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Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation
Neuropsychologia ∎ (∎∎∎∎) ∎∎∎–∎∎∎
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Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation Vinitha Rangarajan, Josef Parvizi n Laboratory of Behavioral & Cognitive Neuroscience, Stanford Human Intracranial Cognitive Electrophysiology Program (SHICEP), Department of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USA
art ic l e i nf o
a b s t r a c t
Article history: Received 16 March 2015 Received in revised form 31 July 2015 Accepted 4 August 2015
The ventral temporal cortex (VTC) contains several areas with selective responses to words, numbers, faces, and objects as demonstrated by numerous human and primate imaging and electrophysiological studies. Our recent work using electrocorticography (ECoG) confirmed the presence of face-selective neuronal populations in the human fusiform gyrus (FG) in patients implanted with intracranial electrodes in either the left or right hemisphere. Electrical brain stimulation (EBS) disrupted the conscious perception of faces only when it was delivered in the right, but not left, FG. In contrast to our previous findings, here we report both negative and positive EBS effects in right and left FG, respectively. The presence of right hemisphere language dominance in the first, and strong left-handedness and poor language processing performance in the second case, provide indirect clues about the functional architecture of the human VTC in relation to hemispheric asymmetries in language processing and handedness. & 2015 Elsevier Ltd. All rights reserved.
Keywords: Fusiform face area Face perception Lateralization Asymmetry Electrocorticography Electrical brain stimulation
1. Introduction The fusiform gyrus (FG) is a well-studied area within the human visual system that contains several regions, which selectively activate during the visual presentation of faces. A large neuroimaging (Grill-Spector et al., 2004; Kanwisher et al., 1997; Sergent et al., 1992) and electrophysiology (Afraz et al., 2006; Anaki et al., 2007; Bentin et al., 1996; Davidesco et al., 2013; McCarthy et al., 1999; Puce et al., 1999; Rangarajan et al., 2014; Tsao et al., 2008) literature suggests bilateral involvement in face processing in humans and primates alike. Several intracranial studies in humans have demonstrated that electrical brain stimulation (EBS) of these areas causes deficits in face naming (Allison et al., 1994a; Puce et al., 1999) and face perception (Mundel et al., 2003; Parvizi et al., 2012; Puce et al., 1999; Rangarajan et al., 2014) in humans. Using advanced anatomical localization methods (Hermes et al., 2010) and several methods of control (Parvizi et al., 2012), our previous work examined how EBS of a single right hemisphere electrode pair could causally disrupt the conscious perception of faces. Consistent with foundational evidence from the lesion literature (De Renzi 1986; De Renzi et al., 1994; Michel et al., 1989), our more recent study demonstrated that EBS of the right, but not the left FG, uniquely impairs face perception (Rangarajan et al., n
Corresponding author. E-mail address: [email protected] (J. Parvizi).
2014). The striking effect of hemisphere that we observed in our EBS cohort is consistent with existing theories regarding the lateralization of face perception. Some have posited that this functional lateralization of face processing occurs as a consequence of language development in humans (Allison et al., 1994b; Dehaene et al., 2010; Dundas et al., 2013), which tends to be strongly left lateralized. Additionally, some have suggested that language and face processing exist as “independent, yet overlapping” systems in which both the ability and impairment of language systems impact face perception performance (Behrmann and Plaut, 2013a, 2013b; Dundas et al., 2013). These language processing networks have also been shown to be intrinsically related to handedness (Fischer et al., 1991; Knecht et al., 2000a, 2000b), as language processing in the majority of right-handed individuals is strongly left lateralized (Broca, 1861; Fischer et al., 1991; Knecht et al., 2000a). Current evidence suggests a relationship between handedness and lateralization of face perception. Many cases of unilateral right lesions causing prosopagnosia have been reported in the literature (De Renzi, 1986; De Renzi et al., 1994; Landis et al., 1988; Sergent and Signoret, 1992; Wada and Yamamoto, 2001). Summarized in Bukowski et al. (2013), however, only 5 cases of unilateral left lesions have been reported resulting in prosopagnosia, of which 4 subjects were left-handed. Despite a strong link between handedness and lateralization of language and face perception, this relationship is complex. For
http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003 0028-3932/& 2015 Elsevier Ltd. All rights reserved.
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
V. Rangarajan, J. Parvizi / Neuropsychologia ∎ (∎∎∎∎) ∎∎∎–∎∎∎
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Table 1 Relevant demographic information for both subjects is presented. Subj Age Gender Hemisphere Handedness Seizure focus
Full-4 IQ Verbal IQ Visuo-spatial IQ
fMRI visual naming language
fMRI object naming language
fMRI auditory naming language
S1
65
Female
Right
Right
113
117
105
Right
Right
Right
S2
47
Male
Left
Left
74
67
87
Left
Left
Left
R anterior temporal L anterior temporal
Fig. 1. ECoG Task and EBS parameters. (a) Subjects were presented with natural images of places, faces, animals, as well as numbers, corporate logos, Spanish and English words, false fonts, and Persian numbers. Stimuli were presented for 400 ms with a 500 ms inter-stimulus interval (ISI). Participants were asked to fixate on the center of the screen and to respond when the red target pound sign stimulus appears. (b) A schematic illustration of the EBS procedure in which two neighboring electrodes are stimulated in a bipolar square wave with varied duration and amplitude.
instance, 4% of right and 27% of left-handed individuals, show right hemisphere language dominance (Knecht et al., 2000b). Additionally, though most right-handed subjects have right lateralized FG face responses, left-handed individuals often have bilaterally equal FG face responses (Bukowski et al., 2013). In the present study, we combined ECoG, EBS, clinical functional magnetic resonance imaging (fMRI), and comprehensive neuropsychological tests in 2 subjects to investigate the functional relationship between face perception, language processing, and handedness.
2. Materials and methods 2.1. Participants Two subjects were implanted with subdural electrodes over the Ventral Temporal Cortex (VTC) for the neurosurgical evaluation of medication-resistant refractory epilepsy. Electrode implantations were done at Stanford Medical Center to localize seizure focus and guide surgical resection and electrode locations were determined solely by clinical needs. Both subjects provided written and verbal consent to participate in all research, as approved by the Stanford Institutional Review Board. Subject 1 (S1) was a 64-year-old, monolingual English-speaking, Caucasian female with medically intractable epilepsy. Subdural electrodes were implanted extensively over the right temporal lobe as pre-surgical surface EEG evaluation indicated a right temporal seizure onset. S1 showed normal intellectual function (Full-4 IQ¼ 113) and strong right-handedness (Edinburgh Handedness Inventory¼ 100) (Oldfield, 1971). A Wada test (Raush et al., 1993) could not be performed, but clinical functional magnetic resonance imaging (fMRI) using auditory, visual, and object
naming paradigms was performed. The clinical use of fMRI has been shown comparable to the use of Wada tests for the identification of language lateralization (Bookheimer, 2007). Clinically, the seizure focus was localized to the right anterior temporal region and no resection was performed because of right lateralized language dominance. Subject 2 (S2) is a 46-year-old monolingual English speaking African American male with medically intractable epilepsy. Subdural electrodes were implanted extensively over the left temporal lobe as pre-surgical surface EEG evaluation indicated a left temporal seizure onset. S2 showed borderline intellectual function (Full-4 IQ ¼74) and left-handedness (Edinburgh Handedness Inventory¼ 80). A Wada test (Raush et al., 1993) and clinical fMRI language mapping was performed. Clinically, the seizure focus was identified as the left anterior temporal lobe and a left hemisphere temporal lobectomy was performed. All demographic information is summarized in Table 1. 2.2. Task design Subjects were presented with a basic localizer task (Fig. 1a) in which pictures of faces, houses, objects, numbers, English words, Spanish words, false fonts, animals, and logos were presented in the center of a computer screen (Fig. 1a). Stimuli were presented for 400 ms with a 500 ms inter-stimulus interval. Subjects were instructed to fixate on the center of the screen and press “1” on a keypad when a red pound sign was displayed; response trials were excluded from analysis. Additionally, animal trials were excluded from all further analysis because the stimuli included animal faces. 2.3. Electrode localization/ECoG data acquisition and analysis Electrode localization was performed as previously described
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
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statistically face-selective (p o0.01, Fig. 3a and c: white halo). A Benjamini–Hochberg false discovery rate (FDR) multiple comparison correction was applied (α ¼ 0.05) for all electrodes (Benjamini et al., 2001). The same mean HFB power values were used to calculate the d′ selectivity index (Fig. 4)
d‵ =
mean(A) − mean(B) σ 2(A) + σ 2(B)/2
where A¼ mean HFB for faces, B ¼mean HFB for non-faces, and s2 ¼ variance. 2.4. Event related potentials (ERP) analysis
Non-faces
R
Min: -25 EBS Face related perceptual effect Non-face related visual effect No perceptual effect
L t
Faces
ERP processing was performed as previously described (Rangarajan et al., 2014). Pathological and artifactual channels were excluded from ERP analysis. The remaining data were notch filtered for 60 Hz line noise and downsample to 100 Hz. The data were then baseline corrected by subtracting the mean voltage of the 100 ms immediately preceding the stimuli. The average ERP for all conditions grouped together was calculated to define the sites with an N200 ERP. Electrodes with a large negative deflection between 100 and 250 ms were included (Allison et al., 1994a; Rosburg et al., 2010; Rossion and Jacques, 2011). Based on this mean ERP, the latency of interest (Lerp) was calculated and the mean amplitude (Aerp,t) between Lerp 20 ms and Lerp þ20 ms was calculated by condition (Luck, 2005). The d′ value for selectivity was then calculated using there Aerp,t measurements for face and non-face conditions (Fig. 4).
Max: 25 ECoG HFB HFB: Face-selective electrode HFB: Non-face-selective electrode No ECoG data (no outline)
Fig. 2. Summary of previous lateralization findings. HFB activity and EBS results from Rangarajan et al. (2014) are presented in MNI brain space. Face-selective HFB responses in the FG were measured bilaterally. For display purposes, the additive spatial distribution of t-values are scaled to the same maximum and minimum, 25 and 25 respectively, and corrected for the spatial distribution of included electrodes. EBS responses are indicated by electrode color and superimposed on the heat maps: red, face-related change; yellow, non-face related visual change; blue, no perceptual change. White halos around each electrode indicate a face-selective HFB response in the ECoG task (p o 0.01, FDR corrected for all electrodes).
(Rangarajan et al., 2014). Briefly, pre-operative T1 MRI scans were aligned with post-operative CT scans. Electrodes were individually localized in single subject brain space, and corrected for surgical brain shift (Hermes et al., 2010). ECoG data were acquired at 1525.88 Hz using a Tucker Davis Technologies recording system. High Frequency Broadband (HFB) power was calculated as previously described (Rangarajan et al., 2014). Briefly, data were digitally bandpass filtered from 0.5 to 300 Hz and referenced online to an electrographically stable intracranial electrode. Pathological channels, identified by the physician (J.P.), and channels greater than five times the mean variance were excluded. The enduring channels were notch filtered at 60 Hz and harmonics, and re-referenced to the common average. The data were then filtered between 70–150 Hz using 5 Hz nonoverlapping bins and a Hilbert transform was applied to each band. The log transform of the resulting estimate of band-limited power was then calculated and the mean log power was subtracted from each band. These power time series calculations were then averaged to obtain a time series of HFB activity, which was then normalized with respect to a 150 ms pre-stimulus baseline. Two-sided t tests (face versus all other categories, excluding animals) were calculated to determine which electrodes were
2.5. Electrical brain stimulation EBS is a clinical paradigm in which electrical current is delivered via electrodes to localize cortical regions involved in seizures and map functions of cortical areas falling within the planned resection boundary. During EBS, a bipolar square wave was delivered to two adjacent electrodes (Fig. 1b). Stimulation parameters (Fig. 1b, Table 2) remained consistent with our previous work (Parvizi et al., 2012; Rangarajan et al., 2014) and trial number was clinically limited because of the rare nature of intracranial stimulation (Selimbeyoglu and Parvizi, 2010). S1 and S2 had 6 and 10 FG electrodes, respectively, which were stimulated multiple times (Fig. 3a/c). As described in (Parvizi et al., 2012), several layers of anatomical and functional control were applied. Subjective reports were classified as (a) face-related changes, (b) non-face related visual changes (such as phosphenes) or (c) no perceptual change. The physician (J.P) monitored simultaneous ECoG signals for the presence of any pathological activity and such trials were excluded from the analysis. Neither patient had experienced a seizure in the 3 h preceding the EBS procedure. 2.6. Clinical fMRI Subjects performed 3 clinical fMRI language tasks: (a) auditory naming: naming an auditory stimulus, (b) visual naming: reading phrases and naming the related object, and (c) object naming: naming line drawings of objects. Scans were acquired on a 3T MRI scanner at Stanford Medical Center. Scan parameters were as follows: TR¼ 2.5, Voxels ¼3.0 mm isotropic whole brain. Each task was presented in 4 min runs, 12 blocks of 3 stimuli per condition, 10 s on and 10 s off per block as described in Bookheimer (2007). The degree of right versus left activations was clinically determined by visual inspection, and therefore, should be interpreted with caution.
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
V. Rangarajan, J. Parvizi / Neuropsychologia ∎ (∎∎∎∎) ∎∎∎–∎∎∎
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ERP
HF B
Faces
Falsefonts
Logos
Numbers
English Words
Persian Numbers
Logos
Numbers
English Words
Persian Numbers
5
elec 5 trial count
10 15 20 25 30 35 0 1
1
2
0.5 time (s)
1
Places
2
3
Spanish Words
3
4 5 6
4 5 6
Faces
Falsefonts
elec 8 trial count
5 10 15 20 25 30 35 0 1
2
1
2
5
3 7 10
8
ERP Face-selective N200 Non-face-selective N200 or No ERP
5
1
Places
4
4 3
0.5 time (s)
Spanish Words
7 10
8
EBS Face-related effect Non-face related visual effect No perceptual effect
HFB Face-selective electrode Non-face-selective electrode
−2.5
0
2.5
HFB Power (z-score)
Fig. 3. Single subject EBS and ECoG task results. (a) S1's EBS results, as in Fig. 2, are presented in the subject’s native brain space and are indicated by electrode color: red, face-related change; yellow, non-face related visual change; blue, no perceptual change. White halos around each electrode indicate a face-selective HFB response in the ECoG task (po 0.01, FDR corrected for all electrodes). (b) Normalized single trial plots for an example electrode (S1, electrode 5) are presented. The z-score values are scaled from 2.5 (red) to 2.5 (blue). (c) S2's EBS results are presented as in (a). (d) Normalize single trial plots for S2, electrode 8 are presented as in (b).
2.7. Comprehensive neuropsychological tests In both patients the following psychometric tests were administered: Auditory Naming Test; Wechsler Abbreviated Scale of Intelligence (WASI-II); Wechsler Memory Scale-III (WMS-III; Information/Orientation); Multilingual Aphasia Examination (MAE; Token Test, Sentence Repetition); Wechsler Memory Scale-Revised (WMS-R; Visual Reproduction I/II); Wechsler Memory Scale-Third Edition (WMS-III; Digit Span, Mental Control, Logical Memory I/II, Faces I/II); California Verbal Learning Test-II (CVLT-II); Neuropsychological Assessment Battery (NAB; Shape Learning); Boston Naming Test; Judgment of Line Orientation (JLO); Hooper
Visual Organization Test (HVOT); Delis–Kaplan Executive Function System (D–KEFS; Design Fluency Test); Letter Fluency; Category Fluency; Trail Making Test; Victoria Stroop Test; Wisconsin Card Sorting Test; Grooved Pegboard Test; Test of Memory Malingering (TOMM); Beck Depression Inventory-II (BDI-II); Beck Anxiety Inventory (BAI)
3. Results Only two subjects were included in our report because the profile of their responses was the opposite of what we recently
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
ERP
HFB
ERP
HFB
ERP
HFB
2 1 −1
0
Face selectivity (d’)
3
4
V. Rangarajan, J. Parvizi / Neuropsychologia ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Face related Visual change change
No change
EBS Response Fig. 4. Comparative ERP and HFB d’ values. D-prime values for all electrodes are plotted and grouped by the evoked EBS result (indicated by electrode color): red, face-related change; yellow, non-face related visual change; blue, no perceptual change.
reported in a larger (n ¼10) cohort of cases. In an experimental visual paradigm (Fig. 1a), we determined the face selectivity of each implanted electrode in VTC. Of the stimulated electrodes, 5 and 3 sites in S1 and S2, respectively, were identified as “faceselective FG sites” because of their significantly greater (p o0.01) HFB responses to faces versus all other categories, excluding animals (Fig. 3a/c). Consistent with our previous work (Rangarajan et al., 2014), we measured robust face-selective ERP N200 and HFB activity across both hemispheres (Figs. 3 and 4). Clinical fMRI language mapping was performed to identify language lateralization in both subjects as a portion of the surgical evaluation for temporal lobectomy. S1's clinical report suggested right language lateralization based on the right greater than left Broca's and Wernicke's area activation across tasks. S2's clinical report indicated left hemisphere language dominance in all tasks. fMRI studies were performed during the patient's clinical evaluation and were processed and interpreted by Stanford Medical Center clinical neuroradiology staff's visual inspection, and therefore, should be interpreted with caution. Next, EBS data was cataloged as previously described (Parvizi et al., 2012; Rangarajan et al., 2014) to examine the effect of stimulation on the conscious perception of faces. Subjects were instructed to look at a real face of a person in the testing room and report any perceptual changes experienced during each EBS trial. The stimulation paradigm utilized repeated trials, sham trials (where no current was delivered), and non-target trials (where the subject was instructed to look at non-face objects) to test the reliability of the results and to ensure that the subject was looking at the correct target (face or non-face). Subjects perceptual reports were categorized as (a) face-related change (b) non-face related visual change or (c) no perceptual change. S1 did not report any face-related changes in the right hemisphere. The low trial count for S1 was determined solely at
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the discretion of the physician (J.P) for clinical reasons. However, S2 did report several face-related perceptual changes in the left hemisphere. He describes, “It changed to someone else's face. Not the whole, but one side (her left) changed. When you clicked it, it changed, and then it changed back.” When another pair was tested, he continues, “Very little-one side of her face. Not as much as the previous one. It was like it was the same person or something that I’ve seen in the movies before, it was less.” These trials were repeated several times with interleaved sham control trials. Details of the EBS parameters and perceptual observations are presented in Table 2. Lastly, preoperative neuropsychological evaluations revealed the following results (summarized in Table 1). S1 showed 100% in Edinburgh Handedness Inventory (right handed); fine motor speed in average range bilaterally; full-4 IQ ¼113 on an abbreviated measure of intellectual functioning; verbal IQ ¼117; performance IQ¼ 105. In addition, S1's performance in the verbal domain ranged from average to very superior (auditory responsive naming and verbal abstract reasoning were average; aural comprehension, repetition of sentences and confrontation naming were high average; oral expression of word meanings was very superior). In the visuospatial and constructional domain (construction of abstract block designs, visual pattern analytic reasoning, judging the distance between lines and integration of fragmented figures), S1 performed uniformly average. In comparison, S2's test results revealed the following: 80% in Edinburgh Handedness Inventory (left handed); fine motor speed in average range bilaterally; full-4 IQ ¼74 on an abbreviated measure of intellectual functioning; verbal IQ ¼67; performance IQ ¼86. In addition, performance in the verbal domain ranged from severely impaired to average (auditory responsive naming was severely impaired; oral expression of word meanings and verbal abstract reasoning were moderately impaired; aural comprehension and confrontation naming were mildly impaired; repeating sentences of increasing length was average). In the visuospatial and constructional domain, S2 performed from mildly impaired to average (judging the distance between lines in space was mildly impaired; construction of abstract block designs was low average; visual pattern analytic reasoning and integration of fragmented figures were average).
4. Discussion In our current report, we describe our observations in 2 subjects wherein the perceptual changes induced by EBS may shed light on multiple facets of hemispheric asymmetries in face perception. The clinical setting in which our observations were made provided a unique platform for acquiring a combination of preoperative neuropsychological evaluations, neuroimaging studies, direct cortical recording and electrical stimulation that otherwise would have been unobtainable in a non-clinical setting. Our ECoG findings of face-selective N200 and HFB power changes in the right and the left FG (in S1 and S2, respectively), are consistent with existing evidence in the literature and with our previous work measuring bilateral face selective activations (Allison et al., 1994b; Bentin et al., 1996; Grill-Spector et al., 2004; Kanwisher et al., 1997; Rangarajan et al., 2014). Consistent with our previous work (Rangarajan et al., 2014), we find a dissociation between HFB and ERP selectivity measurements, where not all face-selective HFB sites produced an N200 (Fig. 4). Moreover, HFB power served as a more sensitive measure for discriminating face selectivity as the spread of d' values was much larger for HFB power than for ERPs (HFB max: 3.46; ERP max: 0.3616, Fig. 4). Our EBS findings in the two subjects presented are contrary to the convincing evidence for distinct right hemisphere advantage
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
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Name
Electrode numbers
Current (mA) Duration (s) Prompt
Subject 1 4–5
4 mA
2s
“Ready? 1, 2, 3. Did anything change?”
4–5 5–6 4–6 4–6 4–6 2–3 2–3 1–2
4 mA 4 mA 4 mA 4 mA 4 mA 4 mA 4 mA 4 mA
2s 2s 2s 2s 2s 2s 2s 2s
“Look at her nose. 1, 2, 3. Any change?” “How about now, 1, 2, 3. Any change?” “1, 2, 3. Did her face change?” “How about now?” “How about now? 1, 2, 3.” “1, 2, 3. Did anything change?” “How about now, 1, 2, 3. Anything change?” “(Look at face) 1, 2, 3. Did anything change?”
Subject 2 5–8
6 mA
1.7 s
5–8
SHAM
N/A
5–8
6 mA
1.5 s
“Look straight ahead and tell me if you notice anything. 1, 2 3.” “Was it vibrating? Shaking?” “This time, look at her face. You are seeing her face now? Eyes, everything in place. Does she have a normal face? Ok, how about now. 1, 2, 3.” “Let's repeat it one more time and see if it changes this time.”
5–8
SHAM
N/A
5–8 5–8
SHAM 4 mA
N/A 2s
5–8
4 mA
1.5 s
5–8
6 mA
2s
5–8
6 mA
2.6 s
8–9
4 mA
1.7 s
5–6 5–6
SHAM 6 mA
N/A 1.8 s
6–9
6 mA
1.8 s
6–9 10–7 10–7 9–10 9–10 9–10 6–7 6–7 6–7 6–7 6–7
6 mA 6 mA SHAM 4 mA SHAM 6 mA SHAM 6 mA 4 mA SHAM 4 mA
2.2 s 2s N/A 1.6 s N/A 1.5 s N/A 1.5 s 1.6 s N/A 1.8 s
Clinical result
“Yes, opthomologically-It was as if like at the eye doctor, you turned on a lens like that. It made your shirt, I could see the ridges more. Like seeing it with better glasses prescription.” “No, I wouldn't have noticed anything that time.” “No.” “No.” “No.” “I don't think so.” “Floral smell.” “No.” “Smell something soapy. Didn't see a face change.” “Things changed a little bit. Changed and flip right back.” “I really didn’t feel a vibration. It changed to something different. I could see the words.” “Nothing changed.”
“Yeah, it changed that time. It changed to someone elses face. Not the whole, but one side (her left) changed. When you clicked it, it changed, and then it changed back.” “Can you describe the kind of person you saw?” “Like a man's face. No hair on her face, but gray hair on her head.” “Ok, this time I am going to do it longer so see if it happens. Ok ready? 1, Nothing changed that time. 2, 3.” “How about now? 1, 2, 3.” Nothing. “Anything changed?” “Yes, something but can't pinpoint. It's like that one side changed again, but I couldn’t really tell what it was.” “Could you understand who she is?” “Yes, I knew who she was.” “How could you tell? Was it shrinking?” “I guess, I could still see the right side. It flipped to a different face.” “Ok, let’s look at her hand right now. Do you see her five fingers? Let’s “Yeah, they were all still there.” see if you see them all intact. Ready?” Instructed to look at hand over her face. “How about now?” “I see the five finger, but the one next to the thumb just like, kinda, changed a little.” (Indicating Index). “Now look at her face and try to describe what's happening. 1, 2, 3.” “It looked like my neighbors wife or something. (laughs).” “How old is she?” “She's forty-something, but no she wasn't looking older” “You're looking at her face, and it’s normal looking? How about now?” “It changed, but I couldn't pinpoint the person, but I've seen it. Somebody that I knew, that I've seen, just on the left side though.” “Eyes were in the same place? Did the face change? Male of female?” “Everything was in the same place, stayed the same shape. That time it was malesomeone familiar.” “Look at her face. Any change?” No. “How about now?” “Yes, seems like face from a movie that I've seen, but I can't remember the face. Just half part changed to another face.” “Look straight ahead. 1, 2, 3. Did anything change?” “Very little-one side of her face. Not as much as the previous one. It was like it was the same person or something that I’ve seen in the movies before, it was less.” “One more time, okay. 1, 2, 3.” “About the same thing.” “Okay, 1, 2, 3.” No change. “How about now? 1, 2, 3.” No. “Any change?” No change. “Any change?” No change. “How about now? 1, 2, 3.” “Feel a little head ache.” “1, 2, 3.” No change. “How about now?” No. “How about now?” “Same thing, person from the movie.” “Okay, this time look at the clock and tell me what happens.” Nothing. “How about now?” “Eh, it just looked like the numbers changed a little bit. They got a little different. The
V. Rangarajan, J. Parvizi / Neuropsychologia ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
Table 2 The EBS parameters and subjects' responses are listed. Purple shaded prompts indicate trials in which the subject was instructed to look at a face. Response cell coloring indicates the EBS effect: red, face-related change; yellow, non-face related visual change; blue, no perceptual change. Electrode numbers correspond to anatomical positions marked in Fig. 3a and c.
3–4 3–4 3–4 3-4 1–3 3–6 3–6 4–7 4–7 2–4 2–4 1–2 1–2 1–2 1–2
4 mA SHAM 4 mA SHAM 4 mA 4 mA 4 mA 4 mA 4 mA 4 mA 4 mA SHAM 4 mA 4 mA 4 mA
1.4 s N/A 1.6 s N/A 1.5 s 1.6 s 1.6 s 1.5 s 1.5 s 1.7 s 1.5 s N/A 1.5 s 1.2 s 1.1 s
“Look at her hand in front of her face. Any fingers change? 1, 2, 3.” “How about now?” “Now you’re going to look at the face. 1, 2, 3.” “One more time, okay. 1, 2, 3.” “Look at her face. 1, 2, 3.” “Anything change?” “Now face, 1, 2, 3.” “Palm out, 1, 2, 3.” “Look at the face, 1, 2, 3.” “Palm out. Anything change?” “Face now?” “Hand out. 1, 2, 3.” “Keep the hand out? 1, 2, 3.” “One more time, 1, 2, 3.” “Face?”
whole clock changed.” No. Nothing. Nothing. Nothing. Nothing. No No. Nothing. Nothing. No. No. Nothing. “Pinky moved a little bit.” “Yes, same thing.” Nothing.
V. Rangarajan, J. Parvizi / Neuropsychologia ∎ (∎∎∎∎) ∎∎∎–∎∎∎
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in face processing in humans (Barton et al., 2002; De Renzi, 1986; Pitcher et al., 2007; Rangarajan et al., 2014; Rhodes, 1993). In our most recent work (Rangarajan et al., 2014), we found a robust lateralization effect wherein EBS of right, but not left, FG sites caused face-related perceptual changes (Fig. 2). In the current study, we found an opposite pattern; EBS in the right FG failed to elicit a face related perceptual change while EBS in the left FG clearly induced such perceptual changes (Table 2). Our observations in S1 and S2 may seem surprising at first, but a closer look reveals an intriguing relationship between the subjects' perceptual changes and their hemispheric dominance for language or handedness and performance on several psychometric tests: S1 had right greater than left hemisphere language fMRI activations (despite being right handed) and S2 was strongly lefthanded (despite having left larger than right hemisphere language fMRI activations). Additionally, while S1's performance on psychometric tests ranged from average to superior, S2's showed extremely low verbal performance (verbal IQ ¼67, 1st percentile) even though his performance across other domains including attention, memory and executive functioning were at expected levels. In other words, in both S1 and S2, the dominance of the left hemisphere in face perception may have been related to less dominant or poorly functioning left hemisphere language processing, especially in the ventral temporal areas involved in word processing i.e., visual word form area (vWFA). This was indicated by S1's clear right great than left fMRI asymmetry and by S2’s severe deficiencies in language processing. It is important to note that S2 did have some omissions, where he reported no change during a real EBS trial, at sites that otherwise produced a face-related change. These omission trials may be the result of varied stimulation parameters, differing in amplitude or duration of the current delivered. Future studies can improve upon our current findings by being performed in clinical settings permitting higher trial counts, and by including time-locked visual presentation of faces during stimulation, and quantitative measurements of language lateralization. Several theories exist regarding the interconnected nature of face and language lateralization (Allison et al., 1994b; Behrmann and Plaut, 2013a; Dehaene et al., 2010; Dundas et al., 2013). One hypothesis suggests that the vWFA co-opts a relatively larger area of the FG (at the expense of fusiform face areas) as literacy improves (Dehaene et al., 2010). This “recycling” hypothesis proposes that cortical areas are fine-tuned during development, showing less diffuse response patterns. This manifests, more specifically, as literacy causing increased word and decreased face activations, respectively, in the FG. Such a competitive interaction between faces and words in the vWFA suggests strongly interconnected mechanisms supporting the functional architecture of the human VTC. Additionally, a relationship exists between handedness and face lateralization (Bukowski et al., 2013) possibly due to the strong relationship between handedness and language lateralization (Knecht et al., 2000, 2000b). In accordance, cases of prosopagnosia due to unilateral left FG lesions have mostly been reported in left-handed subjects (Barton, 2008; Eimer and McCarthy, 1999; Mattson et al., 2000; Tzavaras et al., 1973). Lastly, the interaction of the handedness and language lateralization systems may account for reports of left hemisphere EBS causing face naming deficits (Allison et al., 1994b; Puce et al., 1999) without associated face distortions, as face naming requires the retrieval of language-related semantic information. In this context, we believe that our findings in these two cases are related to S1's right hemisphere language lateralization and S2's deficiencies in language processing skills and left-handedness. In summary, our current report provides additional clues about the multi-faceted nature of hemispheric asymmetry in face perception that is related to handedness and language processing.
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
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Based on our observations, and extant literature, future studies are needed to explore how the asymmetric function of the human fusiform face area is dictated by the functional asymmetries between hemispheres and by the involvement of their adjacent cortices in language processing. Such future studies will shed light on the specialization of interrelated functional networks in the human VTC during learning and development.
Acknowledgments We thank Harinder Kaur, Thi Pham, and Liudmila Schumacher for assistance and collaboration with ECoG and EBS procedures, and Sandra Gattas for help with data collection, and Drs. Kevin Weiner, Brett Foster, and Bruno Rossion for helpful discussion. This research was funded by Stanford NeuroVentures Program, R01 NS078396-01 and BCS1358907 to JP.
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Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
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Neuropsychologia journal homepage: www.elsevier.com/locate/neuropsychologia
Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation Vinitha Rangarajan, Josef Parvizi n Laboratory of Behavioral & Cognitive Neuroscience, Stanford Human Intracranial Cognitive Electrophysiology Program (SHICEP), Department of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USA
art ic l e i nf o
a b s t r a c t
Article history: Received 16 March 2015 Received in revised form 31 July 2015 Accepted 4 August 2015
The ventral temporal cortex (VTC) contains several areas with selective responses to words, numbers, faces, and objects as demonstrated by numerous human and primate imaging and electrophysiological studies. Our recent work using electrocorticography (ECoG) confirmed the presence of face-selective neuronal populations in the human fusiform gyrus (FG) in patients implanted with intracranial electrodes in either the left or right hemisphere. Electrical brain stimulation (EBS) disrupted the conscious perception of faces only when it was delivered in the right, but not left, FG. In contrast to our previous findings, here we report both negative and positive EBS effects in right and left FG, respectively. The presence of right hemisphere language dominance in the first, and strong left-handedness and poor language processing performance in the second case, provide indirect clues about the functional architecture of the human VTC in relation to hemispheric asymmetries in language processing and handedness. & 2015 Elsevier Ltd. All rights reserved.
Keywords: Fusiform face area Face perception Lateralization Asymmetry Electrocorticography Electrical brain stimulation
1. Introduction The fusiform gyrus (FG) is a well-studied area within the human visual system that contains several regions, which selectively activate during the visual presentation of faces. A large neuroimaging (Grill-Spector et al., 2004; Kanwisher et al., 1997; Sergent et al., 1992) and electrophysiology (Afraz et al., 2006; Anaki et al., 2007; Bentin et al., 1996; Davidesco et al., 2013; McCarthy et al., 1999; Puce et al., 1999; Rangarajan et al., 2014; Tsao et al., 2008) literature suggests bilateral involvement in face processing in humans and primates alike. Several intracranial studies in humans have demonstrated that electrical brain stimulation (EBS) of these areas causes deficits in face naming (Allison et al., 1994a; Puce et al., 1999) and face perception (Mundel et al., 2003; Parvizi et al., 2012; Puce et al., 1999; Rangarajan et al., 2014) in humans. Using advanced anatomical localization methods (Hermes et al., 2010) and several methods of control (Parvizi et al., 2012), our previous work examined how EBS of a single right hemisphere electrode pair could causally disrupt the conscious perception of faces. Consistent with foundational evidence from the lesion literature (De Renzi 1986; De Renzi et al., 1994; Michel et al., 1989), our more recent study demonstrated that EBS of the right, but not the left FG, uniquely impairs face perception (Rangarajan et al., n
Corresponding author. E-mail address: [email protected] (J. Parvizi).
2014). The striking effect of hemisphere that we observed in our EBS cohort is consistent with existing theories regarding the lateralization of face perception. Some have posited that this functional lateralization of face processing occurs as a consequence of language development in humans (Allison et al., 1994b; Dehaene et al., 2010; Dundas et al., 2013), which tends to be strongly left lateralized. Additionally, some have suggested that language and face processing exist as “independent, yet overlapping” systems in which both the ability and impairment of language systems impact face perception performance (Behrmann and Plaut, 2013a, 2013b; Dundas et al., 2013). These language processing networks have also been shown to be intrinsically related to handedness (Fischer et al., 1991; Knecht et al., 2000a, 2000b), as language processing in the majority of right-handed individuals is strongly left lateralized (Broca, 1861; Fischer et al., 1991; Knecht et al., 2000a). Current evidence suggests a relationship between handedness and lateralization of face perception. Many cases of unilateral right lesions causing prosopagnosia have been reported in the literature (De Renzi, 1986; De Renzi et al., 1994; Landis et al., 1988; Sergent and Signoret, 1992; Wada and Yamamoto, 2001). Summarized in Bukowski et al. (2013), however, only 5 cases of unilateral left lesions have been reported resulting in prosopagnosia, of which 4 subjects were left-handed. Despite a strong link between handedness and lateralization of language and face perception, this relationship is complex. For
http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003 0028-3932/& 2015 Elsevier Ltd. All rights reserved.
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
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Table 1 Relevant demographic information for both subjects is presented. Subj Age Gender Hemisphere Handedness Seizure focus
Full-4 IQ Verbal IQ Visuo-spatial IQ
fMRI visual naming language
fMRI object naming language
fMRI auditory naming language
S1
65
Female
Right
Right
113
117
105
Right
Right
Right
S2
47
Male
Left
Left
74
67
87
Left
Left
Left
R anterior temporal L anterior temporal
Fig. 1. ECoG Task and EBS parameters. (a) Subjects were presented with natural images of places, faces, animals, as well as numbers, corporate logos, Spanish and English words, false fonts, and Persian numbers. Stimuli were presented for 400 ms with a 500 ms inter-stimulus interval (ISI). Participants were asked to fixate on the center of the screen and to respond when the red target pound sign stimulus appears. (b) A schematic illustration of the EBS procedure in which two neighboring electrodes are stimulated in a bipolar square wave with varied duration and amplitude.
instance, 4% of right and 27% of left-handed individuals, show right hemisphere language dominance (Knecht et al., 2000b). Additionally, though most right-handed subjects have right lateralized FG face responses, left-handed individuals often have bilaterally equal FG face responses (Bukowski et al., 2013). In the present study, we combined ECoG, EBS, clinical functional magnetic resonance imaging (fMRI), and comprehensive neuropsychological tests in 2 subjects to investigate the functional relationship between face perception, language processing, and handedness.
2. Materials and methods 2.1. Participants Two subjects were implanted with subdural electrodes over the Ventral Temporal Cortex (VTC) for the neurosurgical evaluation of medication-resistant refractory epilepsy. Electrode implantations were done at Stanford Medical Center to localize seizure focus and guide surgical resection and electrode locations were determined solely by clinical needs. Both subjects provided written and verbal consent to participate in all research, as approved by the Stanford Institutional Review Board. Subject 1 (S1) was a 64-year-old, monolingual English-speaking, Caucasian female with medically intractable epilepsy. Subdural electrodes were implanted extensively over the right temporal lobe as pre-surgical surface EEG evaluation indicated a right temporal seizure onset. S1 showed normal intellectual function (Full-4 IQ¼ 113) and strong right-handedness (Edinburgh Handedness Inventory¼ 100) (Oldfield, 1971). A Wada test (Raush et al., 1993) could not be performed, but clinical functional magnetic resonance imaging (fMRI) using auditory, visual, and object
naming paradigms was performed. The clinical use of fMRI has been shown comparable to the use of Wada tests for the identification of language lateralization (Bookheimer, 2007). Clinically, the seizure focus was localized to the right anterior temporal region and no resection was performed because of right lateralized language dominance. Subject 2 (S2) is a 46-year-old monolingual English speaking African American male with medically intractable epilepsy. Subdural electrodes were implanted extensively over the left temporal lobe as pre-surgical surface EEG evaluation indicated a left temporal seizure onset. S2 showed borderline intellectual function (Full-4 IQ ¼74) and left-handedness (Edinburgh Handedness Inventory¼ 80). A Wada test (Raush et al., 1993) and clinical fMRI language mapping was performed. Clinically, the seizure focus was identified as the left anterior temporal lobe and a left hemisphere temporal lobectomy was performed. All demographic information is summarized in Table 1. 2.2. Task design Subjects were presented with a basic localizer task (Fig. 1a) in which pictures of faces, houses, objects, numbers, English words, Spanish words, false fonts, animals, and logos were presented in the center of a computer screen (Fig. 1a). Stimuli were presented for 400 ms with a 500 ms inter-stimulus interval. Subjects were instructed to fixate on the center of the screen and press “1” on a keypad when a red pound sign was displayed; response trials were excluded from analysis. Additionally, animal trials were excluded from all further analysis because the stimuli included animal faces. 2.3. Electrode localization/ECoG data acquisition and analysis Electrode localization was performed as previously described
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
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statistically face-selective (p o0.01, Fig. 3a and c: white halo). A Benjamini–Hochberg false discovery rate (FDR) multiple comparison correction was applied (α ¼ 0.05) for all electrodes (Benjamini et al., 2001). The same mean HFB power values were used to calculate the d′ selectivity index (Fig. 4)
d‵ =
mean(A) − mean(B) σ 2(A) + σ 2(B)/2
where A¼ mean HFB for faces, B ¼mean HFB for non-faces, and s2 ¼ variance. 2.4. Event related potentials (ERP) analysis
Non-faces
R
Min: -25 EBS Face related perceptual effect Non-face related visual effect No perceptual effect
L t
Faces
ERP processing was performed as previously described (Rangarajan et al., 2014). Pathological and artifactual channels were excluded from ERP analysis. The remaining data were notch filtered for 60 Hz line noise and downsample to 100 Hz. The data were then baseline corrected by subtracting the mean voltage of the 100 ms immediately preceding the stimuli. The average ERP for all conditions grouped together was calculated to define the sites with an N200 ERP. Electrodes with a large negative deflection between 100 and 250 ms were included (Allison et al., 1994a; Rosburg et al., 2010; Rossion and Jacques, 2011). Based on this mean ERP, the latency of interest (Lerp) was calculated and the mean amplitude (Aerp,t) between Lerp 20 ms and Lerp þ20 ms was calculated by condition (Luck, 2005). The d′ value for selectivity was then calculated using there Aerp,t measurements for face and non-face conditions (Fig. 4).
Max: 25 ECoG HFB HFB: Face-selective electrode HFB: Non-face-selective electrode No ECoG data (no outline)
Fig. 2. Summary of previous lateralization findings. HFB activity and EBS results from Rangarajan et al. (2014) are presented in MNI brain space. Face-selective HFB responses in the FG were measured bilaterally. For display purposes, the additive spatial distribution of t-values are scaled to the same maximum and minimum, 25 and 25 respectively, and corrected for the spatial distribution of included electrodes. EBS responses are indicated by electrode color and superimposed on the heat maps: red, face-related change; yellow, non-face related visual change; blue, no perceptual change. White halos around each electrode indicate a face-selective HFB response in the ECoG task (p o 0.01, FDR corrected for all electrodes).
(Rangarajan et al., 2014). Briefly, pre-operative T1 MRI scans were aligned with post-operative CT scans. Electrodes were individually localized in single subject brain space, and corrected for surgical brain shift (Hermes et al., 2010). ECoG data were acquired at 1525.88 Hz using a Tucker Davis Technologies recording system. High Frequency Broadband (HFB) power was calculated as previously described (Rangarajan et al., 2014). Briefly, data were digitally bandpass filtered from 0.5 to 300 Hz and referenced online to an electrographically stable intracranial electrode. Pathological channels, identified by the physician (J.P.), and channels greater than five times the mean variance were excluded. The enduring channels were notch filtered at 60 Hz and harmonics, and re-referenced to the common average. The data were then filtered between 70–150 Hz using 5 Hz nonoverlapping bins and a Hilbert transform was applied to each band. The log transform of the resulting estimate of band-limited power was then calculated and the mean log power was subtracted from each band. These power time series calculations were then averaged to obtain a time series of HFB activity, which was then normalized with respect to a 150 ms pre-stimulus baseline. Two-sided t tests (face versus all other categories, excluding animals) were calculated to determine which electrodes were
2.5. Electrical brain stimulation EBS is a clinical paradigm in which electrical current is delivered via electrodes to localize cortical regions involved in seizures and map functions of cortical areas falling within the planned resection boundary. During EBS, a bipolar square wave was delivered to two adjacent electrodes (Fig. 1b). Stimulation parameters (Fig. 1b, Table 2) remained consistent with our previous work (Parvizi et al., 2012; Rangarajan et al., 2014) and trial number was clinically limited because of the rare nature of intracranial stimulation (Selimbeyoglu and Parvizi, 2010). S1 and S2 had 6 and 10 FG electrodes, respectively, which were stimulated multiple times (Fig. 3a/c). As described in (Parvizi et al., 2012), several layers of anatomical and functional control were applied. Subjective reports were classified as (a) face-related changes, (b) non-face related visual changes (such as phosphenes) or (c) no perceptual change. The physician (J.P) monitored simultaneous ECoG signals for the presence of any pathological activity and such trials were excluded from the analysis. Neither patient had experienced a seizure in the 3 h preceding the EBS procedure. 2.6. Clinical fMRI Subjects performed 3 clinical fMRI language tasks: (a) auditory naming: naming an auditory stimulus, (b) visual naming: reading phrases and naming the related object, and (c) object naming: naming line drawings of objects. Scans were acquired on a 3T MRI scanner at Stanford Medical Center. Scan parameters were as follows: TR¼ 2.5, Voxels ¼3.0 mm isotropic whole brain. Each task was presented in 4 min runs, 12 blocks of 3 stimuli per condition, 10 s on and 10 s off per block as described in Bookheimer (2007). The degree of right versus left activations was clinically determined by visual inspection, and therefore, should be interpreted with caution.
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
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ERP
HF B
Faces
Falsefonts
Logos
Numbers
English Words
Persian Numbers
Logos
Numbers
English Words
Persian Numbers
5
elec 5 trial count
10 15 20 25 30 35 0 1
1
2
0.5 time (s)
1
Places
2
3
Spanish Words
3
4 5 6
4 5 6
Faces
Falsefonts
elec 8 trial count
5 10 15 20 25 30 35 0 1
2
1
2
5
3 7 10
8
ERP Face-selective N200 Non-face-selective N200 or No ERP
5
1
Places
4
4 3
0.5 time (s)
Spanish Words
7 10
8
EBS Face-related effect Non-face related visual effect No perceptual effect
HFB Face-selective electrode Non-face-selective electrode
−2.5
0
2.5
HFB Power (z-score)
Fig. 3. Single subject EBS and ECoG task results. (a) S1's EBS results, as in Fig. 2, are presented in the subject’s native brain space and are indicated by electrode color: red, face-related change; yellow, non-face related visual change; blue, no perceptual change. White halos around each electrode indicate a face-selective HFB response in the ECoG task (po 0.01, FDR corrected for all electrodes). (b) Normalized single trial plots for an example electrode (S1, electrode 5) are presented. The z-score values are scaled from 2.5 (red) to 2.5 (blue). (c) S2's EBS results are presented as in (a). (d) Normalize single trial plots for S2, electrode 8 are presented as in (b).
2.7. Comprehensive neuropsychological tests In both patients the following psychometric tests were administered: Auditory Naming Test; Wechsler Abbreviated Scale of Intelligence (WASI-II); Wechsler Memory Scale-III (WMS-III; Information/Orientation); Multilingual Aphasia Examination (MAE; Token Test, Sentence Repetition); Wechsler Memory Scale-Revised (WMS-R; Visual Reproduction I/II); Wechsler Memory Scale-Third Edition (WMS-III; Digit Span, Mental Control, Logical Memory I/II, Faces I/II); California Verbal Learning Test-II (CVLT-II); Neuropsychological Assessment Battery (NAB; Shape Learning); Boston Naming Test; Judgment of Line Orientation (JLO); Hooper
Visual Organization Test (HVOT); Delis–Kaplan Executive Function System (D–KEFS; Design Fluency Test); Letter Fluency; Category Fluency; Trail Making Test; Victoria Stroop Test; Wisconsin Card Sorting Test; Grooved Pegboard Test; Test of Memory Malingering (TOMM); Beck Depression Inventory-II (BDI-II); Beck Anxiety Inventory (BAI)
3. Results Only two subjects were included in our report because the profile of their responses was the opposite of what we recently
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
ERP
HFB
ERP
HFB
ERP
HFB
2 1 −1
0
Face selectivity (d’)
3
4
V. Rangarajan, J. Parvizi / Neuropsychologia ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Face related Visual change change
No change
EBS Response Fig. 4. Comparative ERP and HFB d’ values. D-prime values for all electrodes are plotted and grouped by the evoked EBS result (indicated by electrode color): red, face-related change; yellow, non-face related visual change; blue, no perceptual change.
reported in a larger (n ¼10) cohort of cases. In an experimental visual paradigm (Fig. 1a), we determined the face selectivity of each implanted electrode in VTC. Of the stimulated electrodes, 5 and 3 sites in S1 and S2, respectively, were identified as “faceselective FG sites” because of their significantly greater (p o0.01) HFB responses to faces versus all other categories, excluding animals (Fig. 3a/c). Consistent with our previous work (Rangarajan et al., 2014), we measured robust face-selective ERP N200 and HFB activity across both hemispheres (Figs. 3 and 4). Clinical fMRI language mapping was performed to identify language lateralization in both subjects as a portion of the surgical evaluation for temporal lobectomy. S1's clinical report suggested right language lateralization based on the right greater than left Broca's and Wernicke's area activation across tasks. S2's clinical report indicated left hemisphere language dominance in all tasks. fMRI studies were performed during the patient's clinical evaluation and were processed and interpreted by Stanford Medical Center clinical neuroradiology staff's visual inspection, and therefore, should be interpreted with caution. Next, EBS data was cataloged as previously described (Parvizi et al., 2012; Rangarajan et al., 2014) to examine the effect of stimulation on the conscious perception of faces. Subjects were instructed to look at a real face of a person in the testing room and report any perceptual changes experienced during each EBS trial. The stimulation paradigm utilized repeated trials, sham trials (where no current was delivered), and non-target trials (where the subject was instructed to look at non-face objects) to test the reliability of the results and to ensure that the subject was looking at the correct target (face or non-face). Subjects perceptual reports were categorized as (a) face-related change (b) non-face related visual change or (c) no perceptual change. S1 did not report any face-related changes in the right hemisphere. The low trial count for S1 was determined solely at
5
the discretion of the physician (J.P) for clinical reasons. However, S2 did report several face-related perceptual changes in the left hemisphere. He describes, “It changed to someone else's face. Not the whole, but one side (her left) changed. When you clicked it, it changed, and then it changed back.” When another pair was tested, he continues, “Very little-one side of her face. Not as much as the previous one. It was like it was the same person or something that I’ve seen in the movies before, it was less.” These trials were repeated several times with interleaved sham control trials. Details of the EBS parameters and perceptual observations are presented in Table 2. Lastly, preoperative neuropsychological evaluations revealed the following results (summarized in Table 1). S1 showed 100% in Edinburgh Handedness Inventory (right handed); fine motor speed in average range bilaterally; full-4 IQ ¼113 on an abbreviated measure of intellectual functioning; verbal IQ ¼117; performance IQ¼ 105. In addition, S1's performance in the verbal domain ranged from average to very superior (auditory responsive naming and verbal abstract reasoning were average; aural comprehension, repetition of sentences and confrontation naming were high average; oral expression of word meanings was very superior). In the visuospatial and constructional domain (construction of abstract block designs, visual pattern analytic reasoning, judging the distance between lines and integration of fragmented figures), S1 performed uniformly average. In comparison, S2's test results revealed the following: 80% in Edinburgh Handedness Inventory (left handed); fine motor speed in average range bilaterally; full-4 IQ ¼74 on an abbreviated measure of intellectual functioning; verbal IQ ¼67; performance IQ ¼86. In addition, performance in the verbal domain ranged from severely impaired to average (auditory responsive naming was severely impaired; oral expression of word meanings and verbal abstract reasoning were moderately impaired; aural comprehension and confrontation naming were mildly impaired; repeating sentences of increasing length was average). In the visuospatial and constructional domain, S2 performed from mildly impaired to average (judging the distance between lines in space was mildly impaired; construction of abstract block designs was low average; visual pattern analytic reasoning and integration of fragmented figures were average).
4. Discussion In our current report, we describe our observations in 2 subjects wherein the perceptual changes induced by EBS may shed light on multiple facets of hemispheric asymmetries in face perception. The clinical setting in which our observations were made provided a unique platform for acquiring a combination of preoperative neuropsychological evaluations, neuroimaging studies, direct cortical recording and electrical stimulation that otherwise would have been unobtainable in a non-clinical setting. Our ECoG findings of face-selective N200 and HFB power changes in the right and the left FG (in S1 and S2, respectively), are consistent with existing evidence in the literature and with our previous work measuring bilateral face selective activations (Allison et al., 1994b; Bentin et al., 1996; Grill-Spector et al., 2004; Kanwisher et al., 1997; Rangarajan et al., 2014). Consistent with our previous work (Rangarajan et al., 2014), we find a dissociation between HFB and ERP selectivity measurements, where not all face-selective HFB sites produced an N200 (Fig. 4). Moreover, HFB power served as a more sensitive measure for discriminating face selectivity as the spread of d' values was much larger for HFB power than for ERPs (HFB max: 3.46; ERP max: 0.3616, Fig. 4). Our EBS findings in the two subjects presented are contrary to the convincing evidence for distinct right hemisphere advantage
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
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Name
Electrode numbers
Current (mA) Duration (s) Prompt
Subject 1 4–5
4 mA
2s
“Ready? 1, 2, 3. Did anything change?”
4–5 5–6 4–6 4–6 4–6 2–3 2–3 1–2
4 mA 4 mA 4 mA 4 mA 4 mA 4 mA 4 mA 4 mA
2s 2s 2s 2s 2s 2s 2s 2s
“Look at her nose. 1, 2, 3. Any change?” “How about now, 1, 2, 3. Any change?” “1, 2, 3. Did her face change?” “How about now?” “How about now? 1, 2, 3.” “1, 2, 3. Did anything change?” “How about now, 1, 2, 3. Anything change?” “(Look at face) 1, 2, 3. Did anything change?”
Subject 2 5–8
6 mA
1.7 s
5–8
SHAM
N/A
5–8
6 mA
1.5 s
“Look straight ahead and tell me if you notice anything. 1, 2 3.” “Was it vibrating? Shaking?” “This time, look at her face. You are seeing her face now? Eyes, everything in place. Does she have a normal face? Ok, how about now. 1, 2, 3.” “Let's repeat it one more time and see if it changes this time.”
5–8
SHAM
N/A
5–8 5–8
SHAM 4 mA
N/A 2s
5–8
4 mA
1.5 s
5–8
6 mA
2s
5–8
6 mA
2.6 s
8–9
4 mA
1.7 s
5–6 5–6
SHAM 6 mA
N/A 1.8 s
6–9
6 mA
1.8 s
6–9 10–7 10–7 9–10 9–10 9–10 6–7 6–7 6–7 6–7 6–7
6 mA 6 mA SHAM 4 mA SHAM 6 mA SHAM 6 mA 4 mA SHAM 4 mA
2.2 s 2s N/A 1.6 s N/A 1.5 s N/A 1.5 s 1.6 s N/A 1.8 s
Clinical result
“Yes, opthomologically-It was as if like at the eye doctor, you turned on a lens like that. It made your shirt, I could see the ridges more. Like seeing it with better glasses prescription.” “No, I wouldn't have noticed anything that time.” “No.” “No.” “No.” “I don't think so.” “Floral smell.” “No.” “Smell something soapy. Didn't see a face change.” “Things changed a little bit. Changed and flip right back.” “I really didn’t feel a vibration. It changed to something different. I could see the words.” “Nothing changed.”
“Yeah, it changed that time. It changed to someone elses face. Not the whole, but one side (her left) changed. When you clicked it, it changed, and then it changed back.” “Can you describe the kind of person you saw?” “Like a man's face. No hair on her face, but gray hair on her head.” “Ok, this time I am going to do it longer so see if it happens. Ok ready? 1, Nothing changed that time. 2, 3.” “How about now? 1, 2, 3.” Nothing. “Anything changed?” “Yes, something but can't pinpoint. It's like that one side changed again, but I couldn’t really tell what it was.” “Could you understand who she is?” “Yes, I knew who she was.” “How could you tell? Was it shrinking?” “I guess, I could still see the right side. It flipped to a different face.” “Ok, let’s look at her hand right now. Do you see her five fingers? Let’s “Yeah, they were all still there.” see if you see them all intact. Ready?” Instructed to look at hand over her face. “How about now?” “I see the five finger, but the one next to the thumb just like, kinda, changed a little.” (Indicating Index). “Now look at her face and try to describe what's happening. 1, 2, 3.” “It looked like my neighbors wife or something. (laughs).” “How old is she?” “She's forty-something, but no she wasn't looking older” “You're looking at her face, and it’s normal looking? How about now?” “It changed, but I couldn't pinpoint the person, but I've seen it. Somebody that I knew, that I've seen, just on the left side though.” “Eyes were in the same place? Did the face change? Male of female?” “Everything was in the same place, stayed the same shape. That time it was malesomeone familiar.” “Look at her face. Any change?” No. “How about now?” “Yes, seems like face from a movie that I've seen, but I can't remember the face. Just half part changed to another face.” “Look straight ahead. 1, 2, 3. Did anything change?” “Very little-one side of her face. Not as much as the previous one. It was like it was the same person or something that I’ve seen in the movies before, it was less.” “One more time, okay. 1, 2, 3.” “About the same thing.” “Okay, 1, 2, 3.” No change. “How about now? 1, 2, 3.” No. “Any change?” No change. “Any change?” No change. “How about now? 1, 2, 3.” “Feel a little head ache.” “1, 2, 3.” No change. “How about now?” No. “How about now?” “Same thing, person from the movie.” “Okay, this time look at the clock and tell me what happens.” Nothing. “How about now?” “Eh, it just looked like the numbers changed a little bit. They got a little different. The
V. Rangarajan, J. Parvizi / Neuropsychologia ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
Table 2 The EBS parameters and subjects' responses are listed. Purple shaded prompts indicate trials in which the subject was instructed to look at a face. Response cell coloring indicates the EBS effect: red, face-related change; yellow, non-face related visual change; blue, no perceptual change. Electrode numbers correspond to anatomical positions marked in Fig. 3a and c.
3–4 3–4 3–4 3-4 1–3 3–6 3–6 4–7 4–7 2–4 2–4 1–2 1–2 1–2 1–2
4 mA SHAM 4 mA SHAM 4 mA 4 mA 4 mA 4 mA 4 mA 4 mA 4 mA SHAM 4 mA 4 mA 4 mA
1.4 s N/A 1.6 s N/A 1.5 s 1.6 s 1.6 s 1.5 s 1.5 s 1.7 s 1.5 s N/A 1.5 s 1.2 s 1.1 s
“Look at her hand in front of her face. Any fingers change? 1, 2, 3.” “How about now?” “Now you’re going to look at the face. 1, 2, 3.” “One more time, okay. 1, 2, 3.” “Look at her face. 1, 2, 3.” “Anything change?” “Now face, 1, 2, 3.” “Palm out, 1, 2, 3.” “Look at the face, 1, 2, 3.” “Palm out. Anything change?” “Face now?” “Hand out. 1, 2, 3.” “Keep the hand out? 1, 2, 3.” “One more time, 1, 2, 3.” “Face?”
whole clock changed.” No. Nothing. Nothing. Nothing. Nothing. No No. Nothing. Nothing. No. No. Nothing. “Pinky moved a little bit.” “Yes, same thing.” Nothing.
V. Rangarajan, J. Parvizi / Neuropsychologia ∎ (∎∎∎∎) ∎∎∎–∎∎∎
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in face processing in humans (Barton et al., 2002; De Renzi, 1986; Pitcher et al., 2007; Rangarajan et al., 2014; Rhodes, 1993). In our most recent work (Rangarajan et al., 2014), we found a robust lateralization effect wherein EBS of right, but not left, FG sites caused face-related perceptual changes (Fig. 2). In the current study, we found an opposite pattern; EBS in the right FG failed to elicit a face related perceptual change while EBS in the left FG clearly induced such perceptual changes (Table 2). Our observations in S1 and S2 may seem surprising at first, but a closer look reveals an intriguing relationship between the subjects' perceptual changes and their hemispheric dominance for language or handedness and performance on several psychometric tests: S1 had right greater than left hemisphere language fMRI activations (despite being right handed) and S2 was strongly lefthanded (despite having left larger than right hemisphere language fMRI activations). Additionally, while S1's performance on psychometric tests ranged from average to superior, S2's showed extremely low verbal performance (verbal IQ ¼67, 1st percentile) even though his performance across other domains including attention, memory and executive functioning were at expected levels. In other words, in both S1 and S2, the dominance of the left hemisphere in face perception may have been related to less dominant or poorly functioning left hemisphere language processing, especially in the ventral temporal areas involved in word processing i.e., visual word form area (vWFA). This was indicated by S1's clear right great than left fMRI asymmetry and by S2’s severe deficiencies in language processing. It is important to note that S2 did have some omissions, where he reported no change during a real EBS trial, at sites that otherwise produced a face-related change. These omission trials may be the result of varied stimulation parameters, differing in amplitude or duration of the current delivered. Future studies can improve upon our current findings by being performed in clinical settings permitting higher trial counts, and by including time-locked visual presentation of faces during stimulation, and quantitative measurements of language lateralization. Several theories exist regarding the interconnected nature of face and language lateralization (Allison et al., 1994b; Behrmann and Plaut, 2013a; Dehaene et al., 2010; Dundas et al., 2013). One hypothesis suggests that the vWFA co-opts a relatively larger area of the FG (at the expense of fusiform face areas) as literacy improves (Dehaene et al., 2010). This “recycling” hypothesis proposes that cortical areas are fine-tuned during development, showing less diffuse response patterns. This manifests, more specifically, as literacy causing increased word and decreased face activations, respectively, in the FG. Such a competitive interaction between faces and words in the vWFA suggests strongly interconnected mechanisms supporting the functional architecture of the human VTC. Additionally, a relationship exists between handedness and face lateralization (Bukowski et al., 2013) possibly due to the strong relationship between handedness and language lateralization (Knecht et al., 2000, 2000b). In accordance, cases of prosopagnosia due to unilateral left FG lesions have mostly been reported in left-handed subjects (Barton, 2008; Eimer and McCarthy, 1999; Mattson et al., 2000; Tzavaras et al., 1973). Lastly, the interaction of the handedness and language lateralization systems may account for reports of left hemisphere EBS causing face naming deficits (Allison et al., 1994b; Puce et al., 1999) without associated face distortions, as face naming requires the retrieval of language-related semantic information. In this context, we believe that our findings in these two cases are related to S1's right hemisphere language lateralization and S2's deficiencies in language processing skills and left-handedness. In summary, our current report provides additional clues about the multi-faceted nature of hemispheric asymmetry in face perception that is related to handedness and language processing.
Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i
V. Rangarajan, J. Parvizi / Neuropsychologia ∎ (∎∎∎∎) ∎∎∎–∎∎∎
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Based on our observations, and extant literature, future studies are needed to explore how the asymmetric function of the human fusiform face area is dictated by the functional asymmetries between hemispheres and by the involvement of their adjacent cortices in language processing. Such future studies will shed light on the specialization of interrelated functional networks in the human VTC during learning and development.
Acknowledgments We thank Harinder Kaur, Thi Pham, and Liudmila Schumacher for assistance and collaboration with ECoG and EBS procedures, and Sandra Gattas for help with data collection, and Drs. Kevin Weiner, Brett Foster, and Bruno Rossion for helpful discussion. This research was funded by Stanford NeuroVentures Program, R01 NS078396-01 and BCS1358907 to JP.
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Please cite this article as: Rangarajan, V., Parvizi, J., Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia (2015), http://dx.doi.org/10.1016/j.neuropsychologia.2015.08.003i