Elsevier

Medical Hypotheses

Volume 71, Issue 5, November 2008, Pages 788-801
Medical Hypotheses

Paleoneurology: Neurodegenerative diseases are age-related diseases of specific brain regions recently developed by homo sapiens

https://doi.org/10.1016/j.mehy.2008.05.034Get rights and content

Summary

Bipedal locomotion and fine motility of hand and larynx of humans introduced msculoskeletal adaptations, new pyramidal, corticostriatal, corticobulbar, nigrostriatal, and cerebellar pathways and expansions of prefrontal, cingular, parieto-temporal and occipital cortices with derived new brain capabilities. All selectively degenerate in aged homo sapiens following 16 syndromic presentations: (1) Parkinsonism: nigrostriatal control for fast automatic movements of hand, larynx, bipedal posture and gait (“simian gait and hand”). (2) Frontal (highest level) gait disorders (lower body parkinsonism, gait apraxia, retropulsion): prefrontostriatal executive control of bipedal locomotion. (3) ataxia: new synergistic coordination of bipedal gait and fine motility. (4) Dyskinesias (chorea, dystonia, tremor…): intrusions of simian basal ganglia motor subroutines. (5) motoneuron diseases: new proximo-distal and bulbar motoneurones, preserving older ones (oculomotor, abdominal…). (6) Archaic reflexes: prefrontal disinhibition of old mother/tree-climbing-oriented reflexes (sucking, grasping, Babinski/triple retraction, gegenhalten), group alarms (laughter, crying, yawning, grunting…) or grooming (tremor = scratching). (7) Dysautonomia: contextual regulation (orthostatism…). (8) REM sleep disorders of new cortical functions. (9) Corticobasal syndrome: melokinetic control of hand prehension–manipulation and language (retrocession to simian patterns). (10) Frontal/temporal lobe degeneration: medial-orbitofrontal behavioural variant: self monitoring of internal needs and social context: apathy, loss of personal hygiene, stereotypia, disinhibition, loss of concern for consequences of acts, social rules, danger and empathy; dorsolateral executive variant: inadequacy to the context of action (goal, environmental changes…); progressive non-fluent aphasia: executive and praxic processing of speech; temporal variant: abstract concepts for speech, gestures and vision (semantic dementia, progressive nonfluent aphasia) (11) Temporomesial–limbic–paralimbic–associative cortical dementias (Alzheimer’s disease, Lewy body, progressive amnesia): processing of explicit cognition: amnesic syndrome, processing of hand, larynx and eye: disorientation, ideomotor apraxia, agnosia, visuospatial processing, transcortical aphasia. (12) Focal posterior atrophy (Benson, progressive apraxia): visuomotor processing of what and where. (13) Macular degeneration: retinal “spot” for explicit symbols. (14) “Psychiatric syndromes”: metacognition, self monitoring and regulation of hierarchical processing of metacognition: hallucinations, delusions, magic and mystic logic, delusions, confabulations; drive: impulsivity, obsessive–compulsive disorders, mental automatisms; social interactions: theory of mind, autism, Asperger. (15) Mood disorders: control on emotions: anxio-depressive and bipolar disorders, moria, emotional lability. (16) Musculoskeletal: inclusion body myositis: muscles for bipedal gait and fine motility. Paget’s disease: bones for bipedal gait and cranium.

Understanding of the genetic mechanisms underlying the evolution of these recent human brain regions and paleoneurology my be the key to the focal, asymmetrical or systemic character of neurodegeneration, the pathologic heterogeneity/overlap of syndromic presentations associating gait, hand, language, cognition, mood and behaviour disorders.

Section snippets

Introduction/background

Clinical presentations of functional deficits in neurodegenerative diseases, that may be focal, asymmetrical or lumped into multisystem atrophies along functional networks is puzzling to both the clinician and the neuroscientist. Age-relation seems to be the major risk factor, but the “functional dissection “that prevails in these diseases may rely on another logic, that may look for a reappraisal from a darwinian perspective.

Rapoport [1], [2], [3] was the first to think of Alzheimer’s disease

A. Development of the human brain

In the 5 millions of years of evolution of hominoids through the Miocene, Pliocene and Pleistocene, prehuman primates operated a cladic separation from the chimpanzee–bonobo branch (panides) that ended up in the present homo sapiens sapiens. In the 3 billion base-pair of the human genome, only 1% differed from the chimpanzee [20]; however, changes in brain anatomy and consecutive new cognitive capacities, perception and regulation of self and adaptation environment are much more significant [22]

Empirical data

It is known from the revision of the literature [121], [206], [207], [208], [209], [210], [211], [212], [213], [214], [215], [216], [217], [218], [219], [220], [221], [222], [223], [224], [225], [226], [227], [228], [229], [230], [231], [232], [233], [234], [235], [236], [237], [238], [239], [240], [241], [242], [243], that positive selection [218], [223] of genes (morphogens) [220] was instrumental in the shift of humans from the chimpanzee–bonobo branch, new genes specific for size of brain

Consequences of the hypotheses and discussion

This new way of seeing clinical signs in neurodegenerative diseases allows us to lump them as diseases involving new brain areas specific to human primates (homo sapiens sapiens) and to consider the clinical features from a neuroevolutionary (paleoneurological) standpoint specific to Homo and aging [15], [16], [17], [18], [189], [190], [268], [269] and build a new chapter in clinical neurology: paleoneurology. It allows us to understand why functional systems are focally involved, to class

References (274)

  • J.H. Kass

    The evolution of the complex sensory and motor systems of the human brain

    Brain Res Bull

    (2008)
  • D. Stout et al.

    The evolutionary neuroscience of tool making

    Neurpsychologia

    (2007)
  • Stout D, Toth N, Schick K, Chaminade T. Neural correlates of early stone age tool making: technology, language and...
  • R.S. Corrucini et al.

    Primate facial allometry and interpretations of australopithecine variation

    Nature

    (1979)
  • D. Falk

    Comparative anatomy of the larynx in man and the chimpanzee: implications for language in Neanderthal

    Am J Phys Antrhopol

    (1975)
  • N. Ramani et al.

    The evolution of prefrontal inputs to the cortico-pontine system: diffusion imaging evidence from the macaque monkeys and humans

    Cereb Cortex

    (2006)
  • S.I. Rapoport

    Brain evolution and Alzheimer’s disease

    Rev Neurol

    (1988)
  • K.G. Bayle

    The concept of phyllogenic regression

    J Am Acad Psychoanal

    (1978)
  • W.H. Calvin

    The emergence of intelligence

    Sci Am

    (1994)
    W.H. Calvin

    The brain as a Darwin machine

    Nature

    (1987)
  • A. Parent

    The brain in evolution and involution

    Biochem Cell Biol

    (1997)
  • G.M. Martin

    Gene action in the aging brain: an evolutionary biological perspective

    Neurobiol Aging

    (2002)
  • M.P. Mattson

    Brain evolution and lifespan regulation: conservation of signal transduction pathways that regulate energy metabolism

    Mech Ageing Dev

    (2002)
  • F.J. Vallender et al.

    A primate-specific acceleration in the evolution of the caspase-dependent apoptosis pathway

    Hum Mol Genet

    (2006)
  • K.S. Kosik

    The long reach of evolution and development. Effects on the Alzheimer brain

    Ann NY Acad Sci

    (2000)
  • D. Arendt

    Genes and homology in nervous system evolution: comparing gene functions, expression patterns and cell type molecular fingerprints

    Theory Biosci

    (2005)
  • H.J. Jerison

    The paleoneurology of language

    Ann NY Acad Sci

    (1976)
  • R.L. Holloway

    Paleoneurological evidence for language origins

    Ann NY Acad Sci

    (1976)
  • M. Brandt

    Brain evolution of the human from the paleoneurologic viewpoint

    Anthropol Anz

    (1993)
  • Y. Coppens

    L’évolution de l’homme

    Bull Mem Acad R Med Belg

    (1998)
  • E. Bruner

    Geometric morphometric and paleoneurology: brain shape evolution in the genus

    Homo J Hum Evol

    (2004)
  • R.E. Passingham

    Anatomical differences between the neocortex of man and other primates

    Brain Behav Evol

    (1973)
  • H. Creely et al.

    Human brain evolution

    Prog Brain Res

    (2006)
  • C.O. Lovejoy et al.

    Morphological analysis of the mammalian postcranium: a developmental perspective

    Proc Natl Acad Sci USA

    (1999)
  • C.O. Lovejoy

    The origin of man

    Science

    (1981)
  • S.C. Anton

    Natural history of homo erectus

    Am J Phys Antrhopol

    (2003)
  • Y. Coppens

    East side story: the origin of humankind

    Sci Am

    (1994)
  • P. Andrews et al.

    Homoid dietary evolution

    Philos Trans R Soc London B Biol

    (1991)
  • R.A. Foley et al.

    Ecology and energetics of encephalization in hominid evolution

    Philos Trans R Soc London B Biol Sci

    (1991)
  • B. Weiss et al.

    The developing brain and the environment: an introduction

    Environ Health Perspect

    (2000)
  • A. Kuliukas

    Wading for food: the driving force of the evolution of bipedalism?

    Nutr Health

    (2002)
  • W.R. Leonard

    Food for thought, dietary change was a driving force in human evolution

    Sci A

    (2002)
  • M. Uddin et al.

    Distinct genomic signatures of adaptation in pre- and postnatal environment during human evolution

    Proc Natl Acad Sci USA

    (2008)
  • B. Senut
  • S.C. Anton

    Climatic influences on the evolution of early homo?

    BMC Genomics

    (2007)
  • J.L. Romgo

    Neuronal interconectiom as a function of brain size

    Brain Behav Evol

    (1991)
  • P. La Cerra et al.

    The adaptative nature of the human neurocognitive architecture an alternative model

    PNAS

    (1998)
  • J.H. Pinkerton

    Some aspects of the evolution and comparative anatomy of the human pelvis

    J Obstet Gynaecol Br Commonw

    (1973)
  • C.V. Ward
  • R.M. Alexander

    Bipedal animals, and their differences from humans

    J Anal

    (2004)
  • M.L. Shik et al.

    Control of walking and running by means of electrical stimulation of the midbrain

    Biophysics

    (1966)
  • Cited by (20)

    • Involvement of mirror neuron system in prodromal Alzheimer's disease

      2016, BBA Clinical
      Citation Excerpt :

      In prodromal AD both visuo-spatial and language skills are impaired. The presence of melokinetic apraxia is an early sign of MCI due to AD, followed by typical disorientation or ideo-motor apraxia syndrome later in the course of disease [49]. These clinical manifestations are supported by morpho-structural and functional studies.

    • Paratonia and gegenhalten in childhood and senescence

      2012, Clinical Chiropractic
      Citation Excerpt :

      The association of gegenhalten/paratonia in the upper limbs and dyspraxia had been shown to be present in ten consecutive adult patients with dementia and gegenhalten of the upper limbs.4 It has been suggested that the neurodevelopmental/neurodegenerative diseases are age-related diseases of specific brain regions recently developed by homo sapiens.13 Although highly speculative, a common denominator and commonly cited possible causative factor is the second-generation of neurons that develop within the brain principally postnatally.

    View all citing articles on Scopus
    View full text