Prenatal Exposure to SSRIs May Be Linked to Changes in Infant Brain Development

MedicalResearch.com Interview with:

Jiook Cha, PhD Assistant Professor Division of Child and Adolescent Psychiatry  Columbia University Medical Center  New York, NY 10032

Dr. Jiook Cha

Jiook Cha, PhD
Assistant Professor
Division of Child and Adolescent Psychiatry
Columbia University Medical Center
New York, NY 10032

MedicalResearch.com: What did we already know about the connection between maternal SSRI use during pregnancy and infant brain development, and how do the current study findings add to our understanding? What’s new/surprising here and why does it matter for mothers and babies?

Response: Prior studies have shown mixed results in terms of the associations between maternal SRI use during pregnancy and offspring’s brain and cognitive development. Neurobiological studies with animal models suggest that SSRI use perturbs serotonin signaling and that this has important effects on cognitive development (a study conducted an author of this paper, Jay Gingrich, MD, PhD: Ansorge et al., 2004, Science). The human literature has been more mixed in terms of the associations of prenatal exposure to SSRI with brain and cognitive development.

In our study, we used neonatal brain imaging because this is a direct, non-invasive method to test associations between SSRI use and brain development at an early developmental stage, limiting the effects of the post-natal environment. In our study, we had two different control groups, that is, a non-depressed SSRI-free group (healthy controls), and depressed but SSRI-free (SSRI controls) group. Also, in our study we used rigorous imaging analytics that significantly improve the quantitative nature of MR-derived signals from the brain structure using two of the nation’s fastest supercomputers (Argonne National Laboratory and Texas Advanced Computing Center) and allows robust reconstruction of brain’s grey and white matter structure in the infants’ brains.

We report a significant association of prenatal exposure to SSRI with a volume increases within many brain areas, including the amygdala and insula cortex, and an increase in white matter connection strength between the amygdala and insular cortex. We were surprised by the magnitude of the effects (or the statistical effect size), compared with other brain imaging studies in psychiatry with children or adults’ brains. Importantly, it should be noted that our estimates of brain structure are still experimental and for research-purpose only. This means that our data need to be replicated and rigorously tested against confounders in order to make a firm conclusion. While our study suggests a “potential” association between prenatal exposure to SSRI and a change in fetal or infant brain development, we still need more research. 

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Which Brain Circuits Determine Maternal Behavior?

MedicalResearch.com Interview with:
“Mother and Child” by Mary Cassatt (American, Pittsburgh, Pennsylvania 1844–1926 Le Mesnil-Théribus, Oise) via The Metropolitan Museum of Art is licensed under CC0 1.0Yi-Ya Fang

NYU School of Medicine
Dayu Lin, PhD
Neuroscience Institute, New York University Langone School of Medicine,  Department of Psychiatry,
Center for Neural Science
New York, NY

Response: Maternal behaviors are essential for survival of offspring across mammalian species. In rodents, mothers show several characteristic pup caring behaviors including grooming pups, crouching over pups and approaching and retrieving pups. Decades of research has been trying to understand how the neural circuit is wired to generate these elaborate maternal behaviors. Medial preoptic area (MPOA), which is located at anterior part of hypothalamus, has been indicated to be important for maternal behaviors. Many studies consistently found deficits in maternal behaviors after damaging the MPOA. To dissect the maternal circuits in the brain, we looked into the properties of the Esr1+ cells.

In this study, we identify estrogen receptor α (Esr1) expressing cells in MPOA as key mediators of pup approach and retrieval. We focused on Esr1 (Esr1) expressing cells in the MPOA since estrogen has been shown to facilitate maternal behaviors, presumably through its action of estrogen sensing cells. We found that reversible inactivation of MPOA Esr1+ cells impairs maternal behaviors whereas optogenetic activation of MPOA Esr1+ cells induces immediate pup retrieval. Additionally, we found that MPOA Esr1+ cells are preferentially activated during maternal behaviors, and the cell responses changed across reproductive states. Tracing studies revealed that MPOA Esr1+ cells project strongly to ventral tegmental area (VTA), a region that has been indicated in motivation and reward. Specifically, MPOA Esr1+ cells provide strong inhibitory inputs preferentially to the GABAergic cells in the VTA, which in turn could disinhibit the dopaminergic cells.  VTA dopaminergic cells are highly activated during maternal behaviors.

Altogether, our study provides new insight into the neural circuit that generates maternal behaviors.

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How Does the Brain Switch Between Automatic and Controlled Decision Making?

MedicalResearch.com Interview with:
Ksenija Marinkovic and Lauren Beaton

Psychology Department – College of Sciences Spatio-Temporal Brain Imaging Lab Center for Clinical and Cognitive Neuroscience
San Diego State University
San Diego CA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In general, we subjectively perceive our actions to be under our deliberate and voluntary control. However, our results are consistent with other accruing evidence suggesting that a large portion of our behavior is automatic and not accessible to conscious experience. The automatic processing primarily underlies predictable daily routines when we seem to be on an “auto-pilot”. In contrast, situations that are ambiguous or that evoke incompatible response tendencies engage cognitive control which allows conscious override of the preplanned actions and results in flexible behavior. Our study used a multimodal imaging approach that combines perfect time sensitivity of magnetoencephalography (MEG) with structural magnetic resonance imaging (MRI) to investigate spatio-temporal stages of the seamless interplay between automatic and controlled processing. MEG is a highly sensitive method that records magnetic fields generated by the brain’s neural activity in real time.

Young, healthy, participants performed a version of the Eriksen Flanker task, which presents two colored squares on either side of a centrally presented target square that appears after a short delay. Participants are instructed to press a button corresponding to the color of the target square in the middle and to pay no attention to the flankers. Although participants know that the flankers are irrelevant, they are unable to disregard them deliberately. Instead, flankers trigger an automatic preparation to respond. This is particularly apparent on mismatch trials on which the flanker color is misleading and it activates the wrong hand. Target appearance overrides the initial automatic response as the response plan is switched to the other hand to make a correct response. This process reflects recruitment of cognitive control or the decision-making capacity which includes a range of functions such monitoring contextual demands, selecting the correct response, and suppressing an automatic but irrelevant action.

Our multimodal MEG imaging method has allowed us to track the neural response as the brain prepares an incorrect response to flankers and then “switches” motor preparation between hemispheres. This approach makes it possible to investigate the interplay between automatic and controlled processing and dissect decision making as it unfolds.

The addition of a moderate dose of alcohol dysregulates this frontal network involved in motor decision making, which decreases accuracy when response conflict is present and lowers neural activity reflecting cognitive control. Related to this overall decrease, and of clinical importance, is the reduced ability to employ cognitive control to refrain from drinking excessively. However, the underlying patterns of response-switching were preserved under alcohol, suggesting that alcohol primarily induces deficits upstream during decision making and not during executing motor commands.  Continue reading

Shifting Attention Causes Momentary Brain Freeze

MedicalResearch.com Interview with:

Alex Maier, PhD Assistant Professor of Psychology Assistant Professor of Ophthalmology and Visual Science Vanderbilt University

Dr. Maier

Alex Maier, PhD
Assistant Professor of Psychology
Assistant Professor of Ophthalmology and Visual Science
Vanderbilt University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We were interested in finding out about how the brain shifts attention from one location to another. We knew that when we attend a certain location, brain activity increases in a specific way. This increase in activity is how we perform better when we use attention. What we knew less about is what happens when attention moves between locations.

To our surprise, we found that there is a brief moment in between these attentional enhancements, while attention moves from one location to another, where the brain does the complete opposite and decreases its activity. Shifting attention thus has a brief negative effect on our brain’s ability to process information about the world around us.

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Adherence to HIV Treatment May Protect Brain From Further Injury

MedicalResearch.com Interview with:

Ryan Sanford

Ryan Sanford

Ryan Sanford, MEng
Department of Neurology and Neurosurgery
Montreal Neurological Institute
McGill University, Montréal, Québec, Canada
 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: With the introduction of combination antiretroviral therapy (cART) the outlook for HIV+ individuals has dramatically shifted from a fatal disease to a chronic manageable condition. However, HIV-associated neurocognitive disorders are still prevalent. The etiology of this dysfunction remains unknown. Previous work has reported progressive brain atrophy in HIV+ individuals with advanced disease and poor viral suppression, but it is unclear whether stable treatment and effective viral suppression can mitigate the progression of brain atrophy. To examine this issue, we followed well-treated HIV+ individuals with good viral suppression and well-matched controls, and assessed whether ongoing brain atrophy occurs over time.

The main finding in this study was the HIV+ participants had reduced brain volumes and poorer cognitive performance compared to the control group, but the changes in brain volumes and cognitive performance were similar between the groups.

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A Split Brain Has Two Perceptions But One Mind

MedicalResearch.com Interview with:

DR. Y. (YAÏR) PINTO Faculty of Social and Behavioural Sciences Programme group Brain and Cognition UvA

Dr. Pinto

DR. Y. (YAÏR) PINTO
Faculty of Social and Behavioural Sciences
Programme group Brain and Cognition
UvA

MedicalResearch.com: What is the background for this study?

Response: I’ve done research into patients in whom the corpus callosum was entirely removed surgically, at an adult age, to relieve epileptic seizures. The removal of the corpus callosum all but eliminates communication between both cerebral hemispheres. Therefore these patients are referred to as split-brain patients.

The canonical view of these patients is that their consciousness is split as well. That is, the notion, which is found in many textbooks and reviews, is that in a split-brain patient each hemisphere is an conscious agent, independent of the other hemisphere.

This notion is mainly based on the following key observation. When an image is presented to the left visual field, the patient indicates verbally, and with his right hand, that he saw nothing. Yet, with his left hand he indicates that he did see the object! Conversely, if a stimulus appears in his right visual field, he will indicate awareness of this stimulus when he responds verbally or with his right, yet with his left hand he will report that he saw nothing. This exactly fits the notion that in a split-brain patient the two separated hemispheres each become an independent conscious agent. The left hemisphere perceives the right visual field, controls language and the right side of the body. The right hemisphere experiences the left visual field and controls the left hand. This, and other discoveries on split-brain patients, earned Roger Sperry the nobel-prize in Medicine in 1981.

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Neuroanatomy Accounts for Age-Related Changes in Risk Preferences.

MedicalResearch.com Interview with:
Ifat Levy, PhD

Associate Professor
Comparative Med and Neuroscience
Yale School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The proportion of older adults in the population is rapidly rising. These older adults need to make many important decisions, including medical and financial ones, and therefore understanding age-related changes in decision making is of high importance. Prior research has shown that older adults tend to be more risk averse than their younger counterparts when making choices between sure gains and lotteries. For example, asked to choose between receiving $5 for sure and playing a lottery with 50% of gaining $12 (but also 50% of gaining nothing), older adults are more likely than young adults to prefer the safe $5. We were interested in understanding the neurobiological mechanisms that are involved in these age-related shifts in preferences.

An earlier study that we have conducted in young adults provided a clue. In that study, we measured the risk preference of each participant (based on a series of choices they made between safe and risky options), and also used MRI to obtain a 3D image of their brain. Comparing the behavioral and anatomical measures, we found an association between individual risk preferences and the gray-matter volume of a particular brain area, known as “right posterior parietal cortex” (rPPC), which is located at the back of the right side of the brain. Participants with more gray matter in that brain area were, on average, more tolerant of risk (or less risk averse).

This suggested a very interesting possibility – that perhaps the increase in risk aversion observed in older adults is linked to the thinning of gray matter which is also observed in elders. In the current study we set out to test this hypothesis, by measuring risk preference and gray matter density in a group of 52 participants between the ages of 18 and 88. We found that, as expected, older participants were more risk averse than younger ones, and also had less gray matter in their rPPC. We also replicated our previous finding – that less gray matter was associated with higher risk aversion. The critical finding, however, was that the gray matter volume was a better predictor of increased risk aversion than age itself.  Essentially, if both age and the gray matter volume of rPPC were used in the same statistical model, rPPC volume predicted risk preferences, while age did not. Moreover, the predictive power was specific to the rPPC – when we added the total gray matter volume to the model, it did not show such predictive power.

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Non-Invasive Interface Allows Subjects To Control Objects With Just Thoughts

MedicalResearch.com Interview with:

Bin He, Ph.D. Director, Institute for Engineering in Medicine Director, Center for Neuroengineering Distinguished McKnight University Professor of Biomedical Engineering Medtronic-Bakken Endowed Chair for Engineering in Medicine University of Minnesota, Minneapolis, MN 55455

Dr. Bin He

Bin He, Ph.D.
Director, Institute for Engineering in Medicine
Director, Center for Neuroengineering
Distinguished McKnight University Professor of Biomedical Engineering
Medtronic-Bakken Endowed Chair for Engineering in Medicine
University of Minnesota, Minneapolis, MN 55455

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This work is aimed at developing a noninvasive brains-computer interface to allow disabled patients to control their environment by just thinking about it.

We found 8 human subjects were able to accomplish 3D reach and grasp tasks without using any muscle activities but just thinking about it.

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Active Memory Blocker Prevents Experiences During Sleep From Being Remembered

MedicalResearch.com Interview with:
Roi Levy
The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center,
The Mina and Everard Goodman Faculty of Life Sciences
Bar Ilan University
Ramat Gan, Israel

MedicalResearch.com: What is the background for this study?

Response: Long-term memory after an experience takes many hours to be reach its final form. During the consolidation period, the nascent memory is labile: the consolidation can be interrupted by new experiences, or new experiences that are too insignificant to be remembered can capture the consolidation process, and thereby be remembered.

To avoid potentially maladaptive interactions between a new experience and consolidation, a major portion of the consolidation is deferred to the time in which we sleep, when new experiences are unlikely. For over 100 years, studies have demonstrated that sleep improves memory formation. More recent studies have shown that consolidation occurs during sleep, and that consolidation depends on the synthesis of products that support memory formation. Consolidation is unlikely to be shut off immediately when we are awakened from sleep. At this time, even a transient experience could capture the consolidation, leading to a long-lasting memory of an event that should not be remembered, or could interfere with the consolidation. We have identified a mechanism that prevents long-term memories from being formed by experiences that occur when awakened from sleep.

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God Activates Reward Centers In Brain

MedicalResearch.com Interview with:

Jeffrey S. Anderson, MD, PhD Director the fMRI Neurosurgical Mapping Service Principal Investigator for the Utah Functional Neuroimaging Laboratory University of Utah

Dr. Jeffrey S. Anderson

Jeffrey S. Anderson, MD, PhD
Director the fMRI Neurosurgical Mapping Service
Principal Investigator for the Utah Functional Neuroimaging Laboratory
University of Utah

MedicalResearch.com: What is your study about?

Response: Billions of people find meaning in life and make choices based on religious and spiritual experiences. These experiences range from epiphanies that change the lives of celebrated mystics to subtle feelings of peace and joy in the lives of neighbors, friends, or family members that are interpreted as spiritual, divine, or transcendent.

Astonishingly, with all we understand about the brain, we still know very little about how the brain participates in these experiences. We set out to answer what brain networks are involved in representing spiritual feelings in one group of people, devout Mormons.
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