TY - JOUR
T1 - E.L., a modern-day Phineas Gage
T2 - Revisiting frontal lobe injury
AU - de Freitas, Pedro H.M.
AU - Monteiro, Ruy C.
AU - Bertani, Raphael M.
AU - Perret, Caio M.
AU - Rodrigues, Pedro C.
AU - Vicentini, Joana
AU - de Morais, Tagore M.Gonzalez
AU - Rozental, Stefano F.A.
AU - Galvão, Gustavo F.
AU - de Mattos, Fabricio
AU - Vasconcelos, Fernando A.
AU - Dorio, Ivan S.
AU - Hayashi, Cintya Y.
AU - dos Santos, Jorge R.L.
AU - Werneck, Guilherme L.
AU - Tocquer, Carla T.Ferreira
AU - Capitão, Claudia
AU - da Cruz, Luiz C.Hygino
AU - Tulviste, Jaan
AU - Fiorani, Mario
AU - da Silva, Marcos M.
AU - Paiva, Wellingson S.
AU - Podell, Kenneth
AU - Federoff, Howard J.
AU - Patel, Divyen H.
AU - Lado, Fred
AU - Goldberg, Elkhonon
AU - Llinás, Rodolfo
AU - Bennett, Michael V.L.
AU - Rozental, Renato
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/10
Y1 - 2022/10
N2 - Background: How the prefrontal cortex (PFC) recovers its functionality following lesions remains a conundrum. Recent work has uncovered the importance of transient low-frequency oscillatory activity (LFO; < 4 Hz) for the recovery of an injured brain. We aimed to determine whether persistent cortical oscillatory dynamics contribute to brain capability to support ‘normal life’ following injury. Methods: In this 9-year prospective longitudinal study (08/2012-2021), we collected data from the patient E.L., a modern-day Phineas Gage, who suffered from lesions, impacting 11% of his total brain mass, to his right PFC and supplementary motor area after his skull was transfixed by an iron rod. A systematic evaluation of clinical, electrophysiologic, brain imaging, neuropsychological and behavioural testing were used to clarify the clinical significance of relationship between LFO discharge and executive dysfunctions and compare E.L.´s disorders to that attributed to Gage (1848), a landmark in the history of neurology and neuroscience. Findings: Selective recruitment of the non-injured left hemisphere during execution of unimanual right-hand movements resulted in the emergence of robust LFO, an EEG-detected marker for disconnection of brain areas, in the damaged right hemisphere. In contrast, recruitment of the damaged right hemisphere during contralateral hand movement, resulted in the co-activation of the left hemisphere and decreased right hemisphere LFO to levels of controls enabling performance, suggesting a target for neuromodulation. Similarly, transcranial magnetic stimulation (TMS), used to create a temporary virtual-lesion over E.L.’s healthy hemisphere, disrupted the modulation of contralateral LFO, disturbing behaviour and impairing executive function tasks. In contrast to Gage, reasoning, planning, working memory, social, sexual and family behaviours eluded clinical inspection by decreasing LFO in the delta frequency range during motor and executive functioning. Interpretation: Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery, and represents an attractive target for therapeutic interventions. Funding: Fundação de Amparo Pesquisa Rio de Janeiro (FAPERJ), Universidade Federal do Rio de Janeiro (intramural), and Fiocruz/Ministery of Health (INOVA Fiocruz).
AB - Background: How the prefrontal cortex (PFC) recovers its functionality following lesions remains a conundrum. Recent work has uncovered the importance of transient low-frequency oscillatory activity (LFO; < 4 Hz) for the recovery of an injured brain. We aimed to determine whether persistent cortical oscillatory dynamics contribute to brain capability to support ‘normal life’ following injury. Methods: In this 9-year prospective longitudinal study (08/2012-2021), we collected data from the patient E.L., a modern-day Phineas Gage, who suffered from lesions, impacting 11% of his total brain mass, to his right PFC and supplementary motor area after his skull was transfixed by an iron rod. A systematic evaluation of clinical, electrophysiologic, brain imaging, neuropsychological and behavioural testing were used to clarify the clinical significance of relationship between LFO discharge and executive dysfunctions and compare E.L.´s disorders to that attributed to Gage (1848), a landmark in the history of neurology and neuroscience. Findings: Selective recruitment of the non-injured left hemisphere during execution of unimanual right-hand movements resulted in the emergence of robust LFO, an EEG-detected marker for disconnection of brain areas, in the damaged right hemisphere. In contrast, recruitment of the damaged right hemisphere during contralateral hand movement, resulted in the co-activation of the left hemisphere and decreased right hemisphere LFO to levels of controls enabling performance, suggesting a target for neuromodulation. Similarly, transcranial magnetic stimulation (TMS), used to create a temporary virtual-lesion over E.L.’s healthy hemisphere, disrupted the modulation of contralateral LFO, disturbing behaviour and impairing executive function tasks. In contrast to Gage, reasoning, planning, working memory, social, sexual and family behaviours eluded clinical inspection by decreasing LFO in the delta frequency range during motor and executive functioning. Interpretation: Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery, and represents an attractive target for therapeutic interventions. Funding: Fundação de Amparo Pesquisa Rio de Janeiro (FAPERJ), Universidade Federal do Rio de Janeiro (intramural), and Fiocruz/Ministery of Health (INOVA Fiocruz).
KW - Corpus callosum (C.C.)
KW - Low Frequency Oscillations
KW - Magnetic Resonance Imaging (MRI)
KW - Neuropsychological tests
KW - Phineas Gage
KW - Prefrontal cortex (PFC)
KW - Transcranial Magnetic Stimulation
KW - Traumatic brain injury (TBI)
UR - http://www.scopus.com/inward/record.url?scp=85135954130&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85135954130&partnerID=8YFLogxK
U2 - 10.1016/j.lana.2022.100340
DO - 10.1016/j.lana.2022.100340
M3 - Article
AN - SCOPUS:85135954130
SN - 2667-193X
VL - 14
JO - The Lancet Regional Health - Americas
JF - The Lancet Regional Health - Americas
M1 - 100340
ER -