Functional reorganization after hemispherectomy in humans and animal models: What can we learn about the brain’s resilience to extensive unilateral lesions?

Hemispherectomy (HS) is an effective surgical procedure aimed at managing otherwise intractable epilepsy in cases of diffuse unihemispheric pathologies. Neurological recovery in subjects treated with HS is not limited to seizure reduction, rather, sensory-motor and behavioral improvement is often observed. This outcome highlights the considerable capability of the brain to react to such an extensive lesion, by functionally reorganizing and rewiring the cerebral cortex, especially early in life. In this narrative review, we summarize the animal studies as well as the human neurophysiological and neuroimaging studies dealing with the reorganizational processes that occur after HS. These topics are of particular interest in understanding mechanisms of functional recovery after brain injury. HS offers the chance to investigate contralesional hemisphere activity in controlling ipsilateral limb movements, and the role of transcallosal interactions, before and after the surgical procedure. These post-injury neuroplastic phenomena actually differ from those observed after less extensive brain damage. Therefore, they illustrate how different lesions could lead the contralesional hemisphere to play the "good" or "bad" role in functional recovery. These issues may have clinical implications and could inform rehabilitation strategies aiming to improve functional recovery following unilateral hemispheric lesions. Future studies, involving large cohorts of hemispherectomized patients, will be necessary in order to obtain a greater understanding of how cerebral reorganization can contribute to residual sensorimotor, visual and auditory functions.

[1]  P. J. Wilson Cerebral hemispherectomy for infantile hemiplegia. A report of 50 cases. , 2015, Brain : a journal of neurology.

[2]  L M Harrison,et al.  Patterns of central motor reorganization in hemiplegic cerebral palsy. , 1993, Brain : a journal of neurology.

[3]  M. Panigrahi,et al.  Neuroplasticity in hemispheric syndrome: an interesting case report. , 2011, Neurology India.

[4]  K. Funakoshi,et al.  Reorganization of motor circuits after neonatal hemidecortication , 2014, Neuroscience Research.

[5]  F. Benedetti,et al.  There is less thalamic degeneration in neonatal-lesioned than in adult-lesioned cats after cerebral hemispherectomy , 1986, Brain Research.

[6]  Maurice Ptito,et al.  Partial recovery of hemiparesis following hemispherectomy in infant monkeys , 2010, Neuroscience Letters.

[7]  S. Mori,et al.  Cerebral Reorganization after Hemispherectomy: A DTI Study , 2016, American Journal of Neuroradiology.

[8]  B. Tantisira,et al.  Reorganization of sensory pathways after neonatal hemidecortication in rats , 2014, Neuroscience Research.

[9]  W. Dandy,et al.  REMOVAL OF RIGHT CEREBRAL HEMISPHERE FOR CERTAIN TUMORS WITH HEMIPLEGIA: PRELIMINARY REPORT , 1928 .

[10]  H. Qiao,et al.  Ipsilateral and Contralateral Auditory Brainstem Response Reorganization in Hemispherectomized Patients , 2013, Neural plasticity.

[11]  M. Ptito,et al.  Adaptive Neuroplastic Responses in Early and Late Hemispherectomized Monkeys , 2012, Neural plasticity.

[12]  R. Tubbs,et al.  Hemispherectomy for treatment of refractory epilepsy in the pediatric age group: a systematic review. , 2015, Journal of neurosurgery. Pediatrics.

[13]  D. Boire,et al.  Stereological evaluation of neurons and glia in the monkey dorsal lateral geniculate nucleus following an early cerebral hemispherectomy , 2001, Experimental Brain Research.

[14]  J. Sprague,et al.  Interaction of Cortex and Superior Colliculus in Mediation of Visually Guided Behavior in the Cat , 1966, Science.

[15]  J. Villablanca,et al.  Regional Age-Dependent Effects of Hemineodecortication upon Contralateral Neocortical Thickness: Comparison with Other Measures of Cortical Size , 1999, Developmental Neuroscience.

[16]  C. Adams,et al.  Modified hemispherectomy for epilepsy: early results in 10 cases. , 1988, British journal of neurosurgery.

[17]  Michael Erb,et al.  Two types of ipsilateral reorganization in congenital hemiparesis: a TMS and fMRI study. , 2002, Brain : a journal of neurology.

[18]  A. Castro Projections of the superior cerebellar peduncle in rats and the development of new connections in response to neonatal hemicerebellectomy , 1978, The Journal of comparative neurology.

[19]  Kelsey A. Potter-Baker,et al.  Tailoring Brain Stimulation to the Nature of Rehabilitative Therapies in Stroke: A Conceptual Framework Based on their Unique Mechanisms of Recovery. , 2015, Physical medicine and rehabilitation clinics of North America.

[20]  David W. McNeal,et al.  Frontal and frontoparietal injury differentially affect the ipsilateral corticospinal projection from the nonlesioned hemisphere in monkey (Macaca mulatta) , 2016, The Journal of comparative neurology.

[21]  J. V. Van Buren,et al.  Functional representation on the medial aspect of the frontal lobes in man. , 1976, Journal of neurosurgery.

[22]  Kevin D Alloway,et al.  Contralateral corticothalamic projections from MI whisker cortex: Potential route for modulating hemispheric interactions , 2008, The Journal of comparative neurology.

[23]  Akira Yoshikawa,et al.  A Retrograde Tracing Study of Compensatory Corticospinal Projections in Rats with Neonatal Hemidecortication , 2012, Developmental Neuroscience.

[24]  H. Freund,et al.  Reorganisation of descending motor pathways in patients after hemispherectomy and severe hemispheric lesions demonstrated by magnetic brain stimulation , 2004, Experimental Brain Research.

[25]  M Hallett,et al.  Dissociation of the pathways mediating ipsilateral and contralateral motor‐evoked potentials in human hand and arm muscles , 1999, The Journal of physiology.

[26]  D. Guitton,et al.  Oculomotor control after hemidecortication: A single hemisphere encodes corollary discharges for bilateral saccades , 2015, Cortex.

[27]  W. Byblow,et al.  Ipsilateral Motor Pathways after Stroke: Implications for Non-Invasive Brain Stimulation , 2013, Front. Hum. Neurosci..

[28]  J. Ojemann,et al.  Hemispherotomy: efficacy and analysis of seizure recurrence. , 2009, Journal of neurosurgery. Pediatrics.

[29]  P. Kotagal,et al.  Longitudinal seizure outcome and prognostic predictors after hemispherectomy in 170 children , 2013, Neurology.

[30]  Yvonne Sininger,et al.  Dichotic listening after cerebral hemispherectomy: Methodological and theoretical observations , 2007, Neuropsychologia.

[31]  G. Leonhardt,et al.  Cortical motor reorganization following early brain damage and hemispherectomy demonstrated by transcranial magnetic stimulation , 2000, Clinical Neurophysiology.

[32]  B. Bourgeois,et al.  Surgery for intractable epilepsy due to unilateral brain disease: a retrospective study comparing hemispherectomy techniques. , 2014, Pediatric neurology.

[33]  J. Stephens,et al.  Mirror movements studied in a patient with Klippel‐Feil syndrome. , 1990, The Journal of physiology.

[34]  M. Phelps,et al.  Cerebral Metabolism following Neonatal or Adult Hemineodecortication in Cats: I. Effects on Glucose Metabolism Using [14C]2-Deoxy-D-Glucose Autoradiography , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[35]  T. Rasmussen Postoperative superficial hemosiderosis of the brain, its diagnosis, treatment and prevention. , 1973, Transactions of the American Neurological Association.

[36]  H. Lüders,et al.  Hemispherectomy for Catastrophic Epilepsy in Infants , 2005, Epilepsia.

[37]  N. Kapur Paradoxical functional facilitation in brain-behaviour research. A critical review. , 1996, Brain : a journal of neurology.

[38]  T. Maehara,et al.  Enhanced motor cortical excitability in the unaffected hemisphere after hemispherectomy , 2000, Neuroreport.

[39]  J M Freeman,et al.  Hemispherectomy for intractable unihemispheric epilepsy Etiology vs outcome , 2003, Neurology.

[40]  Antonio Oliviero,et al.  Unaffected motor cortex remodeling after hemispherectomy in an epileptic cerebral palsy patient. A TMS and fMRI study , 2009, Epilepsy Research.

[41]  M. Molinari,et al.  Increased collateralization of the cerebellothalamic pathway following neonatal hemicerebellectomy , 1986, Brain Research.

[42]  M. Mishkin,et al.  Onset of speech after left hemispherectomy in a nine-year-old boy. , 1997, Brain : a journal of neurology.

[43]  A. Ptito,et al.  Somatosensory representation in patients who have undergone hemispherectomy: a functional magnetic resonance imaging study. , 2000, Journal of neurosurgery.

[44]  S. Ohgi,et al.  Reorganization of Sensorimotor Function after Functional Hemispherectomy Studied Using Near-Infrared Spectroscopy , 2010, Pediatric Neurosurgery.

[45]  E. Strauss,et al.  Long‐term follow‐up after cerebral hemispherectomy , 1982, Neurology.

[46]  M. Levine,et al.  Reorganization of Pericruciate cortical projections to the spinal cord and dorsal column nuclei after neonatal or adult cerebral hemispherectomy in cats , 1986, Brain Research.

[47]  J. Villablanca,et al.  Reorganization of cerebellorubral terminal fields following hemispherectomy in adult cats , 1983, Brain Research.

[48]  L. J. Karnosh,et al.  Residual function following hemispherectomy for tumour and for infantile hemiplegia. , 1955, Brain : a journal of neurology.

[49]  D. Boire,et al.  Retinal projections to the pregeniculate nucleus in the hemispherectomized monkey , 2000, Brain Research Bulletin.

[50]  Heidi Johansen-Berg,et al.  Unconscious vision: new insights into the neuronal correlate of blindsight using diffusion tractography. , 2006, Brain : a journal of neurology.

[51]  K. Zülch Motor and sensory findings after hemispherectomy: Ipsi- or contralateral functions? , 1974 .

[52]  L. J. Karnosh,et al.  Cerebral hemispherectomy; report of a case 10 years after operation. , 1949, Journal of neurosurgery.

[53]  A. Cowey The blindsight saga , 2009, Experimental Brain Research.

[54]  David Araújo,et al.  Outcome of hemispheric surgeries for refractory epilepsy in pediatric patients , 2007, Child's Nervous System.

[55]  L. French,et al.  Observations on the Motor System following Cerebral Hemispherectomy , 1955, Neurology.

[56]  H. Freund Abnormalities of Motor Behavior After Cortical Lesions in Humans , 2011 .

[57]  R. Asarnow,et al.  Cerebral hemispherectomy , 2004, Neurology.

[58]  P. Ferroli,et al.  Hemispherotomy and functional hemispherectomy: Indications and outcome , 2010, Epilepsy Research.

[59]  S. Müller,et al.  Cortical activation in patients with functional hemispherectomy , 2001, Journal of Neurology.

[60]  D. G. Lawrence,et al.  The functional organization of the motor system in the monkey. I. The effects of bilateral pyramidal lesions. , 1968, Brain : a journal of neurology.

[61]  D G Gadian,et al.  The reorganization of sensorimotor function in children after hemispherectomy. A functional MRI and somatosensory evoked potential study. , 2000, Brain : a journal of neurology.

[62]  L. French,et al.  Examination of the Sensory System in Patients After Hemispherectomy , 1955, Neurology.

[63]  Bruce Dobkin,et al.  Residual Motor Control and Cortical Representations of Function Following Hemispherectomy: Effects of Etiology , 2005, Journal of child neurology.

[64]  M. Lassonde,et al.  Sound localization in hemispherectomized subjects: the contribution of crossed and uncrossed cortical afferents , 2000, Experimental Brain Research.

[65]  W. Bingaman,et al.  Long‐term functional outcomes and their predictors after hemispherectomy in 115 children , 2013, Epilepsia.

[66]  Alan Cowey,et al.  Visual System: How Does Blindsight Arise? , 2010, Current Biology.

[67]  J. Tournier,et al.  Predicting hand function after hemidisconnection. , 2016, Brain : a journal of neurology.

[68]  R. A. Krynauw,et al.  INFANTILE HEMIPLEGIA TREATED BY REMOVING ONE CEREBRAL HEMISPHERE , 1950, Journal of neurology, neurosurgery, and psychiatry.

[69]  E. Rinvik,et al.  SOME COMMENTS ON THE PYRAMIDAL TRACT, WITH SPECIAL REFERENCE TO ITS INDIVIDUAL VARIATIONS IN MAN , 1963 .

[70]  Long-term functional recovery in the rat auditory system after unilateral auditory cortex ablation. , 2010, Acta oto-laryngologica.

[71]  K. Ueki,et al.  Hemispherectomy in the human with special reference to the preservation of function. , 1966, Progress in brain research.

[72]  J. Villablanca,et al.  Recovery of function after neonatal or adult hemispherectomy in cats. II. Limb bias and development, paw usage, locomotion and rehabilitative effects of exercise , 1986, Behavioural Brain Research.

[73]  Susumu Mori,et al.  Sensorimotor function and sensorimotor tracts after hemispherectomy , 2010, Neuropsychologia.

[74]  A. Berg,et al.  Big epilepsy surgery for little people , 2013, Neurology.

[75]  B. Kolb,et al.  Cortical and striatal structure and connectivity are altered by neonatal hemidecortication in rats , 1992, The Journal of comparative neurology.

[76]  K. Zülch,et al.  Hemispherectomy — 25 years later — findings and concepts , 1978, Neurosurgical Review.

[77]  P. Helders,et al.  Functional consequences of hemispherectomy. , 2004, Brain : a journal of neurology.

[78]  G. Ballester,et al.  Mapping of the Rat's Motor Area after Hemispherectomy: The Hemispheres as Potentially Independent Motor Brains , 2003, Epilepsia.

[79]  K. Kawai,et al.  Early hemispherotomy in a patient with multilobar cortical dysplasia with intractable seizure: clinical-neurophysiological study. , 2008, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[80]  J. Villablanca,et al.  Residual cerebellothalamic terminal fields following hemispherectomy in the cat , 1982, Neuroscience Letters.

[81]  R. Müller,et al.  Brain Organization of Motor and Language Functions Following Hemispherectomy: A [15O]-Water Positron Emission Tomography Study , 1998, Journal of child neurology.

[82]  A. No Hemispherectomy for the treatment of epilepsy and behavior disturbance. , 1980 .

[83]  A. Crawley,et al.  Regionalized sensorimotor plasticity after hemispherectomy fMRI evaluation. , 1998, Pediatric neurology.

[84]  P. Gosselaar,et al.  Altered Contralateral Sensorimotor System Organization after Experimental Hemispherectomy: A Structural and Functional Connectivity Study , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[85]  C. D'amato,et al.  Motor-sensory and visual behavior after hemispherectomy in newborn and mature rats. , 1970, Experimental neurology.

[86]  B. Dobkin,et al.  Locomotor Training Remodels fMRI Sensorimotor Cortical Activations in Children After Cerebral Hemispherectomy , 2007, Neurorehabilitation and neural repair.

[87]  A. Damasio,et al.  Nervous function after right hemispherectomy , 1975, Neurology.

[88]  D. Hovda,et al.  Development of a crossed corticotectal pathway following cerebral hemispherectomy in cats: a quantitative study of the projecting neurons. , 1995, Brain research. Developmental brain research.

[89]  T. Isa,et al.  Differential contributions of rostral and caudal frontal forelimb areas to compensatory process after neonatal hemidecortication in rats , 2011, The European journal of neuroscience.

[90]  H. Cairns,et al.  Hemispherectomy in the treatment of infantile hemiplegia. , 1951, Lancet.

[91]  I. Whishaw,et al.  Sparing of skilled forelimb reaching and corticospinal projections after neonatal motor cortex removal or hemidecortication in the rat: support for the Kennard doctine , 1988, Brain Research.

[92]  Nick F Ramsey,et al.  Interhemispheric Reorganization of Motor Hand Function to the Primary Motor Cortex Predicted With Functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation , 2002, Journal of child neurology.

[93]  E. Sherman,et al.  Hemispheric Surgery in Children with Refractory Epilepsy: Seizure Outcome, Complications, and Adaptive Function , 2007, Epilepsia.

[94]  Alain Ptito,et al.  Neural Substrates of Blindsight After Hemispherectomy , 2007, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[95]  F. Chiricozzi,et al.  Developmental plasticity after right hemispherectomy in an epileptic adolescent with early brain injury , 2005, Child's Nervous System.

[96]  Domenico Formica,et al.  Modulation of brain plasticity in stroke: a novel model for neurorehabilitation , 2014, Nature Reviews Neurology.

[97]  Motion perception in the ipsilateral visual field of a hemispherectomized patient , 2002, Journal of Neurology.

[98]  J. Gotman,et al.  Sensorimotor organization in patients who have undergone hemispherectomy: a study with 15O‐water PET and somatosensory evoked potentials , 2000, Neuroreport.

[99]  K. Isa,et al.  Large‐scale reorganization of corticofugal fibers after neonatal hemidecortication for functional restoration of forelimb movements , 2009, The European journal of neuroscience.

[100]  Jian-Guo Zhang,et al.  Hemispheric surgery for refractory epilepsy: a systematic review and meta-analysis with emphasis on seizure predictors and outcomes. , 2016, Journal of neurosurgery.

[101]  S. Lew Hemispherectomy in the treatment of seizures: a review. , 2014, Translational pediatrics.

[102]  P. Rakić,et al.  Development of the corpus callosum and cavum septi in man , 1968, The Journal of comparative neurology.

[103]  V. Hömberg,et al.  Reorganization of motor output in the non-affected hemisphere after stroke. , 1997, Brain : a journal of neurology.

[104]  F. Vargha-Khadem,et al.  Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence. , 2003, Brain : a journal of neurology.

[105]  C. Olmstead,et al.  Recovery of function after neonatal or adult hemispherectomy in cats: I. Time course, movement, posture and sensorimotor tests , 1986, Behavioural Brain Research.

[106]  Jing Zhang,et al.  fMRI and DTI assessment of patients undergoing radical epilepsy surgery , 2013, Epilepsy Research.

[107]  J. Hughlingsjackson,et al.  A CONTRIBUTION TO THE COMPARATIVE STUDY OF CONVULSIONS , 1886 .

[108]  B. Mensour,et al.  Functional reorganization of the human auditory pathways following hemispherectomy: An fMRI demonstration , 2008, Neuropsychologia.

[109]  H. Vinters,et al.  Hemispherectomy for intractable seizures in children: a report of 58 cases , 1996, Child's Nervous System.

[110]  M. Shimada,et al.  Formation of an ipsilateral corticospinal tract after ablation of cerebral cortex in neonatal rat , 1991, Brain and Development.

[111]  D. Muller,et al.  Ontogeny of ipsilateral corticospinal projections: A developmental study with transcranial magnetic stimulation , 1997, Annals of neurology.

[112]  D. Minciacchi,et al.  Crossed thalamo-cortical and cortico-thalamic projections in adult mice , 1996, Neuroscience Letters.

[113]  B. Stanfield,et al.  The recovery of forelimb-placing behavior in rats with neonatal unilateral cortical damage involves the remaining hemisphere , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[114]  M. Molinari,et al.  Efferent fibers from the motor cortex terminate bilaterally in the thalamus of rats and cats , 2004, Experimental Brain Research.

[115]  N. Mizuno,et al.  Morphological evidence for axonal sprouting of cerebellothalamic neurons in kittens after neonatal hemicerebellectomy , 1979, Experimental Brain Research.

[116]  R. Lund,et al.  An aberrant crossed visual corticotectal pathway in albino rats , 1976, Brain Research.

[117]  D. Hovda,et al.  Developmental neuroplasticity in a model of cerebral hemispherectomy and stroke , 1999, Neuroscience.

[118]  A. Hedström,et al.  THE EFFECTS OF EPILEPSY SURGERY ON THE SENSORIMOTOR FUNCTION OF CHILDREN , 1994, Developmental medicine and child neurology.