. More than 36 CAG repeats lead to the generation of mutant HTT (mHTT) fragments. These amino-terminal mutant HTT fragments result in misfolded proteins that give rise to oligomers and subsequent aggregate formation in relevant brain areas. Available therapies mainly focus on ameliorating the symptoms of the disease. Therefore, therapeutic interventions which can delay the onset of disease are imperative for halting disease progression. Peptide-based drug therapy provide such a platform. Previously in our lab, candidate ligand peptides were screened against both willd type (Htt-Q25) and mHTT fragments such as Htt-Q46, and Htt-Q103. This was done using different display technologies This work focuses on the in vitro characterization of those selected peptides. Fibril formation was observed in real-time using Thiofllavin T assay. Selected peptides were added to check their effect on fibril formation by change in fluorescence signal. The effect of peptides on fibril formation was also studied using Atomic Force microscopy. 3 of the 6 selected peptides (HHGANSLSLVSQD), (HGLHSMHNKLTR) and (WMFPSLKLLDYH) successfully showed a blocking in aggregation. These studies show that the selected peptides are affective for inhibiting the aggregation of fibrils in mHTT proteins.
Open Access
Neural underpinnings of biological motion perception under attentional load
(Bilkent University, 2022-06) Çalışkan, Hilal Nizamoğlu; Ürgen, Burcu Ayşen
Humans can detect and differentiate biological motion from non-biological motion stimuli effortlessly, even if the stimuli were shown as simplistic as a composition of moving dots (i.e. point-light displays [PLD]). Considering its survival and social significance, BM perception is assumed to occur automatically. Indeed, Thorn-ton and Vuong [1] showed that task-irrelevant BM in the periphery interfered with task performance at the fovea. However, the neural underpinnings of this bottom-up processing of BM lacks thorough examination in the field. Under selec-tive attention, BM perception is supported by a network of regions including the occipito-temporal, parietal, and premotor cortices. A retinotopy mapping study on BM showed distinct maps for its processing under and away from selective attention [2]. Based on these findings, we investigated how bottom-up percep-tion of BM would be processed under attentional load when it was shown away from the focus of attention as a task-irrelevant stimulus. Participants (N=31) underwent an fMRI study in which they performed an attentionally demand-ing visual detection task at the fovea while intact or scrambled PLDs of BM were shown at the periphery. Our results showed the main effect of attentional load in fronto-parietal regions; as well as, the main effect of peripheral stimuli in occipito-temporal cortex. Both univariate and multivariate pattern analysis results support the attentional load modulation on BM. Lastly, ROI results on each core node of BM processing network expanded these findings by showing that the attentional load modulation on both intact and scrambled BM stimuli were the strongest in bilateral occipito-temporal regions as compared to parietal and premotor cortices. In conclusion, BM was processed within the motion sensi-tive regions in the occipito-temporal cortex when shown away from the selective attention, and was modulated by attentional load.
Open Access
Effects of recreational cannabis use and subclinical psychosis risk on brain white matter integrity and structural connectivity in adolescence
(Bilkent University, 2022-06) Atmaca, Hande Ezgi; Toulopoulou, Timothea
The impact of cannabis use on the psychosis risk in the healthy population has been less examined in the literature. Furthermore, previous diffusion tensor imag-ing and structural connectivity studies investigating the effects of cannabis use and psychosis risk offer contradictory results. To address these gaps and inconsistencies in the literature, the author examined whether recreational use of cannabis increases the risk of subclinical psychosis. The author further ex-amined the relationship between recreational cannabis use, subclinical psychosis, and white matter microstructure or structural network connectivity. Twenty-five adolescent cannabis users and 25 demographically matched controls participated in the study. The Cannabis Experience Questionnaire (CEQ) was used to assess cannabis consumption. Subclinical psychosis was evaluated with the Community Assessment of Psychic Experience (CAPE-42) questionnaire. While ROI-based Tract Based Spatial Statistics (TBSS) was used to examine white matter integrity in specified region of interests, Structural Connectivity Analysis was performed to examine brain structural topology. White matter integrity was assessed by four diffusion tensor derived measures: fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, while structural network topology was examined by several graph-theory metrics: global efficiency, local efficiency and clustering coefficient. In order to eliminate possible confounding effects of alcohol and to-bacco use, weekly alcohol and daily tobacco consumption were also considered. The findings revealed that cannabis users scored higher on subclinical psychosis compared to non-users. ROI-based TBSS analysis indicated that cannabis use and subclinical psychosis do not affect white matter integrity in corpus collosum and superior longitudinal fasciculus. Similarly, the network connectivity parame-ters were not affected by the recreational cannabis use and psychosis risk. These results might indicate that recreational cannabis use increases the psychosis risk in adolescence, but that recreational cannabis use and subclinical psychosis risk together do not affect white matter microstructure and topology.
Open Access
Explicit and implicit measurement of mind perception in social robots through individual differences modulation
(Bilkent University, 2022-06) Saltık, İmge; Ürgen, Burcu Ayşen
The attribution of mental states to the object or subject that an individual interacts with according to its appearance or behavior is called mind perception (Gray et al., 2007). Recent research on human-robot interaction has shown that robots can create mind perceptions like other agents under certain conditions. In addition, while the two dimensions of mind perception (Agency and Experience) are mostly controlled using explicit measurement methods in the literature, the use of implicit measurement methods in the measurement of mind perception is still almost nonexistent. In addition to this fundamental gap, studies examining mind perception in robots have investigated how appearance affects mind perception, while the effect of action perception almost again has never been observed. In this context, we investigated how robots affect mind perception by manipulating differences in action and appearance. Methodologically, we conducted our study using both the explicit measurement method and the implicit measurement method due to the gap in the literature. In this study, individual difference measurement was also used to observe the causes of different attributions in mind perception to robots. In the first study, participants (N=102) evaluated how the robots' performing different actions (biological, verbal and nonverbal communicative and neutral) and appearance (humanoid and mechanical) affect mind perception; in the second study, participants (N=185) evaluated the effect of robots' actions and appearances on mind perception in terms of implicit and explicit measurement methods. In addition, 11 individual difference measures were used to observe individual differences that modulate mind perception. Looking at the results, it has been observed in both studies that the action of robots affects mind perception. In the explicit measurement method, neutral behavior was found to create less mind perception than communicative and biological action. In the implicit measurement method, differences in reaction time were observed between communicative actions and biological \& neutral actions. Individual differences that modulate the perception of the explicit and implicit mind have been observed. According to this, intentionality of behavior, theory of mind, and perception of loneliness are core modulates for explicit mind perception, while negative mood primarily modulates implicit mind perception. Looking at the results, it was observed that the perception of action had an effect on the mind perception, the implicit and the explicit mind perception showed different patterns from each other, and the individual differences predicted the pattern of implicit and explicit mind perception.
Open Access
Modulation of the neuroinflammatory response following genetic and environmental manipulations in the zebrafish (Danio Rerio)
(Bilkent University, 2022-05) Özen, Beyza; Adams, Michelle Marie
Aging is an inevitable process through which organisms experience functional and physical decline. Cellular changes such as mitochondrial dysfunction, telomere attrition, and loss of proteostasis constitute the main components of this process. One of the hallmarks of brain aging is the increased inflammatory status of the brain. This process is named neuroinflammation and is seen both in the development of neurodegenerative disorders and in healthy aging. The over-activation of microglia and astrocytes, increased secretion of pro-inflammatory cytokines and reactive oxygen species, NLRP3/NALP3 inflammasome activation, and the upregulation of NF-κB signaling pathway are among the markers of neuroinflammation. Deregulated nutrient sensing through mammalian target of rapamycin pathway(mTOR), impaired neurogenesis, and synaptic integrity over time are among the common outcomes of this process. Genetic susceptibility is also another factor to contribute the vulnerability to inflammation. Therefore, further studies are necessary to investigate the effects of the inflammation-stimulating agents and the genetic susceptibility. Thus, this study aimed to develop copper sulfate as an inflammatory stimulating agent for both zebrafish embryos and adults. For this objective, we conducted long-term and short-term copper sulfate embryo treatment studies. The gene expression results showed that the inflammatory response was quite predictable in embryos by increasing pro-inflammatory markers early on and later increasing anti-inflammatory cytokines. Secondly, we conducted copper sulfate and rapamycin treatment in very old (38 months) zebrafish animals to investigate the impact of the inflammation on mTOR signaling and synaptic integrity. The protein expression results indicated that rapamycin was an effective for mTOR suppression in very old animals but copper sulfate was not able to stimulate a robust inflammatory response. Also, synaptic integrity markers were mostly stable among treatment groups in very old animals. Finally, we used tsc2+/- adult animals and applied rapamycin treatment to very old (33 months) tsc2+/- adults to assess the effect of overactive mTOR signaling and the possibility of reversing this in the progression of inflammation. Comparatively, we wanted to understand the effect of copper sulfate exposure in very old (43 months) ztor+/- animals that have a downregulated mTOR pathway. The results showed that the rapamycin effect was not significant between wild-type and tsc2+/- animals in terms of pro-inflammatory cytokines and autophagy markers. Similarly, the copper sulfate effect was not different between wild type and ztor+/- animals for pro-inflammatory markers. However, autophagy markers decreased significantly in mutants. In conclusion, this study showed that aging affects the regulation of the inflammatory response within the brain. Also, genetic manipulations on the mTOR pathway would provide crucial insights to investigate the neuroinflammatory profile of the brain in the course of aging.
Open Access
Structural connectivity alters in pediatric systemic lupus erythematosus prior to neuropsychiatric manifestations
(Bilkent University, 2022-02) Eskandarian, Laleh; Atalar, Ergin
Systemic lupus erythematosus (SLE) is an autoimmune multi-system disorder affecting the central nervous system which may exhibit neuropsychiatric manifestations. Pediatric-onset SLE is rare and although there is an increased risk of neuropsychiatric symptoms, underlying pathological mechanisms remain poorly understood. This study explored the entire white matter network with brain structural connectivity and DTI tractography analysis to provide a better understanding of the probable connectivity alterations. Whole-brain structural connectivity and tractography of 17 pediatric-onset SLE patients without neuropsychiatric involvement (non-NPSLE) and 8 age and gender matched healthy controls were explored. To investigate the topological structure, graph theory analysis was applied. Global and nodal network features were derived by estimating structural connectivity matrices between 360 brain regions of the HCP atlas. Non-NPSLE patients demonstrated higher network characteristic path length and assortativity and lower density and global efficiency compared with healthy controls. The hubs were selected according to the strength of the nodes and their structure and distribution were changed in the patients. According to the altered hubs’ network characteristics significant modifications between HCs and non-NPSLE, along with TBSS findings, altered regions were observed in language, visual, auditory, and motor-related areas. These findings are in good agreement with WISC-IV Verbal Comprehension Index. Compared to healthy controls non-NPSLE patients showed significantly lower scores according to WISC-IV score components. To conclude, from a network and connectivity perspective, our research demonstrated an altered topological structure of the brain in non-NPSLE patients. The findings of this study provide a better understanding of the structural alterations underlying pediatric-onset non-NPSLE patients' functional and neurocognitive abnormalities.
Open Access
Neurophysiological investigation of contrast ratio effects on metacontrast masking
(Bilkent University, 2021-08) Akdoğan, İrem; Kafalıgönül, Hacı Hulusi
Visual masking has been used as an investigative tool to understand the dynam-ics of sensory and perceptual processing. Given that masking can also cause aware and unaware visual conditions, it has also found applications in visual awareness studies. Metacontrast is a common type of visual masking in which the target visibility is suppressed by presenting a following and spatially adja-cent mask. However, the neural correlates of this common masking type are still open to discussion. Accordingly, the current thesis examined the inﬂuences of mask-to-target (M/T) contrast ratio on metacontrast masking using electroen-cephalography (EEG). A contour discrimination task was employed to assess target visibility under diﬀerent M/T contrast ratios and stimulus onset asyn-chronies (SOAs). The behavioral results indicated U-shaped masking functions with strong target visibility suppression at intermediate SOA values for both low and high contrast ratios. Importantly, the contrast ratio signiﬁcantly altered the suppression amount (i.e., the amount of masking eﬀect) at these SOAs. Rely-ing on these modulations, we analyzed EEG data and focused on VAN (visual awareness negativity, around 140-200 ms and 200-300 ms) and LP (late positiv-ity, around 300-550 ms) components. In the VAN component range of 200-300 ms, we found an SOA dependency in evoked potentials. For all the component time ranges, the contrast ratio did not reveal signiﬁcant alterations in evoked po-tentials. Taken together, these ﬁndings highlight the signiﬁcant modulations of contrast ratio on metacontrast masking at intermediate SOA values. Neverthe-less, these alterations were not indicated by the studied event-related potentials and components.
Open Access
Characterizing surround suppression in motion direction perception
(Bilkent University, 2021-06) Kurt, Aslı Gül; Boyacı, Hüseyin
Visual perception is often achieved by surround modulation mechanisms, which help us pool individual information in our visual ﬁeld. This mechanism is also prominent in motion perception, namely motion discrimination. A center-surround antagonistic organization aids motion perception using these modula-tion mechanisms, which are facilitation or suppression. Decisions to which modu-lation type will take place are usually manipulated by changing size and contrast of drifting Gabor disc stimuli. Because a systematic investigation of these mech-anisms is not conducted in prior research, we have used three diﬀerent types of stimulus (small disc, annular, and large disc grating) to see whether there is a fa-cilitative or suppressive pattern between duration thresholds of these stimuli. To achieve this, we performed a behavioral study, that would assess motion discrim-ination thresholds of human participants for these stimuli via adaptive staircase procedures. Then, we looked for three possible pooling regimes by comparing duration thresholds of small disc-annular-large disc grating stimulus sets: eﬃ-cient or ineﬃcient (weak or strong suppression) pooling. We found that duration thresholds of large disc gratings were almost greater than small disc or annular gratings almost all the time in both contrast levels, which indicated a strong sup-pression. We have also conducted simulations of divisive normalization models and observed that modulation mechanisms were more prominent in simulated duration thresholds using MT parameters from literature than V1. Although previous literature suggests that MT region produces facilitative or suppressive eﬀects within itself, we are not able to postulate a speciﬁc brain region creating strong suppressive pooling we observed in our behavioral data. This is why this study is a critical next step for future neuroimaging studies.
Open Access
Effects of aging on gene expression levels of inflammatory, cytoskeletal and microglial markers in the brain using the zebrafish (Danio Rerio) model organism
(Bilkent University, 2021-01) Aydoğan, Hande Özge; Adams, Michelle Marie
Age-related cognitive decline burdens the elderly population, limiting their abil-ity to socialize and be independent. To be able to develop proper treatments, healthy aging should be examined. Previous studies focusing on healthy brain aging revealed that abnormal microglial activation was observed. Aging microglia exhibits 0partial loss of motility due to cytoskeletal changes, leading to decreases in their ability to respond to environmental cues. Thus, a more inﬂammatory phe-notype was observed in microglia. These disruptions of the previously established homeostasis in the brain could be the underlying reason for cognitive decline ex-perienced during aging. To understand these changes during aging in the brain, cytoskeletal, microglial, and inﬂammation-related markers were investigated by using both in silico and in vivo approaches. In silico analyses were performed on mice hippocampus and the whole brain revealed that the genes involved in the actin cytoskeleton reorganization (Arpc1b), neurogenesis (Erbb4), and proinﬂam-matory related pathways (Il1b, P2x7r, Elf2b) showed diﬀerential gene expression levels among diﬀerent age groups, genders, and tissue of origin. On the other hand, no diﬀerential expression was observed in microglial (Coro1a and Aif1) and anti-inﬂammatory markers (Tgfb1 and Il10). To further validate these re-sults in vivo, quantitative polymerase chain reaction (qPCR) was performed on young and old zebraﬁsh brains. According to the results, only two genes showed marginally signiﬁcant diﬀerences among young and old brains: arpc1b and p2x7r. These results collectively could mean 1) the overall microglia population does not change during aging, 2) the brain does not exhibit imbalances in terms of pro-and anti-inﬂammatory cytokines, and 3) neurogenesis. Furthermore, the signiﬁ-cant changes observed in arpc1b and p2x7r indicated the iii iv importance of the cytoskeleton and inﬂammation-related pathways in the correct functioning of the cells. Therefore, this study showed that in silico analysis are the reliable indica-tors of in vivo experiments, zebraﬁsh can be used as a gerontological model, and the importance of cytoskeleton in motile cells. However, to understand these de-scribed relations, further investigation on the protein level of these genes should be done.
Open Access
Mineralocorticoid and glucocorticoid receptors as novel targets in breast and liver cancer therapies
(Bilkent University, 2020-12) Güneş, Damla; Karakayalı, Özlen Konu
Cell signaling is a complex phenomenon and is maintained through intertwined signal transmissions within and in-between the cells. Anti-cancer therapies are often challenged by this fact due to crosstalk-associated activation of alternative survival routes. Hence, development of new treatment strategies and identification of novel prognostic markers depends on in-depth knowledge on cell signaling routes altered in cancer and possible crosstalk paths. Herein, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) signaling, two closely related members of steroid receptor hormone family, and their possible crosstalk were studied across breast and liver cancer cell lines. In breast cancer cell lines, estrogen responsive and MR expressing T47D was used in order to study possible crosstalk among Estrogen receptor (ER) and MR. MR-GR ligand aldosterone (ALDO) and ER ligand estrogen (E2) administered to breast cancer cells alone and in combination and, MR, ER and GR and their downstream signaling members were studied employing qRT-PCR and Western blot assays. Furthermore, ALDO, E2, ALDO-E2 hormone administrations were also used for cell viability assessments. Our results implied possible interactions of ALDO-E2 signaling at the level of cell viability, and at mRNA levels of progesterone receptor. In liver cancer cell lines, MR and GR was investigated as targets of a novel treatment. Liver cancer subtype hepatocellular carcinoma (HCC) has high mortality rate with limited treatment options. Multi-kinase inhibitor Sorafenib (SFB) with mild effectivity is most known systemic therapy against HCC. To potentiate the effectiveness of SFB and overcome to the crosstalk associated limitations, combinatorial drug treatment approach targeting multiple signaling modalities has been adopted in literature. Previously in our lab, SFB was combined with repurposed anti-psychotic drug TFP as a novel combinatorial treatment against hepatocellular carcinoma (HCC) and liver cancer cell lines. Cellular viability was synergistically reduced by SFB-TFP in HCC cell line Hep3B, while antagonistic effects on viability in SkHep1 was apparent. Herein, two liver cancer cell lines Hep3B and SkHep1, were used in comparison to unravel mechanism of action of SFB-TFP combination at the protein level. Apoptosis, cell cycle, PI3K/AKT/mTOR and MAPK pathways were investigated in addition to MR and GR. Our results revealed several markers indicating success of drug combinations and targeted pathways at protein level which needs to be pursued further.