Functional organization of monkey brain for abstract operation

When humans manipulate a control device under operational rules, with the goal of indirectly controlling a remote tool to achieve a desired outcome, they may rely on the power of internal representation to organize individual moves of the controller and tool into a set of sequences by mapping the motor space among hand, controller and tool. We recently used functional brain imaging (PET) to investigate activations in monkey brain associated with joystick-controlled remote operation of a shovel to obtain food. Activated areas included the prefrontal cortex, posterior parietal cortex and cerebellum, regardless of the rules relating movements of the joystick to those of the shovel (Obayashi et al., 2004). If those areas are engaged in the mental manipulation of internal representation, then we should expect brain activity in the same regions during any similar remote operation, even with different controllers and/or operational rules. To address the above hypothesis in the current study, we used PET to measure regional cerebral blood flow (rCBF) of two monkeys during a task in which they were required to control a shovel remotely (to fetch a food pellet) by manipulating dual dials. Compared to unplanned movement of the dials, the active dual-dial operation was associated with robust activation of the prefrontal cortex, higher-order motor cortex, posterior parietal cortex and cerebellum, quite similar to that observed during remote operation with a joystick. The present study suggests that monkeys might be able to organize abstract sequential operations according to learned rules, and perhaps indeed to have insight into the nature of the causal relationships, implying the existence of a relatively sophisticated system of internal representation in the absence of language. The fact that the present results are consistent with our previous PET studies strengthens the view that the underlying mechanism for implicit manipulation of internal representations may involve a cerebro-cerebellar neural circuit including the frontal and parietal cortex.     

Dynamic changes in the mental rotation network revealed by pattern recognition analysis of fMRI data

We investigated the temporal dynamics and changes in connectivity in the mental rotation network through the application of spatio-temporal support vector machines (SVMs). The spatio-temporal SVM [Mourao-Miranda, J., Friston, K. J., et al. (2007). Dynamic discrimination analysis: A spatial-temporal SVM. Neuroimage, 36, 88-99] is a pattern recognition approach that is suitable for investigating dynamic changes in the brain network during a complex mental task. It does not require a model describing each component of the task and the precise shape of the BOLD impulse response. By defining a time window including a cognitive event, one can use spatio-temporal fMRI observations from two cognitive states to train the SVM. During the training, the SVM finds the discriminating pattern between the two states and produces a discriminating weight vector encompassing both voxels and time (i.e., spatio-temporal maps). We showed that by applying spatio-temporal SVM to an event-related mental rotation experiment, it is possible to discriminate between different degrees of angular disparity (0 degrees vs. 20 degrees , 0 degrees vs. 60 degrees , and 0 degrees vs. 100 degrees ), and the discrimination accuracy is correlated with the difference in angular disparity between the conditions. For the comparison with highest accuracy (0 degrees vs. 100 degrees ), we evaluated how the most discriminating areas (visual regions, parietal regions, supplementary, and premotor areas) change their behavior over time. The frontal premotor regions became highly discriminating earlier than the superior parietal cortex. There seems to be a parcellation of the parietal regions with an earlier discrimination of the inferior parietal lobe in the mental rotation in relation to the superior parietal. The SVM also identified a network of regions that had a decrease in BOLD responses during the 100 degrees condition in relation to the 0 degrees condition (posterior cingulate, frontal, and superior temporal gyrus). This network was also highly discriminating between the two conditions. In addition, we investigated changes in functional connectivity between the most discriminating areas identified by the spatio-temporal SVM. We observed an increase in functional connectivity between almost all areas activated during the 100 degrees condition (bilateral inferior and superior parietal lobe, bilateral premotor area, and SMA) but not between the areas that showed a decrease in BOLD response during the 100 degrees condition.     

Motor imagery in normal subjects and in asymmetrical Parkinson's disease: a PET study

OBJECTIVE: To investigate, using PET and H2(15)O, brain activation abnormalities of patients with PD during motor imagery. To determine whether motor imagery activation patterns depend on the hand used to complete the task. BACKGROUND: Previous work in PD has shown that bradykinesia is associated with slowness of motor imagery. METHODS: The PET study was performed in eight patients with PD with predominantly right-sided akinesia, and in eight age-matched control subjects, all right-handed. Regional cerebral blood flow was measured by PET and H2(15)O while subjects imagined a predetermined unimanual externally cued sequential movement with a joystick with either the left or the right hand, and during a rest condition. RESULTS: In normal subjects, the prefrontal cortex, supplementary motor area (SMA), superior parietal lobe, inferior frontal gyrus, and cerebellum were activated during motor imagery with either the left or the right hand. Contralateral primary motor cortex activation was noted only when the task was imagined with the right (dominant) hand, whereas activation of the dorsolateral prefrontal cortex was observed only during imagery with the left hand. In patients with PD, motor imagery with the right ("akinetic") hand was characterized by lack of activation of the contralateral primary sensorimotor cortex and the cerebellum, persistent activation of the SMA, and bilateral activation of the superior parietal cortex. Motor imagery with the left ("non-akinetic") hand was also abnormal, with lack of activation of the SMA compared with controls. CONCLUSIONS: In patients with PD with predominantly right-sided akinesia, brain activation during motor imagery is abnormal and may appear even with the less affected hand. In normal subjects, brain activation during motor imagery depends on the hand used in the imagined movement.     

Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study.

Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.     

Globus pallidus stimulation reduces frontal hyperactivity in tardive dystonia.

Tardive dystonia (TD) is a disabling disorder induced by neuroleptics. Internal globus pallidus (GPi) stimulation can dramatically improve TD. The present positron emission tomography and H(2)(15)O study aimed to characterize the abnormalities of brain activation of TD and the impact of GPi stimulation on these abnormalities in five TD patients treated with GPi stimulation and eight controls. Changes of regional cerebral blood flow (rCBF) were determined: (i) at rest; (ii) when moving a joystick with the right hand in three freely chosen directions in on and off bilateral GPi stimulation. A significant increase of rCBF was found in TD patients in off-stimulation condition compared to controls: (1) during motor execution in the prefrontal, premotor lateral, and anterior cingulate cortex; (2) at rest, in the prefrontal and anterior cingulate cortex and the cerebellum. Internal globus pallidus stimulation led to a reduction of rCBF (1) during motor execution, in the primary motor and prefrontal cortex and the cerebellum; (2) at rest, in the primary motor and anterior cingulate cortex and supplementary motor area. The results are as follows: (1) TD is related to an excess of brain activity notably in the prefrontal and premotor areas; (2) GPi stimulation reduces the activation of motor, premotor, and prefrontal cortex as well as cerebellum.     

Activation of cortical and cerebellar motor areas during executed and imagined hand movements: an fMRI study.

Brain activation during executed (EM) and imagined movements (IM) of the right and left hand was studied in 10 healthy right-handed subjects using functional magnetic resonance imagining (fMRI). Low electromyographic (EMG) activity of the musculi flexor digitorum superficialis and high vividness of the imagined movements were trained prior to image acquisition. Regional cerebral activation was measured by fMRI during EM and IM and compared to resting conditions. Anatomically selected regions of interest (ROIs) were marked interactively over the entire brain. In each ROI activated pixels above a t value of 2.45 (p<0.01) were counted and analyzed. In all subjects the supplementary motor area (SMA), the premotor cortex (PMC), and the primary motor cortex (M1) showed significant activation during both EM and IM; the somatosensory cortex (S1) was significantly activated only during EM. Ipsilateral cerebellar activation was decreased during IM compared to EM. In the cerebellum, IM and EM differed in their foci of maximal activation: Highest ipsilateral activation of the cerebellum was observed in the anterior lobe (Larsell lobule H IV) during EM, whereas a lower maximum was found about 2-cm dorsolateral (Larsell lobule H VII) during IM. The prefrontal and parietal regions revealed no significant changes during both conditions. The results of cortical activity support the hypothesis that motor imagery and motor performance possess similar neural substrates. The differential activation in the cerebellum during EM and IM is in accordance with the assumption that the posterior cerebellum is involved in the inhibition of movement execution during imagination.     

Passive tactile recognition of geometrical shape in humans: An fMRI study

Tactile shape discrimination involves frontal other than somatosensory cortex (Palva et al., 2005 [48]), but it is unclear if this frontal activity is related to exploratory concomitants. In this study, we investigated topographical details of prefrontal, premotor, and parietal areas during passive tactile recognition of 2D geometrical shapes in conditions avoiding exploratory movements. Functional magnetic resonance imaging (fMRI) was performed while the same wooden 2D geometrical shapes were blindly pressed on subjects’ passive right palm in three conditions. In the RAW condition, shapes were pressed while subjects were asked to attend to the stimuli but were not trained to recognize them. After a brief training, in the SHAPE condition subjects were asked to covertly recognize shapes. In the RECOGNITION condition, they were asked to overtly recognize shapes, using response buttons with their opposite hand. Results showed that somatosensory cortex including contralateral SII, contralateral SI, and left insula was active in all conditions, confirming its importance in processing tactile shapes. In the RAW vs. SHAPE contrast, bilateral posterior parietal, insular, premotor, prefrontal, and (left) Broca's areas were more active in the latter. In the RECOGNITION, activation of (left) Broca's area correlated with correct responses. These results suggest that, even without exploratory movements, passive recognition of tactile geometrical shapes involves prefrontal and premotor as well as somatosensory regions. In this framework, Broca's area might be involved in a successful selection and/or execution of the correct responses.     

Effects of subthalamic nucleus stimulation on actual and imagined movement in Parkinson's disease : a PET study

BACKGROUND: PET studies in moderately affected Parkinson's disease (PD) patients reveal abnormal cerebral activation during motor execution and imagery, but the effects of subthalamic nucleus (STN) stimulation are not well established. OBJECTIVES: to assess the effect of STN stimulation on cerebral activation during actual and imagined movement in patients with advanced PD. METHODS: seven severely affected PD patients treated with bilateral STN stimulation were studied with PET and H(2)(15)O. The following conditions were investigated: (1). rest; (2). motor execution of a sequential predefined joystick movement with the right hand and (3). motor imagery of the same task. Patients were studied with and without left STN stimulation while right stimulator remained off. RESULTS: Without STN stimulation, the primary motor cortex was activated only during motor execution whereas the dorsolateral prefrontal cortex (DLPFC) was activated only during motor imagery. An activation of the supplementary motor area (SMA) was seen during both motor execution and motor imagery. Left STN stimulation during motor execution increased the regional cerebral blood flow (rCBF) bilaterally in the prefrontal cortex including DLPFC, in the left thalamus and putamen. In addition, a reduction of rCBF was noted in the right primary motor cortex, inferior parietal lobe and SMA. Under left STN stimulation, during motor imagery, rCBF increased bilaterally in the DLPFC and in the left thalamus and putamen and decreased in the left SMA and primary motor cortex. CONCLUSION: STN stimulation during both motor execution and imagery tends to improve the functioning of the frontal-striatal-thalamic pathway and to reduce the recruitment of compensatory motor circuits notably in motor, premotor and parietal cortical areas.     

Functional neuroanatomy of sustained attention in schizophrenia: contribution of parietal cortices

Deficits in sustained attention have been frequently described in schizophrenia. The neuroanatomical basis reported previously have included altered levels of activation in cingulate and prefrontal cortex, but the contribution of further regions remains unclear. We explored the full neuroanatomy underlying the sustained attentional deficits observed in naïve schizophrenics compared with controls. Participants included 10 controls and 11 patients. The experimental design included rest, auditory stimulation using clicks, and two counting tasks. Subjects were instructed to mentally count the clicks, and then to count forward at the same frequency they heard previously when listening to the clicks. Relative cerebral blood flow (relCBF) was measured by means of PET ¹⁵O‐water. Differences were observed between both groups at superior temporal cortex, superior parietal gyrus, and cerebellum during tasks requiring listening. During all counting conditions, additionally to supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPCF), precentral gyrus, cingulate, cerebellum, and inferior parietal (IP) gyrus, patients engaged other frontal structures including inferior, medial, and superior frontal areas. When counting with no auditory stimulation (C; requires components of working memory and time estimation), significant differences were observed in the level of activation of frontal and IP regions. Our naïve patients presented abnormal activation of auditory associative pathways. They failed to activate prefrontal and parietal regions at a similar level during tasks requiring increased cognitive effort, and they required a higher activation of inferior frontal regions to properly respond to cognitive demands. Hum. Brain Mapping 17:116–130, 2002. © 2002 Wiley‐Liss, Inc.     

Differences between actual and imagined usage of chopsticks: an fMRI study

We examined neural basis underlying tool-use behavior to discuss whether or not the usage of a well-learned tool has a specific route. Regional cerebral blood flow was measured in healthy Japanese subjects using functional magnetic resonance imaging (fMRI) during object pick-up using chopsticks, object pick-up using the hand, pantomiming the use of chopsticks, imagining the use of chopsticks, and imagining the use of the hand. First, the left inferior parietal lobule (IPL) was found to selectively contribute to tasks requiring explicit retrieval of tool-related hand movements that were pantomiming task and imagery task. This finding provides supporting evidence for the ideomotor apraxia (IMA) model proposed by Buxbaum (2001). However, departing from Buxbaum's (2001) proposal, the actual use of a well-learned tool displays distinct processing routes to those for pantomime and imagining. A comparison of these tasks revealed that activation in the lateral part of the right cerebellum increased during execution of tool-use, and this activity was considered to reflect the internal model for tools proposed by Imamizu et al. (2000, 2003).