Paradigms 1981

Motor Paradigms

Motor and sensory paradigms were the first to be implemented, both because of the ease with which they can be performed in the scanner with no additional equipment and their easy validation by preoperative and intraoperative cortical monitoring. The good correlation between cortical monitoring and fMRI results made fMRI motor tasks the method of choice for the presurgical evaluation of patients.

There are many motor tasks described in the literature. Owing to the cortical distortion of the sensorimo-tor homunculus, the wider areas of fingers, hands, tongue and lips are the most frequently explored to produce the highest BOLD signal. Furthermore, hands/

fingers and lips/tongue are very important anatomical effectors, involved, respectively, in day-to-day manual activities and speaking. As a consequence, hand and lip movements are the most often used tasks to explore the activity of the primary motor cortex. When the lesion is located near the convexity of the brain, movements of the foot are also used.

As regards the hand movements, there is a wide spectrum of paradigms ranging from the simple opening and closing of the hand or squeezing a sponge, to the more complex sequential tapping of fingers in predetermined fixed order or repetitive opposition of the thumb and each of the remaining fingers. Simple and complex hand motor tasks bring about different cortical activation patterns.

Simple hand movements activate only the contralateral primary motor cortex, the superior part of the pre-central gyrus, in an area called the „precentral knob", otherwise named inverted il, which may also be divided by a sulcus in the middle and in that case is called horizontal £ [43, 44]. Complex hand movements activate not only the contralateral primary motor cortex, but also the ipsilateral motor cortex, the supplementary motor area, the premotor and the somatosensory cortex bilaterally [38]. There are different fundamental

Fig. 19.3 a-d. An example of a motion paradigm (repetitive sequential opposition of the thumb and each of the remaining fingers of the right hand). Note that activated areas are adjacent to the lesion (a meningioma). The patient underwent surgery with no sequelae

Fig. 19.3 a-d. An example of a motion paradigm (repetitive sequential opposition of the thumb and each of the remaining fingers of the right hand). Note that activated areas are adjacent to the lesion (a meningioma). The patient underwent surgery with no sequelae reasons for the primary sensory cortex activation. From the anatomical point of view, cytoarchitectonics show that pyramidal cells can be found either in the pre- or in the postcentral gyrus, and motor fibres in the pyramidal tract originate not only from primary motor areas (Ms I) but also from primary sensitive areas (Sm I). According to classical neurophysiology, it is possible to elicit motor responses by electrically stimulating the precentral gyrus, as well as the postcentral gyrus, with a partial overlapping of the homunculi of cortical motor and sensory representation. Finally, both sensory proprioceptive and esteroceptive afferents can be activated by positional changes during the performance of motor tasks.

When the motor task is complex, there is also an asymmetry in lateralization, as regards the dominant hemisphere. In right-handed subjects, finger movements of the right hand substantially activate the dominant (left) hemisphere with almost no activation in the non-dominant (right) hemisphere [17]. In left-handed subj ects, the activation pattern may show a high degree

of variability, but often both left and right hand movements produce activations comparable between dominant and non-dominant hemispheres [33]. Obviously, all these differences must be taken into account in analysing an activation pattern.

Figure 19.3 shows an example of eloquent areas evoked by the repetitive sequential opposition of the thumb and each of the remaining fingers of the right hand.

Sensory Paradigms

Sensory paradigms are used less often than motor paradigms, but have the advantage of being a passive task, which may also be performed on uncooperative patients (anaesthetized, unconscious, neurologically impaired, disabled, aged, babies, etc.). In this last case, they could be the only way to identify the sensorimotor cortex for surgical planning.

The most common way to perform a sensory paradigm is by tactile stimulation of the skin of the hand or, less frequently, of the foot or face. Simple plastic toothbrushes, blunt nails, air puffs and even the examiner's fingertips may accomplish this kind of stimulation.

Results show eloquent areas in both the postcentral and the precentral gyri [42]. The situation is similar to that which we have seen in motor paradigms: there is an anatomical cytoarchitectonic reason (i.e. the presence of granular cells not only in Sm I but also in Ms I) together with numerous connections through cortico-cortical or thalamocortical relays [42]; moreover, a direct cortical stimulation of the motor cortex in humans evokes sensory experiences [4]. The concept of a narrow, discrete, pre-Rolandic motor cortex separated from post-Rolandic sensory strip, although pervasive, has been challenged by evidence of a broad overlapping sensorimotor cortex [37].

Visual Paradigms

Before the introduction of fMRI, the most common way to obtain functional information about important anatomical visual areas, such as the fibre system of the optic radiations, the lateral geniculate nucleus and the striate/ extrastriate cortices, was by perimetric examination of the visual field. This technique, however, provides only a subjective determination, at each point, of the functional variation in time and lacks direct anatomical information. Conventional neuroradiological imaging, on the other hand, simply outlines lesion location and its gross extent, but it is often difficult to establish if the presence of oedema or structural alterations of local anatomy imply neuronal death. A better understanding of the function-structure correlation of striate organization has been provided by functional PET imaging studies, but the associated radiation exposure and the limited availability of PET units have restricted its application for routine evaluation of patients with visual field defects to those described in a few clinical reports [18].

The enhanced spatial and temporal resolution of non-invasive fMRI, together with its safety and availability, have provided new and valuable information in understanding the organization and functional properties of visual areas in the human cortex. For instance, fMRI has been a precious method in confirming cortical retinotopy and quantitatively defining cortical extension of the central foveal vision [18,32], results that, otherwise, could only have been obtained in an invasive manner. fMRI imaging can detect objective visual field deficits, caused by lesions not only producing destruction of the primary visual cortex, but also interrupting visual pathways and creating a lack of sensory input, without destroying neurons in the occipital cortex [18].

Visual stimulation may be delivered in plenty of modes: frequently used stimuli are flashing of white or coloured lights at certain frequencies, or alternating checkerboards, stripes or bands. Stimuli may be presented by a video screen or by goggles. This last device is often preferred, because it allows different kinds of stimulations (e.g. monocular, different mixes of hemi-fields, quadrants) and allowed us to explore cortical visual retinotopy. Moreover, it provides a better concentration for the patient, who cannot see anywhere but into the goggles. The resting condition is frequently characterized by a black screen with a fixation point in the centre. We implemented visual paradigms in our department by using goggles and alternating (500 ms period) black and red vertical bands (Fig. 19.4).

Language and Lateralization Paradigms

Since the classical works of Wernicke and Broca, the location and definition of brain language areas have been a goal and a challenge for researchers. Language areas

Fig. 19.4. An example of a visual paradigm. a Stimulation (alternating black and red vertical bars with a period of 500 ms) and rest alternating every 30 s. Stimulation may involve full visual fields bilaterally (b) or superior/inferior right quadrants (c, d, respectively). Cortical retinotopy is respected. Note the small meningioma in the left hemisphere. (Modified from [21], with permission)

ACTIVATION (30 s)

500 ms

500 ms

Fig. 19.4. An example of a visual paradigm. a Stimulation (alternating black and red vertical bars with a period of 500 ms) and rest alternating every 30 s. Stimulation may involve full visual fields bilaterally (b) or superior/inferior right quadrants (c, d, respectively). Cortical retinotopy is respected. Note the small meningioma in the left hemisphere. (Modified from [21], with permission)

have traditionally ascribed to two discrete regions: Wernicke's area, which is responsible for the receptive aspects of language (comprehension), and Broca's area, which controls the expressive aspects of language (production). The former is located in the left posterior temporal lobe, the latter in the left inferior frontal lobe, anterior to the central fissure; both are interconnected by the arcuate fasciculus that allows information exchange between the two.

Language areas are usually located in only one hemisphere, more frequently the left, but lateralization may not remain constant: translocation of single Wernicke's [27] or single Broca's [14] areas to the contralateral hemisphere has been demonstrated in right-handed patients, when, for instance, a slowly growing tumour allows brain plasticity mechanisms to come into play.

Owing to the complexity of language-related functions, the exact location of these functional areas is somewhat variable and cannot be predicted on the basis of anatomy alone. Of course these areas are of great importance to the private and social life of the patient and sparing them is essential when a surgical approach is required.

Before the arrival of PET and fMRI and for approximately half of the previous century, the Wada test represented the „gold standard" and the task routinely used to assess the language-dominant hemisphere. Briefly, the Wada test requires the catheterization of both the internal carotid arteries, the successive injection, for each side, of amobarbital (125 mg), followed by hemispheric anaesthetization, to exclude one hemisphere at a time; the final step is the study of the awake hemisphere to establish persistence or disruption of language functions. Of note, the Wada test is possible only when there are no vascular abnormalities allowing arterial crossflow between the two hemispheres.

The advent of fMRI has changed the approach to language exploration. As one can easilyinfer, the Wadatest has many disadvantages with respect to fMRI: invasive ness, higher risk, higher cost, and very short amounts of time (5-10 min) available to explore the awake hemisphere. fMRI, in addition to being non-invasive and cheaper, is not affected by underlying supply patterns, can be easily repeated, if necessary, without additional risk and affords the examiner sufficient time to test a range of cortical functions. Moreover, owing to the fact that the entire brain is examined simultaneously, results are not confounded by difficulties in reproducing test conditions separately for each hemisphere, as in the Wada test. As a consequence, several studies have compared fMRI to the Wada test and have shown a significant correlation between results from both modalities in most cases. fMRI studies typically identify more language regions than direct electrocortical stimulation mapping and the Wada test, suggesting that fMRI not only identifies areas that are critical for language processing, but also areas that participate in a less critical manner in networks that sustain language function. The result is a wider availability of information.

Plenty of paradigms have been used in the literature (cf. [5] for an exhaustive review) to define lateralization and locate language areas. On the whole, language paradigms may be classified into two main categories: the ones exploring receptive language and the ones exploring expressive language.

Receptive Language Paradigms. This kind of task explores the comprehension aspect of language and elicits eloquent areas corresponding to Wernicke's areas proper (the posterior part of the superior temporal gyrus, posterior BA22) and the surroundings (the anterior-superior and middle temporal gyri, anterior BA22, the midsuperior temporal sulcus, midportion of BA21 and BA22), with the adjacent angular (BA39) and su-pramarginal (BA40) gyri, in the dominant hemisphere.

Receptive language paradigms are mainly divided into reading comprehension (visual input) and auditory comprehension (auditory input). The most common

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