An avant-garde professorship of neurobiology in education: Christofredo Jakob (1866-1956) and the 1920s lead of the National University of La Plata, Argentina.

The interdisciplinary trend in "Mind, Brain, and Education" has witnessed dynamic international growth in recent years. Yet, it remains little known that the National University of La Plata in Argentina probably holds the historical precedent as the world's first institution of higher education that formally included neurobiology in the curriculum of an educational department, having done so as early as 1922. The responsibility of teaching neurobiology to educators was assigned to Professor Christofredo Jakob (1866-1956). In the present article, we highlight Jakob's emphasis on interdisciplinarity and, in particular, on the neuroscientific foundations of education, including special education.

Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD).

We screened for the presence of inborn errors of metabolism (IEM) in 187 children (105 males; 82 females, ages 4-14 years old) who presented with confirmed features of autism spectrum disorder (ASD). Twelve patients (7%) manifested increased 3-hydroxyisovaleric acid (3-OH-IVA) excretion in urine, and minor to significant improvement in autistic features was observed in seven patients following supplementation with biotin. Five diagnoses included: Lesch Nyhan syndrome (2), succinic semialdehyde dehydrogenase (SSADH) deficiency (2), and phenylketonuria (1) (2.7%). Additional metabolic disturbances suggestive of IEMs included two patients whose increased urine 3-OH-IVA was accompanied by elevated methylcitrate and lactate in sera, and 30 patients that showed abnormal glucose-loading tests. In the latter group, 16/30 patients manifested increased sera beta hydroxybutyrate (b-OH-b) production and 18/30 had a paradoxical increase of sera lactate. Six patients with elevated b-OH-b in sera showed improved autistic features following implementation of a ketogenic diet (KD). Five patients showed decreased serum ketone body production with glucose loading. Twelve of 187 patients demonstrated non-specific MRI pathology, while 25/187 had abnormal electroencephalogram (EEG) findings. Finally, family history was positive for 22/187 patients (1st or 2nd degree relative with comparable symptomatology) and consanguinity was documented for 12/187 patients. Our data provide evidence for a new biomarker (3-OH-IVA) and novel treatment approaches in ASD patients. Concise 1 sentence take-home message: Detailed metabolic screening in a Greek cohort of ASD patients revealed biomarkers (urine 3-hydroxyisovaleric acid and serum b-OH-b) in 7% (13/187) of patients for whom biotin supplementation or institution of a KD resulted in mild to significant clinical improvement in autistic features.

Christfried Jakob's late views (1930-1949) on the psychogenetic function of the cerebral cortex and its localization: culmination of the neurophilosophical thought of a keen brain observer.

This article follows the culmination of the scientific thought of the neurobiologist Christfried Jakob (1866-1956) during the later part of his career, based on publications from 1930 to 1949, when he was between 64 and 83 years of age. Jakob emphasized the necessity of bridging philosophy to the biological sciences, neurobiology in particular. Thus, we consider him as one of the early protagonists in the emergence of neurophilosophy in the 20th century. The topics that occupied his mind were the foundations for a future philosophy of the brain, and the 'neurobiogenetic', 'neurodynamic', and 'neuropsychogenetic' problems in relation to how consciousness emerges. Jakob's views have many elements in common with great thinkers of philosophy and psychology, including Immanuel Kant, William James, Edmund Husserl, Henri Bergson, Jean Piaget and Willard Quine. A common denominator can also be discerned between Jakob's dynamic approach and certain aspects of cybernetics and neurophenomenology. Jakob propounded the interdisciplinarity of sciences as an indispensable tool for ultimately solving the enigma of consciousness.

Challenging the supremacy of the frontal lobe: early views (1906-1909) of Christfried Jakob on the human cerebral cortex.

This article focuses on a series of six studies that address functional localization in the frontal lobe; they were published in Argentina between 1906 and 1909 by Christfried Jakob (1866-1956), one of the great thinkers in early 20th century neuropathology and neurophilosophy. At that time, the localization-holism controversy was at a peak, having been triggered by the historic Marie-Déjerine aphasiology debate. Jakob held the view that constitutive physiological elements of cognition are localized. Nonetheless, he cast doubt on phrenological approaches that considered the frontal lobe as 'superior' to the other cortical regions. Jakob studied the human frontal lobe from fetal life through senility, in normality and pathology, including tumors, injuries, softening, general paralysis and dementia. Based on those finds, he considered strict localization theories a dead-end. Taking a critical look at Flechsig's ideas on the parallel ontogenies of frontal association centers and intellect, Jakob argued that the frontal lobe does not carry any selective advantage over the remaining human cerebral lobes or even over the frontal lobe in non-human primates. Regarding lesion experiments in laboratory animals, he pointed to methodological caveats, such as insufficient recovery time, that may lead to disorientating conclusions, and rejected élite brain research, calling it superficial and inexact. Jakob was convinced that the verification of the anatomical connections of the frontal lobe would elucidate its functions. Thus, he viewed the frontal lobe as a central station receiving input via olfactory pathways and thalamic radiations, pertinent to muscular and cutaneous senses, and attributed a perceptive character to a brain region traditionally associated with productive functions. Modern neuroscience seems to support Jakob's rejection of distinguishable motor and sensory regions and to adopt a cautious stance concerning oversimplified localization views.

Christfried Jakob's 1921 Theory of the Gnoses and Praxes as fundamental factors in cerebral cortical dynamics.

This study aims at reviving an important contribution by the pioneer neurobiologist and neurophilosopher Christfried Jakob (1866-1956) to the understanding of higher cortical functions. Jakob studied cortical dynamics at multiple levels by comparing gnoses and praxes and their corresponding pathological states, i.e. the agnosias and the apraxias. We herein provide a complete English translation of Jakob's original Spanish article dating to 1921, and further consider some key points under the scope of the neuropsychological knowledge available then, and the research evidence available 90 years later.