Research report

per

a Haatteonk K

yon Ne

versity

Institut

itation,

Cognitive Neuroscience Laboratory Rehabilitation Institute of Chicago, Chicago, IL, USA

Dorsal stream

ishkin put forward the

dedicated to object

years after this dis-

responsible for non-

een suggested to ac-

ated the neural un-

istration of the Visual

n symptom mapping

raumatic brain injury

(pTBI). First, our results provided new support for the complementary role of both hemi-

found to be critical in

frontal regions in the

object discrimination

tion depended on the

relationships in both 2D and 3D representations. Taken together, our results supported the

* Corresponding author. CRNL e ImpAct Team, 16, ave Doyen Lepine, 69676 Bron Cedex, France.** Corresponding author. Molecular Neuroscience Department George Mason University 4400 University Drive, Mails Stop 2A1, Fairfax, VA22030, USA.

ger@gmu.edu (F. Krueger).

Available online at www.sciencedirect.com

ScienceDirect

Journal homepage: www.elsevier.com/locate/cortex

c o r t e x 5 7 ( 2 0 1 4 ) 2 4 4e2 5 3E-mail addresses: selene.schintu@gmail.com (S. Schintu), fkrueintegrity of the right inferior parietal lobule (IPL) and revealed that a network linking

the right IPL with the right premotor cortex was critical for the perception of spatialVentral stream

Lateralization

VLSM

Insula

spheres in object recognition. The right lateral occipital complex was

early perceptual discrimination, whereas more anterior temporal and

left hemisphere were found to be critical in more complex forms of

and recognition. Second, our findings confirmed that space percepgMolecular Neuroscience Department, George Mason University, Fairfax, VA, USAhDepartment of Psychology, George Mason University, Fairfax, VA, USA

a r t i c l e i n f o

Article history:

Received 8 October 2013

Reviewed 3 December 2013

Revised 3 March 2014

Accepted 23 April 2014

Action editor Paolo Bartolomeo

Published online 2 May 2014

Keywords:

a b s t r a c t

In the 1980s, following Newcombes observations, Ungerleider and M

functional subdivision of the visual system into a ventral stream

perception and a dorsal stream dedicated to space perception. Ten

covery, the perception-action model re-defined the dorsal stream as

conscious visual guidance, and most recently a tripartition has b

count for a variety of visuospatial functions. Here, we investig

derpinnings of object and space perception by combining the admin

Object Space Perception (VOSP) battery with a voxel-based lesio

(VLSM) approach in a large sample of patients with penetrating tUniversity of Genoa, Genoa, ItalyfObject and spaceof hemisphere?

Selene Schintu a,b,*, FadilKristine M. Knutson d, MJordan Grafman f and Fraa INSERM, U1028, CNRS, UMR5292, LbUniversity UCBL Lyon 1, FrancecDepartment of Neuropsychology, UnidBehavioral Neurology Unit, National

Bethesda, MD, USAeDepartment of Neuroscience, Rehabilhttp://dx.doi.org/10.1016/j.cortex.2014.04.0090010-9452/ 2014 Elsevier Ltd. All rights reseception e Is it a matter

dj-Bouziane a,b, Olga Dal Monte c,Pardini e, Eric M. Wassermann d,rueger g,h,**

uroscience Research Center, ImpAct Team, Lyon, France

of Turin, Turin, Italy

e of Neurological Disorders and Stroke, National Institutes of Health,

Ophthalmology, Genetics, Maternal and Child Health,rved.

ohe

ing vis

(De Renzi, 1982; Kinsbourne, 1987; McCa

1990; Mesulam, 1981; Newcombe, 1969).

ted a

tionsh

in a large sample of patients with penetrating traumatic brain

injury (pTBI). VLSM studies are of importance in identifying

at the National Naval Medical Center and the National Insti-

c o r t e x 5 7 ( 2 0 1 4 ) 2 4 4e2 5 3 245ioral experiments have demonstra

sphere advantage for processing relacoordinates (i.e., distance evaluation) (Koss

right hemispheres dominance in spatial arthy & Warrington,

A series of behav-

relative right hemi-

ips between spatial

2.2. Neuropsychological assessment and behavioralanalysisIn contrast, general consensus ex

of the right hemisphere in controllthe prominent role

uospatial attention tute of Neurological Disorders and Stroke, Bethesda, MD.categorization and recognition (De Renzi, 1982).

ists onregions are specialized for assigning a meaning to objects forstudy, which was approved by the Institutional Review Boardfunctional subdivision

involved along both t

1. Introduction

Years after the what and where hypothesis suggesting a func-

tional partition of the visual system into two streams e a

ventral stream subserving object perception and a dorsal stream

subserving space perception (Mishkin, Ungerleider, & Macko,

1983; Newcombe, 1969; Ungerleider & Mishkin, 1982), new

frameworks have emerged refining this subdivision both

anatomically and functionally. Notably, the perception-action

model defines the dorsal stream as responsible for non-

conscious visual guidance of action and the ventral stream

for conscious perception (Goodale & Milner, 1992; Milner &

Goodale, 2006). Recently, Kravitz et al. (Kravitz, Saleem,

Baker, & Mishkin, 2011) suggested a tripartition of the dorsal

stream to account for the variety of visuospatial functions.

Three distinct pathways originating in the posterior parietal

cortex (PPC) mediate different visuospatial abilities: (i) a

parieto-premotor pathway for eye movements, several forms

of visually guided action, and grasping; (ii) a parieto-prefrontal

pathway for top-down control of eye movements and spatial

workingmemory; and (iii) a parieto-medial temporal pathway

for spatial abilities related to navigation. Likewise, the same

group proposed a refinement of the ventral object represen-

tation pathway, which is subserved by distinct cortical and

subcortical structures (Kravitz, Saleem, Baker, Ungerleider &

Mishkin, 2013).

Evidence about hemispheric dominance for object

perception and recognition is controversial. Some neuropsy-

chological and neuroimaging studies point toward a right

hemisphere dominance in object perception (Acres, Taylor,

Moss, Stamatakis, & Tyler, 2009; Konen, Behrmann,

Nishimura, & Kastner, 2011), while others suggest a left

hemisphere dominance (Price, Moore, Humphreys,

Frackowiak, & Friston, 1996; Sergent, Ohta, & MacDonald,

1992; Stewart, Meyer, Frith, & Rothwell, 2001; Zelkowicz,

Herbster, Nebes, Mintun, & Becker, 1998). These conflicting

findings can be reconciled by the fact that object recognition

involves hierarchically organized processes (Ungerleider &

Haxby, 1994) that depend on either the left or the right

hemisphere. According to this view, the right posterior oc-

cipital and temporal regions are specialized for the discrimi-

nation of basic features, while more anterior left temporallyn et al., 1989). The

ttention, especiallyregions necessary for cognitive processes and corroborating

evidence from single case, clinical, and neuroimaging studies

(Bates et al., 2003). In our study, we addressed the following

two questions: 1) What are the anatomical correlates of both

object and space perception and 2) Do subjects with lesions in

both hemispheres exhibit any hemispheric dominance in

object and space perception? Our results supported the com-

plementary role of both hemispheres in object recognition

and identified key regions associated with different cognitive

processes along the ventral stream that depended on task

demand. Our findings confirmed that space perception

depended on the integrity of the right IPL within the dorsal

stream, and demonstrated that a network linking the right IPL

with the right premotor cortex was critical for the perception

of spatial relationships in both 2D and 3D representations.

2. Material and methods

2.1. Subjects

Participants were drawn from Phase III of the W.F. Caveness

Vietnam Head Injury Study (VHIS) registry, which is a pro-

spective, long-term follow-up study (Raymont, Salazar,

Krueger, & Grafman, 2011). Out of the 254 veterans, 247

completed the VOSP battery and were divided into two groups

based on the presence or absence of pTBI: a lesion group

(LG 192) and a control group (CG 55). All veterans gavetheir written informed consent before participating in thisthe involvement of the right parietal cortex, is supported by an

abundant literature in neglect patients (e.g., Heilman & Van

Den Abell, 1980; Vallar & Perani, 1986) and by recent evidence

from functional neuroimaging (Thiebaut de Schotten et al.,

2011) and transcranial magnetic stimulation (TMS) (Brighina

et al., 2002; Fierro et al., 2000; Hilgetag, Theoret, & Pascual-

Leone, 2001; Muri et al., 2002; Rounis, Yarrow, & Rothwell,

2007) studies in healthy subjects.

In this study, we investigated the neural underpinnings of

object and space perception by employing the Visual Object

Space Perception (VOSP) battery (Warrington & James, 1991)

and a voxel-based lesion symptommapping (VLSM) approachf the visual system and shed new light on the specific processes

dorsal and the ventral streams.

2014 Elsevier Ltd. All rights reserved.All participants underwent a 5e7 day neuropsychological

assessment. As the experimental measure, we employed the

2000).

To examine the distribution of lesions, a density map was

c o r t e x 5 7 ( 2 0 1 4 ) 2 4 4e2 5 3246VOSP battery (Warrington & James, 1991) with eight visual

perception tasks designed to assess particular aspects of ob-

ject and space perception (Lezak, 2004). First, we administered

the VOSP shape detection screening task that assessed basic

visual discrimination abilities (i.e., detecting whether or not

the letter X was presented in randomly presented patterns).

Failing the screening task prevented the administration of the

entire subsequent battery.

To assess object perception, we selected two out of four

tasks that specifically targeted object perception and excluded

those using numbers or letters as stimuli to minimize the

involvement of other cognitive skills. The silhouette task tested

the ability to recognize and name animate (i.e., animals) or

inanimate (i.e., objects) from two-dimensional silhouettes.

The object decision task tested the ability to identify and point

at the two-dimensional shape of the real object among three

distractors. To assess space perception, we selected two out of

four tasks that specifically targeted space perception, and

excluded the two tasks involving matching-to-sample proce-

dure or numbers as stimuli. The position discrimination task

tested the ability to estimate and point to the relative position

of an object in a two-dimensional space. The cube analysis task

tested the ability to perceive, extract and count three-

dimensional shapes from black and white 3D drawings.

As control measures, we administered the following neu-

ropsychological tests/surveys: the Token Test (TT; (McNeil &

Prescott, 1994)) to test basic verbal comprehension; the Bos-

ton Naming Test (BN; (Kaplan, Goodglass, &Weintraub, 1976))

to test naming abilities; the Beck Depression Inventory (BDI-II;

(Beck, Steer, & Brown, 1996)) to measure the severity of

depression; and the Armed Forces Qualification Test (AFQT-

7A; (United States Department of Defense, 1960)) to evaluate

pre- and post-injury general intelligence. The AFQT was

administered to veterans upon entry into the military; it is

extensively standardized within the U.S. military and its

scores correlate highly with the WAIS IQ scores (Wechsler

Adult Intelligence Scale) (Grafman et al., 1988).

Behavioral data analyses were carried out using SPSS

(Statistical Package for the Social Sciences, version 14.0.1,

SPSS Inc., Chicago, USA, http://www.spss.com) with alpha set

to p < .05 (two-tailed). Patients raw scores from each of the

VOSP tasks were converted into z-scores based on the per-

formance of the control participants. Independent samples t-

tests were performed to compare demographic, experimental,

and control variables between LG and CG.

2.3. Computed tomography (CT) and lesion analysis

Axial CT scans were acquired without contrast on a GE

LightSpeed Plus CT scanner. Images were reconstructed with

an in-plane voxel size of .4 mm .4 mm, an overlapping slicethickness of 2.5 mmand a 1-mm slice interval. Lesion location

and extent were evaluated on the scans, and the contours

were drawn on each slice using the Analysis of Brain Lesion

software implemented in MEDx v3.44 (Medical Numerics)

(Makale et al., 2002; Solomon, Raymont, Braun, Butman, &

Grafman, 2007) with enhancements to support the Auto-

mated Anatomical Labeling (AAL) atlas (Tzourio-Mazoyeret al., 2002). Lesion volume was calculated by summing the

traced areas and multiplying by slice thickness. The tracingcreated by overlaying patients normalized lesionmaps. Then,

whole brain VLSM analyses (1-tailed t-test, q(FDR) < .05,

minimum cluster size of 10 voxels) on lesioned participants

were performed to identify brain regions associated with ob-

ject and/or space perception impairment, using the z-scores

from the four VOSP tasks as the dependent variables and

lesion status of each voxel as the independent variable. To

ensure sufficient statistical power, only voxels in which at

least four participants had lesions were considered for the

VLSM analyses (Glascher et al., 2009).

Moreover, separate conjunction analyses were performed

for the object and space perception tasks to identify the

regions necessary for each of these tasks, while minimizing

the involvement of other cognitive skills related to the specific

tasks demands. The conjunction analyses yielded three sta-

tistical maps: one map revealing brain areas common to the

two tasks and two additional maps showing brain areas

unique to each of the tasks.

Finally, to exclude any potential confounds with verbal

comprehension and language difficulties, one-way analyses of

variance (ANOVAs) were performed on verbal comprehension

(TT) and naming abilities (BN) scores and subgroups (control

group and lesion groups based on the identified lesion pattern

for each tasks) as a between-subjects factor.

3. Results

3.1. Behavioral results

Groups (LG, CG) did not differ significantly in demographic,

experimental, and control measures, except for post-injury

general intelligence, which was within the normal range for

both groups, and the cube analysis task. Further, naming

abilities (BN) and verbal comprehension (TT) tended to

significantly differ between groups (Table 1).

3.2. VLSM results

3.2.1. Lesion results associated with each VOSP tasksThe lesion density map showed sufficient coverage in mostwas performed by a physicianwith clinical experience reading

CT scans, and reviewed by an experienced observer (JG), who

was blind to the results of the clinical evaluation and neuro-

psychological testing. Each CT scan was spatially normalized

to a template in Montreal Neurological Institute (MNI) space,

using the AIR algorithm (Woods, Mazziotta, & Cherry, 1993)

with a 12-parameters affine fit. To optimize efficacy of the

registration procedure, the brain images were first automati-

cally skull-stripped. Voxels inside the traced lesion were not

included in the spatial normalization procedure. For each

patient, the traced lesion image in MNI space was used for

VLSM analysis. Gyri and Talairach coordinates were obtained

using the AAL atlas (Tzourio-Mazoyer et al., 2002), and Brod-

mann areas (BAs) were determined using the Volume Occu-

pancy Talairach Labels (VOTL) database (Lancaster et al.,areas of the temporal, parietal and frontal lobes; allowing the

assessment of the impact of these lesions on the object and

Table 1 e Descriptive (mean standard deviations) and inferential statistics for demographic, experimental, and controlmeasures comparing the lesion group (LG[ 192) with the control group (CG[ 55).

Group LG CG Statistics

Demographic Measures

Age (years) 58.27 2.96 59.00 3.40 t 1.56, p .121Education (years) 14.80 2.49 15.19 2.47 t 1.00, p .316Handedness (R : A : L) 147 : 6 : 21 43 : 4 : 8 c2 7.46, p .113

Experimental Measures

VOSP Screening task 19.80 0.61 19.71 1.45 t 0.66, p .509VOSP Silhouette task 20.10 4.01 20.13 3.86 t 0.04, p .970VOSP Object decision task 17.70 2.08 17.80 2.73 t 0.28, p .777VOSP Position discrimination task 19.01 1.83 19.35 1.80 t 1.22, p .224VOSP Cube analysis task 9.37 1.11 9.69 0.63 t 2.01, p .046

Control Measures

e t

llig

-II:

ob

c o r t e x 5 7 ( 2 0 1 4 ) 2 4 4e2 5 3 247space perception tasks in both hemispheres (Fig. 1) (Note that

brain areas such as the occipital cortex were spared, a pre-

requisite to allow the participants to complete the tasks.)

The whole brain VLSM analyses revealed brain areas

necessary for each of the four VOSP tasks (Fig. 2) and for the

screening task (Supplementary Fig. S1). For the screening task

the lateral occipital complex (LOC) was associated with task

impairment (Supplementary Fig. S1). For the silhouette task,

behavioral impairment was associated with the left middle

Pre-Injury IQ (AFQT, percentile) 60.99 25.07Post-Injury IQ (AFQT, percentile) 52.72 24.92Token Test (Total correct) 97.49 5.86BDI-II (Total score) 9.38 9.15Boston Naming Test (Total score) 53.44 7.53Age: years at the time of VOSP administration; Education: years at th

dextrous; L, left-handed; Pre-injury Intelligence and Post-injury Inte

general intelligence; Token Test: for basic verbal comprehension; BDI

Test: for object naming; VOSP: Visual Object and Space Perception fortemporal gyrus (MTG), and to a less extent parts of the supe-

rior temporal gyrus (STG), inferior temporal gyrus (ITG) and

superior temporal pole (STpole), extending to the boundaries

of the precentral and postcentral gyri (Fig. 2a). For the object

decision task, behavioral impairment was associated with

lesions in theMTG, STG, ITG, alongwith the frontal operculum

and insula in the left hemisphere (Fig. 2b). For the position

discrimination task, behavioral impairment was associated

with lesions in the inferior frontal gyrus (IFG), middle tem-

poral pole (MidTPole), STpole, ITG, along with the insula,

fusiform gyrus, hippocampus and inferior parietal lobule (IPL)

Fig. 1 e Lesion Density Overlap Map for pTBI patients. Axial slice

the number of overlapping lesions at each voxel across the wh

overlap of 4 patients at a given voxel and the color range indica

The maximum overlap of 31 patients occurred in frontal areas.in the left hemisphere, including the STG and MTG bilaterally.

In the right hemisphere, lesions were found in the superior

frontal gyrus (SFG), premotor area including the supplemen-

tary motor area (SMA) and extended to the supramarginal

gyrus (SMG), angular gyrus (AG), IPL, the middle occipital

gyrus (MOG) and superior occipital gyrus (SOG) (Fig 2c). For the

cube analysis task, behavioral impairment was associated

with lesions in the SFG, middle frontal gyrus (MFG), frontal

operculum, insula, and precentral gyrus bilaterally. In the

65.40 22.91 t 0.96, p .33668.50 21.63 t 4.22, p .00198.83 1.55 t 1.67, p .09711.56 9.66 t 1.52, p .12955.44 4.73 t 1.86, p .064

ime of VOSP administration; Handedness: R, right-handed; A, ambi-

ence (percentile scores) AFQT: Armed Forces Qualification Test for

Beck Depression Inventory-II for depression severity; Boston Naming

ject and space perception.right hemisphere, lesions were found in the premotor area

including SMA and extended to the STG, MTG, SMG, post-

central gyrus, superior parietal lobule and (SPL), IPL, extending

to the MOG (Fig. 2d). Percentage of lesions (>1%) within each

brain structures that were critical for the each of the four

VOSP tasks in the lesion group are reported in Supplementary

Table 1.

3.2.2. Lesion results for object perceptionSubgroups derived from the VSLM analysis were then tested

to investigate any potential confounds between object

s (z-coordinates fromL38 toD63 in MNI space) illustrating

ole population. All analyses were restricted to a minimum

tes this overlap, from blue (4 patients) to red (31 patients).

The right hemisphere is on the readers left.

c o r t e x 5 7 ( 2 0 1 4 ) 2 4 4e2 5 3248perception tasks and verbal comprehension and naming

abilities: a silhouette group (n 19) with brain lesions associ-ated with both tasks (i.e., silhouette & object decision task); an

object decision group (n 136) with brain lesions associatedwith the object decision task, and a normal control group

(n 55) serving as a baseline group for normal verbalcomprehension and language processing (Supplementary

Table 2). The one-way ANOVAs on language test scores

showed a main Group effect (BN: F(2,107) 13.60, p < .01; TT:F(2,106) 10.77, p < .01). Follow-up post-hoc comparisonsdemonstrated that only the performance of the silhouette

group differed significantly from the performances of the

other two groups (Ps < .01, after Bonferroni correction).

Given the potential confound of verbal comprehension and

naming abilities in the silhouette group, a subtraction analysis

(object decision task > silhouette task) was performed to

remove the explicit verbal component involved in the

silhouette task and to isolate only those brain areas involved

in object perception as measured by the object decision task.

The subtraction analysis revealed a left hemispheric network:

Fig. 2 e Voxel-Based Lesion Symptom Mapping (VLSM) results

Discrimination Task; D, Cube Analysis Task. For A, B, C, D, all c

performance (q(FDR) [ .05, minimum cluster size of 10 voxels).

displayed on the right side) to yellow (maximum z-score). Axial

The right hemisphere is on the readers left.STG (Brodmann area, BA 22), ITG (BA 20), frontal operculum,

and insula (BA 13) (Fig. 3a).

3.2.3. Lesion results for space perceptionAs for the object group, subgroups derived from the VSLM

analysis were tested to investigate any potential confounds

between space perception tasks and verbal comprehension and

naming abilities: a position discrimination group (n 10) withpatients whose brain lesions were associated only with the

position discrimination task, a cube analysis group (n 40) withpatientswhosebrain lesionswereassociatedonlywith thecube

analysis task, a combined group (n 120) with patients whosebrain lesions were associated with both tasks, and a normal

control group (n 55) serving as a baseline group for normalverbal comprehension and language processing. Note that all

patients having lesions for object-related tasks were included in

the group of patients having lesion for the space tasks.

The one-way ANOVAs on language test scores (BN and TT)

revealed no significant main effect of Group [BN:

F(3,217) 1.83, p .09; F(3, 214) 1.66, p .09] (Supplementary

for A, Silhouette Task; B, Object Decision Task; C, Position

olored regions are critical for the corresponding task

Color range displays z-scores, from red (minimum z-score

slices display z-coordinates fromL38 toD63 in MNI space.

Fig. 3 e Conjunction Maps for A, Object perception, and B, Space

t p

pe

pa

c o r t e x 5 7 ( 2 0 1 4 ) 2 4 4e2 5 3 249Table 2). Given the null main effect, a conjunction analysis

(position discrimination task X cube analysis task) was per-

formed to identify brain regions commonly involved in the

two space perception tasks. The analysis found brain regions

critical for the perception of spatial relationships in 2D and 3D

representations and excluded brain regions thatmay be linked

to more specific task-related cognitive demands (e.g., count-

ing, responding verbally, evaluating distance, and pointing).

The conjunction analysis revealed a network lateralized to

the right hemisphere (Fig. 3b): posterior part of the superior

and medial frontal gyri extending to the precentral gyrus,

premotor area including SMA (BA 6), postcentral gyrus (BA 2

areas of damage associated with space perception and objec

decision task. B, Overlapping brain regions for the two space

Axial slices display z-coordinates from L38 to D63 in MNI sand 3), insula (BA 13), and MOG (BA 19), extending to the

boundaries of the MTG (BA 19), SMG (BA 40), and IPL (BA 40). In

addition, a discrete region in the IFG (BA 47) of the left hemi-

sphere was found. Among these regions, the largest cluster

affecting space perception performance was found within the

right IPL.

4. Discussion

The aim of the study was to investigate the neural un-

derpinnings of object and space perception using VLSM

analysis in a large pTBI cohort. Our findings identified distinct

and lateralized brain regions critical for object and space

perception within the left ventral stream and the right dorsal

stream, respectively. These results support the functional

subdivision of the visual system and shed new light on the

specific processes involved along both the dorsal and ventral

streams.

4.1. Object perception and ventral stream

Object recognition has been described as a hierarchical

process (Ungerleider & Haxby, 1994), where posterior regions

of the ventral stream process low-level features of an object(Grill-Spector et al., 1999), and more anterior regions integrate

those basic features into a more abstract representation

necessary for the object to acquire a meaning (semantic pro-

cessing) (Ungerleider & Mishkin, 1982). The right and

left hemispheres are thought to be differentially involved

in these stages e right brain-damaged patients were found to

be impaired on perceptual processing (apperceptive agnosia),

whereas left brain-damaged patients were found to be

impaired in semantic processing (associative agnosia) (De

Renzi, 2000; De Renzi, Scotti, & Spinnler, 1969; Warrington &

Taylor, 1978). Regions of left posterior temporal cortex,

including the fusiform gyrus, the ITG and the MTG, were

perception. Lesions resulting from conjunction analyses are

erception tasks. A, Unique brain regions for the object

rception tasks (position discrimination and cube analysis).

ce. The right hemisphere is on the readers left.found to be activated during conceptual processing of both

pictures and words in several neuroimaging studies

(Bookheimer, 2002; Thompson-Schill, 2003; Vandenberghe,

Price, Wise, Josephs, & Frackowiak, 1996; Xu, Gannon,

Emmorey, Smith, & Braun, 2009). Focal damage in this area

can lead to a loss of conceptual knowledge, including diffi-

culties in object naming even in the absence of diagnosed

aphasia (Newcombe, Oldfield, Ratcliff, & Wingfield, 1971).

Despite this literature supporting a left hemispheric

dominance in object processing at the level of meaning, the

majority of case studies documenting visual form agnosia

describe patients with diffuse bilateral brain damage (James,

Culham, Humphrey, Milner, & Goodale, 2003; Karnath, Ruter,

Mandler, & Himmelbach, 2009). Recently, Konen et al. (2011)

reported a comprehensive case study of patient SM who suf-

fered from object agnosia and prosopagnosia following a cir-

cumscribed lesion in the right posterior lateral fusiform gyrus.

Using fMRI, the authors found impaired object-related acti-

vation at sites both proximal and distal to the lesion (in both

the temporal and parietal cortex) compared to controls.

Interestingly, the unilateral lesion also altered object-related

activation in the intact left hemisphere, leading the authors

to argue that the proximal and distal induced impairments

following a unilateral lesion essentially mimicked a bilateral

lesion.

c o r t e x 5 7 ( 2 0 1 4 ) 2 4 4e2 5 3250How do our results fit with this framework? First, we did

not include patients suffering from visual agnosia, and

instead investigated performance in various object recogni-

tion tasks in a large sample of patients with lesions that

covered critical brain regions in both hemispheres. Second,

we included only patients whose basic visual discrimination

abilities were intact, as only those who passed the detection

screening task were included. With the silhouette and object

decision tasks, we assessed the subjects ability to recognize

more complex objects. Indeed, for the initial stage of object

perception we found the right LOC as a critical brain region,

while brain structures necessary for object recognition were

identified more anteriorly and were restricted to the left

hemisphere. For the silhouette task, our VSLM analysis un-

covered the left MTG as a necessary region for naming the

presented objects. For the object decision task, we identified a

more widespread network e including the MTG that extended

to the STG, along with the frontal operculum and the insula e

necessary for selecting the meaningful object among dis-

tractors. Since only patients with lesions associated with the

silhouette task differed from patients with lesion associated

with the object decision task and healthy controls in verbal

comprehension and naming abilities (as measured by the

Boston Naming and Token Tests), it is possible that the

involvement of the left MTG is related to naming difficulties

(Baldo, Arevalo, Patterson, & Dronkers, 2013).

Yet, altogether, using a large sample of patients and a

whole brain approach, our data are in line with the abundant

literature supporting a hierarchical organization in the ventral

stream, and they also bring new support for the comple-

mentary role of both hemispheres in object recognition. We

found that the ability to discriminate simple shapes depended

on the integrity of the right LOC, while the ability to recognize

more complex objects (in the silhouette and the object deci-

sion tasks) depended on the integrity of more anterior tem-

poral and frontal regions in the left hemisphere. In addition,

our results suggest that, in object recognition, different re-

gions may be recruited depending on the task demand. It is

possible that the more widespread network identified in the

object decision task compared to the silhouette task was

associated with an increase in task demand. Along this line, it

has been shown that activity in the temporal lobes increases

and spreads more anteriorly (Bar et al., 2001) as more infor-

mation about the objects identity is gained. Similarly, a shift

of activations from STG to the MTG appears when conscious

object recognition takes place (Martens, Wahl, Hassler, Friese,

& Gruber, 2012). In addition, recent neuroimaging results have

shown that bilateral activation of the frontal operculum and

the insula regions were associated with perceptual recogni-

tion when stimuli were gradually revealed to the subjects

(Ploran et al., 2007), and degree of activation for those brain

regions may be associated with stimulus complexity and

saliency (Sterzer & Kleinschmidt, 2010). While neuroimaging

findings only determine the involvement of brain regions, our

VLSM results identified the left frontal operculum and the

insula as necessary regions for object recognition in a context

where a perceptual decisionwas influenced by the presence of

distractors.Object recognition is subserved by distributed and inter-

connected brain regions in the ventral stream (Kravitz et al.,2013), and while our study helped identify critical nodes

along this stream, the precise neural mechanisms occurring

within and between these different regions still remain to be

understood. Surprisingly, critical substrates subserving object

recognition uncovered by our VLSM study did not include the

IFG as typically reported by neuroimaging studies (Haxby

et al., 1991; Konen & Kastner, 2008), despite the presence of

a lesion in this part of the brain in a significant number of

patients. It is therefore possible that compared to regions in

the temporal lobes, the role of the IFG may be more related to

other aspects of object recognition not measured by our tasks,

such as tasks involving top-down attentional control (Bar

et al., 2001). For instance, compared to the temporal regions,

Bar et al. (2001) showed that IFG activity is associated with

recognition ratings in conditions where the stimuli were

masked.

4.2. Space perception and dorsal stream

The dorsal stream, dedicated to space perception, was origi-

nally described as an occipito-parietal circuit projecting from

the early visual cortical areas to the posterior regions of the

parietal cortex (Goodale & Milner, 1992; Ungerleider &

Mishkin, 1982). A new framework has recently been formu-

lated, and describes three different pathways originating from

the PPC that mediate spatial perception and visually guided

actions (Kravitz et al., 2011). Within the dorsal pathway, the

right parietal cortex acts as a fundamental nexus and the large

body of evidence from neglect patients has brought unequiv-

ocal support for its role in space perception and visuospatial

attention (Bartolomeo, Thiebaut de Schotten, & Chica, 2012;

De Renzi, 1982; Kinsbourne, 1987; McCarthy & Warrington,

1990; Mesulam, 1981). Contrary to the ongoing debate about

the lateralization of the ventral stream, the right hemispheric

dominance for space perception is well established, and the

study of the neglect patients has largely contributed to this

knowledge (Taylor & Warrington, 1973). Evidence for the

dorsal stream lateralization has also been repeatedly reported

in healthy subjects. For instance, TMS on the right PPC in-

duces neglect-like behavior (Brighina et al., 2002; Fierro et al.,

2000) and enhances ipsilateral detection compared to that

elicited by left hemisphere stimulation (Hilgetag et al., 2001).

In addition, the volume of the longitudinal parieto-frontal

tract identified as the superior longitudinal fasciculus II was

found to be larger in the right hemisphere compared to the left

hemisphere, and this asymmetry correlates with a deviation

toward the left in a line bisection task (Thiebaut de Schotten

et al., 2011).

In line with these findings, we identified a set of brain re-

gions in the right hemisphere necessary for space perception

using two different space recognition tasks, including regions

fromthePPC to theprecentral gyrus, premotorarea (BA6) to the

postcentral gyrus (BA 2 and 3), and the insula (BA 13). One

critical lesionsiteassociatedwithspaceperception impairment

was the right IPL. This region, known to receive vestibular in-

puts from the cerebellum (Clower, Dum,& Strick, 2005; Clower,

West, Lynch, & Strick, 2001), is strongly connected with so-

matosensory areas (Lewis & Van Essen, 2000), and maintainsvisual somatotopic maps (Ishida, Nakajima, Inase, & Murata,

2009). Maintaining a continuously aligned representation of

regions necessary for object and space perception (Rorden &

Karnath, 2004) added new knowledge to the literature and

involved in a particular process/task; however, its power is

c o r t e x 5 7 ( 2 0 1 4 ) 2 4 4e2 5 3 251visual coordinates relative to the location of body parts is

essential not only for visually guided action in peripersonal

space (Milner & Goodale, 2008), but also for accurate space

perception (Sirigu, Grafman, Bressler, & Sunderland, 1991). Our

results are also in agreement with a previous VLSM study

showing that the right PPC is necessary for visuospatial pro-

cessing as measured by the block design task, a subtest of the

WAIS battery (Glascher et al., 2009) (see Behrmann, Geng, &

Shomstein, 2004 for a review).

In addition to the IPL, another critical region for space

perception was the premotor area (BA 6). The involvement of

this region has been reported in previous functional neuro-

imaging studies employing a task similar to our VOSP position

discrimination task (Ungerleider & Haxby, 1994) and a task

involving visuospatial attention (Corbetta, Miezin, Shulman,

& Petersen, 1993). According to a recent model, the dorsal

stream is subdivided into three separate pathways: parieto-

prefrontal, parieto-premotor and parieto-medial temporal

pathways (Kravitz et al., 2011). Our conjunction analysis

revealed that lesions associatedwith space perception overlap

with the parieto-premotor pathway (Kravitz et al., 2011). This

parieto-premotor pathway mediates not only reaching and

grasping (Fattori et al., 2009, 2010; Galletti et al., 2001), but also

eye movements (Nachev, Kennard, & Husain, 2008) and other

forms of visually guided action, along with the ability to

maintain coordinated maps of space and body position

(Kravitz et al., 2011). Our findings pointed to the critical role of

the parieto-premotor pathway in the perception of spatial

relationships in both 2D and 3D representations as it was a

common region for both space perception tasks in the absence

of visually guided action, reaching or grasping; therefore, its

general rolemay be ofmaintaining coordinatedmaps of space

and body position (Kravitz et al., 2011).

4.3. Conclusion

Our findings added novel support for the necessary involve-

ment of a left temporo-frontal network for object perception

and a right parieto-premotor network for space perception.

Even though our results showed a different hemispheric

dominance for both the ventral and dorsal stream, this does

not preclude any possible interaction between the two streams

(Konen & Kastner, 2008; Kravitz et al., 2013; Ungerleider &

Haxby, 1994; Zachariou, Klatzky, & Behrmann, 2013). It is

possible that both our analysis strategy and the specifics of our

sample did not allow us to uncover the structure(s) common to

both visual streams. Given the nature of the lesions in our pTBI

population, brain injuries were not randomly distributed (i.e.,

some brain areas were over- and others under-represented)

and covariation of damage across brain regions cannot be

excluded. As age has been shown to have an influence onmost

of the VOSP tasks (Bonello, Rapport, & Millis, 1997), the fact

that our sample included only elderly adults is a limitation, as

well as the chronicity of their brain lesions. In fact, all patients

were studiedmore than 35 years after the brain injury, and it is

therefore possible that some functional recovering may have

affected our findings. Finally, our lesion data were entirely

based on CT scans which has lower resolution and less ca-pacity to discriminate between grey and white matter

compared to MRI. Despite these limitations, the results fromlimited when it comes to making inferences about brain areas

that are necessary for the task.

Acknowledgments

The work was supported by the U.S. National Institute of

Neurological Disorders and Stroke intramural research pro-

gram, and a project grant from the United States Army Med-

ical Research and Material Command administrated by the

Henry M. Jackson Foundation (Vietnam Head Injury Study

Phase III: a 30-year post-injury follow-up study, Grant

DAMD17-01-1-0675). Selene Schintu was supported with

funding from the Henry M. Jackson Foundation, and Fadila

Hadj-Bouziane by the NEURODIS Foundation. The authors are

grateful to all the Vietnam veterans who participated in this

study and the National Naval Medical Center for their support

and provision of facilities, as well as V. Raymont, S. Bonifant,

B. Cheon, C. Ngo, A. Greathouse, K. Reding, and G. Tasick for

their invaluable help with the testing of participants and or-

ganization of this study. Note that the views expressed in this

article are those of the authors and do not necessarily reflect

the official policy or position of the Department of the Navy,

the Department of Defense, nor the U.S. Government. For

further information about the Vietnam Head Injury Study,

contact J. G. at jgrafman@northwestern.edu. The authors

declare that the researchwas conducted in the absence of any

commercial or financial relationships that could be construed

as a potential conflict of interest.

Supplementary data

Supplementary data related to this article can be found at

http://dx.doi.org/10.1016/j.cortex.2014.04.009.

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Object and space perception Is it a matter of hemisphere?1 Introduction2 Material and methods2.1 Subjects2.2 Neuropsychological assessment and behavioral analysis2.3 Computed tomography (CT) and lesion analysis

3 Results3.1 Behavioral results3.2 VLSM results3.2.1 Lesion results associated with each VOSP tasks3.2.2 Lesion results for object perception3.2.3 Lesion results for space perception

4 Discussion4.1 Object perception and ventral stream4.2 Space perception and dorsal stream4.3 Conclusion

AcknowledgmentsAppendix A Supplementary dataReferences