Brain Injury, December 2012; 26(13–14): 1750–1755

CASE STUDY

Manual reaction times and brain dynamics after ‘awake surgery’ ofslow-growing tumours invading the parietal area. A case report

ETIENNE SALLARD1,2,3, JEROME BARRAL3, HUGUES DUFFAU4,5, &FRANCOIS BONNETBLANC1,2,6

1Unite de Formation et de Recherche en Sciences et Techniques des Activites Physiques et Sportives, Universite de

Bourgogne, F-21078 Dijon, France, 2Institut National de la Sante et de la Recherche Medicale, Unite 1093, Cognition-

Action et Plasticite Sensori-Motrice, France, 3Institut des Sciences du Sport de l’Universite de Lausanne, Switzerland,4Department of Neurosurgery, Hopital Gui de Chauliac, Centre Hospitalier Universitaire Montpellier, France, 5Institut

des Neurosciences de Montpellier INSERM U1051, France, and 6Universite Montpellier 2 – LIRMM – DEMAR

Team, 161 Rue Ada, F-34095 Montpellier Cedex 5

(Received 25 November 2011; accepted 28 May 2012)

AbstractPrimary objectives: Awake surgeries of slow-growing tumours invading the brain and guided by direct electrical stimulationinduce major brain reorganizations accompanied with slight impairments post-operatively. In most cases, these deficits areso slight after a few days that they are often not detectable on classical neuropsychological evaluations. Consequently, thisstudy investigated whether simple visuo-manual reaction time paradigms would sign some level of functional asymmetriesbetween both hemispheres. Importantly, the visual stimulus was located in the saggital plane in order to limit attentionalbiases and to focus mainly on the inter-hemispheric asymmetry.Methods and procedures: Three patients (aged 41, 59 and 59 years) after resections in parietal regions and a control group(age¼ 44, SD¼ 6.9) were compared during simple uni- and bimanual reaction times (RTs).Main outcomes and results: Longer RTs were observed for the contralesional compared to the ipsilesional hand in theunimanual condition. This asymmetry was reversed for the bimanual condition despite longer RTs.Conclusion and clinical implications: Reaction time paradigms are useful in these patients to monitor more precisely theirfunctional deficits, especially their level of functional asymmetry, and to understand brain (re)organization following slow-growing lesions.

Keywords: Awake surgery, simple reaction time, cerebral plasticity, parietal areas, slow-growing lesions

Introduction

‘Low-grade gliomas’ (LGG, World HealthOrganization grade II gliomas) are slow-growingtumours invading the brain. During surgical resec-tions of these tumours, the use of direct electricalstimulation (DES) is widely advocated for functionalmapping, allowing the structures that are essential tothe function to be identified and preserved at eachstage of the resection [1]. Any reproducible func-tional disturbance induced by DES indicates inter-ruption of the resection. This technique has proved

to be effective and more than 90% of the patients

return to normal socio-professional life, with no func-

tional deficit, usually 3 months after the surgery [2].However, in the context of slow-growing injuries,

brain reorganization is considerably increased thanafter acute lesions. The recruitment of remote brainareas in the ipsi- and contralesional hemispheres ismuch more efficient. Thus, the contrasting recover-ies and plastic processes associated with thetwo types of lesion offer interesting insights thatmay help in understanding brain plasticity [1, 3–5].

Correspondence: Francois Bonnetblanc, Unite de Formation et de Recherche en Sciences et Techniques des Activites Physiques et Sportives, Universite deBourgogne, Dijon, France. E-mail: francois.bonnetblanc@u-bourgogne.fr

ISSN 0269–9052 print/ISSN 1362–301X online � 2012 Informa UK Ltd.DOI: 10.3109/02699052.2012.698792

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For slow-growing tumours, the impressive reorgani-zation capacity of the brain allows the subjects torecover substantially, deficits remained often unde-tectable with classical neuropsychological examina-tions and required extensive and more sensibleevaluations [1, 3, 4, 6]. Despite clinical evidence,precise quantifications of these phenomena arelacking. More particularly, hand functional asym-metries measured using simple reaction times (RT)deserve to be investigated as they are illustrative ofimbalance between both hemispheres for motorareas but also for associative and especially parietalareas involved in higher stages of motor planningand preparation [7]. When deficits cannot beprecisely assessed using standard neuropsychologicaltests, simple reaction time paradigms could beinteresting to probe the slight deficits characterizingpatients with LGG. Indeed, this procedure may beused to track and monitor the level of functionalasymmetry between the two hemispheres occurringafter the large resection performed within a singlehemisphere.

In the context of slow-growing lesions, the inter-hemispheric imbalance after resections of LGGinvading the parietal area for unimanual as well asfor bimanual RT was investigated. Serrien et al. [8]demonstrated that unilateral damage to the parietallobe also impaired the synchronization of continuousbimanual movements. In addition, it is known thatactions driven and triggered by external stimuli(externally-driven) involve the parietal–premotornetwork, which is less the case for self-paced-actions(internally-driven) that mainly involve the basalganglia–supplementary motor network [9]. Thisstudy, thus, contrasted the effect of externally vs

internally generated movements during simulta-neous bimanual movements.

In this case report, it was hypothesized that ifsimple visuo-manual reaction times would sign somelevel of functional asymmetries after an unilateralparietal resection, RT would be longer for thecontralesional compared to the ipsilesional hand inthe unimanual condition. Importantly, the visualstimulus was located in the saggital plane in order tolimit attentional biases and to focus mainly on theinter-hemispheric asymmetry. Finally, resections inthe parietal areas are expected to increase the onsetasynchrony between the two hands during bimanualreaction time in the externally-driven condition,which would be more altered as compared to theinternally-triggered condition.

Methods

Participants

Three patients (P1, P2 and P3) and eight healthyvolunteers (Control Group, age¼ 44, SD¼6.9)participated in the experiment (all right handed).The control group (five males and three females)had no history of previous neurological diseases. Thestudy conformed to the Code of Ethics of the WorldMedical Association (Declaration of Helsinki, 18July 1964) and the local ethics committees approvedthe general procedure.

P1, a 41 years-old man, presented a left parietaltumour (Figure 1, upper and left panel). P2 and P3,two 59 year-old women presented a right parietaltumour (Figure 1, upper middle and right panel). Allthese patients underwent surgical resection of low-

Figure 1. Pre-operative FLAIR-weighted axial and postoperative T1-weighted axial MRI for patient P1 (left panel), preand postoperativeFLAIR-weighted axial MRI for P2 (middle panel) and pre-operative T2-weighted axial and post-operative FLAIR-weighted axial MRI forP3 (right panel), showing an invasion (upper row) and a resection (lower row) of the parietal lobe. Neurological conventions (only for thisfigure).

Simple reaction times after awake surgery 1751

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grade glioma using intra-operative direct electricalstimulation.

P1 attended clinical observation because ofepileptic seizures. He showed no deficit, especiallyno visuo-motor abnormality, on pre-operative neu-rological examination before the surgery. In P1, theglioma was centred on the left parietal area, asillustrated on the post-operative MRI. P2 wasfollowed for a slow-growing right parietal tumourduring 14 years, revealed by inaugural seizures. Theneurological examination showed no visuo-spatialdeficit. P3 experienced three somatosensory partialseizures 3 months before the surgery. The neuro-logical examination was normal. Volumes of thetumour were estimated to � 50 cm3, 40 cm3 and37 cm3 for P1, P2 and P3, respectively.

Task and procedure

Participants comfortably sat in front of two super-imposed light emitting diodes (LED) of differentcolours (red and green) fixed on a table at a distanceof 60 cm from the body in the sagittal axis and 45 cmbelow the eyes. Importantly, the visual stimulus waslocated in the saggital plane in order to limitattentional biases. Two switches were positionedon each side of the participant (distant¼15 cm fromeach other) and located at 45 cm from the body.Motor responses consisted of releasing one or twoswitch(es) by raising their index finger(s). The redLED served as the warning signal. The green LEDrepresented the ‘go-signal’, prompting the partici-pant to raise one or both index finger(s) as fast aspossible. The time elapsed between the warningsignal and the ‘go-signal’, i.e. the stimulusonset asynchrony (SOA), was randomly variedbetween each trial (SOA¼2, 2.5, 3, 3.5, 4 and 4.5seconds).

Each participant performed the simple reactiontime paradigm in four pseudo-randomized experi-mental conditions (three in the externally and one inthe internally condition). In the right externally (RE)or left externally (LE) conditions, they respondedunilaterally with their right or left index fingers. Inthe right and left externally condition (RLE), theyraised both index fingers simultaneously. In thefourth right and left internally condition (RLI),participants performed a bimanual simultaneousresponse without external stimulus and raised theirindexes in a self-paced manner. Between 18–44 trialswere performed for each condition according to theparticipant’s motivation/tiredness. The measures ofRT were performed at þ96 hours, þ72 hours andþ48 hours after the operation for P1, P2 and P3,respectively. RTs were recorded at a sam-pling frequency of 5 kHz and processed with amulti-channel analogue-to-digital converter

(Biopac Systems, Inc., Goleta, CA). RT valuesthat exceeded twice the standard deviation fromthe RT mean were excluded from the analysis(5.39% of all trials).

Data analysis

RTs for the left and right fingers were comparedusing t-tests in the two unimanual conditions (REand LE) as well as in the RLE bimanual condition(paired comparisons for this latter condition).T-tests were also used to compare pooled right andleft RTs between the unimanual and the bimanualRLE condition. The synchronization was measuredbetween the two hands (delta score) by subtractingthe left hand to the right hand at each trial in the twobimanual conditions (externally and internally-driven). The negative values indicate that the lefthand started before the right hand and conversely forthe positive values. Within each bimanual condition,the delta scores were compared to zero to evaluatethe synchrony of the responses of the two hands.T-tests were computed to compare delta scoresbetween the RLI and RLE conditions. Mean RTsand mean delta scores were used for the statisticalanalyses in the control group. The significancethreshold was fixed at 0.05.

Results

Results for the control group did not reveal anydifferences between the RE and LE unimanual RTs(t(7)¼�0.99, p¼ 0.35). However, RTs increasedfor all patients (ps< 0.05). For P1 and P2, analysesrevealed a significant asymmetry between hands withshorter RTs for the ipsilesional (or non-lesed) handcompared to the contralesional (or lesed) hand (P1:t(67)¼ 2.45, p< 0.05 and P2: t(59)¼�2.12,p< 0.05). No significant differences was found forP3 (t(64)¼�0.84, p¼ 0.4). Note that P3 underwentthe smallest resection. Mean RTs for the RE and LEunimanual conditions are shown in Figure 2.

Results suggested that the two hands were per-fectly synchronized for the control group in thebimanual externally condition as no significantdifference was observed (RLE: t(7)¼�0.01,p¼ 0.98). Again, RTs increased for all patients(ps<0.05). For the three patients, RTs werelonger for the ipsilesional hand in comparison tothe contralesional one (t(33)¼�5.73, p< 0.01 forP1; t(32)¼ 7.12, p<0.01 for P2 and t(22)¼ 9.88,p< 0.01 for P3), showing that asymmetries of handsRTs performances were inverted between the unim-anual (RE and LE) and the bimanual (RLE)conditions (Figure 2). In addition, results revealeda general impairment of RTs in the bimanualcondition as compared to the unimanual one for

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the two hands for P1 (t(135)¼�3.26, p< 0.01) andP3 (t(110)¼�5.19, p< 0.01). No such differenceswere found for P2 (t(125)¼ 0.64, p¼ 0.51).

In the bimanual internally condition (RLI), deltascores revealed a tendency to shorter RTs on the

right hand for the control group (t(7)¼ 2.18,p¼ 0.06) and by contrast, shorter RT on the lefthand for all patients (t(29)¼�3.4, p< 0.01 for P1;t(26)¼�4.64, p< 0.01 for P2 and t(34)¼�5.75,p< 0.01 for P3) (Figure 3).

Figure 3. Mean delta scores � standard deviation (vertical lines) in the RLE and RLI conditions, for P1, P2, P3 and the control group.Delta score is positive when the right index finger moved before the left one and negative when the left index move first.

Figure 2. Mean RTs and standard deviation (vertical lines) for the right and left hands in the two unimanual (RE and LE) and thebimanual (RLE) externally conditions, for P1, P2, P3 and the control group.

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Finally, asynchrony between both hands was morepronounced in the RLE condition in comparison tothe RLI condition for all patients (t(62)¼ 5.78,p< 0.01 for P1; t(58)¼�2.63, p<0.05 for P2 andt(56)¼�4.24, p< 0.01 for P3).

Discussion

The aim of this experiment was to investigate simplehand reaction times asymmetries between the twohands following an ‘awake surgery’ of a LGGinvading the parietal area. This question was inves-tigated both for unimanual and bimanualmovements.

For unimanual movements, patients exhibited ageneral increase of hand RTs and longer RTs infavour of the contralesional hand in comparison tothe control group. This functional asymmetry maysign changes in brain dynamics following ‘awakesurgery’ of slow-growing tumours invading theparietal area and is in accordance with the hypothesisof an inter-hemispheric competition in which con-tralesional structures are disinhibited because of thelesions in the damaged hemisphere [10]. Similarfindings, using repetitive transcranial magnetic stim-ulation applied over the parietal area in normalsubjects, revealed that the detection of ipsilateralvisual stimuli was improved over a normal level (i.e.RT decreased), whereas the detection of contralat-eral visual stimuli decreased (i.e. RT increased)[11, 12]. In accordance with these results, virtuallesions induced over the parietal area also provokedfunctional asymmetries in a reaction times paradigm.

For P1 and P3 increased RTs were observedduring the bimanual condition in comparison to theunimanual one. This slowing down of motorresponses during bimanual movements was previ-ously reported for normal subjects [13–17] and isknown as bilateral deficit. Two possible mechanismshave been suggested to explain this result: division ofattention and inter-hemispheric inhibition [18, 19].The division of attention assumes that, when abilateral movement is performed, a limited amountof attention is distributed to each hand. In the inter-hemispheric inhibition hypothesis, it is proposed thatRTs increase during some bilateral movements as aresult of callosal inhibitory mechanisms [20]. Thebilateral deficit may be explained by the result of thecrossing effect of mutual inter-hemispheric inhibi-tion [21]. In any case, the results suggest that thebilateral deficit is greater after the removal of theparietal area and that initiating the two handssimultaneously is more challenged for the patients.It has been suggested that, for slow-growing lesions,the contralesional hemisphere may compensate forthe damaged area [6, 8]. In consequence, one may

speculate that the contralesional homologue under-goes a kind of ‘bottleneck’ effect when the two handsare solicited simultaneously, which delays the motorresponse or challenges even more the bimanual co-ordination.

In contrast to unimanual movements, asymme-tries of hands’ reaction times were inverted forbimanual ones in favour of the contralesional hand,whatever the lesioned hemisphere. Despite no clearexplanation of the mechanisms underlying thisresult, it stresses a strong different dynamic withinthe brain for uni- vs bimanual movements. Finally, itwas observed that when performing bimanual move-ments in both the RLE and RLI conditions the onsetasynchrony between the two hands increased for allpatients. These asynchronies were more importantin the RLE condition suggesting that they can not beexplained solely by pure motor impairments butrather suggest some other attentional deficitsinvolved in this latter condition. Finally, this casestudy confirms the involvement of parietal area inexternally-driven motor response [9].

Limitations of the study

First, the authors are mindful that assessments ofthree patients with right or left parietal lesion andperforming a different number of trials might repre-sent limits of this work. Nevertheless, as a first studyof its kind, it allowed interesting viewings andcomparisons between lesioned sides of the parietalarea after an awake surgery. Secondly, one mightregret the lack of more extensive evaluation ofattention deficits. With the same patients, comple-mentary results about line bisections (l¼ 25 cm)revealed small deviations toward the ipsilesionalhemifield for P1 (�7.85 mm) and P2 (0.95 mm)and toward the contralesional hemifield for P3(�1.4 mm) that slightly contrasted with controlperformances (95% CI¼ [�0.45; 1.27]). In conse-quence, despite small deviations for P2 and P3, onecannot fully exclude some spatial attention deficitsthat would have been confirmed by other neuropsy-chological tests. It is worth noting that patients withLGG are over-solicited during their treatment periodand are regularly involved in other clinicalresearches, which did not permit one to lengthenthe experimental protocol.

Conclusions and clinical implications

In this case report including three patients, consis-tent patterns of functional asymmetries wereobserved with respect to the side of the lesion: (1)in unimanual condition, RTs were steadily longer forthe contralesional hand and (2) in bimanual condi-tion, the RTs were constantly longer for the

1754 E. Sallard et al.

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ipsilesional hand. These patterns of results do notallow a clear-cut interpretation. When deficitscannot be precisely assessed using standard neuro-psychological tests, simple reaction time paradigmsseem to be relevant to probe the slight deficitscharacterizing patients with LGG. Specifically, thismethod might help to monitor the level of functionalasymmetry between the two hemispheres and beuseful to guide the rehabilitation procedure. Forpatients with LGG, further research should applytranscranial magnetic stimulation over the healthyhomologue to determine its level of participationduring recovery processes accompanying slow-grow-ing lesions [6]. The chronometric method combinedwith transcranial magnetic stimulation could be ameaningful approach to increase knowledge aboutintra- and inter-hemispheric cerebral dynamics inpatients with slow-growing lesions.

Acknowledgement

We strongly thank the patients for their participationto this study.

Declaration of Interest: The authors report noconflicts of interest. This study was supported by the‘Association pour la Recherche sur le Cancer’ (ARC-France Subvention Libre n�3184).

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