Structural brain correlates of unconstrained motor activity in people with schizophrenia
TOM F. D. FARROW, PhD and
MICHAEL D. HUNTER, MRCPsych
Sheffield Cognition and Neuroimaging Laboratory (SCANLab), Department of
Academic Clinical Psychiatry
IAIN D. WILKINSON, PhD
Department of Academic Radiology
RUSSELL D. J. GREEN, MBChB and
SEAN A. SPENCE, MD, MRCPsych
SCANLab, Department of Academic Clinical Psychiatry,University of
Sheffield, UK
Correspondence:
DrTom F. D. Farrow, SCANLab, Department of Academic Clinical Psychiatry,
University of Sheffield,The Longley Centre, Northern General Hospital, Norwood
Grange Drive, Sheffield S5 7JT,UK. E-mail:
t.f.farrow{at}sheffield.ac.uk
Declaration of interest None. Funding detailed in
Acknowledgements.
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ABSTRACT
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Avolition affects quality of life in chronic schizophrenia. We investigated
the relationship between unconstrained motor activity and the volume of key
executive brain regions in 16 male patients with schizophrenia. Wristworn
actigraphy monitors were used to record motor activity over a 20 h period.
Structural magnetic resonance imaging brain scans were parcellated and
individual volumes for anterior cingulate cortex and dorsolateral prefrontal
cortex extracted. Patientstotal activity was positively correlated with
volume of left anterior cingulate cortex. These data suggest that the volume
of specific executive structures may affect (quantifiable) motor behaviours,
having further implications for models of the will and
avolition.
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INTRODUCTION
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Some modular theories of brain organisation propose a relationship between
regional volume and psychological function. In this study we recorded the
spontaneous, unconstrained motor behaviour of people with schizophrenia and
examined whether such behaviour was related to the volume of key executive
brain regions: anterior cingulate (Brodmann area (BA) 32) and dorsolateral
prefrontal (BA 9 and BA 46) cortices.
The anterior cingulate cortex plays an integrative role in the frontal
lobes, translating intentions into actions
(Paus, 2001). It contributes to
motor control, complex executive processing, vigilance, arousal and
drive (Spence & Frith,
1999). Together with its involvement in autonomic functioning,
these processes suggest that the anterior cingulate cortex plays a pivotal
role in overall behavioural control
(Devinsky et al,
1995), particularly in goal-directed behaviours
(Spence & Frith, 1999). Conversely, anterior cingulate cortex lesions are associated with reduced
spontaneous behaviour and attention, as manifest in akinetic mutism
(Devinsky et al,
1995).
The role of the medial prefrontal cortex (including anterior cingulate
cortex) in schizophrenia has been much investigated. Structurally there is
evidence of abnormal medial prefrontal gyral patterns and cytoarchitecture,
whereas functionally there is evidence of reduced perfusion in the psychomotor
poverty sub-syndrome (alogia, flatness of affect and decreased spontaneous
movement (Liddle et al,
1992). A negative correlation was found between patients
poverty scores and left ventro-medial prefrontal grey matter density
(Chua et al,
1997).
Dorsolateral prefrontal cortex, particularly BA 9 and BA 46, has been
implicated in behavioural response selection tasks, including finger movement
(Hunter et al, 2004),
random number generation and verbal fluency, all requiring the individual to
generate novelty. Therefore, while anterior cingulate cortex is implicated in
the quantity of motor activity performed by the organism, dorsolateral
prefrontal cortex regions are implicated in behavioural complexity (e.g. how
novel the response patterns are that emerge)
(Spence & Frith,
1999).
We hypothesised that in schizophrenia the extent of motor activity over a
prolonged period (20 h) might be constrained by anatomical features of the
frontal executive system, specifically the anterior cingulate cortex (BA 32)
and dorsolateral prefrontal cortex (BA 9/46).
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METHOD
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Sixteen right-handed patients with DSMIV schizophrenia
(American Psychiatric Association,
1994) gave written informed consent and participated in this
study, approved by the North Sheffield Research Ethics Committee. All
participants were community-based out-patients, but for monitoring purposes
were admitted to a psychiatric ward for 24 h. Participants had a mean age of
36 years (s.d.=8), a mean illness duration of 14 years (s.d.=8), a mean score
on the Scale for the Assessment of Negative Symptoms (SANS;
Andreasen, 1985) of 11.5
(s.d.=2.7), a Scale for the Assessment of Positive Symptoms (SAPS;
Andreasen, 1985) score of 3.6
(s.d.=2.1) and a Beck Depression Inventory (BDI;
Beck et al, 1996)
score of 9.5 (s.d.=10.3). Eleven patients were taking oral atypical
antipsychotic medication (olanzapine, 6; clozapine, 4; quetiapine, 1), one was
taking oral typical medication (sulpiride) and four were receiving typical
depot medication (flupenthixol decanoate, 2; fluphenazine decanoate, 1;
zuclopenthixol decanoate, 1). Patients underwent a structural magnetic
resonance imaging (MRI) scan on a 1.5 Tesla system (Eclipse, Philips Medical
Systems, Ohio, USA) using a three-dimensional acquisition technique
(RF-spoiled FAST; repetition time=15 ms; echo time=4.4 ms; acquisition
matrix=256 x 256 x 190 yielding a voxel size of 1mm3)
which produced a T1-weighted volume dataset covering the entire
brain. Scans were pre-processed using voxel-based morphometry with statistical
parametric mapping (SPM2) (Wellcome Department of Imaging Neuroscience,
London). Smoothed grey matter segmented maps were parcellated using masks
created with WFP_PickAtlas v1.02 (Maldjian
et al, 2003; see data supplement to online version of
this paper). Volumes of anterior cingulate cortex and dorsolateral prefrontal
cortex grey matter regions were obtained for each participant. Following the
scan, participants wore an Actiwatch (Cambridge Neurotechnology,
UK) measuring their cumulative activity over a 20 h period. The Actiwatch is a
wrist-worn device containing a miniature uniaxial accelerometer which produces
a digital integration of the amount and duration of all movement over 0.05 g.
As an indicator of normal daytime activity, a study of 107 healthy 16- to
19-year-old adolescents recorded mean Actiwatch readings of 162 565 (s.d.=68
620) (a dimensionless measure) over a 24 h period (Nancy Butte, personal
communication, 2004). We ran patient-wise parametric bivariate correlations
between total motor activity and volumes of bilateral anterior cingulate
cortex and dorsolateral prefrontal cortex.
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RESULTS
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Over 20 h the mean Actiwatch reading was 106 722 (s.d.=36 553). The mean
regional grey matter volume was 4.7 ml (s.d.=0.6) for left anterior cingulate
cortex, 5.0 ml (s.d.=0.4) for right anterior cingulate cortex, 5.3 ml
(s.d.=1.0) for left dorsolateral prefrontal cortex and 4.4 ml (s.d.=0.6) for
right dorsolateral prefrontal cortex. There were no correlations between
patients ages or durations of illness (which are themselves of course
highly positively correlated) or SANS scores and anterior cingulate cortex or
dorsolateral prefrontal cortex volumes. There were negative correlations
between patients ages and durations of illness and their total activity
measures (r=0.549, P=0.034 and
r=0.621, P=0.014, respectively). There was a negative
correlation between SANS avolition score and Actiwatch-measured motor activity
(r=0.52, P=0.047), although this result should be
interpreted in the light of the ordinal nature of the SANS and small variance
in our patients avolition scores (range 24). There were no
correlations between chlorpromazine-equivalent drug doses or BDI scores and
motor activity. Total activity over 20 h was positively correlated with volume
of the left anterior cingulate cortex (r=0.487, P=0.028;
Fig. 1). There were no
significant correlations between cumulative Actiwatch activity and right
anterior cingulate cortex or left or right dorsolateral prefrontal cortex
volumes (P>0.3).

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Fig. 1 Positive correlation in 16 patients with chronic schizophrenia between
their total cumulative activity over 20 h and left anterior cingulate cortex
(Brodmann area 32) volumes.
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DISCUSSION
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In these people with schizophrenia, motor activity over a 20 h period was
correlated with the volume of left anterior cingulate cortex, a finding
supportive of our central hypothesis that anatomy may constrain function, in
this case spontaneous motor behaviour. In particular, it was the anterior
cingulate cortex rather than the dorsolateral prefrontal cortex that was
implicated, consistent with a methodology that measures volume
of motor behaviour, without regard to its complexity. This finding is
congruent with the role of anterior cingulate cortex in the emergence of motor
acts, and its relative dysfunction in psychomotor poverty
(Liddle et al, 1992;
Chua et al, 1997) and
akinetic mutism (Devinsky et al,
1995).
In terms of methodology, ours is the first study of regional brain volume
in schizophrenia to use an automated measure of spontaneous motor activity.
This novel use of an actigraphy monitor as an objective, scalar measure of
bodily movement, as opposed to the more usually quoted, subjective, ordinal
measure of avolition (in the SANS), has the potential to augment validity in
clinical studies and certainly detects greater between-subject variance. This
may be particularly useful in patient assessments where change is anticipated
(as with behavioural or pharmacological interventions).
We must be cautious in extrapolating our finding to community, ambulatory
patients as our study concerned patients who spent the days in question on a
psychiatric ward. Nevertheless, our data do offer the intriguing possibility
that anatomy and function are related with respect to spontaneous,
unconstrained motor activity. Of course, there is a final caveat in that we do
not know the extent to which measured behaviour is purposeful
(Spence & Frith, 1999), but this is the subject of ongoing work
(Hunter et al,
2004).
In summary, our findings suggest that the volume of the left anterior
cingulate cortex in people with chronic schizophrenia correlates with an
objective measure of their unconstrained motor
activity.

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Data supplement 1 Extent of left anterior cingulate cortex (Brodmann area 32) mask in the
axial (1-ventral to 3-dorsal), coronal (4-anterior to 6-posterior) and
sagittal (7-medial to 8-lateral) planes.
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ACKNOWLEDGMENTS
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This study was funded by an investigator-led grant awarded to S.A.S. by
Cephalon UK. M.D.H. is supported by the Wellcome Trust. We thank Professor
Nancy Butte, Baylor College of Medicine, Texas, USA for normative Actiwatch
data.
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Received for publication September 14, 2004.
Revision received March 4, 2005.
Accepted for publication March 16, 2005.
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