The SEF constitute an integral part of the network controlling eye movements. In their
pioneering research, Penfield and Rasmussen (1950) noticed that electrical stimulation, during
craniotomy, of the human rostral supplementary motor area (SMA), induced gaze shifts. Schlag
and Schlag-Rey (1985, 1987) recorded gaze and head movements when single-unit activity
was administered to the dorsomedial edge of the frontal lobe, above the superior arcuate
sulcus, in three trained monkeys. The authors proposed that this was a supplementary eye
field, separate from the FEF, and termed the area the SEF. The human SEF is thought to
correlate with the dorsal bank of the cingulate sulcus in the monkey brain. Hutchison et al.,
(2012) proposed that the SEF boundary was located along the anterior-posterior axis within the
medial wall, dorsal to the cingulate sulcus. The connective network of the dorsomedial region
is extensive and complex and innervates the FEF and the SC in monkeys (Huerta & Kaas,
1990). The SEF also receives reciprocal projections from the motor cortex (Lu, Preston &
Strick, 1994) and projects to the brainstem and spinal cord nuclei involved in eye, head, and
limb movement (Huerta & Kaas, 1990). Visual centres, including the lateral IPS area and the
medial superior temporal area, innervate the region, while reciprocal connections to the
prefrontal cortex form pathways to thalamic and striatal areas associated with an oculomotor
function (Huerta & Kaas, 1990). Evidence suggests that SEF may contain a topographic map
experiments have demonstrated that eye movements can be evoked when the rostral area is
activated, compared to when stimulation is applied to caudal or between rostral and caudal
areas, which evoked hind-leg and forelimb movement.
Neural recordings from monkey electro-stimulation studies and human imaging studies have
documented activity in the SEF during a range of saccadic tasks including, but not limited to;
distinguishing between successful and unsuccessful cancellation of saccades (Curtis, Cole, Rao, & D’Esposito, 2005), smooth pursuit (Missal & Heinen, 2017), object-centred spatial
awareness (Olson & Gettner, 1995, 1996, 1999), change-of-plan saccades (Nachev, Rees,
Parton, Kennard, & Husain, 2005), memory-guided saccade sequences (Lu, Matsuzawa, &
Hikosaka, 2002), and serial decision-making (Abzug & Sommer, 2018).
Several studies have investigated the functional role of the SEF in oculomotor behaviour after
brain injury in humans (Gaymard, Pierrot-Deseilligny, & Rivaud, 1990; Heide, Kurzidim, &
Kompf, 1996), reporting impairments in sequential eye movements and saccades anticipating
predictable target motion. However, these experiments had small sample sizes, and lesions
were not localized specifically to SEF, therefore, findings cannot be attributed to discreet SEF
damage but probably reflect disruption to multiple systems.
Parton et al., (2007) reported the case study of JR, a 55-year-old male who suffered a small left
medial frontal venous stroke eight months prior. Using high-resolution structural MRI, the
research team precisely localized the bilateral lesion to SEF in both axial and sagittal planes
and confirmed that pathology did not extend beyond this specific area. JR completed anti-
saccade, pro-saccade, and memory-guided saccade tasks, as well as a task that involved
learning arbitrary oculomotor stimulus-response mappings through trial and error. JR’s
performance on the anti and pro-saccade tasks exceeded that of age-matched controls and he
his high accuracy scores; a speed/accuracy trade-off. However, he showed impaired
performance switching from anti to pro-saccades on a conflict task compared to age-matched
controls. He also showed prolonged latencies on the arbitrary stimulus-response task when
selecting the correct saccade compared to controls. These findings suggest that the SEF may
not be necessary for instigating saccades, but mediates the implementation of control when
there is a conflict between competing saccadic responses, but not when saccades need to be
made accurately in sequence. Indeed, it seems likely that that SEF does not directly control
saccades but rather mediate higher-order cognitive variables during saccades, such as
monitoring error, conflict, and reward (Husain, Parton, Hodgson, Mort & Rees, 2003;
Stuphorn, Brown, & Schall, 2009; Roesch & Olson, 2003).
In summary, the role of the SEF in human oculomotor function is still under investigation. It
is generally agreed that the SEF is not directly involved in the generation of eye movements
but instead mediates higher-order cognitive functions during saccades (Husain et al., 2002;
Stuphorn et al., 2010; Roesch & Olson, 2003).
3.4.3. Dorsolateral prefrontal cortex (DLPFC)
The location and connections of the DLPFC are discussed in detail in chapter one but, in brief,
the area encompasses area 8, 9 and 46 and has complex interconnections with subcortical
circuits including the FEF, SEF, and PEF (Cummings & Miller, 2007; Pierrot-Deseillingny,
Müri, Nyffeler & Milea, 2005; Figure 26). Lesion, tDCS, and neuroimaging studies have
reported that the human DLPFC pathways mediate aspects of executive function control, the
capability to undertake goal-directed behaviour using complex mental processes (Manes et al.,
2002; Nejati, Salehinejad & Nitsche, 2018; Yuan & Raz, 2014), and monkey and human
DLPFC have both been associated with executive control of anti-saccades (Coe & Munoz,
The anti-saccade movement requires two mechanisms; firstly executive resources (Tarnowski,
2013) suppressing reflexive saccades (DLPFC inhibits reflexive saccade generated by the PEF),
and secondly, generating the correct anti-saccade (generated by the FEF; Ploner, Gaymard,
Rivaud-Péchoux & Pierrot-Deseilligny, 2005). Human DLPFC lesions have resulted in an
increased percentage of errors in the anti-saccade task, while FEF lesions can cause an increase
in the latency of correct anti-saccades (Gaymard, Ploner, Rivaud-Pechoux & Pierrot-
Deseilligny, 1999; Pierrot-Deseilligny et al., 1991; Rivaud, Müri, Gaymard, Vermersch &
Pierrot-Deseilligny, 1994). This dissociation suggests an inhibitory role of the DLPFC.
Ploner et al., (2005) tested 15 participants with acute unilateral ischemic lesions of the
prefrontal cortex and 20 controls on an anti-saccade task to determine if there was a distinct
sub-region of the human prefrontal cortex responsible for reflexive saccades. They found that
lesions affecting a region in the mid-DLPFC, or the white matter between this region and the
anterior portions of the internal capsule, resulted in increased anti-saccade errors. Lesions
outside of these areas did not appear to affect anti-saccade error rates. These results indicated
that the DLPFC inhibit reflexive saccades. However, the authors excluded participants who had sustained ‘unusual’ strokes such as vasculitis and venous thrombosis, only including
individuals who had sustained unilateral atherothrombotic or embolic infarction. Although
researchers control for differences in lesions, each human brain damage case is essentially
unique. For instance, evidence suggests that different subtypes of typical strokes (e.g.
atherothrombotic or embolic) still produce differences in pathogenesis (Arboix, Oliveres,
Massons, Pujades & Garcia-Eroles, 1997; Kozuka et al., 2002), making it difficult to ascertain
the reliability and validity of human lesion studies and to generalise the results.
It is theorised that there may be a ‘task-set’ neuronal organisation in the DLPFC with different
2005). The DLPFC is active during the preparatory phase of anti-saccades and may also
mediate inhibitory signals to saccade-related regions, such as the SC. Johnston and Everling
(2006) recorded DLPFC activity in monkeys when they performed alternating pro and anti-
saccade trials. The researchers discovered that the DLPFC appeared to generate task-selective
signals (e.g. stimulus location and saccade direction) to the SC, suggesting that the region is
involved in controlling the activity of other brain regions depending on the goal of the task. Although Johnston and Everling’s (2006) research provides evidence of single neuron
behaviour in the monkey DLPFC, it is still not clear how this very specific neuronal activity
functions in the human oculomotor system (Johnston, DeSouza & Everling, 2009), and
therefore it remains a hypothetical model until direct human data are established.
TMS pulse activation over the DLPFC of control participants during the preparatory phase of
anti-saccades increased errors in anti-saccades, while the application of TMS after the
preparatory phase did not affect anti-saccades (Nyffeler et al., 2007). These findings suggest a
critical time frame where the DLPFC can inhibit reflexive saccades during the anti-saccade
task, and this time interval is before the onset of the stimulus. While TMS can provide causal
brain-behaviour information in humans, the method does have some disadvantages. For example, Nyffeler et al.’s (2007) localisation procedure for positioning the TMS coil over the
DLPFC relied upon functionally localising TMS 5cm anteriorly from the motor hand area.
However, there is no guarantee that this TMS placement specifically targeted the DLPFC in
each of the 15 participants, as genetic and environmental effects may contribute to individual
differences in adult human brain structure (Gu & Kanai, 2014).
In other work, human lesion (Pierrot-Deseilligny et al., 2003; Pierrot-Deseilligny et al., 1991;
Ploner et al., 1999) and TMS studies (Müri et al., 2000) have reported that the DLPFC may be
Meager and Curtis (2016) reported that individuals who had sustained damage to the DLPFC,
which did not encroach on the precentral sulcus, performed equally well on a memory-guided
saccade task compared to controls. Mackey et al.’s., (2016) findings may contrast with other
studies conducting similar research because much of the earlier work was based on patient
populations who had sustained strokes affecting large areas of the DLPFC.
In summary, the DLPFC exerts executive control over the programming and preparation of
anti-saccades (Cameron et al., 2015). The region inhibits unnecessary reflexive saccades,
triggered by the PEF, by mediating bias signals to saccade-related areas (Pierrot-Deseillingny
et al., 2005). Therefore, pathology to this region may produce selective deficits in these visual
mechanisms depending on lesion location and severity, thus impacting the processing of visual
stimuli.