Review
The error of Broca: From the traditional localizationist concept to a connectomal anatomy of human brain

https://doi.org/10.1016/j.jchemneu.2017.04.003Get rights and content

Highlights

  • Intraoperative electrical mapping allowed revisiting model of brain processing.

  • The classical Broca's area is not the area of speech.

  • It is time to switch from a localisationist to a connectomal view.

  • A networking model opens the door to a huge potential of neuroplasticity.

  • Brain plasticity is constraint by subcortical connectivity.

Abstract

Neurology, especially aphasiology, was mainly built on behavioral-structural correlations (“lesion method”). In this setting, Broca's area has been considered as the “speech area”; moreover, this observation led to localizationism. However, advances in brain mapping techniques, as functional neuroimaging and direct electrical stimulation in patients undergoing awake surgery for gliomas, has resulted in a paradigmatic shift regarding models of neural architecture. In fact, the brain is organized in distributed complex networks underpinning sensorimotor, visuospatial, language, cognitive and emotional functions. In this connectomal workframe, cerebral processing is not conceived as the sum of segregated subfunctions, but results from the integration and potentiation of parallel (even if partially overlapped) subcircuits. Such a networking model, taking into account cortical and subcortical anatomic constraints, explains interindividual variability in physiology and after brain damage, particularly in aphasiology – e.g. double dissociations during electrostimulations, as comprehension versus naming disorders, semantic versus phonemic paraphasias, or syntactic disturbances versus anomia. This dynamic organization mediated by the well-synchronized functioning of delocalized groups of interconnected neurons (rather than by discrete centers) also explains the huge potential of neuroplasticity following cerebral insult, on the condition that the axonal connectivity is preserved. According to this principle, massive surgical resection of brain regions dogmatically considered as “critical” in a localisationist view can be achieved with no functional deficit, as the removal of Broca's area – which is not the speech area – without disorders. This connectomal account of neural processing may have major implications in cognitive neurosciences and in therapeutic management of brain-damaged patients.

Introduction

As a consequence of the seminal lesional work of Broca (1861) who described that a damage in the left inferior frontal gyrus induced a reduced capacity for articulate speech, a decade before Wernicke (1874), who associated speech comprehension with the left superior posterior temporal gyrus, a localisationist view of the organization of cerebral functioning (especially for language) was inexorably established. According to this fixed work-frame, it has been postulated that the organization of the human brain is based upon highly specialized eloquent regions (such as Broca’s and Wernicke’s areas) for which any damage results in permanent neurological impairments, opposed to “non-eloquent” stuctures for which no functional consequences occur in case of injury In addition, such a dogma of localizationism implicitly resulted in the principle of a similar brain functional anatomy between individuals, as for example the pars opercularis and pars triangularis of the left “dominant” hemisphere, that is, the Broca's area, that is a priori considered to the speech area in all human brains. Of note, this traditional view of a static functional organization of the brain had numerous implications not only in fundamental neurosciences, by resulting notably in the elaboration of simplistic and rigid models of conation and cognition, but also in clinical practice – especially by claiming that surgery was impossible in the so-called “eloquent” structures (Sawaya et al., 1998).

In this article, the aim is to break with this classical modular and inflexible model by proposing a dynamic and connectomal anatomy underlying neural circuits, that explains a major inter-individual anatomo-functional variability (Duffau, 2016) and that allows postlesional cerebral adaptive phenomena able to maintain neurological and cognitive functions (Duffau, 2014a), opening the window to new therapeutic strategies in brain-damaged patients, especially in the field of neurooncology (Duffau and Taillandier, 2015). In this state of mind, recent data provided by serial mappings performed in patients who underwent awake surgery for diffuse glioma infiltrating eloquent structures will be reviewed.

Section snippets

Methodological shortcomings inherent to the classical lesion method

The localizationist concept was mainly built on behavioral-structural correlations based upon lesion method. However, this methodology suffers from serious limitations (Herbet et al., 2015a).

The first is the size of the injuries, which are often large, especially in stroke, with usually an inhomogeneous spatial distribution of lesions and a small number of patients.

Secondly, the accurate three dimensional delineation of damages was very difficult until development of MRI. Indeed, recent MRIs of

Intraoperative electrical cortical and axonal mapping: an original technique to evoke a transient virtual lesion of neural network

Advances in functional neuroimaging have recently provided new insights into the neurobiology of cerebral functions, especially with regard to language, by studying the whole brain during functional tasks, both in healthy subjects and in brain-damaged patients. Using task-based functional MRI, the classical concept of language organization shifted towards distributed models (Vigneau et al., 2006). However, functional MRI can not differentiate cortical areas crucial for the neural functions from

The concept of postlesional neuroplasticity

Neuroplasticity can be defined as a continuous process subserving short, middle and long-term remodeling of the neurono-synaptic organization, in order to optimize the functioning of neural networks – during phylogeny, ontogeny, physiological learning and after brain insult (Duffau, 2006). Neural plasticity is possible solely in a dynamic account of cerebral distribution, in which the nervous system is an ensemble of complex subcircuits that form, reshape and flush information dynamically (

Clinical implications of a networking model of neural processes

From a clinical perspective, such a paradigmatic shift from localizationism to connectomics results in numerous implications. In brain surgery for tumors or epilepsy, it is in fine possible to achieve massive excisions in “eloquent” structures wrongly conceived as inoperable for many decades, with nonetheless preservation or even improvement of the quality of life. Especially in surgical neurooncology, owing to the phenomenon of adaptive neuroplasticity, glioma removal can be performed with a

Conclusions and perspectives

It is time to switch from a modular to a connectomal (delocalized) and dynamic model of neural processes, breaking with the traditional localisationist dogma. Multimodal investigations based upon combination of serial peri-operative functional neuroimaging and intraoperative DES has resulted in original individual and integrative models of functioning of neurono-synaptic circuits. Such networking account permits a greater knowledge of the dynamic potential of spatiotemporal reallocation of

References (92)

  • G. Herbet et al.

    Disrupting posterior cingulate connectivity disconnects consciousness from the external environment

    Neuropsychologia

    (2014)
  • G. Herbet et al.

    Rethinking voxel-wise lesion-deficit analysis: a new challenge for computational neuropsychology

    Cortex

    (2015)
  • T. Ius et al.

    Evidence for potentials and limitations of brain plasticity using an atlas of functional resectability of WHO grade II gliomas: towards a minimal common brain

    Neuroimage

    (2011)
  • S. Moritz-Gasser et al.

    Mapping the connectivity underlying multimodal (verbal and non-verbal) semantic processing: a brain electrostimulation study

    Neuropsychologia

    (2013)
  • S. Moritz-Gasser et al.

    Mapping the connectivity underlying multimodal (verbal and non-verbal) semantic processing: a brain electrostimulation study

    Neuropsychologia

    (2013)
  • C.J. Stam

    Characterization of anatomical and functional connectivity in the brain: a complex networks perspective

    Int. J. Psychophysiol.

    (2010)
  • T. Ueno et al.

    Lichtheim 2: synthesizing aphasia and the neural basis of language in a neurocomputational model of the dual dorsal-ventral language pathways

    Neuron

    (2011)
  • M. Vigneau et al.

    Meta-analyzing left hemisphere language areas: phonology, semantics, and sentence processing

    Neuroimage

    (2006)
  • F. Almairac et al.

    The left inferior fronto-occipital fasciculus subserves language semantics: a multilevel lesion study

    Brain Struct. Funct.

    (2015)
  • J. Alstott et al.

    Modeling the impact of lesions in the human brain

    PLoS Comput. Biol.

    (2009)
  • F. Bartolomei et al.

    How do brain tumors alter functional connectivity? A magnetoencephalography study

    Ann. Neurol.

    (2006)
  • P. Bartolomeo

    The elusive nature of white matter damage in anatomo-clinical correlations

    Front. Hum. Neurosci.

    (2012)
  • E. Bates et al.

    Voxel-based lesion-symptom mapping

    Nat. Neurosci.

    (2003)
  • M. Benzagmout et al.

    Resection of World Health Organization Grade II gliomas involving Broca's area: methodological and functional considerations

    Neurosurgery

    (2007)
  • I. Bosma et al.

    Synchronized brain activity and neurocognitive function in patients with low-grade glioma: a magnetoencephalography study

    Neuro-Oncology

    (2008)
  • P. Broca

    Nouvelle observation d’aphémie produite par une lesion de la moitié postérieure des deuxième et troisième circonvolutions frontale

    Bull. Soc. Anat.

    (1861)
  • L. Capelle et al.

    Spontaneous and therapeutic prognostic factors in adult hemispheric World Health Organization Grade II gliomas: a series of 1097 cases

    J. Neurosurg.

    (2013)
  • M. Catani

    From hodology to function

    Brain

    (2007)
  • J. Cochereau et al.

    Patients with incidental WHO grade II glioma frequently suffer from neuropsychological disturbances

    Acta Neurochir. (Wien)

    (2016)
  • A. de Benedictis et al.

    Brain hodotopy: from esoteric concept to practical surgical applications

    Neurosurgery

    (2011)
  • P.C. De Witt Hamer et al.

    Impact of intraoperative stimulation brain mapping on glioma surgery outcome: a meta-analysis

    J. Clin. Oncol.

    (2012)
  • M. Desmurget et al.

    Contrasting acute and slow growing lesions: a new door to brain plasticity

    Brain

    (2007)
  • N.F. Dronkers et al.

    Paul Broca's historic cases: high resolution MR imaging of the brains of Leborgne and Lelong

    Brain

    (2007)
  • H. Duffau et al.

    Functional recuperation after resection of gliomas infiltrating primary somatosensory fields: study of peroperative electric stimulation

    Neurochirurgie

    (2001)
  • H. Duffau et al.

    New concepts in the management of diffuse low-grade glioma: proposal of a multistage and individualized therapeutic approach

    Neuro-Oncology

    (2015)
  • H. Duffau et al.

    Intraoperative mapping of the cortical areas involved in multiplication and subtraction: an electrostimulation study in a patient with a left parietal glioma

    J. Neurol. Neurosurg. Psychiatry

    (2002)
  • H. Duffau et al.

    Long term reshaping of language, sensory and motor maps following glioma resection: a new parameter to integrate in the surgical strategy

    J. Neurol. Neurosurg. Psychiatry

    (2002)
  • H. Duffau et al.

    Functional recovery after surgical resection of low grade gliomas in eloquent brain: hypothesis of brain compensation

    J. Neurol. Neurosurg. Psychiatry

    (2003)
  • H. Duffau et al.

    New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical stimulations

    Brain

    (2005)
  • H. Duffau et al.

    Intraoperative subcortical stimulation mapping of language pathways in a consecutive series of 115 patients with Grade II glioma in the left dominant hemisphere

    J. Neurosurg.

    (2008)
  • H. Duffau et al.

    Functional outcome after language mapping for insular World Health Organization Grade II gliomas in the dominant hemisphere: experience with 24 patients

    Neurosurg. Focus

    (2009)
  • H. Duffau et al.

    Toward a pluri-component, multimodal, and dynamic organization of the ventral semantic stream in humans: lessons from stimulation mapping in awake patients

    Front. Syst. Neurosci.

    (2013)
  • H. Duffau

    Stimulation mapping of white matter tracts to study brain functional connectivity

    Nat. Rev. Neurol.

    (2015)
  • H. Duffau

    Resecting diffuse low-grade gliomas to the boundaries of brain functions: a new concept in surgical neuro-oncology

    J. Neurosurg. Sci.

    (2015)
  • H. Duffau

    A two-level model of interindividual anatomo-functional variability of the brain and its implications for neurosurgery

    Cortex

    (2016)
  • J.S. Feinstein et al.

    Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala

    Brain Struct. Funct.

    (2016)
  • Cited by (47)

    • Variability of Intraoperative Electrostimulation Parameters in Conscious Individuals: Language Fasciculi

      2022, World Neurosurgery
      Citation Excerpt :

      One important result of this study is the high level of negative subcortical mapping results (23 of our 50 patients). In patients who are awake and undergoing cortical DES, many authors have reported a substantial proportion of negative or highly interindividually variable language mappings.1,4,13,19,21,25,37 Also, many authors have pointed out that in a significant number of patients, no language interference was detected in white matter, presumed to be involved in language function.2,3,37,39-42

    • Lesion-symptom mapping of language impairments in patients suffering from left perisylvian gliomas

      2021, Cortex
      Citation Excerpt :

      The absence of prominent inferior frontal GM is complementary to earlier studies in stroke patients (Bates et al., 2003) and direct electrical stimulation (DES) findings (Sarubbo et al., 2020; Tate, Herbet, Moritz-Gasser, Tate, & Duffau, 2014). The absence of inferior frontal GM clusters in the VLSM results is in line with previous observations on the absence of long lasting aphasia after resection of Broca's area (BA 44 and 45) (Duffau, 2018). A potential explanation for this observation may be seen in neuroplasticity processes, compensating for effects of brain tumor or specifically glioma related lesions on language performance, as it has been reported earlier (Amoruso et al., 2021; Piai et al., 2020; Yuan et al., 2020).

    View all citing articles on Scopus
    View full text