The electrical excitability of the brain: toward the emergence of an experiment.

In 1870, Eduard Hitzig and Gustav Fritsch performed experiments on dogs by which they were able to produce movement through electrical stimulation of specific parts of the cerebral cortex. Contemporaries regarded the experiment as a milestone in the controversially discussed issue of cerebral localization of functions even though this experiment came as a surprise to the community of experimental physiologists who had rejected localization for several decades after the antiphrenological work of the physiologist Pierre Flourens. In this article, I will argue that the context in which this experiment emerged was not so much the French localization debate of the 1860s but rather practical demands in clinical medicine, notably in electrotherapy. At the time of the experiment, Hitzig worked as a medical practitioner in Berlin and was interested in an anatomical and physiological explanation of the specific symptoms of one of his patients. The unpredictable outcome of this interest was the discovery of the electrical excitability of the cortex. Whereas experimental physiologists dominated the discussion on cerebral localization in Germany before 1870, the situation shifted after the publication of Fritsch and Hitzig's paper. Concrete medical necessities forced the discussion about localization and it was mainly due to the authority of clinical physicians that the localization of mental qualities in the brain became a cornerstone of brain research.

Real-time fMRI and its application to neurofeedback.

Real-time fMRI (rtfMRI) allows immediate access to experimental results by analyzing data as fast as they are acquired. It was devised soon after the inception of fMRI and has undergone a rapid development since then. The availability of results during the ongoing experiment facilitates a variety of applications such as quality assurance or fast functional localization. RtfMRI can also be used as a brain-computer interface (BCI) with high spatial resolution and whole-brain coverage, overcoming limitations of EEG based BCIs. This review will focus on the application of rtfMRI BCIs to neurofeedback, i.e., the online feedback of the blood oxygen level dependent (BOLD) response. I will motivate its development and place its beginnings into the contemporary scientific context by providing an account of our early work at the University of Tübingen, followed by a review of the accomplishments and the current state of rtfMRI neurofeedback. RtfMRI neurofeedback has been used to train self-regulation of the local BOLD response in various different brain areas and to study consequential behavioral effects. Behavioral effects such as modulation of pain, reaction time, linguistic or emotional processing have been shown in healthy and/or patient populations. RtfMRI neurofeedback presents a new paradigm for studying the relation between brain behavior and physiology, because the latter can be regarded as the independent variable (unlike in conventional neuroimaging studies where behavior is the independent variable). The initial results in patient populations improving pain, tinnitus, depression or modulating perception in schizophrenia are encouraging and merit further controlled clinical studies.

In quest of constitutional principles of "neurolaw".

The growing use of brain imaging technology and the developing of cognitive neuroscience pose unaccustomed challenges to legal systems. Until now, the fields of Law much affected are the civil and criminal law and procedure, but the constitutional dimension of "neurolaw" cannot be easily underestimated. As the capacity to investigate and to trace brain mechanisms and functional neural activities increases, it becomes urgent the recognition and definition of the unalienable rights and fundamental values in respect of this new techno-scientific power, that must be protected and safeguard at "constitutional level" of norms such as: human dignity, personal identity, authenticity and the pursuit of individual "happiness". As the same as for the law regulating research and experimentation on human genome adopted in the past years, one may also argue if the above mentioned fundamental principles of "neurolaw" must be fixed and disciplined also at European and International level.

Localization of language function in the twentieth century.

In the twentieth century the method of identifying pathology in patients with aphasia has fluctuated between localizing and holistic theories. The practical localization of sensation and voluntary movement became a clinical commonplace in the beginning of the century, but the mental component of aphasia made its localization controversial. In Paris before the war, Pierre Marie made the localization of aphasia the centerpiece of his personal feud with Jules Dejerine. After the war Konstantin von Monakow used the phenomenon of recovery from aphasia to support his holistic views of localization. Henry Head, in a 1926 study that remains influential today, took a neo-Jacksonian approach to localization and the physiology of language. Kurt Goldstein led the postwar anti-localizationists, asserting that physicians must look after the whole person and that brain function was inherently unified. Norman Geschwind reflected 1960s physiological thought in analyzing aphasia as a type of disconnection of distinct functional areas. In the twenty-first century the localization of aphasia remains dependent on theory, with competition between holistic and localizing ideas.