Inactivation of Primate Prefrontal Cortex Impairs Auditory and Audiovisual Working Memory

The prefrontal cortex is associated with cognitive functions that include planning, reasoning, decision-making, working memory, and communication. Neurophysiology and neuropsychology studies have established that dorsolateral prefrontal cortex is essential in spatial working memory while the ventral frontal lobe processes language and communication signals. Single-unit recordings in nonhuman primates has shown that ventral prefrontal (VLPFC) neurons integrate face and vocal information and are active during audiovisual working memory. However, whether VLPFC is essential in remembering face and voice information is unknown. We therefore trained nonhuman primates in an audiovisual working memory paradigm using naturalistic face-vocalization movies as memoranda. We inactivated VLPFC, with reversible cortical cooling, and examined performance when faces, vocalizations or both faces and vocalization had to be remembered. We found that VLPFC inactivation impaired subjects' performance in audiovisual and auditory-alone versions of the task. In contrast, VLPFC inactivation did not disrupt visual working memory. Our studies demonstrate the importance of VLPFC in auditory and audiovisual working memory for social stimuli but suggest a different role for VLPFC in unimodal visual processing. SIGNIFICANCE STATEMENT The ventral frontal lobe, or inferior frontal gyrus, plays an important role in audiovisual communication in the human brain. Studies with nonhuman primates have found that neurons within ventral prefrontal cortex (VLPFC) encode both faces and vocalizations and that VLPFC is active when animals need to remember these social stimuli. In the present study, we temporarily inactivated VLPFC by cooling the cortex while nonhuman primates performed a working memory task. This impaired the ability of subjects to remember a face and vocalization pair or just the vocalization alone. Our work highlights the importance of the primate VLPFC in the processing of faces and vocalizations in a manner that is similar to the inferior frontal gyrus in the human brain.

[1]  Joost X. Maier,et al.  Multisensory Integration of Dynamic Faces and Voices in Rhesus Monkey Auditory Cortex , 2005 .

[2]  Lars Muckli,et al.  Cortical Plasticity of Audio–Visual Object Representations , 2008, Cerebral cortex.

[3]  P. Goldman-Rakic,et al.  Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic "scotomas" , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  H. Burton,et al.  Dissociating cortical regions activated by semantic and phonological tasks: a FMRI study in blind and sighted people. , 2003, Journal of neurophysiology.

[5]  Doris Y. Tsao,et al.  A Cortical Region Consisting Entirely of Face-Selective Cells , 2006, Science.

[6]  Asif A Ghazanfar,et al.  Dynamic faces speed up the onset of auditory cortical spiking responses during vocal detection , 2013, Proceedings of the National Academy of Sciences.

[7]  Stefan Everling,et al.  Functional Specialization within Macaque Dorsolateral Prefrontal Cortex for the Maintenance of Task Rules and Cognitive Control , 2014, Journal of Cognitive Neuroscience.

[8]  T. Robbins,et al.  Differential Contributions of the Primate Ventrolateral Prefrontal and Orbitofrontal Cortex to Serial Reversal Learning , 2010, The Journal of Neuroscience.

[9]  Michael A. Cohen,et al.  Auditory recognition memory is inferior to visual recognition memory , 2009, Proceedings of the National Academy of Sciences.

[10]  R. Zatorre,et al.  Voice-selective areas in human auditory cortex , 2000, Nature.

[11]  S. Petersen,et al.  Functional Anatomic Studies of Memory Retrieval for Auditory Words and Visual Pictures , 1996, The Journal of Neuroscience.

[12]  Yale E Cohen,et al.  Acoustic features of rhesus vocalizations and their representation in the ventrolateral prefrontal cortex. , 2007, Journal of neurophysiology.

[13]  D. Perrett,et al.  Visual neurones responsive to faces in the monkey temporal cortex , 2004, Experimental Brain Research.

[14]  Andreas Kleinschmidt,et al.  Interaction of Face and Voice Areas during Speaker Recognition , 2005, Journal of Cognitive Neuroscience.

[15]  M. Mishkin,et al.  Non-spatial memory after selective prefrontal lesions in monkeys , 1978, Brain Research.

[16]  U. Noppeney,et al.  Perceptual Decisions Formed by Accumulation of Audiovisual Evidence in Prefrontal Cortex , 2010, The Journal of Neuroscience.

[17]  H. E. Rosvold,et al.  Localization of function within the dorsolateral prefrontal cortex of the rhesus monkey. , 1970, Experimental neurology.

[18]  Susan M. Courtney,et al.  Functional topography of working memory for face or voice identity , 2005, NeuroImage.

[19]  S. Iversen,et al.  , Mishkin M:Comparison of superior temporal and inferior prefrontal lesions on auditory and non-auditory tasks in rhesus monkeys. , 1973, Brain research.

[20]  Richard Passingham,et al.  Delayed matching after selective prefrontal lesions in monkeys (Macaca mulatta) , 1975, Brain Research.

[21]  A. Giraud,et al.  Implicit Multisensory Associations Influence Voice Recognition , 2006, PLoS biology.

[22]  R. Desimone,et al.  Visual properties of neurons in a polysensory area in superior temporal sulcus of the macaque. , 1981, Journal of neurophysiology.

[23]  Lizabeth M. Romanski,et al.  Coding of vocalizations by single neurons in ventrolateral prefrontal cortex , 2013, Hearing Research.

[24]  L. Romanski,et al.  Neurons responsive to face-view in the primate ventrolateral prefrontal cortex , 2011, Neuroscience.

[25]  Bruno B Averbeck,et al.  Neural representation of vocalizations in the primate ventrolateral prefrontal cortex. , 2005, Journal of neurophysiology.

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

[27]  Hans Forssberg,et al.  Phonological working memory with auditory presentation of pseudo-words — An event related fMRI Study , 2008, Brain Research.

[28]  Gordon E. Legge,et al.  Learning unfamiliar voices , 1984 .

[29]  Brian E. Russ,et al.  A functional role for the ventrolateral prefrontal cortex in non-spatial auditory cognition , 2009, Proceedings of the National Academy of Sciences.

[30]  J M Fuster,et al.  Auditory memory cells in dorsolateral prefrontal cortex. , 1996, Neuroreport.

[31]  Leslie G. Ungerleider,et al.  The prefrontal cortex and the executive control of attention , 2008, Experimental Brain Research.

[32]  Taraz G. Lee,et al.  The Dynamic Nature of Top-Down Signals Originating from Prefrontal Cortex: A Combined fMRI–TMS Study , 2012, The Journal of Neuroscience.

[33]  Alan C. Evans,et al.  Neural mechanisms underlying melodic perception and memory for pitch , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[34]  Uta Noppeney,et al.  Prior auditory information shapes visual category-selectivity in ventral occipito-temporal cortex , 2010, NeuroImage.

[35]  David Caplan,et al.  Individual differences in rCBF correlates of syntactic processing in sentence comprehension: effects of working memory and speed of processing , 2003, NeuroImage.

[36]  K. Zilles,et al.  Recognition of emotional prosody and verbal components of spoken language: an fMRI study. , 2000, Brain research. Cognitive brain research.

[37]  A. Braun,et al.  Symbolic gestures and spoken language are processed by a common neural system , 2009, Proceedings of the National Academy of Sciences.

[38]  Yale E Cohen,et al.  Coding of auditory-stimulus identity in the auditory non-spatial processing stream. , 2008, Journal of neurophysiology.

[39]  Bruno B Averbeck,et al.  Integration of Auditory and Visual Communication Information in the Primate Ventrolateral Prefrontal Cortex , 2006, The Journal of Neuroscience.

[40]  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.

[41]  Lizabeth M. Romanski,et al.  Responses of Prefrontal Multisensory Neurons to Mismatching Faces and Vocalizations , 2014, The Journal of Neuroscience.

[42]  Mortimer Mishkin,et al.  The role of the inferior prefrontal convexity in performance of delayed nonmatching-to-sample , 1991, Neuropsychologia.

[43]  A. Poremba,et al.  Achilles’ Ear? Inferior Human Short-Term and Recognition Memory in the Auditory Modality , 2014, PloS one.

[44]  N. Cowan,et al.  A central capacity limit to the simultaneous storage of visual and auditory arrays in working memory. , 2007, Journal of experimental psychology. General.

[45]  David Gaffan,et al.  Ventrolateral prefrontal cortex is required for performance of a strategy implementation task but not reinforcer devaluation effects in rhesus monkeys , 2009, The European journal of neuroscience.

[46]  J. Fuster,et al.  Functional interactions between inferotemporal and prefrontal cortex in a cognitive task , 1985, Brain Research.

[47]  A. Poremba,et al.  Neural correlates of auditory recognition memory in primate lateral prefrontal cortex , 2013, Neuroscience.

[48]  Brian E. Russ,et al.  Prefrontal Neurons Predict Choices during an Auditory Same-Different Task , 2008, Current Biology.

[49]  R. Passingham,et al.  Ventral Prefrontal Cortex Is Not Essential for Working Memory , 1997, The Journal of Neuroscience.

[50]  C. Gross A COMPARISON OF THE EFFECTS OF PARTIAL AND TOTAL LATERAL FRONTAL LESIONS ON TEST PERFORMANCE BY MONKEYS 1 , 1963 .

[51]  E. Rolls,et al.  Functional subdivisions of the temporal lobe neocortex , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[52]  C. Gross,et al.  Evidence for dissociation of impairment on auditory discrimination and delayed response following lateral frontal lesions in monkeys. , 1962, Experimental neurology.

[53]  Yale E Cohen,et al.  Spontaneous processing of abstract categorical information in the ventrolateral prefrontal cortex , 2006, Biology Letters.

[54]  Theodore P. Zanto,et al.  Causal role of the prefrontal cortex in top-down modulation of visual processing and working memory , 2011, Nature Neuroscience.

[55]  T. Bussey,et al.  Interaction of ventral and orbital prefrontal cortex with inferotemporal cortex in conditional visuomotor learning. , 2002, Behavioral neuroscience.

[56]  N. Logothetis,et al.  A voice region in the monkey brain , 2008, Nature Neuroscience.

[57]  P S Goldman-Rakic,et al.  Face-selective neurons during passive viewing and working memory performance of rhesus monkeys: evidence for intrinsic specialization of neuronal coding. , 1999, Cerebral cortex.

[58]  M. Mishkin,et al.  In search of an auditory engram. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[59]  R. Desimone,et al.  Stimulus-selective properties of inferior temporal neurons in the macaque , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[60]  Christoph Kayser,et al.  Voice Cells in the Primate Temporal Lobe , 2011, Current Biology.

[61]  L. Romanski Integration of faces and vocalizations in ventral prefrontal cortex: Implications for the evolution of audiovisual speech , 2012, Proceedings of the National Academy of Sciences.

[62]  P S Goldman-Rakic,et al.  Architectonics of the parietal and temporal association cortex in the strepsirhine primate Galago compared to the anthropoid primate Macaca , 1991, The Journal of comparative neurology.

[63]  L. Romanski,et al.  Timing of audiovisual inputs to the prefrontal cortex and multisensory integration , 2012, Neuroscience.

[64]  M. Burns,et al.  Broca’s Area: Rethinking Classical Concepts From a Neuroscience Perspective , 2010, Topics in stroke rehabilitation.

[65]  Lee M. Miller,et al.  Behavioral/systems/cognitive Perceptual Fusion and Stimulus Coincidence in the Cross- Modal Integration of Speech , 2022 .

[66]  David Caplan,et al.  Localization of Syntactic Comprehension by Positron Emission Tomography , 1998, NeuroImage.

[67]  J. Greenlee,et al.  A device for cooling localized regions of human cerebral cortex. Technical note. , 2003, Journal of neurosurgery.

[68]  B. Postle,et al.  The cognitive neuroscience of working memory. , 2007, Annual review of psychology.

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

[70]  Alan C. Evans,et al.  The neural substrates underlying word generation: a bilingual functional-imaging study. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[71]  H. E. Rosvold,et al.  Analysis of the delayed-alternation deficit produced by dorsolateral prefrontal lesions in the rhesus monkey. , 1971, Journal of comparative and physiological psychology.

[72]  Doris Y. Tsao,et al.  Comparing face patch systems in macaques and humans , 2008, Proceedings of the National Academy of Sciences.

[73]  P. Goldman-Rakic,et al.  Areal segregation of face-processing neurons in prefrontal cortex. , 1997, Science.

[74]  L. Romanski,et al.  Prefrontal Neuronal Responses during Audiovisual Mnemonic Processing , 2015, The Journal of Neuroscience.

[75]  P. Goldman-Rakic,et al.  Inactivation of parietal and prefrontal cortex reveals interdependence of neural activity during memory-guided saccades. , 2000, Journal of neurophysiology.

[76]  S. Lomber,et al.  Double dissociation of 'what' and 'where' processing in auditory cortex , 2008, Nature Neuroscience.

[77]  J. Armony,et al.  Sensitivity to voice in human prefrontal cortex. , 2005, Journal of neurophysiology.

[78]  Cheng-Ta Yang,et al.  Individual differences in working memory capacity and workload capacity , 2014, Front. Psychol..

[79]  J. Kaiser,et al.  Object Familiarity and Semantic Congruency Modulate Responses in Cortical Audiovisual Integration Areas , 2007, The Journal of Neuroscience.