Lateral Premotor Cortex Research Articles

The functional neuroanatomy of tourette's syndrome: An FDG-PET study. II: Relationships between regional cerebral metabolism and associated behavioral and cognitive features of the illness

We analyzed F-18 fluoro-deoxyglucose PET scans carried out in 18 drug-free patients with Tourette's syndrome (TS) in order to evaluate relationships between cerebral metabolism and complex cognitive and behavioural features commonly associated with this disorder. These features (obsessions and compulsions, impulsivity, coprolalia, self-injurious behavior, echophenomena, depression, and measures of attentional and visuospatial dysfunction) were associated with significant increases in metabolic activity in the orbitofrontal cortices. Similar increases, although less robust, were observed in the putamen and, in the case of attentional and visuospatial measures, in the inferior portions of the insula. On the other hand, behavioral and cognitive features were not associated with metabolic rates in other subcortical (midbrain, ventral striatum), paralimbic (parahippocampal gyrus), or sensorimotor regions (supplementary motor area, lateral premotor or Rolandic cortices), in which metabolism had, in some cases more robustly, distinguished these TS patients from controls (Braun et al., 1993). These results suggest that a subset of regions in which metabolic activity appears to be associated with the diagnosis of TS per se, may be explicitly associated with the emergence of complex behavioral and cognitive features of the illness. This is most conspicuous in the orbitofrontal cortices, and it is consistent with the observation that these features resemble the elements of a behavioral syndrome typically seen in patients with lesions of the orbitofrontal cortex.

Motor reorganization in acquired hemidystonia.

Regional cerebral blood flow (rCBF) was measured with H2(15)O positron emission tomography in 5 patients with acquired hemidystonia (AHD) due to structural lesions of the basal ganglia or posterior thalamus contralateral to the dystonic limb. Patients were scanned at rest and when performing paced joystick movements in freely chosen directions with the dystonic and then the unaffected arm. Findings were compared with those of 5 age-matched controls performing joystick movements with the right arm. At rest, there was decreased activity in ventroanterior thalamus, posterior thalamus, angular gyrus ipsilateral to the lesion, and bilateral frontoorbital cortex. At a similar level of significance, increased resting activity was found in lentiform nucleus, hippocampus, and anterior insula contralateral to the lesion. Using the affected arm, AHD cases showed significant overactivity of contralateral prefrontal, lateral premotor cortex, rostral supplementary motor area, anterior cingulate area 32, bilateral sensorimotor cortex (SMC) and insula, mesial parietal cortex, and ipsilateral cerebellum. There was similar frontal overactivity when the unaffected arm performed the joystick movements, though SMC and insula overactivity was contralateral rather than bilateral. The associated frontal overactivity on movement is consistent with acquired dystonia being a syndrome of thalamofrontal disinhibition due to structural disruption of basal ganglia inhibitory control. Our findings also suggest that cortical activation during movement of the unaffected limb is abnormal in acquired hemidystonia.

Overactive prefrontal and underactive motor cortical areas in idiopathic dystonia

Regional cerebral blood flow was measured using H2(15)O and positron emission tomography in a group of 6 patients with idiopathic torsion dystonia and in a group of 6 control subjects. Subjects were scanned while at rest and when performing paced joystick movements in freely chosen directions with the right hand. Patients with idiopathic torsion dystonia showed significant overactivity in the contralateral lateral premotor cortex, rostral supplementary motor area, Brodmann area 8, anterior cingulate area 32, ipsilateral dorsolateral prefrontal cortex, and bilateral lentiform nucleus. Significant underactivity was found in the caudal supplementary motor area, bilateral sensorimotor cortex, posterior cingulate, and mesial parietal cortex. These results are consistent with inappropriate overactivity of striatofrontal projections and impaired activity of motor executive areas in idiopathic torsion dystonia and may explain the simultaneous dystonic posturing and bradykinesia evident in these patients.

Functional anatomy of the mental representation of upper extremity movements in healthy subjects.

1. Differences in the distribution of relative regional cerebral blood flow during motor imagery and execution of a joy-stick movement were investigated in six healthy volunteers with the use of positron emission tomography (PET). Both tasks were compared with a common baseline condition, motor preparation, and with each other. Data were analyzed for individual subjects and for the group, and areas of significant flow differences were related to anatomy by magnetic resonance imaging (MRI). 2. Imagining movements activated a number of frontal and parietal regions: medial and lateral premotor areas, anterior cingulate areas, ventral opercular premotor areas, and parts of superior and inferior parietal areas were all activated bilaterally when compared with preparation to move. 3. Execution of movements compared with imagining movements led to additional activations of the left primary sensorimotor cortex and adjacent areas: dorsal parts of the medial and lateral premotor cortex; adjacent cingulate areas; and rostral parts of the left superior parietal cortex. 4. Functionally distinct rostral and caudal parts of the posterior supplementary motor area (operationally defined as the SMA behind the coronal plane at the level of the anterior commissure) were identified. In the group, the rostral part of posterior SMA was activated by imagining movements, and a more caudoventral part was additionally activated during their execution. A similar dissociation was observed in the cingulate areas. Individual subjects showed that the precise site of these activations varied with the individual anatomy; however, a constant pattern of preferential activation within separate but adjacent gyri of the left hemisphere was preserved. 5. Functionally distinct regions were also observed in the parietal lobe: the caudal part of the superior parietal cortex [medial Brodmann area (BA) 7] was activated by imagining movements compared with preparing to execute them, whereas the more rostral parts of the superior parietal lobe (BA 5), mainly on the left, were additionally activated by execution of the movements. 6. Within the operculum, three functionally distinct areas were observed: rostrally, prefrontal areas (BA 44 and 45) were more active during imagined than executed movements; a ventral premotor area (BA 6) was activated during both imagined and executed movements; and more caudally in the parietal lobe, an area was found that was mainly activated by execution presumably SII. 7. These data suggest that imagined movements can be viewed as a special form of "motor behavior' that, when compared with preparing to move, activate areas associated heretofore with selection of actions and multisensory integration.(ABSTRACT TRUNCATED AT 400 WORDS)

Self-initiated versus externally triggered movements. I. An investigation using measurement of regional cerebral blood flow with PET and movement-related potentials in normal and Parkinson's disease subjects.

We investigated the functional anatomy of self-initiated and externally triggered movements. Six patients with Parkinson's disease off medication and six age-matched normals were assessed. All subjects had regional cerebral blood flow (rCBF) measurement with PET and recording of movement-related cortical potentials (MRPs) from frontal (F), fronto-central (FC), central (C) and parietal (P) sites to obtain measures of the Bereitschaftspotential (BP). The tasks were (i) self-initiated extension of the right index finger on average once every 3 s, (ii) externally triggered finger extension with the rate yoked to the self-initiated task, and (iii) rest condition with tones presented at a rate yoked with the self-initiated task. For the self-initiated movements, the amplitude of the early and peak BP were lower in Parkinson's disease relative to normals. For the externally triggered movements, the patients and the normals did not differ on any of the measures of cortical negativity prior to movement. For both groups, the late and peak BP components, but not the early component, had a lower amplitude in the externally triggered than the self-initiated movements. In normals, the left primary sensorimotor cortex, the supplementary motor area bilaterally, anterior cingulate, the lateral premotor cortex bilaterally, the insular cortex bilaterally, the left thalamus and the left putamen, parietal area 40 bilaterally and the right dorsolateral prefrontal cortex (DLPFC) were significantly activated during the self-initiated movements relative to rest. For the normals, greater activation of the right DLPFC during the self-initiated movements was the only area that significantly differentiated them from the externally triggered movements. When Parkinson's disease patients and normals were compared for the self-initiated movements relative to rest, normals showed greater activation of the supplementary motor area and anterior cingulate, left putamen, left insular cortex, right DLPFC and right parietal area 40. When the groups were compared for the externally triggered movements relative to rest, the global pattern of blood flow and rCBF change in the two groups did not differ, confirming the absence of group differences in BPs for the externally triggered movements. During the self-initiated movements, the lower amplitude of the early BP in patients with Parkinson's disease as well as the underactivation of the supplementary motor area relative to normals support the premises that (i) the supplementary motor area contributes to the early BP, and (ii) the deficit is self-initiated movements in Parkinson's disease is due to supplementary motor area underactivation. The DLPFC is activated in situations requiring non-routine decision making as in the self-initiated movements.

Transcallosal connections of the distal forelimb representations of the primary and supplementary motor cortical areas in macaque monkeys.

The goal of the present neuroanatomical study in macaque monkeys was twofold: (1) to clarify whether the hand representation of the primary motor cortex (M1) has a transcallosal projection to M1 of the opposite hemisphere; (2) to compare the topography and density of transcallosal connections for the hand representations of M1 and the supplementary motor area (SMA). The hand areas of M1 and the SMA were identified by intracortical microstimulation and then injected either with retrograde tracer substances in order to label the neurons of origin in the contralateral motor cortical areas (four monkeys) or, with an anterograde tracer, to establish the regional distribution and density of terminal fields in the opposite motor cortical areas (two monkeys). The main results were: (1) The hand representation of M1 exhibited a modest homotopic callosal projection, as judged by the small number of labeled neurons within the region corresponding to the contralateral injection. A modest heterotopic callosal projection originated from the opposite supplementary, premotor, and cingulate motor areas. (2) In contrast, the SMA hand representation showed a dense callosal projection to the opposite SMA. The SMA was found to receive also dense heterotopic callosal projections from the contralateral rostral and caudal cingulate motor areas, moderate projections from the lateral premotor cortex, and sparse projections from M1. (3) After injection of an anterograde tracer (biotinylated dextran amine) in the hand representation of M1, only a few small patches of axonal label were found in the corresponding region of M1, as well as in the lateral premotor cortex; virtually no label was found in the SMA or in cingulate motor areas. Injections of the same anterograde tracer in the hand representation of the SMA, however, resulted in dense and widely distributed axonal terminal fields in the opposite SMA, premotor cortex, and cingulate motor areas, while labeled terminals were clearly less dense in M1. It is concluded that the hand representations of the SMA and M1 strongly differ with respect to the strength and distribution of callosal connectivity with the former having more powerful and widespread callosal connections with a number of motor fields of the opposite cortex than the latter. These anatomical results support the proposition of the SMA being a bilaterally organized system, possibly contributing to bimanual coordination.

Motor sequence learning: a study with positron emission tomography

We have used positron emission tomography to study the functional anatomy of motor sequence learning. Subjects learned sequences of keypresses by trial and error using auditory feedback. They were scanned with eyes closed under three conditions: at rest, while performing a sequence that was practiced before scanning until overlearned, and while learning new sequences at the same rate of performance. Compared with rest, both sequence tasks activated the contralateral sensorimotor cortex to the same extent. Comparing new learning with performance of the prelearned sequence, differences in activation were identified in other areas. (1) Prefrontal cortex was only activated during new sequence learning. (2) Lateral premotor cortex was significantly more activated during new learning, whereas the supplementary motor area was more activated during performance of the prelearned sequence. (3) Activation of parietal association cortex was present during both motor tasks, but was significantly greater during new learning. (4) The putamen was equally activated by both conditions. (5) The cerebellum was activated by both conditions, but the activation was more extensive and greater in degree during new learning. There was an extensive decrease in the activity of prestriate cortex, inferotemporal cortex, and the hippocampus in both active conditions, when compared with rest. These decreases were significantly greater during new learning. We draw three main conclusions. (1) The cerebellum is involved in the process by which motor tasks become automatic, whereas the putamen is equally activated by sequence learning and retrieval, and may play a similar role in both. (2) When subjects learn new sequences of motor actions, prefrontal cortex is activated. This may reflect the need to generate new responses. (3) Reduced activity of areas concerned with visual processing, particularly during new learning, suggests that selective attention may involve depressing the activity of cells in modalities that are not engaged by the task.

The Functional Neuroanatomy of Tourette's Syndrome: An FDG-PET Study. I. Regional Changes in Cerebral Glucose Metabolism Differentiating Patients and Controls

Regional metabolic rates for glucose estimated using [18F]fluorodeoxyglucose positron-emission tomography were compared in 16 drug-free patients with Tourette's syndrome (TS) and 16 age- and sex-matched normal volunteers. Tourette's syndrome patients were characterized by decreased normalized metabolic rates in paralimbic and ventral prefrontal cortices, particularly in orbitofrontal, inferior insular, and parahippocampal regions. Similar decreases were observed in subcortical regions, including the ventral striatum (nucleus accumbens/ventromedial caudate) and in the midbrain. These changes were more robust and occurred with greater frequency in the left hemisphere. They were associated with concomitant bilateral increases in metabolic activity the supplementary motor, lateral premotor, and Rolandic cortices. Effects of prior exposure to neuroactive drugs did not account for these findings. These results suggest that an altered relationship between limbic-related regions of the cortex and striatum and cortical regions involved in the initiation of movement may play a role in the pathogenesis of this illness.

Cortical function in amyotrophic lateral sclerosis. A positron emission tomography study.

Positron emission tomography was used to measure regional cerebral blood flow (rCBF) in 12 patients with amyotrophic lateral sclerosis (ALS) and six age-matched controls. Scans were performed at rest, and while subjects performed stereotyped and freely selected movements of a joystick with their right hand. Statistical parametric mapping was used to determine significant differences in rCBF between the two groups at rest and during activation. The ALS group showed no significant difference in global cerebral blood flow at rest compared with controls. However, rCBF at rest was significantly (P < 0.01) reduced in the ALS group in the primary sensorimotor cortex, the lateral premotor cortex, the supplementary motor area, the anterior cingulate cortex, the paracentral lobule and the superior and inferior parietal cortex. Comparison of the increase in rCBF caused by freely selected joystick movements over the resting state between the two groups of subjects showed significantly (P < 0.001) greater activation in ALS patients in the ventral third (face area) of the contralateral primary sensorimotor cortex and in the adjacent contralateral ventral premotor and parietal association cortices; significantly (P < 0.01) greater activation of the contralateral anterior insula and the ipsilateral anterior cingulate cortex (dorso-caudal area 24) was also present in ALS patients. When a comparison of the rCBF response to the free selection task with that to the stereotyped task was performed between the two groups of subjects, ALS patients showed significantly impaired (P < 0.01) activation of the rostral anterior cingulate cortex (area 32), medial prefrontal cortex (area 10), left parahippocampal gyrus and retrosplenial cortex. The pattern of reduced rCBF at rest in ALS patients probably reflects a combination of neuronal loss in all areas of cortex projecting through the pyramidal tract together with loss of projections from the sensorimotor cortex to the motor association areas. The expansion of the upper limb output zone of the sensorimotor cortex in ALS patients during contralateral upper limb movement may represent cortical reorganization in response to Betz cell loss or corticospinal tract disruption. Abnormal recruitment of non-primary motor areas may also represent functional adaptation to a corticospinal tract lesion. Focally impaired activation of the medial prefrontal cortex and parahippocampal gyrus in ALS patients during the process of internal generation of movement could underlie the frontal lobe cognitive deficits reported in previous neuropsychological studies of ALS.

Intracranial Recordings of Movement-Related Potentials to Voluntary Saccades

Movement-related potentials evoked by voluntary and self-initiated horizontal saccades were recorded from subdural electrodes placed over the lateral (premotor and motor cortex) and the mesial (supplementary motor area) surfaces of the frontal lobe, in four patients with intractable focal seizures. An extremely localized bereitschaftspotential showing approximately the same latencies and amplitudes was simultaneously recorded from the frontal eye field and supplementary motor area (SMA). Our data suggest that both regions are equally active prior to saccades and do not support the view that the SMA acts as a supramotor cortex, being activated during the planning of the movement and the primary motor cortex only later on, close to the execution of the movement. In addition, we never observed the spike potential in our intracranial recordings, thus supporting the hypothesis of its extracerebral origin.

Cortical and subcortical afferent connections of the squirrel monkey's (lateral) premotor cortex: evidence for visual cortical afferents.

The afferent connections of the squirrel monkey's lateral premotor cortex were investigated with the horseradish peroxidase (HRP) technique. Seven monkeys received small, unilateral injections of HRP spaced between the most dorsal and the most lateral region of the premotor cortex. Results are based on six brains, all of which showed a considerable number of labeled neurons both cortically and subcortically. At the cortical level, labeled cells were found both ipsi- and contralateral to the injection site. Heavy labeling occurred in the fields surrounding the prefrontal, central, and precentral cortex, while the temporal regions usually innervated the premotor cortex with a moderate number of cells, and the parietal fields with only a minor number. Surprisingly, in all brains, but especially in those with the more lateral injections, we also found a considerable number of afferents originating from occipital fields, including a few neurons from the striate cortex. Subcortically, a few labeled cells were seen in basal forebrain regions, the amygdala, and the claustrum; a considerable number of thalamic nuclei and also some hypothalamic nuclei contained labeled cells; and within the brainstem, labeling was found most consistently in the locus ceruleus and in the tegmental fields. It is concluded that the (lateral) premotor cortex is involved in sensorimotor integration to a higher degree than has been recognized up to now.

Movement-related brain potentials in various body positions

Previous studies have demonstrated that cortical potentials representing motor preparation for visually-cued movements are enhanced following a single session of visually-cued bimanual movement training (BMT). The neuroanatomical sources that contribute to these rapid training-induced adaptations were unclear. To address this, we compared cortical potentials associated with motor preparation for visually-cued (movement-related potential, MRP) and self-paced (Bereitschaftspotential, BP) movements and investigated adaptations of these following BMT.EEG recorded the cued MRP and self-paced BP during two experiments. In experiment one, pre and post self-paced unimanual trials were interspersed with cued inphase BMT. In experiment two, self-paced and visually-cued movement trials were performed to assess the differences between and the contributing neural sources to the cued MRP and self-paced BP.Inphase BMT does not affect the early BP. Source localization analysis revealed that the preparatory portion of the cued MRP and self-paced BP are generated by the lateral premotor cortex and the supplementary motor area, respectively.The early cued MRP and self-paced BP have unique cortical generators and are independently modulated by specific training types.These novel findings have implications for interpreting rapid, single-session, training adaptations previously observed. These cortical potentials may also be useful measurement tools to gauge within-session cortical modulations in response to specific modes of rehabilitative training in the stroke population.

Arterial supply of the feline motor cortex.

The arterial supply of the feline motor cortex is derived from both the anterior and middle cerebral arteries. The anterior cerebral artery supplies most of cortical area 6 (premotor cortex), the intrafundal cruciate and medial postcruciate cortex, (hindlimb motor cortex), and the midline and medial portions of the sensory areas 3a-7. The middle cerebral artery supplies the lateral prorean cortex, (lateral premotor cortex), precruciate and lateral sigmoid cortex, (forelimb motor cortex), and the remainder of the coronal and Sylvian cortical areas.