Superior Premotor Cortex Research Articles

P143 Navigated transcranial magnetic stimulation of premotor cortex and long latency responses elicited in hand muscles during handwriting

Introduction The nTMS technique is often used in preoperative mapping of motor, speech and language related cortical areas in patients undergoing neurosurgical operation. Only few intraoperative studies investigated network underlying the production of written language and found that the superior premotor cortices close to the superior frontal sulcus was involved in handwritten production of words. The nTMS methodology for identification of the motor frontal areas involved in handwriting that can be used in preoperative mapping of patients is not yet established. Objectives To evaluate for the first time the feasibility of patterned rTMS protocol for locating premotor writing function in healthy volunteers. Materials & methods The ten healthy and right-handed volunteers (three female, and seven males, mean age 40.2 ± 11.17 (range 24–63 years) underwent rTMS of the left primary motor cortex (M1) and superior premotor cortices including the posterior part of superior and middle frontal gyri. Patterned bursts of rTMS consisted of 4 bursts of 4 stimuli each, with an interstimulus interval of 6 ms, and a burst repetition rate of 4 Hz were applied during writing to a dictation task and with EMG recording from right APB and FDI muscles. Two trains of these rTMS bursts were applied in a single trial, therefore after auditory presenting the sentence two rTMS trains (separated 2–7 s depending on the length of sentence) were given while the participant was writing with the pen. Results The rTMS of the left superior premotor cortex close to the superior frontal sulcus elicited long latency responses (LLRs) from the hand muscles with the latency of 70.72 ± 8.25 ms followed by MEPs (Fig. 1), as well as writing related disturbances (writing arrest, trembling, poor grapheme production, slow writing, lifting of the hand). Conclusion The application of rTMS to the premotor cortex close to superior frontal sulcus elicited writing interferences and LLR responses that were recorded in dominant hand muscle during writing. Further rTMS studies would be needed to clarify an exact neurophysiologic mechanism of LLR generation in hand muscles during voluntary writing task, as well as during different voluntary motor tasks. Although still preliminary, the results might have clinical value for preoperative use of rTMS in functional mapping of writing. Download high-res image (211KB) Download full-size image

How specialized are writing-specific brain regions? An fMRI study of writing, drawing and oral spelling

Several brain imaging studies identified brain regions that are consistently involved in writing tasks; the left premotor and superior parietal cortices have been associated with the peripheral components of writing performance as opposed to other regions that support the central, orthographic components. Based on a meta-analysis by Planton, Jucla, Roux, and Demonet (2013), we focused on five such writing areas and questioned the task-specificity and hemispheric lateralization profile of the brain response in an functional magnetic resonance imaging (fMRI) experiment where 16 right-handed participants wrote down, spelled out orally object names, and drew shapes from object pictures. All writing-related areas were activated by drawing, and some of them by oral spelling, thus questioning their specialization for written production. The graphemic/motor frontal area (GMFA), a subpart of the superior premotor cortex close to Exner's area (Roux et al., 2009), was the only area with a writing-specific lateralization profile, that is, clear left lateralization during handwriting, and bilateral activity during drawing. Furthermore, the relative lateralization and levels of activation in the superior parietal cortex, ventral premotor cortex, ventral occipitotemporal cortex and right cerebellum across the three tasks brought out new evidence regarding their respective contributions to the writing processes.

Resting state default mode network connectivity in children and adolescents with ADHD after acute tryptophan depletion.

Alterations of the default mode network (DMN) have been described in patients with neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), and the neurotransmitter serotonin (5-HT) is known to modulate DMN activity. This study aimed to explore the role of 5-HT on the DMN and its functional connectivity (FC) in young patients with ADHD. Young male patients with ADHD (n=12) and healthy controls (n=10) (both aged 12-17years) were subjected to acute tryptophan depletion (ATD) and subsequently diminished brain 5-HT synthesis. Three hours after challenge intake (ATD or a balanced control condition, BAL), resting state fMRI scans were obtained. In patients, ATD led to attenuated FC of the right superior premotor cortex (BA 6) with the DMN, comparable to the extent found in controls after BAL administration. ATD lowered FC of the left somatosensory cortex (BA 3) with the DMN, independently of the factor group, but with stronger effects in controls. Data reveal a serotonergic modulation of FC between BA 6 and 3, known to be relevant for motor planning and sensory perception, and the DMN, thereby possibly pointing toward ATD acting beneficially on neural planning of motor activity in patients with ADHD.

Speech motor brain regions are differentially recruited during perception of native and foreign-accented phonemes for first and second language listeners.

Brain imaging studies indicate that speech motor areas are recruited for auditory speech perception, especially when intelligibility is low due to environmental noise or when speech is accented. The purpose of the present study was to determine the relative contribution of brain regions to the processing of speech containing phonetic categories from one's own language, speech with accented samples of one's native phonetic categories, and speech with unfamiliar phonetic categories. To that end, native English and Japanese speakers identified the speech sounds /r/ and /l/ that were produced by native English speakers (unaccented) and Japanese speakers (foreign-accented) while functional magnetic resonance imaging measured their brain activity. For native English speakers, the Japanese accented speech was more difficult to categorize than the unaccented English speech. In contrast, Japanese speakers have difficulty distinguishing between /r/ and /l/, so both the Japanese accented and English unaccented speech were difficult to categorize. Brain regions involved with listening to foreign-accented productions of a first language included primarily the right cerebellum, left ventral inferior premotor cortex PMvi, and Broca's area. Brain regions most involved with listening to a second-language phonetic contrast (foreign-accented and unaccented productions) also included the left PMvi and the right cerebellum. Additionally, increased activity was observed in the right PMvi, the left and right ventral superior premotor cortex PMvs, and the left cerebellum. These results support a role for speech motor regions during the perception of foreign-accented native speech and for perception of difficult second-language phonetic contrasts.

The evolution of primary progressive apraxia of speech.

Primary progressive apraxia of speech is a recently described neurodegenerative disorder in which patients present with an isolated apraxia of speech and show focal degeneration of superior premotor cortex. Little is known about how these individuals progress over time, making it difficult to provide prognostic estimates. Thirteen subjects with primary progressive apraxia of speech underwent two serial comprehensive clinical and neuroimaging evaluations 2.4 years apart [median age of onset = 67 years (range: 49-76), seven females]. All underwent detailed speech and language, neurological and neuropsychological assessments, and magnetic resonance imaging, diffusion tensor imaging and (18)F-fluorodeoxyglucose positron emission tomography at both baseline and follow-up. Rates of change of whole brain, ventricle, and midbrain volumes were calculated using the boundary-shift integral and atlas-based parcellation, and rates of regional grey matter atrophy were assessed using tensor-based morphometry. White matter tract degeneration was assessed on diffusion-tensor imaging at each time-point. Patterns of hypometabolism were assessed at the single subject-level. Neuroimaging findings were compared with a cohort of 20 age, gender, and scan-interval matched healthy controls. All subjects developed extrapyramidal signs. In eight subjects the apraxia of speech remained the predominant feature. In the other five there was a striking progression of symptoms that had evolved into a progressive supranuclear palsy-like syndrome; they showed a combination of severe parkinsonism, near mutism, dysphagia with choking, vertical supranuclear gaze palsy or slowing, balance difficulties with falls and urinary incontinence, and one was wheelchair bound. Rates of whole brain atrophy (1.5% per year; controls = 0.4% per year), ventricular expansion (8.0% per year; controls = 3.3% per year) and midbrain atrophy (1.5% per year; controls = 0.1% per year) were elevated (P ≤ 0.001) in all 13, compared to controls. Increased rates of brain atrophy over time were observed throughout the premotor cortex, as well as prefrontal cortex, motor cortex, basal ganglia and midbrain, while white matter tract degeneration spread into the splenium of the corpus callosum and motor cortex white matter. Hypometabolism progressed over time in almost all subjects. These findings demonstrate that some subjects with primary progressive apraxia of speech will rapidly evolve and develop a devastating progressive supranuclear palsy-like syndrome ∼ 5 years after onset, perhaps related to progressive involvement of neocortex, basal ganglia and midbrain. These findings help improve our understanding of primary progressive apraxia of speech and provide some important prognostic guidelines.

Spatial and temporal relationships of electrocorticographic alpha and gamma activity during auditory processing

Neuroimaging approaches have implicated multiple brain sites in musical perception, including the posterior part of the superior temporal gyrus and adjacent perisylvian areas. However, the detailed spatial and temporal relationship of neural signals that support auditory processing is largely unknown. In this study, we applied a novel inter-subject analysis approach to electrophysiological signals recorded from the surface of the brain (electrocorticography (ECoG)) in ten human subjects. This approach allowed us to reliably identify those ECoG features that were related to the processing of a complex auditory stimulus (i.e., continuous piece of music) and to investigate their spatial, temporal, and causal relationships. Our results identified stimulus-related modulations in the alpha (8–12Hz) and high gamma (70–110Hz) bands at neuroanatomical locations implicated in auditory processing. Specifically, we identified stimulus-related ECoG modulations in the alpha band in areas adjacent to primary auditory cortex, which are known to receive afferent auditory projections from the thalamus (80 of a total of 15,107 tested sites). In contrast, we identified stimulus-related ECoG modulations in the high gamma band not only in areas close to primary auditory cortex but also in other perisylvian areas known to be involved in higher-order auditory processing, and in superior premotor cortex (412/15,107 sites). Across all implicated areas, modulations in the high gamma band preceded those in the alpha band by 280ms, and activity in the high gamma band causally predicted alpha activity, but not vice versa (Granger causality, p<1e−8). Additionally, detailed analyses using Granger causality identified causal relationships of high gamma activity between distinct locations in early auditory pathways within superior temporal gyrus (STG) and posterior STG, between posterior STG and inferior frontal cortex, and between STG and premotor cortex. Evidence suggests that these relationships reflect direct cortico-cortical connections rather than common driving input from subcortical structures such as the thalamus. In summary, our inter-subject analyses defined the spatial and temporal relationships between music-related brain activity in the alpha and high gamma bands. They provide experimental evidence supporting current theories about the putative mechanisms of alpha and gamma activity, i.e., reflections of thalamo-cortical interactions and local cortical neural activity, respectively, and the results are also in agreement with existing functional models of auditory processing.

Editorial introductions

Editorial introductions

Neuroimaging comparison of primary progressive apraxia of speech and progressive supranuclear palsy

Primary progressive apraxia of speech, a motor speech disorder of planning and programming, is a tauopathy that has overlapping histological features with progressive supranuclear palsy. We aimed to compare, for the first time, atrophy patterns, as well as white matter tract degeneration, between these two syndromes. Sixteen primary progressive apraxia of speech subjects were age- and gender-matched to 16 progressive supranuclear palsy subjects and 20 controls. All subjects were prospectively recruited, underwent neurological and speech evaluations and 3.0-Tesla magnetic resonance imaging. Grey and white matter atrophy was assessed using voxel-based morphometry and atlas-based parcellation, and white matter tract degeneration was assessed using diffusion tensor imaging. All progressive supranuclear palsy subjects had typical oculomotor/gait impairments, but none had speech apraxia. Both syndromes showed grey matter loss in supplementary motor area, white matter loss in posterior frontal lobes and degeneration of the body of the corpus callosum. Whilst lateral grey matter loss was focal, involving superior premotor cortex, in primary progressive apraxia of speech, loss was less focal extending into prefrontal cortex in progressive supranuclear palsy. Caudate volume loss and tract degeneration of superior cerebellar peduncles were also observed in progressive supranuclear palsy. Interestingly, area of the midbrain was reduced in both syndromes compared to controls, although this was greater in progressive supranuclear palsy. Although neuroanatomical differences were identified between these distinctive clinical syndromes, substantial overlap was also observed, including midbrain atrophy, suggesting these two syndromes may have common pathophysiological underpinnings.

Diffusion tensor imaging of freezing of gait in patients with white matter changes

Freezing of gait is a common and disabling symptom of parkinsonism. However, the corresponding anatomic structures have yet to be clearly elucidated. We performed diffusion tensor imaging on 40 subjects with white matter changes. We compared apparent diffusion coefficient values and fraction anisotropy values of 7 candidate anatomic structures between 14 patients with freezing of gait (freezing of gait group) and 26 without freezing of gait (control group). Fraction anisotropy values of the bilateral pedunculopontine nucleus, bilateral superior premotor cortex, right orbitofrontal area, and left supplement motor area were significantly lower in the freezing of gait group than in the control group. In contrast, there were no significant differences in apparent diffusion coefficient values between freezing of gait and control groups. Our findings suggest that the bilateral pedunculopontine nucleus, bilateral superior premotor cortex, right orbitofrontal area, and left supplement motor area are closely related to freezing of gait.

The difference between uni- and bilateral auditory phantom percept

ObjectiveTinnitus can be considered an auditory phantom percept, in which patients hear an internal sound in the absence of any external sound source, mimicking tonal memory. Tinnitus however can be perceived exclusively uni- or bilaterally. MethodsThe neurophysiological differences were investigated between unilateral and bilateral tinnitus using LORETA source localized resting state EEG recordings. ResultsThe difference between unilateral and bilateral tinnitus is reflected by high frequency activity (beta and gamma) in the superior prefrontal gurus, right parahippocampus, right angular gyrus and right auditory cortex. Unilateral tinnitus is characterized by contralateral beta2 in the superior prefrontal gyrus in comparison to bilateral tinnitus, but gamma in comparison to non-tinnitus subjects. Bilateral tinnitus has delta activity in the ventrolateral prefrontal cortex in comparison to unilateral tinnitus, and bilateral beta1 in comparison to non-tinnitus subjects. Bilateral tinnitus is also characterized by bilateral frontopolar beta1 activity. ConclusionsUnilateral and bilateral tinnitus can be differentiated based on their resting state oscillation patterns: beta3 and gamma-band activity in the superior premotor cortex, parahippocampal area and angular gyrus seem to form the core of a spatial localization network involved in tinnitus. SignificanceThese differences should be taken into account when evaluating functional neuroimaging data relating to tinnitus.

TC18B ALTERED CORTICAL THICKNESS IN ADOLESCENTS AND YOUNG ADULTS AT GENETIC RISK FOR SCHIZOPHRENIA

Tinnitus can be considered an auditory phantom percept, in which patients hear an internal sound in the absence of any external sound source, mimicking tonal memory. Tinnitus however can be perceived exclusively uni- or bilaterally.The neurophysiological differences were investigated between unilateral and bilateral tinnitus using LORETA source localized resting state EEG recordings.The difference between unilateral and bilateral tinnitus is reflected by high frequency activity (beta and gamma) in the superior prefrontal gurus, right parahippocampus, right angular gyrus and right auditory cortex. Unilateral tinnitus is characterized by contralateral beta2 in the superior prefrontal gyrus in comparison to bilateral tinnitus, but gamma in comparison to non-tinnitus subjects. Bilateral tinnitus has delta activity in the ventrolateral prefrontal cortex in comparison to unilateral tinnitus, and bilateral beta1 in comparison to non-tinnitus subjects. Bilateral tinnitus is also characterized by bilateral frontopolar beta1 activity.Unilateral and bilateral tinnitus can be differentiated based on their resting state oscillation patterns: beta3 and gamma-band activity in the superior premotor cortex, parahippocampal area and angular gyrus seem to form the core of a spatial localization network involved in tinnitus.These differences should be taken into account when evaluating functional neuroimaging data relating to tinnitus.

Subthalamic nucleus stimulation and dysarthria in Parkinson's disease: a PET study.

In Parkinson's disease, functional imaging studies during limb motor tasks reveal cerebral activation abnormalities that can be reversed by subthalamic nucleus (STN) stimulation. The effect of STN stimulation on parkinsonian dysarthria has not, however, been investigated using PET. The aim of the present study was to evaluate the effect of STN stimulation on regional cerebral blood flow (rCBF) during speech production and silent articulation in patients with Parkinson's disease. Ten Parkinson's disease patients surgically implanted bilaterally in the STN and with significant improvement of their dysarthria induced by STN stimulation were included. Ten healthy control subjects also participated in this study. Control subjects performed six sessions of [15O]H2O-PET scanning corresponding to three duplicated conditions externally cued by an auditory signal. The conditions were: (i) rest; (ii) production of a short, simple sentence; and (iii) silent articulation of the same sentence. Parkinson's disease patients carried out the six PET sessions twice, i.e., in the ON and OFF STN stimulation states. PET data analysis was performed using statistical parametric mapping (SPM99). In control subjects, speech production (SP) compared with rest was associated with increased rCBF bilaterally in the primary motor cortex (M1) corresponding to the orofacial somatotopy, the supplementary motor area (SMA), the associative auditory cortex and the cerebellar hemispheres. Silent articulation (SA) compared with rest induced a bilateral rCBF increase restricted to the orofacial M1 and cerebellar hemispheres. In Parkinson's disease patients in the OFF stimulation condition, during both SP and SA there was a lack of activation in the right orofacial M1 and in the cerebellum, abnormal increased rCBF in the right superior premotor cortex, and overactivation of the SMA. There was also an abnormal, increased rCBF in the dorsolateral prefrontal cortex (DLPFC) only during SP and increased rCBF in the left insula only during SA. In Parkinson's disease patients ON stimulation, for both SP and SA the activation pattern appeared similar to that in control subjects. In conclusion, our results suggest that parkinsonian dysarthria is associated with altered recruitment of the main motor cerebral regions (orofacial M1, cerebellum), and increased involvement of the premotor and prefrontal cortices (DLPFC, SMA, superior premotor cortex). These abnormal activations are different from those reported during hand motor tasks. They could be a compensatory mechanism, but might also arise directly as part of the pathophysiology of Parkinson's disease. STN stimulation tends to reverse these abnormal activations, which is consistent with the observed improvement of Parkinson's disease dysarthria.

Cortical potentials preceding voluntary movement: Evidence for three periods of preparation in man

We have recorded movement-related cortical potentials (MRCPs) to voluntary middle finger extension from 10 young and 10 old subjects free of neurological disease using the method of detecting EMG onset associated with each movement described by Barrett et al. (1985). The slow potential shifts preceding movement were measured by fitting a linear regression line to the wave forms to obtain a measure of their slope. Three separate potential shifts were identified. The first had a scalp distribution and onset latency similar to the Bereitschaftspotential (BP) first reported by Kornhuber and Deecke (1964, 1965). The potential shift immediately preceding movement corresponded with the NS′ of Shibasaki et al. (1980). We identified, for the first time, a third shift intervening between BP and NS′ and named it the intermediate shift (IS). The onset of BP occurred about 1.6 sec before EMG onset and was followed by IS which began about 875 msec before movement. The onset of NS′ occurred 300 msec before EMG onset and0 terminated about 90 msec before this event. The slope of BP preceding right finger movement was steeper than that preceding left hand movement in all our right-handed subjects. The distribution of BP was symmetric about the midline. The IS potential shift had a slope which was steeper on the average preceding left finger movement than right. The distribution of IS was symmetric about the midline preceding left finger movement but had a contralateral tendency preceding right hand movement. NS′ had a maximum slope at contralateral electrodes over the hand motor area and parietal areas. It was suggested that the BP potential shift originates in the supplementary motor area on the medial surface of the cerebral cortex. The differing distribution of the IS shift for the two hands suggests that this potential may be generated bilaterally preceding left finger movement but from the contralateral hemisphere only preceding movement of the right finger. The most likely origin of this potetial was thought to be superior premotor cortex. NS′ was considered to originate in primary motor cortex with possible contributions from other cortical areas associated with movement.