Functional connections within the human inferior frontal gyrus

The highly convoluted and cytoarchitectonically diverse inferior frontal gyrus (IFG) of humans is known to be critically involved in a wide range of complex operations including speech and language processing. The neural circuitry that underlies these operations is not fully understood. We hypothesized that this neural circuitry includes functional connections within and between the three major IFG subgyri: the pars orbitalis, pars triangularis, and pars opercularis. To test this hypothesis we employed electrical stimulation tract‐tracing techniques in 10 human patients undergoing surgical treatment for intractable epilepsy. The approach involved delivering repeated bipolar electrical stimuli to one site on the IFG while recording the electrical response evoked by that stimulus from a 64‐contact grid overlying more distant IFG sites. In all subjects, stimulation of a site on one subgyrus evoked polyphasic potentials at distant sites, either on the same subgyrus or on an adjacent subgyrus. This provided prima facie evidence for a functional connection between the site of stimulation and the sites of the evoked response. The averaged evoked potentials tended to aggregate as response fields. The spatial spread of a response field indicated a divergent projection from the site of stimulation. When two or more sites were stimulated, the resulting evoked potentials exhibited different waveforms while the respective response fields could overlap substantially, suggesting that input from multiple sites converged but by engaging different neural circuits. The earliest deflection in the evoked potential ranged from 2 to 10 msec. No differences were noted between language‐dominant and language‐nondominant hemispheres. J. Comp. Neurol. 503:550–559, 2007. © 2007 Wiley‐Liss, Inc.

[1]  G. Hutchins,et al.  Functional Heterogeneity of Inferior Frontal Gyrus Is Shaped by Linguistic Experience , 2001, Brain and Language.

[2]  P. Broca,et al.  Remarques sur le siege de la faculte du langage articule suivies d'une observation d'aphemie , 1861 .

[3]  A. Nambu,et al.  Motor speech centres in the frontal cortex , 1995, Neuroscience Research.

[4]  T. Rasmussen,et al.  Intracarotid injection of sodium amytal for the lateralization of cerebral speech dominance. 1960. , 2007, Journal of neurosurgery.

[5]  Michael P. Kaschak,et al.  Neuroimaging studies of language production and comprehension. , 2003, Annual review of psychology.

[6]  R L Buckner,et al.  Spatiotemporal Maps of Brain Activity Underlying Word Generation and Their Modification during Repetition Priming , 2001, The Journal of Neuroscience.

[7]  G. Waters,et al.  Activation of Broca's area by syntactic processing under conditions of concurrent articulation , 2000, Human brain mapping.

[8]  H. Swadlow,et al.  Characteristics of interhemispheric impulse conduction between prelunate gyri of the rhesus monkey , 1978, Experimental Brain Research.

[9]  G A Ojemann,et al.  Individual variability in cortical localization of language. , 1979, Journal of neurosurgery.

[10]  T. Deacon Cortical connections of the inferior arcuate sulcus cortex in the macaque brain , 1992, Brain Research.

[11]  Thomas P. Naidich,et al.  Anatomic Relationships along the Low-middle Convexity , 1995 .

[12]  Jeffrey H. Kordower,et al.  Tracing neuronal connections in postmortem human hippocampal complex with the carbocyanine dye DiI , 1990, Neurobiology of Aging.

[13]  Alan C. Evans,et al.  Obligatory role of the LIFG in synonym generation: evidence from PET and cortical stimulation , 1997, Neuroreport.

[14]  M. Arbib,et al.  Language within our grasp , 1998, Trends in Neurosciences.

[15]  M. Mishkin,et al.  Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex , 1999, Nature Neuroscience.

[16]  G. Ojemann,et al.  Cortical language localization in left, dominant hemisphere. An electrical stimulation mapping investigation in 117 patients. , 1989, Journal of neurosurgery.

[17]  Alan C. Evans,et al.  Morphology, morphometry and probability mapping of the pars opercularis of the inferior frontal gyrus: an in vivo MRI analysis , 1999, The European journal of neuroscience.

[18]  H. Swadlow Efferent neurons and suspected interneurons in motor cortex of the awake rabbit: axonal properties, sensory receptive fields, and subthreshold synaptic inputs. , 1994, Journal of neurophysiology.

[19]  K. Amunts,et al.  Broca's region subserves imagery of motion: A combined cytoarchitectonic and fMRI study , 2000, Human brain mapping.

[20]  J. E. Hind,et al.  Auditory cortex on the human posterior superior temporal gyrus , 2000, The Journal of comparative neurology.

[21]  T. Rasmussen,et al.  INTRACAROTID INJECTION OF SODIUM AMYTAL FOR THE LATERALIZATION OF CEREBRAL SPEECH DOMINANCE EXPERIMENTAL AND CLINICAL OBSERVATIONS , 1960 .

[22]  R. Reale,et al.  Functional connections between auditory cortex on Heschl's gyrus and on the lateral superior temporal gyrus in humans. , 2003, Journal of neurophysiology.

[23]  D. Perani,et al.  Functional heterogeneity of left inferior frontal cortex as revealed by fMRI , 1997, Neuroreport.

[24]  S. Cobb Speech and Brain-Mechanisms. , 1960 .

[25]  U Klose,et al.  Functional lateralization of speech production at primary motor cortex: a fMRI study. , 1996, Neuroreport.

[26]  G. H. Bishop,et al.  THE SIZE OF NERVE FIBERS SUPPLYING CEREBRAL CORTEX. , 1964, Experimental neurology.

[27]  G. Smith,et al.  Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen. , 1927 .

[28]  Randi C. Martin,et al.  Language processing: functional organization and neuroanatomical basis. , 2003, Annual review of psychology.

[29]  P. Crago,et al.  Applied electric fields accelerate the diffusion rate and increase the diffusion distance of DiI in fixed tissue , 2005, Journal of Neuroscience Methods.

[30]  Edward E. Smith,et al.  A Parametric Study of Prefrontal Cortex Involvement in Human Working Memory , 1996, NeuroImage.

[31]  C. Wilson,et al.  Functional connections in the human temporal lobe , 1990, Experimental Brain Research.

[32]  D. Sparks,et al.  Neural tract tracing using Di-I: a review and a new method to make fast Di-I faster in human brain , 2000, Journal of Neuroscience Methods.

[33]  Pratik Mukherjee,et al.  Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping , 2004, NeuroImage.

[34]  S. Bookheimer,et al.  Activation of language cortex with automatic speech tasks , 2000, Neurology.

[35]  W. Singer,et al.  Interhemispheric asymmetries of the modular structure in human temporal cortex. , 2000, Science.

[36]  R. J. Frank,et al.  Brainvox: An Interactive, Multimodal Visualization and Analysis System for Neuroanatomical Imaging , 1997, NeuroImage.

[37]  H. Lüders,et al.  Functional connectivity in the human language system: a cortico-cortical evoked potential study. , 2004, Brain : a journal of neurology.

[38]  T L Babb,et al.  Functional connections in the human temporal lobe , 2004, Experimental Brain Research.

[39]  Y. Huang,et al.  Topography and identification of the inferior precentral sulcus in MR imaging. , 1989, AJNR. American journal of neuroradiology.

[40]  R. Pearson,et al.  The Human Nervous System. Basic Elements of Structure and Function , 1967, The Yale Journal of Biology and Medicine.

[41]  R. J. Frank,et al.  Three-dimensional in vivo mapping of brain lesions in humans. , 1992, Archives of neurology.

[42]  J Pile-Spellman,et al.  Interhemispheric transfer of language in patients with left frontal cerebral arteriovenous malformation , 2000, Neuropsychologia.

[43]  G. Bonin On the cerebral cortex. , 1950 .

[44]  Christopher K. Kovach,et al.  A functional connection between inferior frontal gyrus and orofacial motor cortex in human. , 2004, Journal of neurophysiology.

[45]  J. Chason The Isocortex of Man , 1952 .

[46]  A. Valavanis,et al.  Anatomic relationships along the low-middle convexity: Part I--Normal specimens and magnetic resonance imaging. , 1995, Neurosurgery.

[47]  A R Damasio,et al.  The neural basis of language. , 1984, Annual review of neuroscience.

[48]  M. Otsuki,et al.  Transcortical sensory aphasia following left frontal infarction , 1998, Journal of Neurology.

[49]  P. Chauvel,et al.  Localization of the primary auditory area in man. , 1991, Brain : a journal of neurology.

[50]  J. Mazziotta,et al.  The essential role of Broca's area in imitation , 2003, The European journal of neuroscience.

[51]  R P Lesser,et al.  The location of speech and writing functions in the frontal language area. Results of extraoperative cortical stimulation. , 1984, Brain : a journal of neurology.

[52]  K. Kurata Site of origin of projections from the thalamus to dorsal versus ventral aspects of the premotor cortex of monkeys , 1994, Neuroscience Research.

[53]  K. Brodmann Vergleichende Lokalisationslehre der Großhirnrinde : in ihren Prinzipien dargestellt auf Grund des Zellenbaues , 1985 .

[54]  P. McGuire,et al.  Cortical substrates for the perception of face actions: an fMRI study of the specificity of activation for seen speech and for meaningless lower-face acts (gurning). , 2001, Brain research. Cognitive brain research.

[55]  M. Petrides,et al.  Orofacial somatomotor responses in the macaque monkey homologue of Broca's area , 2005, Nature.

[56]  D. Pandya,et al.  Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey , 2002, The European journal of neuroscience.

[57]  A. Schleicher,et al.  Broca's region revisited: Cytoarchitecture and intersubject variability , 1999, The Journal of comparative neurology.

[58]  R G Grossman,et al.  Electrophysiological connections between the hippocampus and entorhinal cortex in patients with complex partial seizures. , 1989, Journal of neurosurgery.

[59]  P. Goldman-Rakic,et al.  An auditory domain in primate prefrontal cortex , 2002, Nature Neuroscience.