P. M. S. Hacker - Philosophical Foundations of Neuroscience

Figure 1.1 Significant activations over the whole brain revealed following averaging BOLD fMRI signals over 100 neuropsychological tests on a subject. (A) axial view of a map of the significant signal changes through the entire cortex to a simple motor response to a visual decision neuropsychological test, described in the text. (B) corresponding sagittal view of the map. (C) time course of the BOLD fMRI signals corresponding to coloured regions in the brain.

Source: Gonzalez-Castillo et al., 2012

Furthermore, there is no objective basis for accepting some shapes and rejecting others. Many of the fMRI determinations of the spatial distribution of activations of the cortex during neuropsychological tests are based on box-car temporal profiles and so assume that only these are relevant when defining the term ‘activation’. This assumption is unlikely to be correct and neglects important information regarding cortical activity accompanying a neuropsychological test. A plausible explanation for the large deviations of the fMRI signals from a box-car shape has recently been offered in terms of their originating from different extents of impulse activity in the region of interest conditional on temporal changes in the amount of inhibitory and excitatory activity there. 103This being so, all shapes of the fMRI signal provide important information concerning the integrative activity in a given region.

The amplitude of BOLD signals over the cortex of single subjects during a neuropsychological test and on-going cortical activity

The threshold at which a particular fMRI signal is to be accepted for determining the sites over the cortex involved in a neuropsychological test depends on both the signal-to-noise ratio, as well as the amplitude of the signal taken to be of the box-car variety. However, it has been known for some time that the amplitude of the signal, taken as a measure of the transient activity during a neuropsychological test, is conditional on the activity of the part of the cortex of interest at the time of the test: the larger the background signal the smaller the transient signal and vice versa, independent of the neuropsychological test being used. 104Using quantitative relations integrating BOLD responses, energetics and impulse firing, it has been shown how baseline activity can determine the amplitude of both positive and negative sustained BOLD signals. 105It may therefore be necessary to measure the ongoing activity in the area of interest in order to correct for the fMRI amplitude during the neuropsychological test. In animal studies this can be done by using PET to determine the ongoing glucose metabolism, a direct measure of activity, in conjunction with the fMRI measurements. 106This can be carried out using combined MRI/PET, but involves the injection of radioactive fluorodeoxyglucose as a ligand, a procedure that is invasive for human subjects. The extent that the baseline varies between different cortical areas of interest in the cortex is not clear at this time, so there are reservations concerning the interpretation of the amplitude of the BOLD signal recorded in different areas during a psychological test. 107

The existence of a ‘global BOLD signal’ across the cortex, and the question of the regression of the signal

In fMRI the ‘global signal’ refers to the average signal across all brain voxels in the time series of signal intensity. Given that most fMRI studies aim to specify changes in activity that are specific to particular brain areas, and that this global signal is at least in part generated by sources other than those due to such activity, such as the cardiac and respiratory cycles, 108it is important to identify such contributions and eliminate them from the global signal. The easiest path to take here involves elimination of the entire global signal from measurements by simply regressing it from the time series of the signals in each voxel, using linear regression. 109An important caveat to this apparently straightforward procedure is that the mathematical techniques involved can introduce spurious relations between fMRI measurements in different brain voxels. Opposite conclusions have been reached by senior brain imaging experts concerning whether to regress out the global signal or not. 110This has left researchers in a quandary as to how to proceed, a quandary that has been highlighted by the contending groups in joint papers. 111Such difficulties are compounded by the possibility that the global signal might contain biological information concerning brain function, for which there is evidence. 112All in all, there is a need for caution when deliberating on fMRI observations claiming to delineate different functional networks of activity in the brain.

1 1For a history of the identification of sensory systems see M. R. Bennett, S. Hatton, D. F. Hermens and J. Lagopoulos, ‘Behaviour, neuropsychology and fMRI’, Progress in Neurobiology, 145–6 (2016), pp. 1–25.

2 2Aristotle, De Anima 412a20. Subsequent references to this treatise in the text will be flagged ‘DA’.

3 3It should be noted that Aristotle held that a sightless eye is no more an eye than a painted eye, just as a corpse is no more an animal than a statue.

4 4Note that when Aristotle says that we do these things with our soul, this is not like doing something with our hands or eyes, but rather like doing something with our talents and abilities.

5 5We disregard here the complexities, and incoherences, that arise with regard to Aristotle’ s distinction between the active and passive intellect and the intimation that the active intellect may be capable of existing without a body (DA 429a18–29, 430a18–25). These passages were crucial for the later scholastic synthesis of Aristotelian philosophy of mind with Christian doctrine concerning the immortality of the soul.

6 6For his reasoning, see De Partibus Animalium 647a22–34. In this respect he differed from the Hippocratic tradition. The Hippocratic lecture on epilepsy noted that ‘It ought to be generally known that the source of our pleasure, merriment, laughter and amusement, as of our grief, pain, anxiety and tears, is none other than the brain. It is especially the organ which enables us to think, see and hear, and to distinguish the ugly and the beautiful, the bad and the good, pleasant and unpleasant… . It is the brain too which is the seat of madness and delirium, of the fears and frights which assail us, often by night, but sometimes even by day; it is there where lies the cause of insomnia and sleepwalking’ (‘The sacred disease’, §17, in G. E. R. Lloyd (ed.), Hippocratic Writings (Penguin Books, Harmondsworth, 1978). The Hippocratic insight is wonderful; the physiological reasoning is, however, no less erroneous than Aristotle’ s reasoning in support of his different hypothesis.

7 7Aristotle, De Somno 455a21. This is the Barnes translation; an alternative translation of the sentence in which this term appears is ‘For there exists a single sense-faculty, and the master organ is single’.

8 8His term is aisthe¯sis koine¯, which occurs only in De Anima 425a27, De Memoria 450a10 and De Partibus Animalium 686a27.

9 9Aristotle, De Sensu 449a5–11.

10 10See, e.g., F. Crick, The Astonishing Hypothesis (Touchstone, London, 1995), p. 22; A. Damasio, The Feeling of What Happens (Heinemann, London, 1999), p. 320; E. Kandel and R. Wurtz, ‘Constructing the visual image’, in E. R. Kandel, J. H. Schwartz and T. M. Jessell (eds), Principles of Neural Science (Elsevier, New York, 2001), p. 492. For a discussion of the binding problem, see §5.2.3.