Comparison between patients with and without ventromedial prefrontal lesions

Neuropsychological performance

Two-tailed t-tests did not reveal any significant difference between the two clinical groups. Again, neuropsychological profiles of patient groups are shown to provide an overview on their performance on single tests.

-2 -1,5 -1 -,5 0 ,5 1 1,5 2 2,5

TIB SPM_A_D V_FL_LET V_FL_CAT MEM_BRAN TMT_A TMT_B WCST_CAT WCST_TRL WCST_ERR WCST_PSV TOWLOND LIST_ANM ATT_MAT MEM_SPAN

Fig.5.21. Neuropsychological test performance of patients with and without VMPFC lesions means of z- transformed values and standard errors are shown)

TIB – Errors Raven SPM V. fluency – letters Verbal fluency – cat. Semantic memory TMT-A – RT TMT-B – RT WCST – categories WCST – trials WCST – errors WCST – persev. Tower of London Incidental Memory Attentive Matrices Digit span

Neuropsychological profile of patients with and without VMPFC lesions

Lesion No lesion

Visual evoked potentials

Differences between patients with and without VMPFC-lesions became already evident in the earliest time window (160-220ms) that revealed a significant Group x Category x Hemisphere effect. Figure 5.2.2. illustrates that stimulus processing in the right hemisphere, compared to the left hemisphere, showed marked differences with respect to picture content and clinical sample. Both patient groups differentiated between arousing and non arousing (pleasant and unpleasant) pictures, but their response pattern was very dissimilar. Whereas patients with no VMPFC lesion exhibited the expected response with a negative going deflection during viewing of arousing slides compared to neutral pictures, patients with VMPFC lesions show a nearly reverse picture with an enhanced positivity in response to arousing slides, in particular after unpleasant stimuli, which also elicited higher amplitudes than pleasant pictures.

Fig. 5.2.2. Left- and right-hemispheric parieto-occipital sites: mean amplitudes in response to different emotional picture content

This effect persisted till the subsequent time window from 220 to 280 ms, but became weaker and thus failed to reach statistical significance (F(2.36= 2.81, p< .08, Σ= .92).

Both P300 time intervals did not exhibit any important effect including “group”. Further group differences became evident only with respect to the late slow wave starting from 650 ms after stimulus onset. Figure 5.2.3. illustrates late picture processing in patients with and without damage to the VMPC by mapping surface activity for each group and picture condition in the 1-3 s time interval. Maps indicate differences in the activity pattern of the two patient groups in response to specific emotional content. Patients without VMPFC lesions show more positivity (red color) to both pleasant and unpleasant pictures compared to neutral stimuli, whereas patients with damage to

the VMPFC seem to show this enhanced positivity only to pleasant slides. Their surface activity following unpleasant pictures looks quite similar to the one elicited by neutral slides.

Fig 5.2.3. 1-4 s following picture onset:

Grand mean topography of surface activity for pleasant, neutral and unpleasant picture content, shown separately for patients with and without VMPFC-lesions

(map scaling: 0.7000 µV/contour)

This impression is confirmed by statistical analyses. A very stable Group x Category interaction, lasting up to the end of picture presentation, resulted for each of the four late time windows: 650 - 1000ms ( F(2.38)= 2.80, p< .08, Σ= .76), 1-2s (F(2.38= 4.18, p< .05, Σ= .68) , 2-3s (F(2.38)= 4.1, p< .05, Σ= .93), 3-4s (F(2.38)= 3.86, p< ,05, Σ= .73). To exemplify this dynamic, figure 5.2.4.

illustrates the interaction found in the time window 1-2 s. Post-hoc conducted analyses revealed that patients with damage to the VMPC showed higher amplitudes to unpleasant and neutral slides compared to patients without lesions in this specific cortical area (p< .01). Even more interesting is the result, that in patients with VMPFC lesions, mean amplitudes in response to unpleasant slides did not differ from amplitudes yielded by neutral stimuli, whereas the difference between mean voltages during viewing of neutral slides and pleasant pictures was pronounced (p< .01). Patients

without VMPFC lesions, instead, exhibited overall enhanced amplitudes to both types of arousing slides compared to neutral content (p< .01).

VMPFC - lesion No VMPFC- lesion Interval 1-2 s

Interaction Group x Category F(2.38)= 4.18, p< ,05, Epsilon= .68

Amplitude (µV)

The illustration of surface activity also seems to reveal some differences with respect to laterality of emotional processing. For example, in response to pleasant pictures, patients without lesions of the VMPFC appear to show more positive activity in the right hemisphere compared to the left hemisphere (see Figure 5.2.3), whereas patients with VMPFC lesions seem to be less lateralized.

Surprisingly, statistical analyses did not lead to any effect including the factor hemisphere.

Skin conductance response

No significant differences between patients with and without VMPFC lesions resulted for mean amplitude of skin conductance response.

Subjective evaluation and recall of emotional material

With respect to both SAM Arousal and SAM Pleasure ratings, no important effects including factor group could be observed. Also the recall of prior presented pictures was similar in both patients with and without damage of the VMPFC.

Discussion

A series of lesion and functional imaging studies in humans (Bechara et al., 2000; Elliot et al., 2000), as well as neurophysiological studies in nonhuman primates (Schönbaum, Chiba &

Gallagher, 1998), have emphasized the role of the ventromedial prefrontal cortex in representing the Fig. 5.2.4.

emotional value of sensory stimuli. In particular, the VMPFC is assumed to constitute part of the circuitry via which associations are formed between visual cues and the actions or choices that they specify. The VMPFC would, therefore, represent a cortical area that can represent cues, responses, and outcomes.

The present comparison between patients with and without lesions of the VMPFC revealed that damage to this cortical area was associated with more severely impaired elaboration of unpleasant stimuli as indicated by findings from event-related potentials. At a very early cortical processing stage (160-220 ms), only patients without VMPFC lesions displayed the typical ERP pattern with a relative negative deflection over right occipital areas in response to arousing slides. Patients with lesions to ventromedial cortices, instead, showed an enhanced positivity over right posterior areas during viewing of emotionally salient slides. Considering that early activity over visual cortices repeatedly has been assumed to index rapid allocation of motivated attention towards relevant stimuli (Keil, 2001; Pizzagalli et al., 1999), the atypical positivity found after VMPFC lesions might reflect less efficient processing of emotional pictures. Thus, the present result suggests that an intact right VMPFC is necessary to successfully modulate early affective encoding of visual stimuli.

This conclusion is in line with recent evidence from single-unit recordings obtained in human right VMPFC in response to facial expression of fear and happiness (Kawasaki, Adolphs, Kaufmann, Damasio et al., 2001); neuronal discrimination between the two valence types already appeared after 120 -170 ms. It can be assumed that the right-hemispheric ventromedial prefrontal cortex exerts, the right-hemispheric ventromedial prefrontal, can be assumed to exert an important top-down influence on early visual processing of emotionally relevant cues.

Furthermore, the VMPFC appears to have a decisive role for affective modulation during later stages of stimulus elaboration, as well. In fact, the late potential consistently differed between patients with and those without damage to this particular area of the frontal lobe demonstrating that only patients with intact VMPFC discriminated unpleasant and pleasant slides from neutral content.

Instead, from 650 ms up to the end of picture presentation, patients with VMPFC lesions displayed more positive amplitudes only in response to pleasant stimuli, whereas the slow wave during viewing of unpleasant slides did not differ from late processing of neutral pictures. This result is in accordance with previous studies reporting a stronger involvement of the ventromedial part of the frontal lobe in the recognition and elaboration of negative stimuli. In this regard, Harmer and co-workers found that disruption of processing within medial prefrontal cortex with transcranial magnetic stimulation produces longer reaction times in response to angry faces but not in response to happy facial expressions (Harmer, Thilo, Rothwell & Goodwin, 2001). Furthermore, Northoff et al. (2000) combined fMRI and MEG to investigate spatiotemporal activation of different prefrontal

subdivisions during emotional stimulation and revealed that negative affective processing generates activation in ventromedial frontal areas whereas elaboration of positive stimuli is more related to lateral prefrontal cortex.

In sum, the present ERP findings distinguished patients with and those without VMPFC lesions by showing that damage to this particular frontal area is associated with an abnormal modulation of rapid visual processing of emotional content and with an impaired discrimination of unpleasant stimuli during later stages of attentional visual elaboration. Surprisingly, these deficits were not reflected by any other indicator of affective stimulus processing; neither skin conductance responses nor subjective evaluation of pictures nor memory performance could reveal any differences between patients with and those without damage to the VMPFC.