The Cognitive Neuroscience of Apraxia

Claudia C Schmidta and Peter H Weissa,b, a Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research
Centre Juelich, Juelich, Germany; and b Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of
Cologne, Cologne, Germany
© 2022 Elsevier Ltd. All rights reserved.

Definition and Taxonomy of Apraxia 669

Differential Contributions of the Left and Right Hemispheres to Apraxia 669
Cognitive and Neuroanatomical Models of Apraxia 670
Dual-Route Model of Gesture Production and Associated Actions Streams 670
Distinction Between the Processing of Meaningless and Meaningful Gestures 671
Distinction Between the Production of Communicative and Tool-Related Gestures 671
Distinction Between Manipulation and Function Tool Knowledge 672
Distinction Between Structure-Based and Function-Based Actions for Object Manipulation 672
Technical Reasoning vs. Manipulation Knowledge Hypothesis 673
Functional Imaging Findings in Apraxia (Following Stroke) 674
Open Questions 674
References 675

Glossary
Dorso-dorsal processing stream Neural pathway that projects from visual areas to regions within the intraparietal sulcus (IPS)
and superior parietal lobule (SPL), and eventually to the dorsal premotor cortex. Functionally, the dorso-dorsal stream is
considered to process structural features of objects and representations of body parts to mediate online sensorimotor control of
ongoing actions.
Function knowledge Conceptual representations of the prototypical function of a tool or an object (i.e., what an object is for).
Function-based actions Skilled movements for the functional use of a tool or an object that rely on semantic knowledge,
a given context and/or mechanical problem solving.
Intransitive gestures Symbolic/communicative or abstract/meaningless gestures that are not related to a tool or an external
object.
Manipulation knowledge Action representations of the prototypical manipulation of a tool or an object (i.e., how an object is
used).
Structure-based actions Prehensile movements that are mainly afforded by the structural properties of a tool or an object (e.g.,
shape, size, position), for the purpose of reaching or grasping (to pick-up or move) this tool or object.
Transitive gestures Meaningful gestures related to the (actual or pretended) use of a tool and its target object (recipient), for
example, the production of pantomimes of tool/object use.
Ventral processing stream Neural pathway that traverses from visual areas in the ventral occipito-temporal cortex through
regions mainly located in the anterior temporal lobe (ATL) and from there to the inferior frontal gyrus (IFG). The functional
role of the ventral stream is thought to account for visual object recognition and retrieval of semantic properties of objects.
Ventro-dorsal processing stream Neural pathway that consists of projections from visual areas to the supramarginal gyrus
(SMG) of the inferior parietal lobule (IPL), and eventually projects to the ventral premotor cortex. Functionally, the ventro-
dorsal stream is considered to mediate skilled actions for manipulating objects and functionally using tools.

Abbreviations
AG Angular gyrus
ATL Anterior temporal lobe
DLPFC Dorsolateral prefrontal cortex
IFG Inferior frontal gyrus
IPL Inferior parietal lobule
IPS Intraparietal sulcus
MTG Middle temporal gyrus
SMG Supramarginal gyrus

668 Encyclopedia of Behavioral Neuroscience, 2nd edition, Volume 2 https://doi.org/10.1016/B978-0-12-819641-0.00143-2

 The Cognitive Neuroscience of Apraxia 669

SPL Superior parietal lobule

STG Superior temporal gyrus
VLSM Voxel-based lesion-symptom mapping

Definition and Taxonomy of Apraxia

Apraxia refers to a set of disorders of higher (cognitive) motor abilities leading to impaired performance of specific, goal-directed,
skilled and/or learned actions that cannot be (fully) accounted for by elementary sensory or motor deficits (e.g., impaired visual
recognition, ataxia, dyskinesia, paresis), disturbances in language comprehension or communicative skills (e.g., aphasia), general
cognitive impairments (e.g., inattention, dementia), or uncooperativeness (Cubelli, 2017).
A variety of different clinical subtypes of apraxia have been described in the literature and diverse schemas exist to classify them.
Specifically, there are classifications of apraxias that characterize the praxis disorders based upon deficits in the execution/produc-
tion of (lower-level) motor programs (e.g., limb-kinetic apraxia, apraxia of speech), in modality-specific sensorimotor control (e.g.,
tactile apraxia, visuo-motor/optic apraxia), or in the cognitive mechanisms of action control (e.g., ideational apraxia, ideo-motor
apraxia (Binkofski and Fink, 2005)). The terms ideational apraxia and ideo-motor apraxia were elaborated by Hugo Liepmann
(Goldenberg, 2003) to refer to deficits in planning an action (i.e., in the generation of the concept of gestures or actions) and
the accurate motor execution of an action plan (i.e., its conversion into motor commands), respectively (De Renzi et al., 1980;
Poeck, 1983). However, these terms have been also used by various research groups to indicate impairments in performing commu-
nicative, tool-related and/or imitative actions (ideo-motor apraxia) or sequences of actions using (various) objects/tools (ideational
apraxia (Buxbaum, 2001)) leading to inconsistencies in terminology, whichdin turndhinder a clear distinction between these
apraxia subtypes (Buxbaum and Randerath, 2018; Hanna-Pladdy and Rothi, 2001).
Other forms of apraxic disorders are labeled according to the specific task (e.g., apraxia of eyelid opening, dressing apraxia) or
function involved (e.g., apraxia of gait, apraxic agraphia (Cubelli, 2017). However, it has been questioned whether these subtypes
truly represent disorders of higher motor functions and hence constitute variants of apraxia (Poeck, 1986; Tate and McDonald,
1995).
Furthermore, a more descriptive taxonomy has been established determining praxis deficits with respect to the body part affected
(i.e., limb apraxia, bucco-facial apraxia) and/or the disturbed (main) action domain (i.e., imitation, pantomime, actual tool use
(Cubelli, 2017)). The latter description of apraxia in relation to the various clinical motor deficits that may pertain to different
body parts has been suggested to be particularly appropriate to clinically assess patients with assumed praxis deficits as well as
to unveil the putative cognitive motor mechanisms underlying these apraxic deficits (Goldenberg, 2014b).
The current article focuses on (upper) limb apraxia referring to a bilateral impairment of purposeful, skilled movements of the
hand and/or arm, including deficits in gesture imitation, pantomime of object use and actual object/tool use. Furthermore, despite
the association between apraxia and various neurological disorders ((Johnen et al., 2016; Stamenova et al., 2011); see also the
article “Clinical Aspects of Apraxia” in this volume), the following sections will focus on post-stroke limb apraxia for which the
majority of research into the cognitive and neurofunctional mechanisms underlying apraxia has been conducted.

Differential Contributions of the Left and Right Hemispheres to Apraxia

Limb apraxia is commonly associated with lesions to a left hemispheric large-scale praxis network, including parietal, temporal,
frontal, and subcortical regions (Sperber et al., 2019), with differing extent and localization of the critical structures associated
with particular praxis deficits (for example (Dressing et al., 2018; Hanna-Pladdy et al., 2001b; Hoeren et al., 2014; Martin et al.,
2016a; Randerath et al., 2010; Salazar-López et al., 2016)). Specifically, behavioral associations and dissociations between deficits
in imitation, pantomime and actual tool use are (partly) reflected in the differential roles of critical regions in the praxis networks
within the motor-dominant, left hemisphere (Goldenberg, 2017). A schematic representation of the left hemispheric core regions
associated with limb apraxia, along with the main praxis functions to which they have been found to contribute, is shown in Fig. 1.
However, manifestations of apraxia have also been observed after damage to the right hemisphere. In particular, stroke patients
with right hemisphere lesions appear to be predominantly impaired on imitating finger (compared to hand (Goldenberg, 1999;
Goldenberg and Strauss, 2002)) and transitive (i.e., tool-related compared to non-tool-related/intransitive (Hanna-Pladdy et al.,
2001a; Stamenova et al., 2010)) gestures as well as facial movements (Bizzozero et al., 2000; Della Sala et al., 2006). Besides,
the right hemisphere appears to be critically involved in performing multi-step actions including the use of different objects during
naturalistic tasks (Hartmann et al., 2005; Schwartz et al., 1999), which may reflect an important role of the right hemisphere in
actions that put great demands on (spatial) attention and (visuo-spatial) working memory (Flores-Medina et al., 2014; Goldenberg,
2014a).
Patients with right hemisphere stroke are often considered to be less severely affected by apraxia than patients suffering from left
hemisphere stroke (Buchmann et al., 2020). However, some studies report a comparable frequency and severity of praxis
670 The Cognitive Neuroscience of Apraxia

Fig. 1 Schematic representation of the left hemispheric core regions associated with limb apraxia. For each of the regions, the main praxis
functions that have been commonly found to be impaired after damage to these regions, as evidenced by lesion studies in left hemisphere stroke
patients (1–12), are provided. AG: angular gyrus; ATL: anterior temporal lobe; IFG: inferior frontal gyrus; IPL: inferior parietal lobule; IPS: intraparietal
sulcus; pMTG: posterior middle temporal gyrus; SMG: supramarginal gyrus; SPL: superior parietal lobule; STG: superior temporal sulcus. 1: Achilles
et al. (2019); 2: Buxbaum et al. (2014); 3: Finkel et al. (2018); 4: Goldenberg et al. (2007b); 5: Goldenberg and Randerath (2015); 6: Goldenberg and
Spatt (2009); 7: Hoeren et al. (2014); 8: Martin et al. (2016a); 9: Mengotti et al. (2013); 10: Randerath et al. (2010); 11: Salazar-López et al. (2016);
12: Weiss et al. (2016).

impairments (i.e., imitation and pantomime deficits) following left and right hemisphere stroke (Civelek et al., 2015; Heath et al.,
2001; Roy et al., 2000), pointing to a (partially) bi-hemispheric representation of praxis abilities.

Cognitive and Neuroanatomical Models of Apraxia

Several cognitive and neuroanatomical models of action processing have been proposed to explain the (dissociating) patterns of
apraxic deficits, mostly following left hemisphere stroke. The current section provides a selective overview of current theoretical
models and their putative neural correlates, which is followed by summarizing the evidence from neuropsychological and lesion
studies in stroke patients in favor of these models.

Dual-Route Model of Gesture Production and Associated Actions Streams

A current cognitive model of (limb) apraxia proposes the existence of the following two routes for gesture production: a semantic
(indirect) route for (re)producing familiar, habitually used (i.e., meaningful) gestures (transitive and intransitive) and a non-
semantic (direct) route for producing mainly novel, abstract (i.e., meaningless) gestures. More specifically, along the non-semantic
(direct) route, gestures are imitated by transforming the visual perception of an action into motor control commands, whereas the
semantic (indirect) route enables the processing of familiar, meaningful gestures by retrieving pre-existing motor representations
of the action (action semantics (Cubelli et al., 2000; Rothi et al., 1991)). Notably, in principle, any visually presented gesture
(i.e., whether meaningless or meaningful) could be produced by means of the direct route without requiring semantic processing
(Tessari and Rumiati, 2004).
With regard to the neural substrates of the two routes of gesture production, several authors have proposed that the semantic and
non-semantic routes may rely on anatomically distinct processing streams (Rumiati et al., 2005). That is, a ventral “what” stream
originally suggested to mediate vision-for-(object)-perception and a dorsal “where/how” stream initially described as processing
 The Cognitive Neuroscience of Apraxia 671

vision-for-action (Goodale and Milner, 1992). Both neural pathways are assumed to arise from early visual regions within the occip-
ital lobe, and then either traverse across the posterior parietal lobe to frontal areas (premotor cortex; dorsal stream) or project to the
anterior temporal lobe (ATL; and eventually to inferior frontal regions; ventral stream). In this vein, the dorsal stream was presumed
to mediate the visual control of skilled actions on a moment-to-moment basis, while the ventral stream was suggested to account for
visual object recognition and retrieval of semantic properties of objects (Milner and Goodale, 2008). More recently, a reconsidera-
tion of previous functional imaging and lesion studies implied a further anatomical and functional subdivision of the dorsal
pathway into a dorsal component with involvement of the posterior intraparietal sulcus (IPS) and superior parietal lobule (SPL;
i.e., a dorso-dorsal substream) and a ventral component with core regions in the inferior parietal lobule (IPL; i.e., a ventro-
dorsal substream (Rizzolatti and Matelli, 2003)). Within the context of tool/object use, the dorso-dorsal stream has been considered
to process structural features of objects supporting online sensorimotor control of ongoing actions, e.g., for the purpose of grasping
an object (“grasp system”), whereas the ventro-dorsal stream has been linked to skilled actions needed for the proper manipulation
and functional use of objects and tools (“use system” (Binkofski and Buxbaum, 2013; Buxbaum and Kalénine, 2010)).
Recent research attempting to relate the cognitive dual-route model of gesture production to accounts of multiple neural action
streams has further contributed to a better understanding of the distinct clinical patterns of apraxia.

Distinction Between the Processing of Meaningless and Meaningful Gestures

The proposed different processing strategies along the two routes for gesture production can well account for observed (double)
dissociations between the imitation of meaningful and meaningless gestures in left hemisphere stroke patients with apraxia
(Achilles et al., 2016, 2019; Bartolo et al., 2001; Goldenberg and Hagmann, 1997; Tessari et al., 2007). In particular, selective
impairments in imitating meaningless gestures could be explained by a disturbed visuo-motor transformation accomplished via
the direct route, while preserved access to the action semantic system along the indirect route would still allow for the reproduction
of meaningful gestures (Cubelli et al., 2000; Goldenberg and Hagmann, 1997). In this vein, voxel-based lesion-symptom mapping
(VLSM) studies in (stroke) patients with left brain damage indicated differential contributions of the proposed neural action stream
areas to the two dissociating processing routes. Specifically, impaired meaningless gesture imitation has been more strongly related
to lesions in the dorsal portion of the angular gyrus (AG) as well as in the pre- and postcental gyri, regions forming part of the dorso-
dorsal stream. In contrast, the imitation of meaningful gestures has been specifically associated with the ventral portion of the supra-
marginal gyrus (SMG) as well as with the superior temporal gyrus (STG) and posterior middle temporal gyrus (MTG), areas mainly
belonging to the ventro-dorsal stream (Achilles et al., 2019; Mengotti et al., 2013).
Conversely, an isolated deficit in meaningful gesture imitation is less commonly observed, as meaningful actions could theoret-
ically be imitated along both the direct and indirect (semantic) processing routes (Achilles et al., 2016; Bartolo et al., 2001; Tessari
et al., 2007). Accordingly, impaired imitation of meaningful gestures (but preserved meaningless gesture imitation) could result
from a disturbed indirect semantic route and additionally an inability to switch to the direct route (which is putatively intact).
Indeed, it has been proposed that when a seen gesture is recognized as a familiar one, it is automatically processed along the indirect
route by accessing the semantic system. Moreover, it is assumed that once a processing strategy is selected (here: the indirect
semantic route), switching to another one (i.e., the direct route) demands (additional) cognitive resources, which might be compro-
mised in patients with apraxia (Bartolo et al., 2001; Tessari et al., 2007; Tessari and Cubelli, 2014). Single case analyses revealed that
patients with a selective deficit in imitating meaningful gestures presented with temporo-parietal lesions involving the SMG, STG
and MTG (Bartolo et al., 2001; Tessari et al., 2007).
On the other hand, a selective deficit in the execution of meaningful gestures on command (e.g., pantomiming object-related
actions or producing communicative gestures), but preserved (meaningless and meaningful) gesture imitation might be (solely)
accounted for by an impairment within the action semantic system along the indirect route accessing long-term memory for mean-
ingful actions (Cubelli et al., 2000; De Renzi et al., 1982; Heath et al., 2001). In line with this notion, VLSM analyses in left hemi-
sphere stroke patients revealed shared neural correlates between impairments in meaningful gesture production (including
pantomime) and language within areas that are more associated with the ventral stream such as the anterior MTG and inferior
frontal gyrus (IFG (Goldenberg and Randerath, 2015; Mengotti et al., 2013; Weiss et al., 2016)), indicative of disturbed access
to semantic memory and/or processing of meaning (Goldenberg, 2017).

Distinction Between the Production of Communicative and Tool-Related Gestures

Contrary to the assumption of a common route for producing (any) meaningful gestures (i.e., the semantic route), clinical double
dissociations between the pantomime of object use (i.e., impaired processing of meaningful transitive actions) and the production
of symbolic, communicative gestures (i.e., preserved processing of meaningful intransitive actions) have also been reported
following left hemisphere stroke (Dumont et al., 1999; Rapcsak et al., 1993). The reverse dissociation (i.e., preserved panto-
mime/transitive gesture production and impaired production of symbolic, intransitive gestures) has been mainly observed after
lesions in the right hemisphere (Stamenova et al., 2010). Taken together, these findings suggest that the processing of tool-
related and communicative gestures are mediated by (partially) different cognitive mechanisms within the semantic route.
Comparing the critical lesion sites between deficient production of intransitive (i.e., communicative) and transitive (i.e., tool-
related) meaningful gestures in left hemisphere stroke patients, a recent VLSM study revealed distinct contributions of the ventral
and (ventro-)dorsal action streams to both types of meaningful gesture. While lesions in the ATL were specifically related to deficits
in the production of communicative gestures, pantomime production was relatively more affected by lesions of the premotor and
lateral occipito-parietal cortex (including the IPS). Notably, both meaningful transitive and intransitive gestures shared neural
672 The Cognitive Neuroscience of Apraxia

correlates in the left IPL and lateral temporal lobe (Dressing et al., 2018). Thus, these recent clinical findings suggest that (at least
partially) separate regions of the ventro-dorsal and ventral streams support the processing of tool-related (pantomimes) and
communicative gestures, respectively.
On the other hand, however, pantomime of tool use has been commonly found to be affected by lesions in areas belonging to
both the ventro-dorsal and ventral streams (e.g., the IFG, posterior MTG, STG, and anterior IPL/SMG (Buxbaum et al., 2014;
Goldenberg et al., 2007b; Hoeren et al., 2014; Niessen et al., 2014)). In particular, impairments in processing the semantic char-
acteristics of tool use pantomimes have been associated with more ventral fronto-temporal lesions (IFG, ATL). Conversely, deficient
motor features of pantomimed tool use actions (i.e., pretended grip and movement) were related to lesions in more dorsal
temporo-parietal brain regions (MTG, SMG/IPL) in the ventro-dorsal processing stream (Finkel et al., 2018).
While communicative (intransitive) gestures are certainly meaningful and habitually used, pantomimes of transitive (i.e., tool-
related) actionsdalthough carrying meaningdare relatively unfamiliar and not commonly used in daily life (Bartolo and Cubelli,
2014). Moreover, pantomimed actions are only partially produced by replicating the motor programs of actual tool-/object-related
actions, but are rather based on modified spatial and kinematic movement characteristics (Hermsdörfer et al., 2012). Furthermore,
unlike other meaningful (intransitive) gestures, pantomimes of object use pose additional demands on (domain-general) working
memory, in which knowledge about tool use (retrieved from action semantics) has to be converted into new motor programs
(Bartolo et al., 2003). Therefore, pantomimes could be considered an intermediate gesture type in-between the classical meaningful
and meaningless gestures.

Distinction Between Manipulation and Function Tool Knowledge

With regard to actual object/tool use, there are reports of dissociations between the preserved recognition of an object’s function
(i.e., preserved conceptual knowledge about tool function) and impairments in actually using an object (i.e., impaired action
knowledge about tool manipulation) in patients with apraxia (Buxbaum and Saffran, 2002; Buxbaum et al., 2000). Conversely,
a selective deficit in conceptual knowledge of object function (but spared knowledge of object manipulation) is mainly seen in
patients with semantic dementia or other neurodegenerative diseases associated with temporal lobe damage (Buxbaum et al.,
1997; Negri et al., 2007). These clinical double dissociations provide strong evidence in support of functionally distinct systems
for object function knowledge (“what for”) and object manipulation knowledge (“how” (Buxbaum et al., 2000)). In line with
this notion of separable mechanisms subserving the different types of object-related knowledge, VLSM analyses in left hemisphere
stroke patients revealed distinct roles for ventral and ventro-dorsal stream areas for semantic knowledge about objects and the
skilled actions for object manipulation. In particular, conceptual knowledge about tool use (here: the selection of the appropriate
recipient object for a given tool) was specifically related to regions within the ventral stream, including the anterior MTG and IFG,
whereas manipulation knowledge about tool use (here: the performance of the typical tool-associated action) was relatively more
associated with ventro-dorsal stream areas, particularly within the IPL (Martin et al., 2016a).

Distinction Between Structure-Based and Function-Based Actions for Object Manipulation

However, the dissociation between manipulation and function knowledge does not directly map onto the seminal cognitive dual-
route model of praxis (Cubelli et al., 2000; Rothi et al., 1991) since the action semantic system accessed along the indirect semantic
route is suggested to contain both conceptual knowledge about tool/object function (i.e., information on what an object is used for;
object representations) and motor representations of skilled actions involving objects (i.e., information on how an object is used;
gesture representations (Bartolo and Ham, 2016)). Recently, by integrating the cognitive neuropsychological model of apraxia
(Cubelli et al., 2000; Rothi et al., 1991) and the concept of multiple neural processing streams (Goodale and Milner, 1992; Milner
and Goodale, 2008), an expanded model of two routes to action has been proposed. The “two action systems model” assumes that
there is, on the one hand, a “structure action system” that processes structural object properties (e.g., shape, size, and location) and
that might map onto the direct (non-semantic) route, putatively subserved by the dorso-dorsal stream areas. On the other hand, it
postulates a “function action system” that computes and stores representations of skilled actions for the functional manipulation of
objects and that might use the indirect (semantic) route, probably associated with the ventro-dorsal stream regions (Buxbaum and
Kalénine, 2010). In that context, the dorso-dorsal stream has been referred to as a “grasp system”, while the ventro-dorsal stream has
been termed a “use system” (Binkofski and Buxbaum, 2013). Furthermore, it was suggested that the representation of skilled func-
tional actions (mediated by the ventro-dorsal stream) is supported by the ventral stream, which subserves the recognition of concep-
tual aspects of skilled object-specific actions (e.g., the processing of tool-action associations (Martin et al., 2017; Valyear and
Culham, 2010)).
Apraxia has been found to be predominantly associated with impaired manipulation knowledge (i.e., the function or “use”
system), while structure-based sensorimotor control (i.e., the structure or “grasp” system) is often preserved (Buxbaum and
Kalénine, 2010; Randerath et al., 2009, 2010). By investigating the putative differing neural correlates for grasping a tool compared
to its subsequent use in left hemisphere stroke patients with apraxia, impairments in functional tool manipulation were mainly
related to lesions in the SMG of the IPL. In contrast, deficits in grasping a tool (i.e., non-functional grasping) were particularly asso-
ciated with lesions in the left IFG and more posterior regions of the parietal cortex, including the parieto-occipital junction and the
AG (Randerath et al., 2010). Accordingly, these findings are consistent with the assumption that the ventro-dorsal stream primarily
mediates the functional use of tools (function-based actions), whereas the dorso-dorsal stream is specialized for the appropriate
grasping of tools (structure-based actions).
 The Cognitive Neuroscience of Apraxia 673

Intriguingly, the (visual) processing of structural object properties (mediated by the “grasp system”) has been suggested to pose
an advantage on the subsequent use of an object, presumably by facilitating the activation of (components of) associated action
representations (Ellis and Tucker, 2000; Schubotz et al., 2014). However, it has been shown that single (familiar) objects can
also evoke more than one associated action representation (i.e., a structure-based action for grasping versus a function-based action
for skillful use), and that both representations may interfere with one another. For example, a calculator may be associated with
a structural “clench” gesture for grasping (to pick-up or move) and a functional “poking” gesture for skillful use (to achieve a func-
tional goal), which might compete during the production of use hand postures (Jax and Buxbaum, 2010). Moreover, patients with
apraxia were found to present with increased response interference between the structural and functional object-related actions
compared to left hemisphere stroke patients without apraxia or healthy control subjects (Jax and Buxbaum, 2013). In recent
VLSM studies in apraxic patients, the SMG (and to a lesser extend the IFG) were identified as crucial brain regions for resolving inter-
ference between multiple tool-based action alternatives, that is for selecting an appropriate tool-use hand gesture in the presence of
conflicting tool-grasp options (Garcea et al., 2019; Watson and Buxbaum, 2015). These findings further support the proposed two
action systems (i.e., the structure/dorso-dorsal and function/ventro-dorsal systems) that might mediate (partially) independent
tool-directed actions (i.e., “grasp” versus “use” actions).

Technical Reasoning vs. Manipulation Knowledge Hypothesis

The cognitive dual-route model of (limb) apraxia described above (Cubelli et al., 2000; Rothi et al., 1991) assumes that stored repre-
sentations of skilled actions, particularly involving tools/objects (i.e., manipulation knowledge), are retrieved for pantomiming
object/tool use as well as for the actual use of tools and objects. In contrast, an alternative account proposes that the correct func-
tional manipulation of tools and objects results solely from technical reasoning supported by mechanical problem solving skills
(Osiurak and Badets, 2016). Mechanical problem solving refers to the ability to directly infer possible uses for objects from func-
tionally significant structural and/or physical properties of objects or tools. Accordingly, it allows one to not only infer the function
that is typical for a (familiar) tool/object, but also to uncover alternative ways of using familiar tools/objects or possible uses of
novel, unfamiliar tools/objects (Goldenberg, 2014a; Osiurak et al., 2011). Importantly, both the manipulation knowledge and
technical reasoning approach assume a distinction between the actual use of tools and objects (either based on stored action repre-
sentations or technical reasoning) and semantic/conceptual knowledge about tool function, with the latter represented within the
ventral stream (Osiurak, 2013).
The practical relevance of mechanical problem solving has been demonstrated by the finding that impaired actual tool/object
use was associated with both a disturbed retrieval of tool knowledge (as assessed by pantomime of object use) and difficulties in
mechanical problem solving (as assessed by a test of selecting and applying novel tools) in left hemisphere stroke patients with
apraxia (Goldenberg and Hagmann, 1998). Moreover, mechanical problem solving abilities might account for observed dissocia-
tions between a selective deficit in pantomiming object/tool use (putatively due to impaired access to the action semantic system;
among other possible disturbed cognitive processes), but preserved actual tool use in apraxic patients (Goldenberg and Hagmann,
1998; Goldenberg et al., 2004; Hermsdörfer et al., 2006). Conversely, however, the potential to directly infer possible functions
from the structure of tools/objects (i.e., from the visual and tactile exploration of an object) did not appear to compensate for
impairments in actual tool use in patients with apraxia following left hemisphere stroke (Goldenberg et al., 2001). Accordingly,
manipulation knowledge about tools and mechanical problem solving abilities could be independently affected by lesions in
the left hemisphere, and hence might selectively contribute to apraxic deficits (Goldenberg and Hagmann, 1998; Osiurak et al.,
2013).
Indeed, there is growing evidence to suggest that a core deficit in apraxic patients with impaired actual tool use lies in the
inability to reason about (i.e., to identify and combine) the technical means provided by the physical properties of tools and objects
(Baumard et al., 2019; Goldenberg and Spatt, 2009; Jarry et al., 2013; Osiurak et al., 2009). Technical means (i.e., physical object
properties, for example sharp, resistant) relevant for a given technical end (e.g., cutting, screwing) are abstract principles that are not
related to any specific tool/object representation, since the same technical property (e.g., resistant) can be linked to a variety of
different physical materials (e.g., metal, plastic, wood (Osiurak and Badets, 2016)). In this regard, recent studies emphasized the
concept of technical reasoning by demonstrating strong associations between deficits in the prototypical use of familiar tools/
objects and difficulties in the non-conventional use of familiar tools/objects (Osiurak et al., 2009) or in solving mechanical prob-
lems involving novel, unfamiliar tools/objects (Hartmann et al., 2005; Jarry et al., 2013) in patients with apraxia following left
hemisphere stroke. Moreover, left parietal lesions (here: lesions in the SMG extending to the inferior and superior parietal lobule)
were found to contribute to the impaired actual use of both common/familiar and novel tools in apraxic patients, but not to impair-
ments in the knowledge about the conventional use of familiar tools/objects (as assessed by a functional tool-recipient association
task). Accordingly, the ventro-dorsal stream appeared to subserve mechanical problem solving (supporting both familiar and novel
tool use (Goldenberg and Spatt, 2009)). Conversely, deficits in technical reasoning and/or mechanical problem solving were not
related to deficient general executive functions (e.g., planning, maintenance of goals (Goldenberg et al., 2007a; Jarry et al., 2013)) or
frontal lobe lesions (Goldenberg and Hagmann, 1998).
The inability to perform technical reasoning and/or to solve mechanical problems might account for tool use deficits in apraxic
patients in whom manipulation knowledge was found to be intact, but apparently not sufficient to support proper actual tool/
object use (Jarry et al., 2016). On the other hand, the technical reasoning account does not easily apply to clinical dissociations
between a selective deficit in the actual use of tools/objects and the preserved pantomime of object use (Fukutake, 2003; Heath
674 The Cognitive Neuroscience of Apraxia

et al., 2003; Motomura and Yamadori, 1994; Westwood et al., 2001), when assuming that the pantomime of object use involves the
ability to perform technical reasoning on mental images of a tool and recipient object (Lesourd et al., 2017; Osiurak et al., 2009).
Accordingly, further and/or additional (cognitive) processes underlying the actual use of tools and objects have been proposed,
including the visual and haptic/kinesthetic processing of object properties as well as executive functions. Recently, disturbances
in some of these processes have been discussed in relation to (limb) apraxia following left hemisphere stroke (e.g., (Barde et al.,
2007; Pellicano et al., 2017; Pizzamiglio et al., 2020)).
Given the finding that both manipulation knowledge and the ability to perform technical reasoning/solve mechanical problems
were found to (independently) account for aspects of actual tool use (Goldenberg and Hagmann, 1998; Jarry et al., 2013) and to be
associated with the IPL (Goldenberg and Spatt, 2009; Martin et al., 2016a), further research on a cognitive framework that might
integrate both approaches is warranted. For detailed discussions on the technical reasoning versus manipulation knowledge
hypothesis, the reader is referred to Osiurak and Badets (2016) and Buxbaum (2017).

Functional Imaging Findings in Apraxia (Following Stroke)

In contrast to the large number of lesion mapping studies in apraxic patients, there is currently little research investigating the neural
correlates of cognitive motor processes related to (limb) apraxia in stroke patients using functional neuroimaging. Early single-case
reports using positron emission tomography showed hypometabolism in the left IPS and SPL in patients with multiple apraxic defi-
cits, including gesture imitation (Peigneux et al., 2000), gesture production on command, and object use (Kareken et al., 1998).
More recently, exploring the functional activation patterns that were associated with better imitative abilities (obtained outside
the scanner) following left hemisphere stroke revealed a region within the left dorsolateral prefrontal cortex (DLPFC), while (off-
line) tool-related skills (here: a composite score for actual tool use, pantomime and imitation of transitive gestures) were correlated
with activity in the right premotor, right inferior frontal, and left anterior temporal areas (Martin et al., 2016b). Notably, these
regions were mainly located outside the core areas of the left parieto-frontal praxis networks, commonly suggested to support cogni-
tive motor functions as documented by functional imaging studies in healthy subjects as well as structural lesion findings (Niessen
et al., 2014). Thus, these functional imaging findings in left hemisphere stroke patients highlight the functional relevance of addi-
tional ipsi- and contralateral brain regions for the recovery from apraxic (imitation and tool-related) deficits. Moreover, they might
help to explain variability in the severity of apraxic deficits across patients with similar lesion sites within the left hemisphere
(Martin et al., 2016b).
Later, the same research group identified network effects of apraxia by showing deficit-specific changes in the activation patterns
within task-specific (here: praxis) as well as domain-general (here: cognitive control) functional networks during the observation of
tool-related actions. Moreover, the altered pattern of (task-based) activation in post-stroke apraxic patients was further modulated
by the specific lesion location within the praxis networks (i.e., frontal versus parietal regions), indicating the differential impact of
structural lesions to distinct critical hubs and connecting fiber tracts on functional network activity (Dressing et al., 2019).
In a similar vein, a study by Watson et al. (2019) emphasized the relevance of both the specific lesion location within the left
hemisphere and the connectivity pattern between functional brain networks in both hemispheres for apraxic deficits following
stroke. More specifically, by combining information about a patient’s lesion location and functional connectivity, two specific
patterns were found to contribute to deficits in tool use pantomimes. On the one hand, lesions within the left posterior MTG
and the thalamus along with weakened functional connectivity between these areas and a bilateral set of regions in the DLPFC
and medial prefrontal cortex were associated with impairments in pantomiming tool use. In addition, functional connectivity
between the left superior parietal cortex and (mainly) bilateral frontal (e.g., postcentral gyrus, premotor cortex) and parietal
(SMG) brain regions was found to be related to pantomime accuracy (independent of the lesion location (Watson et al., 2019)).
In conclusion, these functional neuroimaging findings contribute to an understanding of altered (ipsi- and contralateral) acti-
vation patterns and disrupted (intra- and interhemispheric) functional connectivity states characterizing (stroke) patients suffering
from apraxia. Furthermore, they reflect the impact of disrupted communication with brain regions remote from a given lesion on
the occurrence of apraxic deficits, which still warrants further investigations.

Open Questions

What is the role of (deficient) cognitive control mechanisms in the occurrence of limb apraxic deficits following stroke? Recent
studies have already proposed that impairments in executive functions contribute to (at least some types of) apraxia. In this regard,
action competition when multiple action possibilities are afforded (Rounis and Humphreys, 2015; Watson and Buxbaum, 2015) or
when incompatible neighboring actions are present (Garcea et al., 2019; Pizzamiglio et al., 2020) have been discussed as potential
sources of action errors in apraxic patients. Further research into these mechanisms may prove useful in understanding apraxic defi-
cits particularly in complex naturalistic tasks entailing multi-object use.
Deficits in language (i.e., aphasia) and visuospatial attention (i.e., neglect) have been associated with apraxia following left and
right hemisphere stroke affecting the left and right posterior parietal cortex, respectively. Another cognitive process that has been
linked to the parietal cortex is agency. A sense of agency is defined as the experience of controlling one’s own motor actions
(Haggard, 2017). It is currently under debate whether a loss of agency might be associated or even contribute to some aspects of
 The Cognitive Neuroscience of Apraxia 675

apraxic deficits (Osiurak et al., 2019; Pazzaglia and Galli, 2014). Neuropsychological and lesion mapping studies assessing agency
in the context of apraxia are needed to investigate this hypothesis further.
In summary, limb apraxia refers to various disorders of higher motor functions that are characterized by deficits in gesture imita-
tion, pantomime of object use and actual object/tool use. Apraxia is primarily caused by damage to left hemisphere parieto-frontal
praxis networks, involving a dorso-dorsal, ventro-dorsal, and ventral processing stream. Neuropsychological and lesion studies have
contributed to relating dissociable forms of apraxia to these neural processing streams, which in turn are thought to mediate
different (cognitive) routes for gesture production. In addition, several further accounts (e.g., deficits in technical reasoning or exec-
utive functions) have been proposed to explain apraxic deficits, which may provide further research avenues for studying this
syndrome.

References

Achilles, E.I.S., Fink, G.R., Fischer, M.H., Dovern, A., Held, A., Timpert, D.C., Schroeter, C., Schuetz, K., Kloetzsch, C., Weiss, P.H., 2016. Effect of meaning on apraxic finger
imitation deficits. Neuropsychologia 82, 74–83.
Achilles, E.I.S., Ballweg, C.S., Niessen, E., Kusch, M., Ant, J.M., Fink, G.R., Weiss, P.H., 2019. Neural correlates of differential finger gesture imitation deficits in left hemisphere
stroke. Neuroimage 23, 101915.
Barde, L.H.F., Buxbaum, L.J., Moll, A.D., 2007. Abnormal reliance on object structure in apraxics’ learning of novel object-related actions. J. Int. Neuropsychol. Soc. 13, 997–1008.
Bartolo, A., Cubelli, R., 2014. The cognitive models of limb apraxia and the specific properties of meaningful gestures. Cortex 57, 297–298.
Bartolo, A., Ham, H.S., 2016. A cognitive overview of limb apraxia. Curr. Neurol. Neurosci. Rep. 16, 75.
Bartolo, A., Cubelli, R., Della Sala, S., Drei, S., Marchetti, C., 2001. Double dissociation between meaningful and meaningless gesture reproduction in apraxia. Cortex 37, 696–699.
Bartolo, A., Cubelli, R., Della Sala, S., Drei, S., 2003. Pantomimes are special gestures which rely on working memory. Brain Cogn. 53, 483–494.
Baumard, J., Lesourd, M., Remigereau, C., Merck, C., Jarry, C., Etcharry-Bouyx, F., Chauviré, V., Belliard, S., Moreaud, O., Osiurak, F., Le Gall, D., 2019. Thedweakdrole of
memory in tool use: evidence from neurodegenerative diseases. Neuropsychologia 129, 117–132.
Binkofski, F., Buxbaum, L.J., 2013. Two action systems in the human brain. Brain Lang. 127, 222–229.
Binkofski, F., Fink, G.R., 2005. Apraxien [apraxias]. Nervenarzt 76, 493–509.
Bizzozero, I., Costato, D., Della Sala, S., Papagno, C., Spinnler, H., Venneri, A., 2000. Upper and lower face apraxia: role of the right hemisphere. Brain 123, 2213–2230.
Buchmann, I., Dangel, M., Finkel, L., Jung, R., Makhkamova, I., Binder, A., Dettmers, C., Herrmann, L., Liepert, J., Möller, J.C., Richter, G., Vogler, T., Wolf, C., Randerath, J.,
2020. Limb apraxia profiles in different clinical samples. Clin. Neuropsychol. 34, 217–242.
Buxbaum, L.J., Kalénine, S., 2010. Action knowledge, visuomotor activation, and embodiment in the two action systems. Ann. N. Y. Acad. Sci. 1191, 201–218.
Buxbaum, L.J., Randerath, J., 2018. Limb apraxia and the left parietal lobe. Handb. Clin. Neurol. 151, 349–363.
Buxbaum, L.J., Saffran, E.M., 2002. Knowledge of object manipulation and object function: dissociations in apraxic and non-apraxic subjects. Brain Lang. 82, 179–199.
Buxbaum, L.J., Schwartz, M.F., Carew, T.G., 1997. The role of semantic memory in object use. Cogn. Neuropsychol. 14, 219–254.
Buxbaum, L.J., Veramonti, T., Schwartz, M.F., 2000. Function and manipulation tool knowledge in apraxia: knowing “what for” but not “how”. Neurocase 6, 83–97.
Buxbaum, L.J., Shapiro, A.D., Coslett, H.B., 2014. Critical brain regions for tool-related and imitative actions: a componential analysis. Brain 137, 1971–1985.
Buxbaum, L.J., 2001. Ideomotor apraxia: a call to action. Neurocase 7, 445–458.
Buxbaum, L.J., 2017. Learning, remembering, and predicting how to use tools: distributed neurocognitive mechanisms: comment on Osiurak and Badets (2016). Psychol. Rev. 124,
346–360.
Civelek, G.M., Atalay, A., Turhan, N., 2015. Association of ideomotor apraxia with lesion site, etiology, neglect, and functional independence in patients with first ever stroke. Top.
Stroke Rehabil. 22, 94–101.
Cubelli, R., Marchetti, C., Boscolo, G., Della Sala, S., 2000. Cognition in action: testing a model of limb apraxia. Brain Cogn. 44, 144–165.
Cubelli, R., 2017. Definition: apraxia. Cortex 93, 227.
De Renzi, E., Motti, F., Nichelli, P., 1980. Imitating gestures: a quantitative approach to ideomotor apraxia. Arch. Neurol. 37, 6–10.
De Renzi, E., Faglioni, P., Sorgato, P., 1982. Modality-specific and supramodal mechanisms of apraxia. Brain 105, 301–312.
Della Sala, S., Maistrello, B., Motto, C., Spinnler, H., 2006. A new account of face apraxia based on a longitudinal study. Neuropsychologia 44, 1159–1165.
Dressing, A., Nitschke, K., Kümmerer, D., Bormann, T., Beume, L., Schmidt, C.S.M., Ludwig, V.M., Mader, I., Willmes, K., Rijntjes, M., Kaller, C.P., Weiller, C., Martin, M., 2018.
Distinct contributions of dorsal and ventral streams to imitation of tool-use and communicative gestures. Cereb. Cortex 28, 474–492.
Dressing, A., Kaller, C.P., Nitschke, K., Beume, L.-A., Kümmerer, D., Schmidt, C.S.M., Bormann, T., Umarova, R.M., Egger, K., Rijntjes, M., Weiller, C., Martin, M., 2019. Neural
correlates of acute apraxia: evidence from lesion data and functional MRI in stroke patients. Cortex 120, 1–21.
Dumont, C., Ska, B., Schiavetto, A., 1999. Selective impairment of transitive gestures: an unusual case of apraxia. Neurocase 5, 447–458.
Ellis, R., Tucker, M., 2000. Micro-affordance: the potentiation of components of action by seen objects. Br. J. Psychol. 91, 451–471.
Finkel, L., Hogrefe, K., Frey, S.H., Goldenberg, G., Randerath, J., 2018. It takes two to pantomime: communication meets motor cognition. Neuroimage 19, 1008–1017.
Flores-Medina, Y., Chávez-Oliveros, M., Medina, L.D., Rodríguez-Agudelo, Y., Solís-Vivanco, R., 2014. Brain lateralization of complex movements: neuropsychological evidence from
unilateral stroke. Brain Cogn. 84, 164–169.
Fukutake, T., 2003. Apraxia of tool use: an autopsy case of biparietal infarction. Eur. Neurol. 49, 45–52.
Garcea, F.E., Stoll, H., Buxbaum, L.J., 2019. Reduced competition between tool action neighbors in left hemisphere stroke. Cortex 120, 269–283.
Goldenberg, G., Hagmann, S., 1997. The meaning of meaningless gestures: a study of visuo-imitative apraxia. Neuropsychologia 35, 333–341.
Goldenberg, G., Hagmann, S., 1998. Tool use and mechanical problem solving in apraxia. Neuropsychologia 36, 581–589.
Goldenberg, G., Randerath, J., 2015. Shared neural substrates of apraxia and aphasia. Neuropsychologia 75, 40–49.
Goldenberg, G., Spatt, J., 2009. The neural basis of tool use. Brain 132, 1645–1655.
Goldenberg, G., Strauss, S., 2002. Hemisphere asymmetries for imitation of novel gestures. Neurology 59, 893–897.
Goldenberg, G., Daumüller, M., Hagmann, S., 2001. Assessment and therapy of complex activities of daily living in apraxia. Neuropsychol. Rehabil. 11, 147–169.
Goldenberg, G., Hentze, S., Hermsdörfer, J., 2004. The effect of tactile feedback on pantomime of tool use in apraxia. Neurology 63, 1863–1867.
Goldenberg, G., Hartmann-Schmid, K., Sürer, F., Daumüller, M., Hermsdörfer, J., 2007a. The impact of dysexecutive syndrome on use of tools and technical devices. Cortex 43,
424–435.
Goldenberg, G., Hermsdörfer, J., Glindemann, R., Rorden, C., Karnath, H.-O., 2007b. Pantomime of tool use depends on integrity of left inferior frontal cortex. Cereb. Cortex 17,
2769–2776.
Goldenberg, G., 1999. Matching and imitation of hand and finger postures in patients with damage in the left or right hemispheres. Neuropsychologia 37, 559–566.
Goldenberg, G., 2003. Apraxia and beyond: life and work of Hugo Liepmann. Cortex 39, 509–524.
Goldenberg, G., 2014a. Apraxiadthe cognitive side of motor control. Cortex 57, 270–274.
676 The Cognitive Neuroscience of Apraxia

Goldenberg, G., 2014b. Challenging traditions in apraxia. Brain 137, 1858–1859.

Goldenberg, G., 2017. Facets of pantomime. J. Int. Neuropsychol. Soc. 23, 121–127.
Goodale, M.A., Milner, A.D., 1992. Separate visual pathways for perception and action. Trends Neurosci. 15, 20–25.
Haggard, P., 2017. Sense of agencyin the human brain. Nat. Rev. Neurosci. 18, 197–208.
Hanna-Pladdy, B., Rothi, L.J.G., 2001. Ideational apraxia: confusion that began with Liepmann. Neuropsychol. Rehabil. 11, 539–547.
Hanna-Pladdy, B., Daniels, S.K., Fieselman, M.A., Thompson, K., Vasterling, J.J., Heilman, K.M., Foundas, A.L., 2001a. Praxis lateralization: errors in right and left hemisphere
stroke. Cortex 37, 219–230.
Hanna-Pladdy, B., Heilman, K.M., Foundas, A.L., 2001b. Cortical and subcortical contributions to ideomotor apraxia: analysis of task demands and error types. Brain 124,
2513–2527.
Hartmann, K., Goldenberg, G., Daumüller, M., Hermsdörfer, J., 2005. It takes the whole brain to make a cup of coffee: the neuropsychology of naturalistic actions involving technical
devices. Neuropsychologia 43, 625–637.
Heath, M., Roy, E.A., Black, S.E., Westwood, D., 2001. Intransitive limb gestures and apraxia following unilateral stroke. J. Clin. Exp. Neuropsychol. 23, 628–642.
Heath, M., Almeida, Q.J., Roy, E.A., Black, S.E., Westwood, D.A., 2003. Selective dysfunction of tool-use: a failure to integrate somatosensation and action. Neurocase 9, 156–163.
Hermsdörfer, J., Hentze, S., Goldenberg, G., 2006. Spatial and kinematic features of apraxic movement depend on the mode of execution. Neuropsychologia 44, 1642–1652.
Hermsdörfer, J., Li, Y., Randerath, J., Goldenberg, G., Johannsen, L., 2012. Tool use without a tool: kinematic characteristics of pantomiming as compared to actual use and the
effect of brain damage. Exp. Brain Res. 218, 201–214.
Hoeren, M., Kümmerer, D., Bormann, T., Beume, L., Ludwig, V.M., Vry, M.-S., Mader, I., Rijntjes, M., Kaller, C.P., Weiller, C., 2014. Neural bases of imitation and pantomime in
acute stroke patients: distinct streams for praxis. Brain 137, 2796–2810.
Jarry, C., Osiurak, F., Delafuys, D., Valérie, C., Etcharry-Bouyx, F., Le Gall, D., 2013. Apraxia of tool use: more evidence for the technical reasoning hypothesis. Cortex 49,
2322–2333.
Jarry, C., Osiurak, F., Besnard, J., Baumard, J., Lesourd, M., Croisile, B., Etcharry-Bouyx, F., Chauviré, V., Le Gall, D., 2016. Tool use in left brain damage and Alzheimer’s disease:
what about function and manipulation knowledge. J. Neuropsychol. 10, 154–159.
Jax, S.A., Buxbaum, L.J., 2010. Response interference between functional and structural actions linked to the same familiar object. Cognition 115, 350–355.
Jax, S.A., Buxbaum, L.J., 2013. Response interference between functional and structural object-related actions is increased in patients with ideomotor apraxia. J. Neuropsychol. 7,
12–18.
Johnen, A., Brandstetter, L., Kärgel, C., Wiendl, H., Lohmann, H., Duning, T., 2016. Shared neural correlates of limb apraxia in early stages of Alzheimer’s dementia and behavioral
variant frontotemporal dementia. Cortex 84, 1–14.
Kareken, D.A., Unverzagt, F., Caldemeyer, K., Farlow, M.R., Hutchins, G.D., 1998. Functional brain imaging in apraxia. Arch. Neurol. 55, 107–113.
Lesourd, M., Baumard, J., Jarry, C., Etcharry-Bouyx, F., Belliard, S., Moreaud, O., Croisile, B., Chauviré, V., Granjon, M., Le Gall, D., Osiurak, F., 2017. Rethinking the cognitive
mechanisms underlying pantomime of tool use: evidence from Alzheimer’s disease and semantic dementia. J. Int. Neuropsychol. Soc. 23, 128–138.
Martin, M., Beume, L., Kümmerer, D., Schmidt, C.S.M., Bormann, T., Dressing, A., Ludwig, V.M., Umarova, R.M., Mader, I., Rijntjes, M., Kaller, C.P., Weiller, C., 2016a. Differential
roles of ventral and dorsal streams for conceptual and production-related components of tool use in acute stroke patients. Cereb. Cortex 26, 3754–3771.
Martin, M., Nitschke, K., Beume, L.-A., Dressing, A., Bühler, L.E., Ludwig, V.M., Mader, I., Rijntjes, M., Kaller, C.P., Weiller, C., 2016b. Brain activity underlying tool-related and
imitative skills after major left hemisphere stroke. Brain 139, 1497–1516.
Martin, M., Dressing, A., Bormann, T., Schmidt, C.S.M., Kümmerer, D., Beume, L., Saur, D., Mader, I., Rijntjes, M., Kaller, C.P., Weiller, C., 2017. Componential network for the
recognition of tool-associated actions: evidence from voxel-based lesion-symptom mapping in acute stroke patients. Cereb. Cortex 27, 4139–4152.
Mengotti, P., Corradi-Dell’Acqua, C., Negri, G.A.L., Ukmar, M., Pesavento, V., Rumiati, R.I., 2013. Selective imitation impairments differentially interact with language processing.
Brain 136, 2602–2618.
Milner, A.D., Goodale, M.A., 2008. Two visual systems re-viewed. Neuropsychologia 46, 774–785.
Motomura, N., Yamadori, A., 1994. A case of ideational apraxia with impairment of object use and preservation of object pantomime. Cortex 30, 167–170.
Negri, G.A.L., Lunardelli, A., Gigli, G.L., Rumiati, R.I., 2007. Degraded semantic knowledge and accurate object use. Cortex 43, 376–388.
Niessen, E., Fink, G.R., Weiss, P.H., 2014. Apraxia, pantomime and the parietal cortex. Neuroimage 5, 42–52.
Osiurak, F., Badets, A., 2016. Tool use and affordance: manipulation-based versus reasoning-based approaches. Psychol. Rev. 123, 534–568.
Osiurak, F., Jarry, C., Allain, P., Aubin, G., Etcharry-Bouyx, F., Richard, I., Bernard, I., Le Gall, D., 2009. Unusual use of objects after unilateral brain damage: the technical reasoning
model. Cortex 45, 769–783.
Osiurak, F., Jarry, C., Le Gall, D., 2011. Re-examining the gesture engram hypothesis: new perspectives on apraxia of tool use. Neuropsychologia 49, 299–312.
Osiurak, F., Jarry, C., Lesourd, M., Baumard, J., Le Gall, D., 2013. Mechanical problem-solving strategies in left-brain damaged patients and apraxia of tool use. Neuropsychologia
51, 1964–1972.
Osiurak, F., Lesourd, M., Rossetti, Y., Baumard, J., 2019. Is there really a loss of agency in patients with apraxia of tool use. Front. Psychol. 10, 87.
Osiurak, F., 2013. Apraxia of tool use is not a matter of affordances. Front. Hum. Neurosci. 7.
Pazzaglia, M., Galli, G., 2014. Loss of agency in apraxia. Front. Hum. Neurosci. 8, 751.
Peigneux, P., van der Linden, M., Andres-Benito, P., Sadzot, B., Franck, G., Salmon, E., 2000. Exploration neuropsychologique et par imagerie fonctionnelle cérébrale d’une apraxie
visuo-imitative [A neuropsychological and functional brain imaging study of visuo-imitative apraxia]. Rev. Neurol. 156, 459–472.
Pellicano, A., Borghi, A.M., Binkofski, F., 2017. Editorial: bridging the theories of affordances and limb apraxia. Front. Hum. Neurosci. 11, 148.
Pizzamiglio, G., Zhang, Z., Duta, M., Rounis, E., 2020. Factors influencing manipulation of a familiar object in patients with limb apraxia after stroke. Front. Hum. Neurosci. 13, 465.
Poeck, K., 1983. Ideational apraxia. J. Neurol. 230, 1–5.
Poeck, K., 1986. The clinical examination for motor apraxia. Neuropsychologia 24, 129–134.
Randerath, J., Li, Y., Goldenberg, G., Hermsdörfer, J., 2009. Grasping tools: effects of task and apraxia. Neuropsychologia 47, 497–505.
Randerath, J., Goldenberg, G., Spijkers, W., Li, Y., Hermsdörfer, J., 2010. Different left brain regions are essential for grasping a tool compared with its subsequent use. Neuroimage
53, 171–180.
Rapcsak, S.Z., Ochipa, C., Beeson, P.M., Rubens, A.B., 1993. Praxis and the right hemisphere. Brain Cogn. 23, 181–202.
Rizzolatti, G., Matelli, M., 2003. Two different streams form the dorsal visual system: anatomy and function. Exp. Brain Res. 153, 146–157.
Rothi, L.J.G., Ochipa, C., Heilman, K.M., 1991. A cognitive neuropsychological model of limb praxis. Cogn. Neuropsychol. 8, 443–458.
Rounis, E., Humphreys, G., 2015. Limb apraxia and the “affordance competition hypothesis”. Front. Hum. Neurosci. 9, 429.
Roy, E.A., Heath, M., Westwood, D., Schweizer, T.A., Dixon, M.J., Black, S.E., Kalbfleisch, L., Barbour, K., Square, P.A., 2000. Task demands and limb apraxia in stroke. Brain
Cogn. 44, 253–279.
Rumiati, R.I., Weiss, P.H., Tessari, A., Assmus, A., Zilles, K., Herzog, H., Fink, G.R., 2005. Common and differential neural mechanisms supporting imitation of meaningful and
meaningless actions. J. Cogn. Neurosci. 17, 1420–1431.
Salazar-López, E., Schwaiger, B.J., Hermsdörfer, J., 2016. Lesion correlates of impairments in actual tool use following unilateral brain damage. Neuropsychologia 84, 167–180.
Schubotz, R.I., Wurm, M.F., Wittmann, M.K., van Cramon, D.Y., 2014. Objects tell us what action we can expect: dissociating brain areas for retrieval and exploitation of action
knowledge during action observation in fMRI. Front. Psychol. 5, 636.
Schwartz, M.F., Buxbaum, L.J., Montgomery, M.W., Fitzpatrick-DeSalme, E., Hart, T., Ferraro, M., Lee, S.S., Coslett, H.B., 1999. Naturalistic action production following right
hemisphere stroke. Neuropsychologia 37, 51–66.
 The Cognitive Neuroscience of Apraxia 677

Sperber, C., Wiesen, D., Goldenberg, G., Karnath, H.-O., 2019. A network underlying human higher-order motor control: insights from machine learning-based lesion-behavior
mapping in apraxia of pantomime. Cortex 121, 308–321.
Stamenova, V., Roy, E.A., Black, S.E., 2010. Associations and dissociations of transitive and intransitive gestures in left and right hemisphere stroke patients. Brain Cogn. 72,
483–490.
Stamenova, V., Roy, E.A., Black, S.E., 2011. Limb apraxia in corticobasal syndrome. Cortex 47, 460–472.
Tate, R.L., McDonald, S., 1995. What is apraxia? The clinician’s dilemma. Neuropsychol. Rehabil. 5, 273–297.
Tessari, A., Cubelli, R., 2014. Route selection in action imitation: a matter of strategic choice? Cortex 57, 277–278.
Tessari, A., Rumiati, R.I., 2004. The strategic control of multiple routes in imitation of actions. J. Exp. Psychol. Hum. Percept. Perform. 30, 1107–1116.
Tessari, A., Canessa, N., Ukmar, M., Rumiati, R.I., 2007. Neuropsychological evidence for a strategic control of multiple routes in imitation. Brain 130, 1111–1126.
Valyear, K.F., Culham, J.C., 2010. Observing learned object-specific functional grasps preferentially activates the ventral stream. J. Cogn. Neurosci. 22, 970–984.
Watson, C.E., Buxbaum, L.J., 2015. A distributed network critical for selecting among tool-directed actions. Cortex 65, 65–82.
Watson, C.E., Gotts, S.J., Martin, A., Buxbaum, L.J., 2019. Bilateral functional connectivity at rest predicts apraxic symptoms after left hemisphere stroke. Neuroimage 21, 101526.
Weiss, P.H., Ubben, S.D., Kaesberg, S., Kalbe, E., Kessler, J., Liebig, T., Fink, G.R., 2016. Where language meets meaningful action: a combined behavior and lesion analysis of
aphasia and apraxia. Brain Struct. Funct. 221, 563–576.
Westwood, D.A., Schweizer, T.A., Heath, M.D., Roy, E.A., Dixon, M.J., Black, S.E., 2001. Transitive gesture production in apraxia: visual and nonvisual sensory contributions. Brain
Cogn. 46, 300–304.