The CCNC has various ongoing studies. For more information on the current projects in the lab or to find contact information to participate in a study, please see the information below.
Current Studies
What: Participation involves interviews about your past mental health, tests of concentration and memory, and completing two decision-making computer task involving making decisions such as choosing between gamble options and risking potential reward and loss in an MRI scanner.
Who: Currently recruiting individuals with Schizophrenia and non-clinical control subjects with no history of mental health issues.
Where: This study takes place across two visits, the 1st may be at Goodman Hall in Indianapolis or IU-Bloomington, the 2nd visit must be at IU-Bloomington.
For more info, visit https://legacy.indianactsi.
If interested in partipating, please contact iubccnc@indiana.edu
Cannabis use represents a significant and increasing public health concern as social acceptance accompanies legalization of this drug for medicinal and recreational purposes. These factors make understanding the health consequences of cannabis urgent and critical. Cerebellar Biobehavioral Markers in Cannabis Users is an ongoing study that will compare cannabis users and non-users on neurobiological and behavioral measures of cerebellar function, functional magnetic resonance imaging (fMRI) task-related effective connectivity, and cerebellar regional connectivity to cortical resting state networks.
This study will measure resting state functional connectivity (rsFC) between cerebellum sub-regions and established cortical resting state brain networks (RSNs). The project will also test whether cerebellar fMRI activation during cerebellar-dependent delay eyeblink conditioning (dEBC) is reduced in cannabis users; and whether task-based cerebellar activations produce different patterns of RSN connectivity that are differentially sensitive to cannabis use. Lastly, we will test the sensitivity of a set of cerebellar-dependent behavioral tasks to cannabis use.
The results of this research could be utilized in a wide range of studies, including longitudinal studies of high risk groups and cannabis users which would be critical for future research projects, direct administration of cannabis compounds in humans, studies of comparable measures in animal models of cannabis use and consequences, genetically informed familial and twin studies and field studies of cannabis intoxication.
Converging findings from diverse levels of analysis provide compelling evidence of cerebellar abnormalities in autism spectrum disorder (ASD), including decreased Purkinje cell numbers, neurochemical abnormalities, and increased glial cell activation. However, little is known about in vivo CB structure and function, nor the behavioral consequences of cerebellar abnormalities. This research project will test a novel theoretical model using cutting-edge brain connectivity approaches to explore pathophysiological mechanisms associated with ASD and explicitly targets the cerebellum, a brain area known to be abnormal in ASD.
We will determine how cerebellar functional and structural abnormalities contribute to documented CB-dependent task-related deficits in the disorder. Specifically, we will determine if cerebellar fMRI activation and cerebellar gray matter volumes predict CB-dependent delay eyeblink conditioning (dEBC) behavioral abnormalities in ASD.
We will also determine cerebellar task-related (dEBC) effective connectivity and resting state functional connectivity to brain regions with which it has strong neuroanatomical connections, and the extent to which connectivity is disrupted in ASD. Path analysis will be used to determine cerebellar effective connectivity and directionality. Resting state functional connectivity will be quantified using seed-based and ROI-based approaches. These functional analyses will explore cerebellar connectivity and directional influence in the context of a network and rule out models where the deficit is systemic or due to extra-CB areas.
Lastly, will determine whether core ASD symptom domains correlate with functional connectivity within specific closed-loop CB-cortical circuits.
This research could identify critical mechanisms underlying ASD by re-shaping ideas about the role of the cerebellum in the disorder’s fundamental motor, social, and cognitive deficits.
What: We’re interested in examining the underlying neuronal correlates of facial recognition utilizing electroencephalography (EEG) methods. We examine how faces correspond with brain activity and how features of personality impact the processing of face and related brain activity. Participants will also complete questionnaires and computer tasks.
Who: Individuals age 18-59 with no current debilitating medical, physical, and psychological conditions.
Where: This study takes place at IU-Bloomington.
Though the precise etiology of schizophrenia remains unclear, exogenous influences such as childhood adversity, elevated basal stress hormones, and stress reactivity during critical periods increase psychosis risk 2-5 fold. Moreover, emerging evidence indicates that the stress response is modulated by endocannabinoids. Such findings are especially interesting given evidence that adolescent cannabis use hastens psychotic disease onset and exacerbates symptom severity. However, the mechanisms by which childhood adversity affect the endocannabinoid and stress response systems and how adversity-induced perturbations in these systems affect behavior are unknown.
Cerebellar circuits and related behaviors are especially well-suited to investigate these effects because the cerebellum is (a) highly susceptible to stress due to its protracted developmental window, (b) densely populated with endocannabinoid receptors, and (c) has been implicated in schizophrenia, as is the endocannabinoid system. In particular, delayed eye-blink conditioning is a sensitive measure of cerebellar function that is modulated, perhaps in a sex-specific manner, by endocannabinoid signaling. Delayed eyeblink conditioning is robustly impaired in individuals with schizophrenia and their relatives, suggesting that this task captures a neural deficit inherent in psychosis.
This study, led by graduate student Alexandra Moussa-Tooks, hypothesizes that early life stress in rat pups will result in long-term down-regulation of the cerebellar endocannabinoid system and this will be reflected by deficits in delay eyeblink conditioning in adulthood. This question is being addressed through two specific aims, which: (1) test the hypothesis that limited bedding ELS from PND2-9 leads to long-term down-regulation of cerebellar endocannabinoids at PND70 and (2) will test the hypothesis that ELS-induced endocannabinoid aberrations will predict EBC performance.
The impact of these results would be significant for the field, as they would (a) link perturbations in a well-defined neural circuit to behavioral deficits (i.e., EBC), demonstrating for the first time that early life stress down-regulates the endocannabinoid system within the cerebellum, inducing deficits in a cerebellar-dependent task and (b) unveil novel therapeutic targets that have sound translational power due to the ecological validity of the animal model chosen and conservation of the circuit under investigation across species.
Graduate student Nancy Lundin is leading a series of collaborative projects focused on characterizing semantic, phonemic, and organizational aspects of speech in individuals across the psychotic spectrum.
These projects focus on data from the verbal fluency task (VFT) and free speech discourse samples. In VFT, individuals are asked to name items from a particular category (e.g., “animals”) or words that begin with a certain letter (e.g., “S”) in a short time period. Task performance requires executive function ability, semantic memory, and adequate processing speed, and performance is often reduced in individuals with psychosis. We apply automated techniques to VFT data to measure the semantic and phonemic clustering of responses and examine individuals’ ability to efficiently search through memory similar to the ways in which animals forage for food. We also use fMRI to investigate the neural mechanisms of clustering and switching in VFT, including the specific role of the cerebellum. Lastly, we analyze linguistic cohesion in discourse samples from individuals with psychosis to quantify one’s tendency to make connections between ideas that promote effective communication.
Overall, we combine theories and methods from fields of psychopathology, neuroscience, and cognitive science to characterize thought disorder and further our understanding of the cerebellum’s role in fluid linguistic processes.
Lab Techniques
Methods
The CCNC uses a broad range of methods, including behavioral testing, diagnostic interviewing, cognitive and neurological assessment, and neuroimaging and neurostimulation techniques.Electroencephalography (EEG) is a technique used to measure brain activity. Sensors on the scalp detect weak voltage fluctuations that arise from the summation of neural activity, specifically post-synaptic potentials largely from cortical pyramidal cells oriented in the same direction. EEG is used to measure neural dynamics on a millisecond-level scale while individuals are resting and/or performing a task (e.g., working memory, language, auditory tasks). Some benefits of EEG are its noninvasive and relatively inexpensive nature as well as its precise temporal resolution. A limitation of EEG is its poor spatial resolution (locating where in the brain the activity is coming from) relative to techniques such as functional magnetic resonance imaging (fMRI).
Common methods of analyzing EEG data include: 1) event-related potentials (ERPs), or peaks in neural activity time-locked to stimuli (e.g., pictures, sounds), and 2) time-frequency analysis, or examining the strength and synchrony of neural activity in particular frequencies (e.g., alpha activity is considered to be synchronized neuronal activity oscillating around 8-13 Hz). EEG can be useful in studying basic neural functioning in healthy humans as well as in detecting differences in cognitive and sensory processes across individuals with psychopathology. Common applications of EEG in clinical settings are characterizing seizures in individuals with epilepsy and aiding in diagnosing sleep disorders.
Magnetic resonance imaging (MRI) is a noninvasive technique used to produce three dimensional images of tissue structures and to observe various physiological functions. The MRI produces a strong magnetic field, and the protons within the body of a subject must align with this field. During the imaging process, a subject is placed under a large magnetic field and must remain very still in order to capture clear images of the brain.
One specific type of MRI is functional magnetic resonance imaging (fMRI), which allows for observation of both neural structure and function. While a subject performs specific cognitive tasks in the MRI scanner, it enables researchers to determine which brain regions are activated by detecting changes in neural blood flow. When a brain region becomes more active, more blood also flows to that region. Blood-oxygen-level dependent (BOLD) signals produced by fMRI measure the changes in blood flow to certain areas of the brain while performing a task. fMRI can also measure neural activity via BOLD signal when a subject is not engaged in a specific task (resting state fMRI)
Some advantages of MRI (and fMRI) is its noninvasive nature, allowing subjects to be safely scanned without risks of radiation, and its high degree of spatial resolution which provides better tissue contrast than other imaging modalities. For clinical uses, this high spatial resolution is key to making many different psychological and physiological diagnoses. In research, fMRI also has the advantage of detecting both altered brain activation patterns and altered brain connectivity. However, BOLD signal is only an indirect measure of brain activity, and may be influenced by a variety of other factors. Also, fMRI tends to have poorer temporal resolution because the blood flow changes lag behind the electrical communication between neurons.
Magnetic resonance spectroscopy (MRS), also termed nuclear magnetic resonance (NMR) when not in vivo, is a neuroimaging technique that quantifies the concentration of select brain metabolites that are highly abundant, including compounds such as glutamate, phenylalanine, taurine, creatine, choline, and GABA. Metabolites are identified by their chemical shifts. Chemical shifts are determined by deflections of applied magnetic field gradients and radio frequencies at which hydrogen protons resonate within a given compound or chemical environment. Phosphorous, sodium, carbon, and fluorine are also often used to characterize resonance frequencies. MRS data is typically measured from a small three-dimensional portion of the brain, or “voxel”, selected by the researcher.
Although MRS has low spatial and temporal resolution, it can be a valuable non-invasive technique. In addition to identifying time- and psychopathology-related metabolite differences, MRS is commonly used to identify tumors, neural trauma, and metabolic disorders.
Diffusion tensor imaging (DTI) is a neuroimaging technique used to depict the white matter anatomy of the brain. It is currently the only measure that allows for visualization of white matter in vivo. Images are created based on the diffusion of water molecules, utilizing a process called tractography to select and follow the direction of neuronal tracts within the brain. Due to DTI’s high sensitivity to micro properties of tissues, DTI has become increasingly popular for both clinical and research purposes.
Transcranial direct current stimulation (tDCS) is a non-invasive neurostimulation technique. tDCS can be used to indirectly induce excitation (termed “anodal” stimulation) or inhibition (termed “cathodal” stimulation) of brain regions. This is thought to occur by changing the threshold at which large groups of neurons fire. tDCS is accomplished by placing thin, wide sponge electrodes soaked in saline (i.e. salt solution) on the scalp or other parts of the body. The active and reference electrodes are configured to send a weak excitatory or inhibitory current through the scalp and skull to a brain region of interest. tDCS stimulation is 1000 times smaller than the strength of a static shock, like that received when you touch a metal doorknob after dragging your feet on a carpet.
tDCS can be used with behavioral, neuroimaging, or cognitive tasks to determine the role of various neural regions in task performance by attempting to improve or dampen participant performance/ability. Moreover, tDCS can be used in both healthy populations and individuals with psychopathology to understand differences in the contribution of neural regions in various diagnostic/demographic groups. Because tDCS is such a new technique, its mechanisms of action and the extent of its effects are not yet fully understood.
Population
The CCNC is interested in understanding psychosis and related disorders. Our studies often recruit individuals with schizophrenia, bipolar disorder, schizotypal personality disorder, past and present cannabis users, and relatives. We are so thankful to the individuals who participate in our studies and their families!Schizophrenia is a mental health condition characterized by several symptoms which may occur in a variety of combinations. The two cardinal symptoms of schizophrenia, and psychotic disorders in general, are delusions and hallucinations. Delusions are adamant beliefs that are typically not susceptible to conflicting evidence, and can be paranoid, grandiose, referential, religious, or somatic in nature. Hallucinations are experiences involving the conscious perception of stimuli (e.g. hearing voices, seeing shadow figures) that are not present or perceived by other people.
Several other symptoms are typical in psychotic disorders and schizophrenia. Disorganized speech and thinking may be observed as loose-associations, tangentially, and incoherence during discussion. Movement can be abnormal or uncoordinated, and in some cases catatonic (e.g. lack of movement or stereotyped movements).
Schizophrenia is also associated with a cluster of negative symptoms, which are the absence of typical qualities such as motivation to achieve goals, interest in socialization, pleasure in enjoyable activities, self-produced amount of speech, and emotion expressivity in appearance and voice.
While schizophrenia is often considered a “severe mental illness”, the impacts of schizophrenia may occur anywhere along a spectrum of impairment. For more information about schizophrenia according to the National Institute of Mental Health, see the links below:
Bipolar disorder is a mental health condition characterized by several days of mood irregularity, usually in the form of having “highs” and “lows.” Periodic episodes of mania are characteristic of this disorder, typically involving extremely positive feelings or intense anger, accompanied by excessive talkativeness, overabundance of energy, decreased need for sleep, difficulty concentrating or staying on-track, racing thoughts, and increased engagement in activities. During these periods of mania, individuals may also engage in risky activities that they normally would not, due to the potential for long-term problems (e.g., reckless spending, risky sexual behavior).
Bipolar I disorder is considered more severe due to periods of mania, while Bipolar II disorder is associated with periods of hypomania, or “lesser mania” lasting only several days or causing less impaired daily functioning. While periods of depression are common in Bipolar disorder, they are not required for a diagnosis. Some people with bipolar disorder also experience psychotic symptoms such as having hallucinations or odd/unrealistic beliefs during episodes of mania or depression.
While bipolar disorder is often considered a “severe mental illness,” the impact of the disorder depends on the individual. For more information about bipolar disorder, visit the National Institute of Mental Health.
Cannabis, also known as marijuana, is a substance derived from the cannabis sativa plant and its medical and recreational use has become increasingly popular over recent years. Common uses of cannabis include treating anxiety, pain, insomnia, and other conditions. The main chemical compound from which cannabis derives its psychoactive properties from is delta-9-tetrahydrocannabinol (THC). The effects of cannabis depend on the individual and the method through which it is consumed (smoking versus oral consumption). Some common effects include: relaxation, euphoria, altered sensory and time perception, and increased appetite. In larger doses, cannabis may also induce psychotic-like experiences such as hallucinations, delusions, and a loss of identity. Within the brain, THC attaches to and activates cannabinoid receptors, which results in the variety of effects cannabis has on cognitive processes and behavior. THC also impacts the brain’s reward system, consequently providing the “high” that many people who use cannabis experience.
Cannabis use may progress to cannabis use disorder in some individuals; research suggests that up to 30% of people who use cannabis will develop some form of use disorder. Cannabis dependence occurs when the brain adapts to high quantities of cannabis over time through reducing its sensitivity to cannabinoid neurotransmitters, and cannabis addiction may occur if an individual cannot stop their use of cannabis even if it interferes in interpersonal, occupational, and/or academic areas of life. Over the last couple of decades, cannabis potency is on the rise, with average THC content in present day samples of 15% compared to 4% in the 1990s. Rising potency of cannabis may lead to more severe effects and consequences following use, especially for younger individuals.
For more information on cannabis and its effects, please visit the National Institute of Drug Abuse.
Autism Spectrum Disorder is a developmental disorder that is characterized by deficits in social communication and interactions. In the U.S., the frequency of autism spectrum disorder is about 1% of the population. Autism Spectrum Disorder is said to be a developmental disorder because symptoms are present in the early developmental period. These symptoms include deficits in social communication and maintenance of relationships as well as restrictive and repetitive patterns of behavior. Symptoms are typically recognized during the second year of life but may be seen earlier. The first symptoms of autism spectrum disorder involve a delayed language development and lack of social interests.
Autism is known as a spectrum disorder because the symptoms include a wide range of severities. These social deficits range from failure to initiate a normal back-and-forth conversation to severe deficits in verbal and nonverbal communication skills. The restricted and repetitive behaviors also range from an inability to switch between activities to an inflexibility of behavior and extreme difficulty coping with change. Some restricted and repetitive behaviors include repetition of certain motor movements (e.g., finger flicking), repetitive use of objects, repetitive speech, or a fascination with certain routines and interests (e.g., preoccupation with vacuum cleaners, writing out time tables).
Currently, as many as 15% of cases of autism spectrum disorder appear to be associated with a known genetic mutation. Autism spectrum disorder is also diagnosed four times more often in males than females. Treatment for autism spectrum disorder should begin as soon as possible after diagnosis. Early treatment for autism spectrum disorder is important as proper care can reduce individuals’ difficulties while helping them learn new skills and make the most of their strengths. There are many social services programs and other resources that can help. Here are some tips for finding these additional services:
Past Studies and Collaborations
What: There are currently 4 studies that seek to understand the effects of transcranial direct current stimulation on cerebellar function. Participants may or may not recieve a small amount of stimulation (smaller than 1000th the strength of a static shock) and will be asked to complete questionnaires.
For more information on each of these studies, visit the links below.
- A Study on Touch Perception
- Effects of Cerebellar Stimulation on Postural Sway
- Effects of Varying Doses of Transcranial Direct Current Stimulation on Neurotransmitter Levels
- Investigation of Cerebellar Stimulation on Information Processing
Who: Current IU undergraduates with no current psychiatric diagnoses or history of serious medical illnesses, no history of seizures, or neurostimulation.
Where: Visits will be completed at the Bloomington Lab.
What: We’re interested in how the brain processes and perceives information, especially sounds. Participation involves questionnaires, structured interviews, and pen and paper tests of memory, concentration, and thinking ability, coordinated body movements, motor tests, and computer assessments.
Who: Individuals age 18-55 with a diagnosis of schizophrenia, first degree relatives of individuals with schizophrenia, and individuals with no current psychiatric diagnoses or history of serious medical illnesses.
Where: Initial visits may be in both sites, while our returning visits (testing sessions) must be at Larue Carter Memorial Hospital.
If interested in participating, please contact the Bloomington or Indianpolis Lab.