Ernst Strüngmann Forum

 

Manifestations and Mechanisms of Dynamic Brain Coordination over Development

March 5–10, 2017

Frankfurt am Main, Germany

April A. Benasich and Urs Ribary, Chairpersons

Program Advisory Committee

Yehezkel Ben-Ari, INMED-INSERM, France
April A. Benasich, Center for Molecular & Behavioral Neuroscience, Rutgers University-Newark, U.S.A.
Julia Lupp, Ernst Strüngmann Forum, Frankfurt, Germany
Charles A. Nelson, Harvard University, U.S.A.
Urs Ribary, Simon Fraser University and University of British Columbia, Canada
Wolf Singer, ESI for Neuroscience in Cooperation with the Max-Planck-Society, Frankfurt, Germany
Terry Sejnowski, Salk Institute, La Jolla, CA 92037, U.S.A.

Goals

  • To extend the exploration of dynamic brain coordination and synchrony, and their underlying mechanisms, using a developmental perspective.
  • To explore the possibility that abnormalities in neuronal synchronization and dynamic integration might be causal in developmental disorders such as attention deficit hyperactivity disorder (ADHD), language-learning disorders (LLDs), schizophrenia, and autism.
  • To foster synergies and changes in research foci concerning dynamic coordination across development to move the field forward and produce a lasting, meaningful impact across the fields of behavioral and systems neuroscience, cognitive science, computational neuroscience, genetics, molecular biology, neurology, and psychiatry.
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Synchronization of oscillations among brain areas across development is thought to mediate network assembly, coordination, and plasticity and to support emerging cognition, perception, and language. This process depends crucially on ongoing neural plasticity and the exquisite sensitivity to environmental cues that characterize early brain development. Many studies suggest that dynamic coordination is a key factor in these experience-dependent changes. Exploration of how maturational trajectories of local and large-scale brain networks unfold as well as the role that oscillatory mechanisms play in this process is a topic of intense interest across disciplines. Although much research has been conducted in this domain using animal models, similar questions are just beginning to be actively explored and defined in human development. However, the physiological mechanisms by which functionally related intrinsic and extrinsic elements are attended to, selected, and incorporated to construct evolving, maturing networks, and the computational theories that are invoked to describe this process, are still imprecisely defined.

For example, how is brain coordination accomplished at multiple levels across age? What central mechanisms are critical to maturation of the developing brain, and what roles do critical/sensitive periods play across maturation for both typical and atypical development. We know that the dynamics of local and long-range networks, within critical periods, are influenced by many factors (including genetics, epigenetics, neurotransmitter systems, cell-to-cell interactions and variation in structure and function) and that this equation may be altered either concurrently or predicatively in a number of neuropsychiatric disorders.

Several studies have shown that early insults, whether genetic or environmental, heavily impact developmental sequences of ionic currents and brain patterns leading to the presence of immature activity in the adult brain. These aberrant oscillations and synchronizations and/or enhanced or reduced functional connectivity constitute preclinical signatures of future disorders. The underlying concept is that pathological neurons recapitulate, to some extent, more immature neuronal stages. Such events have been shown to occur in relation to autism and migration disorders but may also be a factor in ADHD and LLDs. These issues have not been sufficiently investigated due to the large number of genetic mutations and putative relevant animal models and the difficulty of performing detailed anatomo-physiological studies of their features in embryonic brains. As a result, no consensus exists on the extent to which developmental and neuropsychiatric disorders may reflect early disruption in dynamic coordination and/or a failure to establish structural and functional connectivity and synchronization between cortical areas that support emerging cognitive processes. Thus, further investigation on a number of fronts, including the properties of misplaced and misconnected neurons, is essential.

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Dynamic coordination over development is a rapidly expanding area of study, yet many unanswered questions persist as well as divergent views on how to approach such questions. Through this Forum we hope to make headway in defining key components across local and large-scale networks over development. Intense discussion within four working groups will be employed to identify gaps in current knowledge, identify priorities in this relatively unexplored area, and provide recommendations for multidisciplinary basic and clinical research. Overarching issues to be explored in all groups include:

  • What is the role of dynamic coordination in the establishment and maintenance of brain networks and of structural and functional connectivity?
  • How are local and global functional networks assembled and transformed over normative development?
  • To what degree do oscillatory patterns vary across development? Are there age-linked “oscillatory signatures” that can serve as maturational biomarkers?
  • Do early developmental circuit vulnerability deficits in oscillatory domains have relevance for later developmental disorders?
  • Is there a way to quantify the multiple intrinsic and extrinsic factors over development, and how they may differentially impact early brain mechanisms including plasticity?
  • How might emerging technology enhance early identification, diagnosis, prognosis, and remediation of developmental/neuropsychiatric disorders that may reflect early disruption in dynamic coordination and/or a failure to establish structural and functional connectivity and synchronization between cortical areas?

Group 1: Fetal to Birth (preterm delivery)

  • How do early networks organize and what role do temporal dynamics play in this process?
  • What is the impact of genetic/epigenetic mechanisms at this early point in development?
  • What role do early guidance molecules and cell-to-cell interactions play in neuronal migration and the construction of dynamic circuits?
  • When and how are local thalamocortical networks integrated into global large-scale brain connectivity?
  • What constitutes the developmental sequences of ionic currents and network activity? Is delivery a critical period that impacts these critical sequences?
  • How does an early intrauterine insult impact these developing circuits and produce long-lasting deleterious sequelae?
  • What is the process by which genetic polymorphisms lead to abnormalities in neurotransmission and/or neuromodulation in developmental disorders such as autism and schizophrenia? How are essential neurotransmitter systems signals, which we know play crucial roles in brain development (GABA, glutamate, serotonine or catecholamines), affected by intrauterine insults ?

Group 2: Early Childhood (0–3 yr)

  • What is the role of critical/sensitive periods, and what are the factors that initiate and terminate such periods? Does their duration vary in different regions of the brain?
  • What are the mechanisms of critical periods (pruning, sprouting, consolidation of synapses)?
  • Do inhibitory interneurons and their widespread networks play a special role in the organization of developmental processes and neuronal specification?
  • Is “more” connectivity better? What are the consequences and long-lasting effects of hyperconnectivity/ hypoconnectivity?
  • What neural oscillatory signatures are most closely related to the development of cortical circuits, how do they change across maturation, and what are the underlying physiological correlates?
  • How do networks behave during critical periods? Are there specific differences in stability, efficiency, and flexibility? How do they impact dynamic coordination?
  • To what degree do developing cognitive functions depend on the coordination of local and distributed large-scale neural responses such as perceptual grouping, attention-dependent stimulus selection, subsystem integration, and working memory?
  • How might abnormalities in neuronal synchronization and integration be causal in developmental disorders (e.g., autism, ADHD, and schizophrenia)? How early might they be detected and possibly measured with noninvasive technologies?

Group 3: Early Adolescence (peripuberty)

  • How does early insult affect the entry into the peripubertal phase of adolescence?
  • What hormonal influences are seen on brain maturation and sleep over this very dynamic period of brain reorganization?
  • Are there identifiable critical periods surrounding the maturation of specific brain structures over the pubertal period?
  • What is the influence of reward systems and motivation on late-maturing brain structures and circuitry and their functioning?
  • As elaboration of cognitive and sensorimotor networks proceeds, what attentional changes occur? How might this best be captured?
  • How do brain dynamics change over the peripubertal period? Might these differences track maturational trajectories or serve as biomarkers for later dysfunction or disorder?
  • How does synchronized oscillatory activity in the delta-, theta-, alpha-, beta-, and gamma-bands develop during formation of more advanced functional thalamocortical networks, such as those that underlie attention and language acquisition? How do these oscillations interact?
  • How might changes within and across local and large-scale thalamocortical circuits during puberty lead to higher-level cognition?

Group 4: Late Adolescence (postpuberty)

  • What neural oscillatory signatures are most closely related to the ongoing development of cortical circuits, how do they change across adolescence, and what are the underlying physiological correlates?
  • When does the adult brain come on line? Can we define the end of the adolescent period, the closing of critical and sensitive periods, and the transition towards “the adult brain” (i.e., morphological, functional and behavioral signatures)?
  • How should we interpret the ongoing de novo insertion of new neurons in brain regions whose number seems to increase steadily? Does this imply “never-ending” development? What effects might this process have on the stability, efficiency, and flexibility of functional networks?
  • Why is the manifestation of psychiatric disorders prevalent in this developmental phase?
  • How might abnormalities in neuronal synchronization and large-scale integration over adolescence be causal in developmental disorders such as autism, ADHD and schizophrenia among others?
  • Are there pathological events specific to this developmental stage or are we seeing the consequences of previous events (e.g., which took place in utero or early childhood)? Alternatively, is adolescence a vulnerable phase where “second hits” have dramatic consequences?
  • How is the adolescent/maturing brain protected against trauma and to what extent can the brain recover?
  • How is it that we can achieve greater perspective taking and “wisdom” later in life? What does it mean to have an “adult brain”?
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