How early damage to the dorsomedial prefrontal hub in human brain networks affects long term cognitive, behavioral, and neuroanatomical outcomes.

Abstract

Objective: Functional brain networks, which include important “hub” regions, provide important ways to understand recovery after brain damage. One crucial hub previously identified in adult human functional brain networks is in the dorsomedial prefrontal cortex (dmPFC). An open question is whether this hub is vulnerable during development. Method: Here, we describe the neuropsychological and neuroanatomical outcomes of a woman who sustained focal damage to the dmPFC hub from a stroke at age 7. Her rare lesion, acquired early in life and affecting the left dmPFC and underlying white matter, afforded a compelling opportunity for new insights into brain–behavior relationships from a developmental perspective. Results: Cognitive impairment ratings by clinical neuropsychologists showed stable cognition over 2 decades with moderate impairments in personal adjustment and adaptive functioning. The cognitive profile of this childhood-onset case is similar to two previously reported adult-onset cases with similar lesion locations. The results suggest that for the hub we sampled with these cases (midline dmPFC), cognitive and behavioral outcomes do not differ for childhood-onset versus adult-onset brain damage, as in both instances there were long-lasting moderate to severe impairments in personal adjustment and adaptive functioning. Preliminary resting-state fMRI data from the childhood-onset case and one of the adult-onset cases are used to propose future directions for exploring questions of neural plasticity and neurorestoration. Conclusions: This case study provides a rare window into cognitive and neural development following early injury to the dmPFC, enhancing understanding of the complex relationships between age at neurological injury, lesion location, and long-term cognitive and behavioral recovery.

Considerations for advancing a well integrated comparative psychology research approach directed toward improving our understanding of fronto-executive functions.

“…The papers within this special issue encapsulate a broader and more integrative approach to understanding fronto-executive functions as we approach the conclusion of the year 2020. The special issue has brought to light the following human studies: how early damage to the dorsomedial prefrontal cortex in humans can cause long-term alterations in fronto-executive functions (Okerstrom-Jezewski et al, 2020), children exhibiting disruptions in perception, cognition, and response inhibition (Zamora et al, 2020), the neurodevelopment of executive function skills (Zelazo & Carlson, 2020), how developmental lead exposure can cause fronto-executive dysfunctions (Neuwirth, Lopez, Schneider, & Markowitz, 2020), an assessment of the relationships between inhibitory mechanisms of Stroop matching and stop-signal tasks associated with impulsivity (Afonso et al, 2020), the benefits of Cogmed working memory interventions on intelligence, but not working memory capacity (de Jong & Smit, 2020), fronto-executive multidomain self-report assessments in Spanish-speaking adults (Miranda, Rivadero, Serra, & André Soria, 2020), the relationships between dual-tasking and processing speed in healthy aging (Argiris, MacPherson, Della Sala, & Foley, 2020), and the effects of age on medial prefrontal functions and associated behaviors (Iveson, Della Sala, & MacPherson, 2020). The breadth of these human studies on fronto-executive functions were complemented by the following animal studies: rodent models of cognitive aging (Blujus et al, 2020), the effects of neurodevelopmental methylphenidate treatment and behavioral outcomes (Comeau & Kolb, 2020), glutamatergic and serotonergic modulation of rat medial and lateral orbitofrontal cortex in visual serial reversal learning (Hervig et al, 2020), and the role of the ventromedial prefrontal cortex and context regulating fear learning and extinction in rats (Gonzalez & Fanselow, 2020).…”

Fronto-executive functions.

“…The present issue reflects new directions in the study of the development of fronto-executive functions in normal children and those with neurodevelopmental disorders. Zelazo and Carlson (2020) provide an extensive review of the development of executive functions; Okerstrom-Jezewski et al (2020) describe how early prefrontal injury to the dorsomedial prefrontal region alters behavior and resting state functional magnetic resonance imaging; de Jong and Smit (2020) explore the effectiveness of working memory training in adolescents at risk for school dropout; Zamora, Richardś, Juric, Aydmune, and Introzzi (2020) investigate inhibitory processes in children; and, Neuwirth, Lopez, Schneider, and Markowitz (2020) review the effects of neurodevelopmental lead exposure on fronto-executive functions. Three papers investigated fronto-executive functions in aging.…”