while there is a large body of evidence in favor of a clustering of representations of body effectors in the posterior parietal cortex , recent advances have revealed a hierarchical organization beyond a flat intentional map composed of functionally distinct subdivisions operating in parallel at same level . in particular , the parietal reach region ( prr ) and dorsal area 5 ( area 5d ) have been found to play distinct roles in visually - guided reach .
based on three lines of neurophysiological studies on nonhuman primates that utilize sophisticated behavioral tasks , including reference frame , effector choice , and sequential reach , this essay proposes that the prr and area 5d are involved in translation of general motor intentions into detailed motor programs at different stages .
the posterior parietal cortex ( ppc ) has historically been considered a typical association cortex , important for spatial attention and multisensory integration in the generation of a unitary map whose output is relayed to the frontal lobe to guide behavior ( critchley , 1953 ; ungerleider and mishkin , 1982 ; colby and goldberg , 1999 ) . since the 1970s , tremendous progress in neurophysiology , neuroanatomical tracing , functional imaging , and experimental intervention has yielded evidence of a variety of distinct functional subareas in the ppc , as opposed to a homogeneous area that constructs a single unified perceptual representation ( rizzolatti et al . , 1997 ; mountcastle , 1998 ; andersen and buneo , 2002 ) .
furthermore , the ppc has been shown to be involved in movement planning in a number of different contexts ( andersen and cui , 2009 ; rizzolatti and kalaska , 2013 ) .
the ppc seems to be composed of a mosaic of intentional maps , each of which is thought to be specialized for a different kind of movement for a particular body part ( andersen and buneo , 2002 ; scherberger et al . , 2013 ) .
recent advances have further suggested that the individual effector - specific regions are heterogeneous ( heed et al . , 2011 ; leone et al . , 2014 ) , with a hierarchical organization among different subdivisions preferring the same effector ( cui and andersen , 2011 ; verhagen et al . , 2013 ) , indicating that some subareas in ppc are involved in sensorimotor integration at multiple levels , instead of working in parallel within a flat intentional map .
this essay will focus on two reach - related areas in brodmann s area 5 ( fig .
1a ) , the parietal reach region ( prr ) , and dorsal area 5 ( area 5d ) , and discuss the functional relationship between them based on recent neurophysiological studies using a variety of sensorimotor contingencies .
b , three paradigms to distinguish general motor intention from detailed motor programs . in the reference frame task , general motor intention is represented in extrinsic space , while physical movement is prepared in intrinsic space . in the effector - choice task , multiple potential action plans can be formed prior to specification of the concrete motor parameters controlling the end - effector . in the sequential reach task ,
an action sequence encompassing all motor components at a cognitive level is formed before it is unfolded into a series of detailed programs of element movements .
the prr was originally defined as an area medial and posterior to the lateral intraparietal area ( lip ) , including more than one cytotectonic area , whose cells are more active for reaching arm movements than for saccadic eye movements ( snyder et al . , 1997 ; quian quiroga et al . , 2006 ; cui and andersen , 2007 ) .
many subsequent neurophysiological studies of the prr have targeted the medial bank of the ips ( mip ) ( baldauf et al . , 2008 ; cui and andersen , 2007 , 2011 ; pesaran et al . , 2006 , 2008 ;
reversibly inactivating the prr in monkeys causes miss - reach , similar to the optic ataxia reported in human patients ( hwang et al .
in addition , pre - movement activity is not simply related to the cue , because the prr has been found to encode the desired movement goal during an anti - reach task ( gail and andersen , 2006 ) . moreover ,
the reaching plan embedded in the prr includes not only target locations or end - points , but also high - level kinematics such as movement trajectories ( torres et al . , 2013 ) , supporting the view that movement trajectories are geometrically formed , independently of physical motor commands ( torres and zipser , 2002 ; torres and andersen , 2006 ) .
area 5d , which is located caudal to the primary somatosensory cortex ( si ) and medial to the ips , is involved in representing spatial information for limbs and control of reaching arm movements ( lacquaniti et al . 1995 ; kalaska et al .
1978 ; pearson and powell 1985 ) , and is reciprocally interconnected with primary and premotor cortex ( strick and kim , 1978 ) .
it was previously thought of as a higher somatosensory area that codes posture and joint positions ( sakata et al .
however , studies on behaving monkeys demonstrate that cells in area 5 became much more active during arm movements ( mountcastle et al . , 1975 ) , with strong directional tuning ( kalaska et al . , 1983 ) .
during delayed reach , many area 5 cells exhibit sustained activity far before the earliest increase in electromyographic activity ( kalaska and crammond , 1995 ) . compared with primary and premotor cortex , area 5 seems to be less directly involved in control of musculoskeletal dynamics : it appears to be insensitive to external force load , and to encode movement kinematics instead of dynamics ( kalaska et al . ,
also , many area 5 neurons show strong firing patterns that continuously covary with hand trajectory ( archambault et al . , 2011 ; hauschild et al . ,
2012 ) , a manually / brain controlled cursor ( mulliken et al . , 2008 ) , or even the seen position of a realistic fake arm ( graziano et al . , 2000
although both the prr and area 5d have been found to be intimately involved in planning of reach , several recent studies of reference frame , decision making , and sequential movement suggest that they might play distinct roles in planning and control of reaching arm movement at different ( abstract vs concrete ) levels of complexity ( fig .
1b ) , indicating a hierarchical circuitry that is involved in translation from cognitive intention into detailed motor programs to implement a key step of the complex sensorimotor transformations from receptors to muscle activation patterns .
the first findings in favor of a hierarchical prrarea 5d circuitry emerged from experiments characterizing sensorimotor coordinates with a variety of combinations of target , eye , and hand positions ( andersen at al . , 1997 ) . unlike an oculomotor plan in eyecentered
coordinates that is always registered to its sensory target in a retinotopic map , goal - directed reach initially planned in visual space ( flanagan and rao , 1995 ; wolpert et al . , 1995 ) requires a transformation from extrapersonal to joint / muscle coordinates .
recent studies demonstrate that different coordinate systems are employed in the prr and area 5d ( batista et al . , 1999 ; bremner and andersen , 2012 ) , suggesting that these areas are involved in reach planning in extrinsic and intrinsic spaces , respectively .
neurophysiological recordings during a delayed - reach task revealed a gradient distribution in the medial wall of the ips , with deep ( superficial ) neurons tending to be more modulated in the cue ( movement ) epoch ( johnson et al . , 1996 ) , suggesting that they are involved in different stages of the sensorimotor transformation ( battaglia - mayer et al . , 2003 ) .
reaching goals have been found to be represented in retinal coordinates ( batista et al . , 1999 ; pesaran et al . 2006 ) in the prr , indicating a cognitive plan at a more conceptual level than at the subsequent stages of motor planning .
that is , the prr only conveys abstract information ( i.e. , the spatial goal ) about upcoming movements , without specifying physical movement parameters ( i.e. , joint angles ) .
nonetheless , accurate motor control must take into account intrinsic variables , such as posture , hand position , the dynamics and structure of muscles , etc .
therefore , abstract motor intentions ultimately must be converted into detailed physical motor plans , with movement parameters specified in muscle / joint coordinates to activate musculoskeletal system ( kalaska et al . , 1997 ) .
the first step in converting target location in gaze - centered coordinates into limb motor commands for reaching is to incorporate proprioceptive and efference copy information about starting hand position and intrinsic arm posture .
it seems likely that area 5d plays a key role in this stage by providing target information with respect to initial hand position to specify action parameters in musculoskeletal coordinates ( buneo et al . , 2002 ) . from the prr to area 5d , neuronal representations of the reaching goal progressively shift from eye - centered to hand - centered along the ventraldorsal axis of the medial bank of the ips ( buneo and andersen , 2006 ) , so that pre - movement activity in area 5d predominantly encodes the reach vector ( bremner and andersen , 2012 ) .
however , this hand - centered coding is not static , but gradually emerges during the reach planning period ( bremner and andersen , 2014 ) , supporting the view that area 5d integrates the intrinsic biomechanics of the musculoskeletal system by dynamically incorporating information about intrinsic arm posture .
another approach to elucidating parietal sensorimotor circuitry is to identify distinct functional areas for decision making and motor planning .
decision making initially was assumed to be a neural process separate from action planning ( miller et al . , 1960 ; keele , 1968 ) .
nevertheless , attempts to distinguish decision making from motor planning with target selection tasks have proven frustrating , because virtually all motor - related areas seem to convey potential movements to candidate targets , and multiple potential plans exist concurrently before the final action is chosen ( riehle and requin , 1989 ; platt and glimcher , 1997 ; basso and wurtz , 1998 ; cisek and kalaska , 2005 ) .
consequentially , it is commonly believed that target selection and movement preparation involve overlapping brain circuits , and are performed in an integrated manner , as opposed to a serial model in which decision making occurs before action planning ( shadlen and newsome , 2001 ; wang , 2008 ; cisek and kalaska , 2010 ) . from the evolutionary point of view , forming multiple potential action plans prior to choosing among them might not only benefit reward prediction , but might also reduce reaction time ( andersen and cui , 2009 ; cisek and kalaska , 2010 ) .
nevertheless , the idea of integrated circuitry for decision making and motor planning has only been tested for spatial target selection ( cisek , 2007 ) , which involves spatial attention , and in turn engages numerous cortical areas ( desimone and duncan , 1995 ) .
it is unclear if plan selection and action preparation are embedded in segregated areas for other kinds of decision making , such as nonspatial effector choice . to examine anatomical overlap for decision making and motor planning in nonspatial action selection
, an effector - choice task was designed in which monkeys autonomously chose between a saccade and a hand reach to the same visual stimulus ( cui and andersen , 2007 ) .
monkeys were required to play a mixed - strategy game against a computer ( barraclough et al . , 2004 ) to compensate for a potential bias due to movement costs .
the effector - choice trials were pseudo - randomly interleaved with effector - instructed trials in which the monkeys were explicitly cued to make either a saccade or a reach to the target in the middle of a trial to discourage premature decisions .
the effector - choice task allows potential motor plans to be formed without immediate specification of concrete motor parameters controlling a particular end - effector , providing an ideal paradigm to determine whether action selection and motor preparation are encoded in overlapping or in distinct areas in nonspatial decision making .
if a brain region is involved in effector decision formation , then it should encode potential motor plans prior to effector selection .
conversely , if an area only carries selected motor plans , then it should only reflect the decision outcome after the effector is unambiguously specified .
interestingly , recent studies demonstrate remarkable qualitative differences between lip / prr and area 5d ( cui and andersen , 2007 , 2011 ) . whereas the lip and ppr encode potential motor plans , area 5d encodes only selected reach plans after the arm is chosen as the effector , suggesting that it is downstream to the prr in a serial visuomotor cortical circuit ( cui and andersen , 2011 ) . while the prr and area 5d presumably work in concert with premotor and primary motor areas , respectively ( wise et al . , 1997 ) , the functional relationship between the parietal and frontal areas in effector choice remains unclear .
in contrast to the prefrontal cortex ( tanji , 2001 ) , the ppc has historically received little attention in studies of sequential planning . nonetheless , neurological studies have suggested that the ppc is crucial for serial behaviour ( buxbaum , 1998 ; zadikoff and lang , 2005 ) .
patients with damage to the left parietal lobe appear normal in performing elementary movements , but are impaired in generating complex action sequences , indicating a profound role of the ppc in integrating multiple spatial goals into a motor sequence . to reveal the functional role of ppc in sequential arm movements , single - neuron activity from the prr ( baldauf et al . , 2008 ) and
area 5d ( li and cui , 2013 ) has been recorded from monkeys performing a double - reach task .
when the monkeys prepared to reach two simultaneously presented targets with sequential arm movements , most prr neurons carried information about both the immediate and the subsequent goals ( baldauf et al . , 2008 ) . situated at the early stage of the visuomotor transformation ,
the prr presumably is involved in the first step to generate a coherent sequence , integrating information about all component movements into a high - level movement plan at an abstract level .
nevertheless , a conceptual sequential plan encompassing multiple goals in parallel ultimately must be decomposed into serial motor commands to drive the musculoskeletal system .
in contrast to the prr , area 5d has been found to only encode the immediate upcoming reach , and not the subsequent movement ( li and cui , 2013 ) .
area 5d activity is tightly coupled only to the next upcoming movement , suggesting it might play a key role in integrating the visual goals from the prr with physical limb information to form a state estimation ( mulliken et al . , 2008 ;
moreover , the component reach encoded in area 5d , as opposed to the sequential information being conveyed in the prr and other cortical sensorimotor areas , suggests that unfolding of the movement sequence begins in the parietal - frontal cortex , including the ppc , prefrontal cortex , premotor cortex , primary motor cortex , and supplemental motor cortex , instead of being exclusively conducted by downstream subcortical and spinal circuits .
again , decomposition of the motor sequence appears to engage a larger sensorimotor network via mutual communication between parietal and frontal cortices ( pesaran et al . , 2008 ) .
a series of recent experiments have been conducted on monkeys performing a variety of sensorimotor tasks to elucidate distinct roles of the prr and area 5d at different stages of the sensorimotor transformation .
first , the reference frame task allowed us to isolate general motor intentions in extrinsic space and physical movement preparation in intrinsic space .
second , the effector - choice task allowed potential action plans to be formed without immediate specification of the concrete motor parameters controlling the end - effector .
third , the sequential reach task enabled us to isolate the cognitive action sequence from the detailed motor program of element movements .
three lines of evidence obtained with these tasks suggest that the prr and area 5d form a hierarchical sensorimotor circuitry that translates abstract intentions into detailed motor plans . despite the markedly different functional roles between prr and area 5d
, we should keep in mind that they are not sequentially involved in converting extrinsic stimuli into intrinsic motor plans in a hardwired fashion .
first , although a serial neural process was observed in the sensorimotor tasks mentioned above , effector specificity and information flow might be different in behavioral contexts other than visually guided reach ( e.g. , swaminathan et al . , 2013 ; woloszyn and shadlen , 2013 ) .
secondly , behavioral and computational studies have suggested that the sensorimotor transformation emerges through an intimate interplay between sensory inflow and motor outflow through paired forward and inverse internal models ( wolpert and kawato , 1998 ; shadmehr and wise , 2005 ) : the forward model translates motor commands into anticipated sensory outcomes , whereas the inverse model converts desired sensory consequences into motor commands ( franklin and wolpert , 2011 ; shadmehr and mussa - ivaldi , 2012 ) .
although the prevalent view posits that sensorimotor control largely relies on forward prediction of sensory consequences ( wolpert et al . , 2011 ) , direct neurophysiological evidence that persuasively links neural firing to predicted sensory consequences is still lacking , because the internal prediction of sensory consequences is inherently different from actual sensorimotor variables , and seems not to be behaviorally measurable . since most previous studies have used reactive movements to stationary goals predefined by sensory cues , it is difficult to determine whether the neural activity observed reflects sensory stimuli or predicts impending movements .
although corollary discharges have been found in diverse species ( crapse and sommer , 2008 ) for gating sensory inputs ( e.g. , lee and malpeli , 1998 ) and updating perception ( e.g. , duhamel et al . , 1992 ; sommer and wurtz , 2002 ; synofzik et al . , 2008 ) , as well as for distinguishing sensory signals between active and passive motion ( e.g. , roy and cullen , 2004 ) ,
it remains unclear how they are integrated with sensory inflow in recipient structures to form internal models for directing movement .
further elucidation of the ppc sensorimotor circuitry calls for novel behavioral tasks that are highly dependent on predictive spatiotemporal transformations .
the author did not consent to publish the author response letter the decision was a result of the reviewing editor ranulfo romo , universidad nacional autonoma de mexico and the peer reviewers coming together and discussing their recommendations until a consensus was reached . a fact - based synthesis statement explaining their decision and outlining what is needed to prepare a revision is listed below .
the following reviewers agreed to reveal their identity : christos constandtinidis and w. pieter medendorp the reviewers found your review paper of potential interest for publication in eneuro , provided you address their comments . in general , the reviewers think that you must lay down the scope of your review in the introduction section : input out - put organization of ppc and 5d .
also , there are many issues regarding what you mean by sensory - motor hierarchy , sensory - to - motor transformation , and integrated circuits for decision making , planning , and the link with frontal cortex . in the absence of a clear lay - out of these terms
. it would be useful to place the prr-5d circuit in a broader context , at least in the introduction .
it would be worth considering the inputs to the prr area from other parietal areas and outputs of area 5d to the premotor cortex .
line 77 : please , discuss the effector specificity could change over time , and that the network is not hardwired . line 88 : be more specific about the involvements of ppc and 5d in the different stages of the sensory - motor transforms . here and again , what is it a hierarchy and should refer also to caminiti and colleagues .
but , there are so many examples of hierarchy and sensory - to - motor transformation and their roles in planning , and decision making , etc .
lines 123 - 125 : it is unclear what is meant by integrated circuitry for decision making and motor planning for spatial target selection .
the source being cited is a review ( and a 20-year old one , as such ) .
line 145 : what is the implication of this finding and the link with frontal cortices ?
line 170 : clarify the term parietal - frontal cortex , by spelling out the relevant areas .
line 171 : expand communication via synchronization and de - synchronization between ppc and frontal cortices .
line 174 : it is unnecessary to start the discussion with  in summary  .
line 195 : could you please explain or consider that sensory consequences are not behaviorally measurable ?
the reviewers found your review paper of potential interest for publication in eneuro , provided you address their comments . in general , the reviewers think that you must lay down the scope of your review in the introduction section : input out - put organization of ppc and 5d .
also , there are many issues regarding what you mean by sensory - motor hierarchy , sensory - to - motor transformation , and integrated circuits for decision making , planning , and the link with frontal cortex . in the absence of a clear lay - out of these terms
. it would be useful to place the prr-5d circuit in a broader context , at least in the introduction .
it would be worth considering the inputs to the prr area from other parietal areas and outputs of area 5d to the premotor cortex .
line 77 : please , discuss the effector specificity could change over time , and that the network is not hardwired .
line 88 : be more specific about the involvements of ppc and 5d in the different stages of the sensory - motor transforms . here and again , what is it a hierarchy and should refer also to caminiti and colleagues .
but , there are so many examples of hierarchy and sensory - to - motor transformation and their roles in planning , and decision making , etc
. lines 123 - 125 : it is unclear what is meant by integrated circuitry for decision making and motor planning for spatial target selection .
the source being cited is a review ( and a 20-year old one , as such ) .
line 145 : what is the implication of this finding and the link with frontal cortices ?
line 170 : clarify the term parietal - frontal cortex , by spelling out the relevant areas .
line 171 : expand communication via synchronization and de - synchronization between ppc and frontal cortices .
line 174 : it is unnecessary to start the discussion with  in summary  .
line 195 : could you please explain or consider that sensory consequences are not behaviorally measurable ?
 while there is a large body of evidence in favor of a clustering of representations of body effectors in the posterior parietal cortex , recent advances have revealed a hierarchical organization beyond a flat intentional map composed of functionally distinct subdivisions operating in parallel at same level . in particular , the parietal reach region ( prr ) and dorsal area 5 ( area 5d ) have been found to play distinct roles in visually - guided reach . 