Article Figures & Data
Figures
- Figure 1.
a, Rationale and hypotheses of the current study. Neural activity persists in the monkey dlPFC during the retention interval of MGS tasks (Funahashi et al., 1989). Lesions to the monkey dlPFC cause impaired MGSs, especially when made into the visual field contralateral to the lesion (Funahashi et al., 1993). Hypothesis 1: These monkey data predict that lesions to human dlPFC will impair spatial WM performance, including the accuracy of MGSs. However, human neuroimaging studies typically find persistent activity or multivoxel decoding of information restricted to the PCS, posterior to the likely homolog of the monkey principal sulcus in the dlPFC (Courtney et al., 1998; Srimal and Curtis, 2008; Jerde et al., 2012; Sprague et al., 2014). Hypothesis 2: These data predict that lesions to human PCS, not dlPFC, will impair WM performance. b, MGS task used to measure WM ability. c, Dependent variables measured in the current study. Derived from eye tracking data, we measured the following: saccadic response time (in milliseconds), time between the offset of the fixation after the delay and the initiation of the MGS; primary saccade error (in degrees of visual angle), the deviation between the position of the eye following the first primary saccade and the target; final saccade error (in degrees of visual angle), the deviation between the target and the position of the last fixation before the target feedback was re-presented; saccade gain (ratio), amplitude of the saccade divided by the amplitude of the target.
- Figure 2.
a, dlPFC lesions from patients overlaid on the left hemisphere of structural MRI slices. Five patients had dlPFC lesions that spared the PCS but impacted portions of the middle and superior frontal gyri as can be seen in the lesion overlap reconstruction. Three patients had dlPFC lesions that further encroached upon the PCS. The Z numbers below indicate the slice planes in standardized MNI space (millimeters above anterior commissure). Color bar represents the number of patients (n = 8) with lesions to that part of brain. These lesions are more circumscribed than those typically caused by neurovascular events. Patients with right hemisphere lesions (n = 4) were flipped to generate the overlap lesion reconstruction. b, Example patient (dlPFC2) with a resection of the dlPFC (blue area) that spared the PCS (red line). c, Example patient (PCS1) with a resection (red area) that removed a portion of the PCS (white line). For more details, see Materials and Methods. For demographic, etiologic, and neuropsychologic data, see Table 1. d, Individual lesion reconstructions for each of the PFC patients with resections of dlPFC sparing the PCS. e, PCS patients with resections of dlPFC impacting the PCS. Asterisks denote that the patient was excluded because of failure to maintain central fixation when the memory cue appeared in the periphery for at least 50 trials (for details, see Table 3).
- Figure 3.
Performance on WM (MGS) and control (VGS) tasks. a, Radial histograms of the accuracy of primary MGSs, the final position of the eye after corrective saccades, but before feedback, and the accuracy of visually guided saccades. Each line indicates the mean error of an individual patient or healthy control at each radial location. Shaded half represents performance in the visual field contralateral to the lesion. b, Group average error on MGS and VGS tasks. Error bars indicate SEM. Patients with PCS lesions generated primary MGSs with more spatial error than controls. *p < 0.01. The individual performance is plotted in Figure 4.
- Figure 4.
Performance on WM (MGS) and control (VGS) tasks. Each dot represents the mean performance of an individual patient or healthy control, and lines connect the same participant. Open dots represent the performance in the visual field contralateral to the lesion; or in the healthy controls, it represents the left visual field. Filled dots represent the ipsilesional visual field (or right visual field in controls). The group mean performance is plotted in Figure 3.
- Figure 5.
Group average (a) saccade gains and (b) response times of MGS and control VGS tasks. The MGS errors made by the PCS patients were hypometric in gain and slower (∼75 ms) compared with the control group. *p < 0.05. Error bars indicate SEM.
- Figure 6.
Corrective saccades following initial MGSs. a, Example trace of typical MGS from a healthy control participant showing a primary MGS to the upper left quadrant, quickly followed by a single corrective saccade that brings the eye within a degree of the remembered target (black trace). Later the eye fixates that target shortly after it is re-presented as feedback. b, Example trace from a patient with a PCS lesion generating an extremely hypometric primary MGS that is followed by multiple rapid corrective saccades that eventually bring the eye close to the remembered target. c, Cumulative distribution of the frequency (y-axis) of single and multiple MGSs (x-axis) by group and visual field with respect to lesion. PCS patients generated many more multistep MGSs, especially into the contralesional hemifield. Error bars indicate SEM. d, Percentage of trials in which more than two saccades were made. The example trial depicted in a is an example of a trial that would not be counted (n = 2 saccades), whereas the example in b is an example that would be counted (n = 4 saccades). PCS patients had many more trials with more than two saccades, especially into the contralesional visual field, compared with controls. *p < 0.05. Open bars represent trials in which the target was in the contralesional visual field (or in the case of controls, the right visual field). Closed bars represent ipsilesional (or left visual field for controls). Error bars indicate SEM.
Tables
- Table 1.
Demographic data and lesion information on the sample of patients with prefrontal cortex resectionsa
Age (years) Gender Handedness Education (years) Lesion size (ml) Years since resection Hemisphere Cause for resection dlPFC 1 46 M Right 16 41.07 5.9 Left Glial tumor dlPFC 2 41 F Right 17 139.62 16.42 Right Epilepsy dlPFC 3 23 F Right 16 36.24 0.73 Left Oligodendroglioma (low-grade) dlPFC 4 45 M Right 16 1.98 0.88 Left Cavernoma dlPFC 5 19 M Right 14 2.01 0.22 Right Astrocytoma (low-grade) dlPFC 6b 44 F Right 18 28.36 2.5 Left Oligodendroglioma (low-grade) dlPFC 7b 43 M Right 13 33.79 4.67 Left Neoplasm (glioma) dlPFC 8b 33 M Right 17 114.03 3.65 Right Focal cortical dysplasia dlPFC 9b 30 M Right 16 22.24 6.97 Left Hamartoma with balloon cells PCS 1 39 M Right 14 56.56 4.3 Right Tumor PCS 2 27 M Right 18 154.45 5.78 Left Epilepsy PCS 3 37 F Right 17 28.37 5.64 Right Focal cortical dysplasia WAIS-IV Digit Span WCST Cognitive level FSIQ VCI PRI PSI WMI Forw Back Cat PE NPE CL LTL dlPFC 1 Superior 124 132 111 111 122 81 36 3 19 34 25 21 dlPFC 2 Average 106 110 92 111 108 62 16 0 3 2 1 1 dlPFC 3 Average 100 122 94 92 83 64 32 5 50 45 55 25 dlPFC 4 Average 100 103 98 89 111 96 31 4 27 27 34 16 dlPFC 5 High average 118 150 102 94 105 85 90 1 10 2 2 1 dlPFC 6b High average 119 122 113 114 111 81 86 5 42 61 45 25 dlPFC 7b Low average 82 98 86 71 80 95 86 3 14 12 16 16 dlPFC 8b Low average 80 83 86 84 80 97 97 3 5 34 16 5 dlPFC 9b Superior 126 130 115 114 122 62 19 4 27 92 58 25 PCS 1 Average 99 100 97 97 100 62 86 5 70 61 55 25 PCS 2 High average 110 108 109 105 108 86 19 5 77 50 45 25 PCS 3 Low average 82 95 88 74 83 97 97 0 2 1 1 1 ↵adlPFC, dlPFC resection sparing the PCS; PCS, prefrontal cortex resection impacting the PCS; FSIQ, Full-Scale Intelligence Quotient; VCI, Verbal Comprehension Index; PRI, Perceptual Reasoning Index; PSI, Processing Speed Index; FSIQ, VCI, PRI, PSI, and WMI were derived from the WAIS-IV and have a mean of 100 and SD of 15. Digit Span: Forw, immediate recall of aurally presented digits in the order given (in performance percentiles); Back, same but recall in reverse order; Cat, number of categories completed; PE, perseverative errors; NPE, nonperseverative errors; CL, conceptual level responding; LTL, learning to learn (all in percentiles relative to normative performance from general population matched for age and education).
↵bExcluded because of failure to maintain central fixation when the memory cue appeared in the periphery for a minimum of 50 trials.
- Table 3.
Descriptions of the amount, usability, and reasons for excluding trials during the MGS task used with the study samplea
Group Trials Usable trials (%) No MGS (%) No left MGS (%) No right MGS (%) Broke fixation (%) Broke fixation left (%) Broke fixation right (%) CTL 1 270 78 0 0 0 22 14 8 CTL 2 300 87 7 4 3 6 4 2 CTL 3 300 91 4 2 2 5 3 2 CTL 4 300 86 3 2 1 11 5 6 CTL 5 210 91 4 3 1 5 0 5 CTL 6 120 99 0 0 0 1 1 0 CTL 7 300 95 3 2 1 2 2 0 CTL 8 300 55 14 7 7 31 15 16 CTL 9 300 92 4 2 2 4 2 2 dlPFC 1 300 97 1 1 0 2 1 1 dlPFC 2 240 62 14 8 6 25 11 14 dlPFC 3 240 88 1 0 1 11 7 4 dlPFC 4 300 82 1 1 0 17 10 7 dlPFC 5 300 81 6 3 3 13 7 6 dlPFC 6b 300 0 100 56 44 100 56 44 dlPFC 7b 300 0 78 41 37 100 52 48 dlPFC 8b 150 28 48 22 26 50 26 24 dlPFC 9b 300 0 97 52 45 100 55 45 PCS 1 300 54 8 5 3 37 18 19 PCS 2 300 58 1 1 0 41 26 14 PCS 3 300 62 24 13 11 17 7 10 ↵adlPFC, dlPFC resection sparing the PCS; PCS, prefrontal cortex resection impacting the PCS; No MGS, percentage of trials in which the subject did not generate an MGS before the feedback was presented; No left/right MGS, same broken down by whether the cue was in the left or right visual field; Broke fixation, looked away from the fixation point (almost always towards the location of the visual cue) during the cue or delay period; Broke fixation left/right, same broken down by whether the cue was in the left or right visual field.
↵bExcluded because of failure to maintain central fixation when the memory cue appeared in the periphery for a minimum of 50 trials.
- Table 4.
Correlations between demographic, neuropsychologic, and lesion variables with dependent variables derived from performance on MGS taska
Age (years) Years since resection Lesion size (ml) WAIS-IV Digit Span WCST FSIQ VCI PRI WMI Forw Back Cat PE NPE CL LTL Primary saccade error, contralateral −0.21 (0.61) −0.04 (0.91) 0.07 (0.85) −0.62 (0.10) −0.68 (0.06) −0.16 (0.70) −0.41 (0.31) −0.02 (0.97) 0.57 (0.14) 0.19 (0.64) 0.44 (0.27) 0.38 (0.36) 0.29 (0.49) 0.20 (0.63) Primary saccade error, ipsilateral −0.48 (0.23) −0.01 (0.97) 0.23 (0.58) −0.43 (0.28) −0.51 (0.20) −0.06 (0.88) −0.36 (0.37) −0.31 (0.46) 0.48 (0.23) 0.30 (0.48) 0.60 (0.11) 0.48 (0.23) 0.39 (0.33) 0.27 (0.51) Saccadic response time, contralateral 0.22 (0.59) 0.71 (0.04) 0.68 (0.06) 0.10 (0.80) −0.12 (0.77) 0.03 (0.94) 0.30 (0.46) 0.19 (0.66) −0.18 (0.66) −0.56 (0.17) −0.25 (0.55) −0.46 (0.25) −0.59 (0.13) −0.51 (0.20) Saccadic response time, ipsilateral 0.10 (0.81) 0.65 (0.08) 0.77 (0.02)* −0.01 (0.97) −0.32 (0.43) 0.08 (0.84) 0.24 (0.56) 0.10 (0.81) −0.13 (0.77) −0.30 (0.47) 0.06 (0.90) −0.18 (0.67) −0.32 (0.44) −0.29 (0.50)
