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Title
Case study: A selective tactile naming deficit for letters and numbers due to
interhemispheric disconnection

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https://escholarship.org/uc/item/5fx2f42s

Authors
Schendel, Krista
Herron, Timothy J
Curran, Brian
et al.

Publication Date
2021

DOI
10.1016/j.nicl.2021.102614
Peer reviewed

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NeuroImage: Clinical 30 (2021) 102614

Contents lists available at ScienceDirect

NeuroImage: Clinical
journal homepage: www.elsevier.com/locate/ynicl

Case study: A selective tactile naming deficit for letters and numbers due to
interhemispheric disconnection
Krista Schendel a, *, Timothy J. Herron a, Brian Curran a, Nina F. Dronkers b, Maria Ivanova b,
Juliana Baldo a
a
b

VA Northern California Health Care System, United States
University of California, Berkeley, United States

A R T I C L E I N F O

A B S T R A C T

Keywords:
Stroke
Corpus Callosum
Tactile recognition
Disconnection syndromes
Interhemispheric transfer
Haptics

The role of white matter pathways in cognition is a topic of active investigation that is vital to both the fields of
clinical neurology and cognitive neuroscience. White matter pathways provide critical connectivity amongst
numerous specialized brain regions thereby enabling higher level cognition. While the effects of dissections and
lesions of the corpus callosum have been reported, it is less understood how unilateral focal white matter lesions
may impact cognitive processes. Here, we report a unique case study in which a small left lateralized stroke in the
white matter adjacent to the body of the corpus callosum selectively impaired the ability to name letters and
numbers presented to the ipsilesional, left hand. Naming of letters, numbers and objects was tested in both the
visual and tactile modalities in both hands. Diffusion-weighted imaging showed a marked reduction in white
matter pathway integrity through the body of the corpus callosum. Clinically, this case highlights the significant
impact that a focal white matter lesion can have on higher-level cognition, specifically the integration of verbal
and tactile information. Moreover, this case adds to prior reports on tactile agnosia by including DTI imaging
data and emphasizing the role that white matter pathways through the body of the corpus callosum play in
integrating tactile input from the right hemisphere with verbal naming capabilities of the left hemisphere.
Finally, the findings also provoke fresh insight into alternative strategies for rehabilitating cognitive functioning
when structural connectivity may be compromised.

1. Introduction
Norman Geschwind (1965) introduced the notion that impairments
in many domains including language, action and emotion could arise
from white matter pathway disconnection, as opposed to strictly cortical
damage. This concept has since resulted in various disconnection hy­
potheses as explanations for a variety of neuropsychological disorders
(the hodological approach per Catani and Ffytche, 2005). For example,
both visuospatial neglect (Doricchi and Tomaiuolo, 2003; Doricchi
et al., 2008) and various speech and language deficits (Bajada et al.,
2015; Dick et al., 2013; Duffau, 2014; Ivanova et al., 2016) have been
described as disconnection syndromes involving white matter fiber
pathway disruption within either the right or left hemisphere, respec­
tively. In particular, these studies have indicated the importance of
stroke-related intra-hemispheric white matter pathway damage in
cognitive processes such as language and attention. However, there has
been far less research on the impact that unilateral focal lesions may

have on inter-hemispheric white matter connectivity through the corpus
callosum. Here, we describe a case of disconnection due to a small focal
stroke adjacent to the corpus callosum.
The corpus callosum is the largest collection of white matter fibers,
consisting of over 200 million axons that interconnect cortical areas in
the two cerebral hemispheres (Aboitz et al., 1992; Innocenti, 1995;
Schmahmann and Pandya, 2006). Studies of callosotomy and callosal
agenesis patients, where the corpus callosum is surgically severed or
underdeveloped, have demonstrated two important findings, namely
that the corpus callosum is critical for interhemispheric transfer and that
the two cerebral hemispheres are specialized for different cognitive
processes (Bogen and Vogel, 1962; Gazzaniga et al., 1962; Wilson et al.,
1977). Several studies, for example, have demonstrated that the corpus
callosum plays a central role in transferring and integrating information
between the left and right hemispheres of the brain (Banich, 1995;
Banich and Shenker, 1994; Bloom and Hynd, 2005; Schulte and MüllerOehring, 2010) and that callosal connectivity is related to

* Corresponding author at: VA Northern California Healthcare System, 150 Muir Road, Building 26, Martinez, CA 94553, United States.
E-mail address: Krista.Parker@va.gov (K. Schendel).
https://doi.org/10.1016/j.nicl.2021.102614
Received 8 July 2020; Received in revised form 5 February 2021; Accepted 24 February 2021
Available online 10 March 2021
2213-1582/Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

K. Schendel et al.

NeuroImage: Clinical 30 (2021) 102614

interhemispheric transfer time (Reuter-Lorenz et al., 1995; Forster and
Corballis, 1998; Iacoboni et al., 2000; Zaidel and Iacoboni, 2003; Paul
et al., 2007). Meanwhile, other studies have highlighted the different
functional specializations of the left and right cerebral hemispheres (for
review see Gazzaniga, 2005; and Zaidel, 1991). For example, the right
hemisphere appears to be superior for face recognition, visuospatial
tasks, processing of global/holistic forms, and performing mental rota­
tion (Bogen and Gazzaniga, 1965; Nebes, 1973; Gazzaniga and Smylie,
1983; Corballis and Sergent, 1988; Robertson et al., 1993). Similarly, in
the vast majority of adults, the left hemisphere is specialized for most
aspects of language (Lassonde et al., 1990; Reuter-Lorenz and Baynes,
1992; Gazzaniga, 2000). In addition, each hemisphere contains senso­
rimotor cortices that correspond to the contralateral side of the body.
Together, these findings emphasize the role that the corpus callosum
may play in linking information gathered through visual spatial and
manual exploration of the physical environment with linguistic/
communication abilities.
Brain imaging studies in healthy adults have confirmed many of the
findings from callosotomy studies including evidence for hemispheric
specialization (Bogen et al., 1988; Kanwisher et al., 1997; McCarthy
et al., 1996; Pujol et al., 1999; Szaflarski et al., 2006; Thiebaut de
Schotten et al., 2011; Sergent et al., 1992) and interhemispheric transfer
time being associated with corpus callosum integrity (e.g. Clarke and
Zaidel, 1994; Iacoboni and Zaidel, 2004). Importantly, fMRI studies by
Fabri and colleagues (2001, 2011) have further demonstrated that ac­
tivations associated with specific task modalities are associated with
activation within discrete regions of the corpus callosum. Specifically,
central-posterior portions of the body of corpus callosum have been
associated with touch stimulation, while the splenium is more active
during visual stimulation.
Recent advances in white matter imaging and tractography analysis
techniques have provided a further means of studying connectivity and
communication between different brain regions via specific white mat­
ter pathways. Tractography studies by Fabri and colleagues in healthy
controls, for example, have confirmed that interhemispheric connec­
tions between homotopic areas of the cortex are organized within
various segments of the corpus callosum. Of particular relevance to the
current report, the midbody and posterior half of the body of the corpus
callosum have been associated with motor and sensory control of the
hands (Fabri et al., 2014). To date, however, there is little research on
the impact that unilateral focal lesions may have on interhemispheric
white matter connectivity through the corpus callosum, especially in
regard to connections between non-homotopic regions.
The paucity of research in this area stems in part from the rarity of
small focal infarcts that are confined to white matter regions. While
strokes are a common cause of unilateral focal lesions, infarcts due to
stroke are often sizable and have a wide range of behavioral conse­
quences. Strokes impacting frontal or frontal-parietal cortices, for
example, will often result in somatosensory and motor (hemiparesis)
impairments, while other strokes can affect visual perception and lan­
guage abilities, depending on the side and location of the lesion. Uni­
lateral strokes resulting in well-confined infarcts involving primarily or
only white matter pathways are rare. Such cases, however, can be
especially informative in providing a greater understanding of the role
of interhemispheric white matter pathways in cognition and perception.
In the case reported here, a patient with a small, unilateral focal
lesion near the central body of the corpus callosum exhibited difficulty
identifying a number that was traced onto her hand during a neuro­
logical exam. Her primary sensorimotor cortices and language areas
were completely intact. Thus, in an effort to determine the degree to
which callosal fibers were disrupted between the language dominant left
hemisphere and primary sensory cortex in the right hemisphere, we
analyzed diffusion-weighted imaging data using high angular resolution
diffusion imaging (HARDI) deterministic tractography. This allowed us
to determine the extent to which white matter pathways through the
corpus callosum were compromised. In order to further explore the

extent of this patient’s tactile naming impairment, we also conducted a
series of tactile naming tests (described below). This case is important as
it highlights the potentially significant impact of a small white matter
lesion on cognition, as well as the importance of callosal white matter
fibers in establishing connectivity between different functional domains.
In particular, this case suggests the corpus callosum may play a critical
role in linking information gathered through manual exploration of the
physical environment with linguistic/communication abilities.
2. Methods and materials
This research was approved by the Institutional Review Board at the
VA Northern California Health Care System and was HIPAA compliant.
Informed consent was obtained prior to data collection.
2.1. Case description
The patient was a right-handed, native-English speaking, female
with 16 years of education who suffered a stroke at age 39 due to left
carotid artery dissection. She had no prior neurologic history or history
of substance abuse. Medical records indicated that the patient presented
acutely with speech difficulties and right-sided sensorimotor symptoms.
Primary complaints immediately after the stroke included weakness and
decreased sensation in the dominant right hand, arm and foot; difficulty
speaking; and an inability to continue her work as a graphic designer.
The patient was referred to our stroke research program at 3 years postonset, and a neurological exam was conducted at that time. During this
exam, visual confrontation testing revealed a mild quadranopsia in the
lower right visual field, mild weakness in the right hand and arm
compared to the left, and difficulty identifying numbers that were traced
onto the palm of her hands (tactile agraphesthesia).
2.1.1. Neuropsychological profile
An Edinburgh Handedness Inventory indicated that the patient was
unequivocally right-hand dominant prior to the stroke (score 100/100).
In addition, a series of neuropsychological tests were administered as
part of a research battery. Table 1 shows the individual raw scores and
normative percentiles (when available) for the neuropsychological as­
sessments that were administered. Based on the Weschler Test of Adult
Reading (WTAR), the patient had an estimated pre-morbid Verbal IQ of
102. To test for signs of hemispatial neglect, the Behavioral Inattention
Test (BIT-Conventional) was administered. The patient scored in the
unimpaired range, above the cutoff score (<128) for hemispatial
neglect. In fact, no lateralized attentional bias was apparent on any of
the individual BIT subtests (including clock drawing). Verbal short-term
memory was assessed via the WAIS-IV Digit Span test revealing a normal
forward digit span of 7 items. However, the Spatial Span score fell in the
5th percentile (impaired range). In addition, the Repeatable Battery for
the Assessment of Neuropsychological Status (RBANS) was adminis­
tered. All RBANS Index scores were within the low average to average
range, except for the Attention Index which is based on Digit Span and
Symbol Coding and was in the impaired range. Speech, language, and
reading were all within normal limits as assessed by the Western
Aphasia Battery (WAB; Kertesz, 1982). The patient received an overall
WAB Aphasia Quotient (AQ) of 99.8/100, where the normal cutoff is
>93.7. Scores on the individual subtests of the WAB AQ (Spontaneous
Speech, Comprehension, Repetition & Naming – which included object
naming) were all at ceiling. Scores on the WAB Cognitive Quotient
subtests (Reading, Praxis, Drawing & Constructional Drawing) also
approached ceiling.
Two-point sensory discrimination thresholds were tested at the time
of tactile testing and were found to be normal for the patient’s left and
right palms (within 1 cm, for each) and left and right index fingers (5
mm and 5–6 mm, respectively). When asked about motor symptoms and
hand use after her stroke, the patient reported more frequent use of her
non-dominant, left hand due to right-handed weakness. She denied any
2

K. Schendel et al.

NeuroImage: Clinical 30 (2021) 102614

could be held within one hand and palpated. Test type (Visual, Tactile)
and Stimulus Type (Letters, Numbers, Objects) were blocked, while
Hand (left, right) was always randomly interleaved within blocks. For all
tests, stimulus order was randomized with the constraint that each
stimulus was presented an equal number of times to each hand. There
were no response time limits.

Table 1
Neuropsychological test scores grouped by cognitive domain. Raw or index
scores and normative percentiles (when available) are shown. Where normative
percentiles were not available, the raw score out of the total possible score is
listed. WNL = Within Normal Limits, WTAR = Weschler Test of Adult Reading,
CLQT = Cognitive Linguistic Quick Test, BIT-C = Behavioral Inattention TestConventional, RBANS = Repeatable Battery for the Assessment of Neuropsy­
chological Status, WAB = Western Aphasia Battery, AQ = Aphasia Quotient.
Domain

Test

Score

Percentile

Clinical
Range

Intellectual
ability

WTAR (Pre-Morbid
IQ)
Raven’s Coloured
Progressive Matrices

32

46th

Average

28

10th

Low average

Executive
functioning

CLQT

10

68th
percentile

WNL

Attention &
working
memory

BIT-C

134/
146

RBANS Immediate
Memory Index
RBANS Delayed
Memory Index
RBANS Attention
Index
Digit Span Forward
(WAIS-IV)
Spatial Span (WMSIII)

83

13th

No
hemispatial
neglect
Low average

81

10th

Low average

64

1st

Impaired

10

50th

Average

9

5th

Impaired

RBANS
Visuospatial/
Constructional Index
WAB Drawing
subtest
WAB Constructional
Drawing subtest
WAB Praxis subtest

92

30th

Average

RBANS Language
Index
Western Aphasia
Battery (WAB) AQ
Total
Spontaneous speech
subtest
Comprehension
subtest
Repetition subtest

95

Visuospatial/
Construction

Language

Naming subtest
(included objects)
WAB Reading
subtest

2.2.1. Visual naming tests
In order to assess visual naming, 24 physical objects, 23 wooden
letters, and 9 numbers were used. The wooden stimuli were approxi­
mately 2 in. in height and 1.5 in. in width, depending on the particular
stimulus. In all cases, each stimulus was visually presented one at a time
and the patient was asked to name the item as it was presented in view.
During these visual naming tests, the patient was not allowed to touch or
interact with any of the stimuli. In a separate test session, the letter and
number stimuli were also traced via stylus onto a blank piece of paper
while the patient watched. In this case, the patient was asked to watch as
each stimulus was traced in view and then to name the item. For the
visual object and letter naming tests, each item was presented once for a
total of 24 and 23 trials, respectively. For number naming, each item was
presented twice for a total of 18 trials.
As an additional control for the tactile naming tests (described
below), the letter and number stimuli were also traced onto the patient’s
hands in random order, while she watched. For letter naming, each letter
was traced once onto each hand (23 trials per hand) in random order for
a total of 46 trials. For number naming, each number was presented
twice to each hand (18 trials per hand) in random order for a total of 36
trials.
2.2.2. Tactile naming tests
During the tactile naming tests, the patient wore an eye mask to
prevent access to any visual information about the stimuli. In the passive
condition, two blocks each of letters and numbers stimuli were traced
via stylus approximately 2-inches in height onto the patient’s palm. For
letter naming, each block consisted of 23 trials administered to each
hand for a total of 46 trials. For number naming, each block consisted of
18 trials administered to each hand for a total of 36 trials.
For comparison, two blocks of letters (46 trials per block, 23 per
hand) and two blocks numbers (36 trials per block, 18 per hand) were
also administered in an active palpation condition. In these blocks, the
same wooden block stimuli used in the visual naming task above were
placed directly into the patient’s left or right hand to manually palpate
and name. In addition, one block of object naming was conducted using
24 real-world objects which were each placed once into each hand in
random order for naming (a total of 48 trials).
During the active palpation tasks, the participant often manually
flipped items over or turned them upside down during exploration. For
this reason, orientation-only errors were disregarded (e.g. a response of
either 6 or 9 was scored as correct for both 6 and 9, and similarly for 2/5,
M/W and Z/N).

25/30
25/30
58/60

99.8/
100

37th

Average
WNL

20/20
10/10
9.9/
10
10/10
99/
100

unwanted activity or interference from either hand and did not endorse
any feelings of any body parts not belonging to her. Rather, she reported
that she had full control of both hands despite some weakness and
reduced sensation in her dominant right hand, consistent with her
neurological exam. Based on these reports and the medical history ob­
tained, there was no indication of alien hand syndrome (Scepkowski and
Cronin-Golomb, 2003).

2.2.3. Control participant
In order to compare the patient’s performance to that of a healthy
control, we also tested a right-handed, age-matched female with no
neurological history on the tactile naming tests described above. The
control participant performed one block each for tactile naming of let­
ters and numbers, in both the traced and palpated conditions (for a total
of 4 blocks). Each block was conducted using the same stimuli and
procedures as outlined above. Diffusion Tensor Imaging was conducted
in the control as well, as per the protocol described below.

2.2. Behavioral testing
Several tests of Visual and Tactile naming were administered to the
patient over the course of four sessions. Number stimuli included the
digits 1–9, and letter stimuli included 23 uppercase letters from the
English alphabet (Y, G, and F were omitted due to a high degree of
similarity in the tactile domain to X, C, and E, respectively). The same
numbers and letters were presented either visually or via tactile pre­
sentation in alternate tests. Object stimuli included a set of unique ob­
jects (e.g. fork, knife, spoon, paperclip, key, coin, rubber band, etc.) that

2.3. Brain imaging
High resolution 3T MRI scans were acquired on a Siemens Magnetom
Verio open-bore 3T MRI scanner using a 3D T1-weighted (T1W)
MPRAGE (magnetization-prepared rapid gradient echo) protocol with 1
3

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NeuroImage: Clinical 30 (2021) 102614

Fig. 1. Naming accuracy for letters, numbers, or objects that were visually presented to the patient (leftmost gray bars), or alternatively, traced in view onto a piece
of paper (rightmost gray bars) or onto the patient’s left or right palm (colored bars) while the participant watched. The latter condition (colored bars) was conducted
as a control for the tactile naming conditions in which letter and number stimuli were traced via stylus onto the palms of the blindfolded participant.

Fig. 2. Tactile naming accuracy for letters, numbers, and objects that were either passively traced onto the palmar surface of the hands (leftmost bars) or actively
palpated (rightmost bars), always while the participant was blindfolded. The control participant performed at ceiling, as indicated by the gray lines.

mm 3 isotropic resolution (TR/TE/TI = 2400/3.16/1000 ms, flip angle
= 8◦ ; FOV = 256 mm; imaging matrix = 256 × 256; acquisition time =
4.5 min). Two T1W images were acquired and averaged to improve the
contrast-to-noise ratio. FLAIR and fast spin echo T2-weighted (T2W)
images were also acquired with the default Siemens pulse sequences to
improve the visual assessment of brain lesions. Diffusion-weighted im­
aging (DWI) sequences were also collected with the parameters: TR =
4500 ms, TE = 79.0 ms, flip angle = 90◦ , b = 1200 s/mm2, 64 directions,
11 b0, FOV = 220 mm, voxel size 2 × 2 × 2 mm, 72 axial slices,
bandwidth = 1228 Hz/voxel, and GRAPPA factor = 2.
The participant’s lesion was visualized and reconstructed using
MRIcron software (Rorden and Brett, 2000). First, the lesion was traced
directly onto the patient’s native T1-weighted digital images, with
yoked T2-weighted and FLAIR images to verify lesion boundaries. Le­
sions were then registered onto the Montreal Neurological Institute
(MNI) template using the standard nonlinear spatial normalization
procedure from statistical parametric mapping (SPM8). A cost function
masking procedure was used to avoid distortions due to the presence of

the lesion (Brett et al., 2001).
Tractography. DWI data were first pre-processed in FSL version 5.09
(Jenkinson et al., 2012) using a fieldmap correction for susceptibility
induced distortions and then in ExploreDTI ver. 4.8.6 (Leemans et al.,
2009) using eddy current and motion corrections. Next HARDI deter­
ministic tractography based on constrained spherical deconvolution was
implemented in StarTrack beta version (Dell’Acqua et al., 2013) with
the following parameters: ALFA = 1.8, iterations = 300, n = 0.002, r =
15, ABS threshold = 0.003, step size (mm) = 0.5, angle threshold = 35,
minimal length (mm) = 50. Finally, manual virtual tract dissections of
the Corpus Callosum (CC), left Arcuate Fasciculus (AF), left Superior
Longitudinal Fasciculus (SLF) and left Extreme Capsule (EmC) were
done in native diffusion space in TrackVis ver. 0.6.1 (Wang et al., 2007)
according to the following criteria.
CC streamlines were identified with a single seed ROI placed on the
whole corpus callosum along several consecutive midsagittal slices and
refined by removing any confounding cortico-spinal and cingulum fibers
that were not part of the corpus callosum (all ROIs were drawn on the b0
4

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NeuroImage: Clinical 30 (2021) 102614

were included in the models, as reported below.

map). AF was defined as fibers running dorsally between frontal and
temporal lobes. AF was segmented by placing two ROIs: one on the
coronal slice at the entrance to the frontal lobe (anterior to the central
sulcus) and another one on the axial slice at the entrance to the temporal
lobe (just below the Sylvain fissure). SLF was defined as a tract running
between frontal and parietal lobes laterally to the AF. It was segmented
using the same frontal ROI as the AF and an additional ROI placed
posteriorly in the parietal lobe. EmC fibers were segmented by placing
an ROI in the white matter underneath Broca’s area and insular cortex
and a second ROI underneath the middle-posterior portion of the su­
perior temporal gyrus.
It was predicted that the patient’s visual naming performance would
be intact and that only tactile naming of stimuli would be impacted by
the lesion. More specifically, it was hypothesized that naming of items
presented to the left hand would be impaired relative to that of the right
hand, due to compromised transfer of sensory information from the left
hand to left hemisphere language regions.

3.1. Visual naming
Consistent with performance on the WAB naming tasks, the patient
performed at or near ceiling on all of the Visual naming tasks (both for
stimuli presented visually or traced onto the palm of the hand while the
participant watched). These data (see Fig. 1) confirmed that visual
recognition of objects and alphanumeric shapes was intact.
3.2. Tactile naming
Tactile naming accuracy (while blindfolded) for passively traced
letters and numbers differed between the two hands (see left side of
Fig. 2, below). For letter naming, the patient accurately named 11/46
letters that were traced onto her left palm and 26/46 of those traced onto
her right palm. For number naming, she accurately named 15/36
numbers that were traced onto her left hand and 26/36 of those traced
onto her right hand. To test whether performance was reliably different
between the two hands, McNemar’s paired data Chi-Squared test was
conducted to directly compare left- versus right-hand performance for
letter and number naming in the passively traced condition where leftand right-hand trials were paired having the same item (specific number
or letter), session (T1 vs. T2), and repetition number (see Table 2). The
test found significantly worse tactile naming performance for letters and
numbers that were traced onto the left hand, X2 (1, N = 36) = 17.36, p =
0.00003, CI [0.191, 0.427]. Other main effects and interactions were
analyzed using a mixed effects logistic regression model. Repeated
measures included Hand (L, R), Stimulus Type (Letters, Numbers),
Session (T1, T2), with Item (specific letters or numbers) as the random
effect. Results revealed a significant main effect of Hand (z-score = 3.3, p
< 0.001), with no other main effects or Hand × Stimulus Type inter­
action (all p > 0.1). The patient’s errors were striking in that she often

3. Analysis and results
All behavioral analyses were conducted using R software 3.6.3 (R
Project for Statistical Computing, RRID:SCR_001905; http://www.r-pro
ject.org/). McNemar’s paired data tests were used to test for significant
differences in performance between the patient’s left and right hands
across conditions. For these Chi-Squared tests, p-values were based on
the asymptomatic estimate with correction and the Wald confidence in­
terval was computed with an R function that is based on the technique
described in Bonett and Price (2012). In addition, logistic mixed effects
tests were conducted using v. 1.1–21-2 of the lme4 package in R (Bates
et al., 2015) in order to test for other main effects and interactions. These
analyses were conducted on individual trials rather than percentages.
Wald z scores and p-values for the mixed effects analyses were produced
by lme4’s regression function “glmer”. When possible, random slopes

Table 2
Top: McNemar’s Chi-Square Test for Letters and Numbers that were passively traced onto the palmar surface of the hands. Bottom: McNemar’s Chi-Square Test for
Letters and Numbers that were actively palpated.

5

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NeuroImage: Clinical 30 (2021) 102614

whether tactile letter and number naming performance differed based
on the hand used, McNemar’s paired data Chi-Squared test was con­
ducted to compare performance in the two hands in the active palpation
condition. The Chi-Square test revealed a significant left-hand impair­
ment for letter and number naming in the active palpation condition, X2
(1, N = 36) = 12.25, p = 0.0005, CI [0.142, 0.382]. A mixed effects
logistic regression model was used to examine tactile naming accuracy

reported a letter that was very different from the one she was presented,
such as reporting ‘M’ for an S, or reporting ‘L’ for an O.
Tactile naming performance for the actively palpated letters,
numbers and objects is shown on the right in Fig. 2. For letter naming in
this condition, the patient accurately named 17/46 using her left hand
and 36/46 using her right hand. For number naming, she accurately
named 28/36 using her left hand and 31/36 using her right hand. To test

Fig 3. Left top panel: 3-D rendering of the left hemisphere infarct located adjacent to the midbody section of the corpus callosum. Right top panel: Midline sagittal
MRI slices. Bottom panel: Multislice coronal view of the lesion reconstruction, with slice position indicated on the far right.

Fig. 4. Panel A: Whole-brain tractography viewed axially from above shows spared fiber tracts in the genu and splenium and an absence of tracts throughout the
body of the corpus callosum in the patient (left) compared to that of an age- and sex-matched control (right). Panel B: Left lateral view of the corpus callosum fibers
(viewed on a b0 image in native space) again revealing tracts only in most anterior and posterior portions of the corpus callosum in the patient. Conventional DTI
color coding is used to show fiber orientation: red reflects tracts in the left–right direction, green in the antero-posterior direction, and blue in the inferior-superior
direction. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
6

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NeuroImage: Clinical 30 (2021) 102614

Fig. 5. Reconstruction of left hemisphere fiber tracts including the Arcuate Fasciculus (red), Superior Longitudinal Fasciculus (green), Extreme Capsule (cyan) and
Corpus Callosum (dark blue). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

for alphanumeric stimuli across conditions (i.e. actively palpated or
passively traced). Repeated measures included Condition (Traced,
Palpated), Hand (L, R), and Stimulus Type (Letters, Numbers), with Item
(specific letters or numbers) being the random effect. The mixed-effects
model included both an intercept and slope with respect to Hand for
each Item in case there were consistent Hand modulation differences
between specific letters and numbers. Results revealed significant effects
of Hand (z-score = 5.0, p < 0.001), Condition (z-score = 3.2, p < 0.01),
and Stimulus Type (z-score = 3.3, p < 0.001). There were no Item
specific effects and the Hand effect did not significantly interact with
either Condition (Passively Traced vs. Actively Palpated) or Stimulus
Type (all p > 0.1). Thus, in the actively palpated condition, performance
was still reliably worse for letters and numbers presented to the left hand
compared to the right hand.
Remarkably, the patient performed at ceiling in naming actively
palpated objects (24/24 with each hand). Thus, an additional analysis
combining tactile naming of all actively palpated letters, numbers, and
objects was conducted to directly compare the three different stimulus
types. A mixed effects logistic regression model with repeated measures
of Stimulus Type (Letters, Number, Objects) and Hand (L, R), was used
with Item being the random effect. Again, the mixed-effects model
included both an intercept and slope with respect to Hand for each Item.
Significant main effects of Hand (z-score = 4.1, p < 0.001) and Stimulus
Type (z-score = 3.5, p < 0.001) were observed, but there was no sig­
nificant Hand × Stimulus Type interaction (p > 0.1).
Unlike the patient, the age-matched control participant performed at
ceiling (100% accuracy) on tactile naming of letters and numbers,
regardless of which hand was used.

Table 3
Tractography metrics and mean FA data for the patient and an age- and sexmatched control participant. Tracts of interest include the Corpus Callosum
(CC), along with the left hemisphere (Lh) language production network tracts
including the Arcuate Fasciculus (AF), Superior Longitudinal Fasciculus (SLF),
and the Extreme Capsule (EmC). Data for the Right hemisphere (Rh) tracts are
shown to the right of the backslash /. *Proportional volume is the voxel volume
of the tract relative to the total voxel count of the whole brain tractogram. SD =
standard deviation.
Patient

AF (Lh/
Rh)

SLF (Lh/
Rh)

EmC
(Lh/Rh)

CC

Whole brain
tractogram

Track count

1425 /
807
1455 /
1161)
0.0244 /
0.0194
0.40 /
0.44
0.13 /
0.11

858 /
773
1093 /
1013
0.0183 /
0.0170
0.40 /
0.40
0.13 /
0.12

1026 /
1049
1089 /
1602
0.0182 /
0.0268
0.45 /
0.41
0.13 /
0.13

5352

119,926

4062

59,745

0.0680

–

0.42

0.43

0.13

0.16

Control

AF (Lh/
Rh)

SLF (Lh/
Rh)

EmC
(Lh/Rh)

CC

Whole brain
tractogram

Track count

6536 /
2735
4419 /
2875
0.0533 /
0.0347
0.48 /
0.46
0.12 /
0.13

2038 /
2997
2198 /
2399
0.0265 /
0.0289
0.45 /
0.45
0.13 /
0.12

345 /
894
1043 /
1561
0.0126 /
0.0188
0.40 /
0.43
0.15 /
0.14

49,695

191,436

24,425

82,905

0.2946

–

0.55

0.48

0.18

0.17

Volume (voxel
count)
*Proportional
Volume
Mean FA
SD FA

Volume (voxel
count)
*Proportional
Volume
Mean FA
SD FA

3.3. Imaging and tractography
Structural MRI revealed a small deep subcortical watershed infarct in
the left hemisphere adjacent to the central body of the corpus callosum
(lesion reconstruction shown in Fig. 3) and including the left superior
corona radiata. The normalized lesion volume was 20.83 cc.
Reconstruction based on HARDI deterministic tractography revealed
a marked reduction in the volume of the patient’s corpus callosum.
Specifically, streamlines extending laterally from the body of the corpus
callosum were absent, while residual interhemispheric connectivity
remained through the genu and splenium (shown in Fig. 4).
In addition, several left hemisphere fiber tracts relevant to language
production, including the Arcuate Fasciculus (AF), Superior Longitudi­
nal Fasciculus (SLF), and Extreme Capsule (EmC) were also recon­
structed. Importantly, each of these left hemisphere language network
fiber tracts could be reconstructed in the patient (illustrated in Fig. 5).
Although a reduction in tract counts was expected due to the pres­
ence of the white matter lesion, the tractography data revealed that the

AF, SLF, and EmC could all be visualized in both hemispheres of the
patient and had Mean FA values that were comparable to that of the
control subject. The most striking finding from the tractography data,
therefore, was the difference in CC fiber tracts in the patient versus the
control. This difference is best captured by the reduced proportional
volume and Mean FA of the CC fiber tracts in the patient compared to the
control (see Table 3).
4. Conclusions and discussion
Over half a century of research has established that direct severing or
under-development of the corpus callosum can impair interhemispheric
transfer of information (Bogen and Gazzaniga, 1965; Bloom and Hynd,
2005; Fabri et al., 2001; Gazzaniga et al., 1962; Gazzaniga, 2000;
Robertson et al., 1993; Reuter-Lorenz and Baynes, 1992; Schulte and
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NeuroImage: Clinical 30 (2021) 102614

Müller-Oehring, 2010). Thus, it is also reasonable to expect that uni­
lateral focal lesions adjacent to or impinging on the corpus callosum may
also disrupt communication between the two hemispheres. The current
case study presents a patient with a small left hemisphere infarct
confined to the white matter adjacent to the midbody portion of the
corpus callosum. Interestingly, behavioral testing indicated a selective
tactile naming deficit for letters and numbers that were presented to the
patient’s ipsilesional left hand. Visual naming, visual object recognition,
and language were all normal, confirming that this deficit could not be
explained by more general impairments in verbal naming or visual ob­
ject recognition. Instead, tactile information from the left hand, specif­
ically for letters and numbers, was less accessible for identification via
verbal naming.
Consistent with this interpretation, a spontaneous comment from the
patient was particularly striking. After palpating and exploring a
wooden number 6 in her left hand for some time, she offered a response
of ‘two’, then switched her response to ‘three’. Then, with some frus­
tration, she said, “I can visualize it, but when I try to say it, it’s just not
right”. When the experimenter then prompted her to draw what she was
“visualizing” using her left hand, she correctly drew a 6. Thus, it
appeared that tactile perception was intact, as also evidenced by her
accurate haptic object identification. Rather, the problem appeared to
be one of integrating specific tactile information from the right hemi­
sphere with verbal naming abilities of the left hemisphere.
The idea that brain injury can result in a tactile-verbal disconnection
is not new. In 1992 Endo et al. reported a case in which a unilateral
subcortical lesion in the area of the left angular gyrus and posterior
callosal radiations was hypothesized to have created a tactile-verbal
disconnection, which the authors described as tactile aphasia. Under­
standing the specific pathways that might have been compromised or
disconnected in that case, however, is complicated since the patient had
also sustained a severe traumatic brain injury resulting in posterior
subcortical damage thought to involve callosal radiations from the
splenium as well as the posterior arcuate fasciculus, the external capsule,
the inferior longitudinal fasciculus, and optic radiations. Moreover, DTI
imaging was not available at that time. Thus, to our knowledge, our case
is the only focal stroke case with tactile aphasia that has been presented
in the literature along with DTI brain imaging showing the impact on
specific white matter tracts.
In keeping with the hypothesis that our patient suffered from a
tactile-verbal disconnection, DTI fiber tract reconstruction confirmed a
lack of fiber tracts extending laterally from the body of the corpus cal­
losum. This is consistent with other findings that somatosensory transfer
of information, including that of the hands, likely relies on communi­
cation through the central to posterior portion of the body of the corpus
callosum (Fabri et al., 2005; Hofer and Frahm, 2006; also see Fabri and
colleagues, 2001, 2011, 2014). This is important since the hands play a
critical, albeit possibly underappreciated, role in cognition and
perception. Hands not only enable significant functionality in day-today activities, such as grasping, manipulating, and exploring objects,
tools, and a myriad of surfaces, they are also important in guiding visual
attention and perception (di Pellegrino et al., 1997; Reed et al., 2006;
Schendel and Robertson, 2004).
It should be noted that the case reported here did not show any signs
of alien hand syndrome which often consists of involuntary motor
movements and/or apparent lack of ownership of the left hand in
particular. Alien hand syndrome is rare and has been associated with
medial frontal cortex lesions or a combination of frontal and collosal
lesions (Banks et al., 1989 and Scepkowski and Cronin-Golomb, 2003,
for a review). It is notable in the case reported here that there was little
to no cortical damage and that white matter tracts passing through both
the genu and splenium of the corpus callosum were visualized with
diffusion tensor imaging. Although symptoms consistent with alien hand
syndrome have been observed after callosotomy in the absence of
cortical damage, such cases almost always exhibit intermanual conflict
as the primary symptom (Feinberg et al., 1992). However, the patient

studied here did not report or show any signs of intermanual conflict at
any time since her stroke, or during any of the tactile naming tests
conducted in this study.
Although it could be reasoned that right-handed individuals might
have finer discrimination abilities on the surfaces of their dominant
hand, it is unlikely that this could explain our patient’s left-handed
deficit for several reasons. For one, the patient’s left hemisphere
stroke resulted in weakness and decreased sensation in her contrale­
sional right hand which should have biased the results in the opposite
direction. Moreover, two-point sensory discrimination thresholds were
found to be similar on the patient’s left and right hands during the time
of testing. Finally, testing of a healthy control participant (matched for
age, gender and handedness) in both the active and passive conditions
revealed performance at ceiling (100%) for both letter and number
stimuli in both hands. Given these observations, the most parsimonious
explanation is that tactile naming of stimuli presented to the patient’s
left hand likely suffered for reasons that were not of a purely sensory
nature.
The fact that tactile naming accuracy was higher in this case for
stimuli that were actively palpated, as compared to passively traced, is
also noteworthy. One explanation could be order or practice effects with
repeated exposure to the same set of alphanumeric stimuli. However,
there were no effects of block order or trial order (within blocks).
Another explanation for the higher naming accuracy of actively palpated
items is that active tactile exploration may rely on different and/or more
extensive brain networks. As reported by Homke and colleagues (2009),
areas of the superior parietal lobule and intraparietal sulcus along with
the ventral premotor cortex form an extensive fronto-parietal network
for haptic object manipulation, with the anterior versus posterior por­
tions of this network mapping onto the somatosensory versus actionrelated aspects of haptic recognition. Thus, active tactile manipulation
may have resulted in the recruitment of a larger network of posterior
brain regions which consequently may have been less vulnerable to
disconnection.
The role of the hands in haptic recognition is particularly relevant to
instances of tactile agnosia. Tactile agnosia is commonly defined as an
impairment in recognizing objects after tactile exploration despite
relatively intact sensory functioning and cognitive abilities. Unilateral
tactile agnosia (affecting only one hand) has typically been associated
with contralateral lesions involving the somatosensory cortex or other
parietotemporal structures (Veronelli et al., 2014; Caselli, 1991, 1997;
Reed et al., 1996; Homke et al., 2009), in addition to lesions to the
corpus callosum (e.g. Balsamo et al., 2008; Marangolo et al., 1998). The
case reported here is unique in that a chronic tactile naming deficit was
observed for alphanumeric shapes presented to the ipsilesional left hand
as a consequence of a focal pericallosal lesion in the left hemisphere.
Thus, this case underscores the fact that white matter damage can result
in the disconnection of otherwise intact cortices, such that an impair­
ment may even be observed ipsilaterally, particularly in the case of the
left hand which is controlled by the non-language dominant hemisphere.
A difference in connectivity between the left and right hands and the
language dominant hemisphere may partially explain why unilateral
associative tactile agnosia is more commonly observed in the left hand
(for right-hand dominant individuals).
The literature on tactile agnosia has also made a distinction between
apperceptive agnosia and associative agnosia. Apperceptive agnosia is
defined as a deficit in discriminating different tactile sensory features
such as weight or texture. As such, apperceptive agnosia has been
regarded as a perceptual deficit and has been associated in the literature
with damage to supplementary motor and somatosensory cortices, as
well as inferior parietal cortex (Caselli, 1997; Reed et al., 1996; Saetti
et al., 1999). Associative agnosia, on the other hand, is defined as a
deficit in associating tactile sensations with a particular object shape or
name, despite spared perceptual abilities (Balsamo et al., 2008; Caselli,
1991; Casellim, 1993; Veronelli et al., 2014). Notably, our patient did
not have sensory problems in the left hand and was able to identify
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NeuroImage: Clinical 30 (2021) 102614

objects held in the left hand, which rules out apperceptive agnosia. Thus,
our case is more similar to cases of associative tactile agnosia, some of
which have been observed following lesions involving the corpus cal­
losum. For example, Balsamo et al., (2008) reported a case in which
impaired recognition and naming of objects was observed in the left
hand after a lesion to the posterior third of the trunk of the corpus cal­
losum. In contrast, our case showed relatively intact object naming, but
rather poor performance for letters and numbers. This begs the question
as to whether there may be a dissociation between tactile recognition of
objects versus other alphanumeric shapes.
However, before considering whether the brain may recruit different
regions for tactile object recognition compared to tactual identification
of alphanumeric shapes, it is important to acknowledge that there are
some critical differences between alphanumeric stimuli and real-world
objects. One difference is that letters and numbers differ from one
another primarily in shape whereas real-world objects are inevitably
more variable in shape, size, and texture. Furthermore, haptic object
recognition may rely on both cutaneous sensory information as well as
kinetic information from hand finger joint positions and movement
(Gibson, 1962; Loomis and Lederman, 1986; Turvey and Carello, 2011).
Handheld objects are certain to provide more of this latter type of in­
formation and as such may also be more readily associated with action
schemas (e.g. what you do with a fork versus a pencil etc.). Thus, it is
important to acknowledge that real-world objects provide more cues for
differentiation via tactual manipulation than do alphanumeric stimuli.
Nonetheless, Veronelli et al. (2014) reported findings from a patient
with a right hemisphere stroke who exhibited a pattern of impaired
tactile object recognition, despite intact recognition of alphanumeric
shapes. Meanwhile, our case involved a lesion of the left hemisphere and
showed the opposite pattern, suggesting that there may be differences in
brain regions needed for object versus letter naming. Another dissocia­
tion in haptic recognition of letters and objects was also described in a
case report by Marangolo and colleagues (1998). Similar to our case,
Marangolo et al.’s patient also demonstrated a left-handed impairment
in matching and identifying letters (as well as colors), despite intact
identification of real-world objects. Marangolo et al. reported that the
patient’s lesion was in the left cingulum, parallel to the corpus callosum,
but also included a small lesion of the genu and a larger lesion of the
splenium. The authors thus reasoned that the left hemisphere was
necessary for letter/grapheme identification (but not for objects) and
concluded that the lesion “probably interrupted the callosal pathways of
the trunk within the left hemisphere” therefore interrupting the path­
ways linking the right sensorimotor cortex to the verbal left hemisphere.
However, given the involvement of the genu and splenium the and the
lack of DTI data from this 1998 case, it was not possible to discern which
part of the corpus callosum may be most critical for linking right
hemisphere somatosensory cortex to the left hemisphere language areas.
The case study reported here therefore helps confirm and refine prior
postulations from prior case reports by Endo et al. (1992), Marangolo
et al. (1998), and Veronelli et al. (2014). First, our case confirms that a
focal unilateral pericallosal lesion can produce a tactile-verbal discon­
nection. Secondly, the current study adds to the evidence that letters
may be a unique category of stimuli. Finally, the DTI data from the
current case indicated that pathways throughout the body of the corpus
callosum were patently disrupted, while those through the genu and
splenium were spared. Thus, the current case refines and builds upon the
prior studies by emphasizing the importance of the pathways through
the midbody of the corpus callosum as being critical for tactile-verbal
interaction.
Although interpretations must be made cautiously in a case study,
our findings suggest that the specific difficulty in naming letters and
numbers drawn on or placed in this individual’s left hand is likely due to
a disruption in the transfer of sensory information from the left hand to
the language dominant left hemisphere. DTI data from this case revealed
a marked reduction in white matter pathways through the midbody of
the corpus callosum which have been shown to play a role in the

interhemispheric transfer of tactile information (Fabri et al., 2005).
Based on other recent human DTI and resting state functional connec­
tivity analyses along with non-human primate tract tracing studies, it
has been shown that left hemisphere frontal language areas including
Broca’s area are well connected with left temporal and parietal regions
(Kelly et al., 2010). Fiber tracts supporting this connectivity include the
Superior Longitudinal Fasciculus (SLF), Arcuate Fasciculus (AF) and the
Extreme Capsule Fasciculus (ECF). Given that each of these language
pathways could still be visualized in the left hemisphere of our patient
and that she performed within normal limits on an extensive language
battery, we conclude that the patient’s lesion likely disconnected
sensorimotor regions of the right hemisphere from access to the rela­
tively intact left hemisphere language network.
With regard to the preserved tactile object recognition observed in
our patient, prior case reports of bilateral tactile agnosia are noteworthy.
For example, both Endo et al. (1992) and Nakamura et al. (1998) have
reported cases of bilateral tactile agnosia in which objects could not be
recognized via either hand. Since these cases had extensive bilateral
lesions involving the parietal and temporal lobes (as well as portions of
the arcuate fasciculus, inferior longitudinal fasciculus, and collosal ra­
diations), the authors postulated that tactile agnosia for objects specif­
ically requires a bilateral disconnection between somatosensory
association cortex and the semantic memory stores in the inferotemporal
cortex in both hemispheres. In other words, the semantic meaning of
objects appears to be represented bilaterally in the brain. This is also
consistent with neuroimaging studies that have implicated the lateral
occipital complex bilaterally in visual object recognition (see GrillSpector et al., 2001). In contrast, our case did not have bilateral damage,
nor any damage within the inferotemporal or lateral occipital cortices in
either hemisphere, which may explain the spared tactile object recog­
nition capabilities.
Another way of understanding the current findings is in terms of
separate ventral and dorsal streams for processing haptic information
(Sathian, 2016). The tactile naming tasks used in the current study
would be most consistent with reliance on the dorsally directed pathway
which is involved in transmitting information from object features to the
intraparietal sulcus and/or the lateral occipital complex for shape pro­
cessing. Although these cortical regions were intact in our patient
bilaterally, it is possible that connectivity between these regions was
affected. However, given the location of the lesion within the left
hemisphere, one would predict a greater impact on connectivity be­
tween parietal and occipital regions within the left hemisphere, thereby
producing a greater deficit for items presented to the right hand. Instead,
the deficit appeared to be unique to the left hand and predominantly
affected letter naming.
Recent neuroimaging studies have implicated left lateralized acti­
vations during letter processing and identification. In particular, letter
processing has been associated with activations in the left fusiform, left
pars opercularis, and left parietal regions, consistent with possible word
recognition and reading networks (Carreiras et al., 2015; Park et al.,
2012). All together, these findings support the idea that recognition of
letters may be left lateralized and therefore not as easily accessed when
input is restricted to the right hemisphere (i.e., tactile stimulation of the
left hand). Since the tactile naming of letters was most detrimentally
impacted in the case reported here, this could be due to the fact that
letter identification relies on different left-lateralized regions that may
be part of a reading network. This is somewhat speculative as prior
studies investigating brain activations associated with letter identifica­
tion have only investigated visual or auditory stimulus presentations.
However, if the left fusiform or visual word form area (VWFA) is
involved in letter identification, one implication the current study is that
this region may also be recruited when letters are processed via the
tactile modality as well.
In summary, both lesion case studies and neuroimaging data seem to
be converging on the notion that haptic recognition of objects involves
bilateral neural circuitry involving the lateral occipital complex and
9

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K. Schendel et al.

inferotemporal cortices (Sathian, 2016; Endo et al., 1992; Nakamura
et al., 1998). These areas were intact in both hemispheres in the case
described here, so the fact that our patient showed no impairment in
naming real word objects with either hand suggests that access to this
circuity within either hemisphere was sufficient for haptic object iden­
tification. In contrast, letters, which may require left-lateralized brain
regions for identification appear to be more vulnerable to tactile naming
impairments. The current case exemplifies this vulnerability by
demonstrating a left-hand specific deficit in naming letters and numbers,
despite intact tactile object recognition. This is broadly consistent with
the interpretation that pathways through the midbody of the corpus
callosum play a critical role in tactile letter naming, but not necessarily
in object naming. Although, it is difficult to speculate from the present
case study as to the specific regions (or final destinations) within the left
hemisphere that must be accessed via connections through the corpus
callosum, the tractography data suggest that fibers through the body of
the corpus callosum may be essential for a collaborative interface be­
tween the tactile somatosensory cortices of the right hemisphere and the
left hemisphere language/reading network.
Growing evidence now confirms that connectivity between different
specialized areas of the brain is essential to enabling higher level
cognition. The spared naming of actively palpated objects in the current
case suggests that more complex stimuli or tasks (e.g. real world objects
or active palpation in the case described here) recruit a broader (or
potentially more bilateral) network of brain regions that may be less
vulnerable to white matter pathway disconnection. This interpretation
has implications for cognitive rehabilitation and suggests that more
complex stimuli might be preferable for re-training, rather than starting
with simple stimuli as is often the traditional approach.

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CRediT authorship contribution statement
Krista Schendel: Conceptualization, Investigation, Project admin­
istration, Methodology, Formal analysis, Visualization, Writing - orig­
inal draft. Timothy J. Herron: Formal analysis, Validation, Software,
Writing - review & editing. Brian Curran: Data curation, Software,
Formal analysis. Nina F. Dronkers: Funding acquisition, Resources.
Maria Ivanova: Methodology, Software, Formal analysis, Visualization,
Writing - review & editing. Juliana Baldo: Funding acquisition, Su­
pervision, Conceptualization, Visualization, Writing - review & editing.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Acknowledgements
This work was supported by a VA CSR&D Grant #CX000254-04
(Language Disorders Due to Fiber Tract Disconnection in Aphasic Pa­
tients), Martinez, CA, USA. In addition, M.V.I. and N.F.D. contributions
were supported by NIH/NIDCD R01-DC016345. The contents of this
report do not represent the views of the U.S. Department of Veterans
Affairs or the United States Government.
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