Weight Gain following Pallidal Deep Brain Stimulation: A PET Study

The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi-DBS in patients with Parkinson’s disease (PD). Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040). There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6), left superior gyrus (BA 8), the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46), and the left and right somatosensory association cortices (BA 7). However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067). These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target.     

Pain Modulation in Waking and Hypnosis in Women: Event-Related Potentials and Sources of Cortical Activity

Using a strict subject selection procedure, we tested in High and Low Hypnotizable subjects (HHs and LHs) whether treatments of hypoalgesia and hyperalgesia, as compared to a relaxation-control, differentially affected subjective pain ratings and somatosensory event-related potentials (SERPs) during painful electric stimulation. Treatments were administered in waking and hypnosis conditions. LHs showed little differentiation in pain and distress ratings between hypoalgesia and hyperalgesia treatments, whereas HHs showed a greater spread in the instructed direction. HHs had larger prefrontal N140 and P200 waves of the SERPs during hypnotic hyperalgesia as compared to relaxation-control treatment. Importantly, HHs showed significant smaller frontocentral N140 and frontotemporal P200 waves during hypnotic hypoalgesia. LHs did not show significant differences for these SERP waves among treatments in both waking and hypnosis conditions. Source localization (sLORETA) method revealed significant activations of the bilateral primary somatosensory (BA3), middle frontal gyrus (BA6) and anterior cingulate cortices (BA24). Activity of these contralateral regions significantly correlated with subjective numerical pain scores for control treatment in waking condition. Moreover, multivariate regression analyses distinguished the contralateral BA3 as the only region reflecting a stable pattern of pain coding changes across all treatments in waking and hypnosis conditions. More direct testing showed that hypnosis reduced the strength of the association of pain modulation and brain activity changes at BA3. sLORETA in HHs revealed, for the N140 wave, that during hypnotic hyperalgesia, there was an increased activity within medial, supramarginal and superior frontal gyri, and cingulated gyrus (BA32), while for the P200 wave, activity was increased in the superior (BA22), middle (BA37), inferior temporal (BA19) gyri and superior parietal lobule (BA7). Hypnotic hypoalgesia in HHs, for N140 wave, showed reduced activity within medial and superior frontal gyri (BA9,8), paraippocampal gyrus (BA34), and postcentral gyrus (BA1), while for the P200, activity was reduced within middle and superior frontal gyri (BA9 and BA10), anterior cingulate (BA33), cuneus (BA19) and sub-lobar insula (BA13). These findings demonstrate that hypnotic suggestions can exert a top-down modulatory effect on attention/preconscious brain processes involved in pain perception.     

Lesions to primary sensory and posterior parietal cortices impair recovery from hand paresis after stroke

Background

Neuroanatomical determinants of motor skill recovery after stroke are still poorly understood. Although lesion load onto the corticospinal tract is known to affect recovery, less is known about the effect of lesions to cortical sensorimotor areas. Here, we test the hypothesis that lesions of somatosensory cortices interfere with the capacity to recover motor skills after stroke.

Methods

Standardized tests of motor skill and somatosensory functions were acquired longitudinally over nine months in 29 patients with stroke to the pre- and postcentral gyrus, including adjacent areas of the frontal, parietal and insular cortices. We derived the recovery trajectories of each patient for five motor subtest using least-squares curve fitting and objective model selection procedures for linear and exponential models. Patients were classified into subgroups based on their motor recovery models. Lesions were mapped onto diffusion weighted imaging scans and normalized into stereotaxic space using cost-function masking. To identify critical neuranatomical regions, voxel-wise subtractions were calculated between subgroup lesion maps. A probabilistic cytoarchitectonic atlas was used to quantify of lesion extent and location.

Results

Twenty-three patients with moderate to severe initial deficits showed exponential recovery trajectories for motor subtests that relied on precise distal movements. Those that retained a chronic motor deficit had lesions that extended to the center of the somatosensory cortex (area 2) and the intraparietal sulcus (areas hIP1, hIP2). Impaired recovery outcome correlated with lesion extent on this areas and somatosensory performance. The rate of recovery, however, depended on the lesion load onto the primary motor cortex (areas 4a, 4p).

Conclusions

Our findings support a critical role of uni-and multimodal somatosensory cortices in motor skill recovery. Whereas lesions to these areas influence recovery outcome, lesions to the primary motor cortex affect recovery dynamics. This points to a possible dissociation of neural substrates for different aspects of post-stroke recovery.     

Using Hypnotic Suggestion to Model Loss of Control and Awareness of Movements: An Exploratory fMRI Study

The feeling of voluntary control and awareness of movement is fundamental to our notions of selfhood and responsibility for actions, yet can be lost in neuropsychiatric syndromes (e.g. delusions of control, non-epileptic seizures) and culturally influenced dissociative states (e.g. attributions of spirit possession). The brain processes involved remain poorly understood. We used suggestion and functional magnetic resonance imaging (fMRI) to investigate loss of control and awareness of right hand movements in 15 highly hypnotically suggestible subjects. Loss of perceived control of movements was associated with reduced connectivity between supplementary motor area (SMA) and motor regions. Reduced awareness of involuntary movements was associated with less activation in parietal cortices (BA 7, BA 40) and insula. Collectively these results suggest that the sense of voluntary control of movement may critically depend on the functional coupling of SMA with motor systems, and provide a potential neural basis for the narrowing of awareness reported in pathological and culturally influenced dissociative phenomena.     

Somatic and motor components of action simulation

Seminal studies in monkeys report that the viewing of actions performed by other individuals activates frontal and parietal cortical areas typically involved in action planning and execution. That mirroring actions might rely on both motor and somatosensory components is suggested by reports that action observation and execution increase neural activity in motor and in somatosensory areas. This occurs not only during observation of naturalistic movements but also during the viewing of biomechanically impossible movements that tap the afferent component of action, possibly by eliciting strong somatic feelings in the onlooker. Although somatosensory feedback is inherently linked to action execution, information on the possible causative role of frontal and parietal cortices in simulating motor and sensory action components is lacking. By combining low-frequency repetitive and single-pulse transcranial magnetic stimulation, we found that virtual lesions of ventral premotor cortex (vPMc) and primary somatosensory cortex (S1) suppressed mirror motor facilitation contingent upon observation of possible and impossible movements, respectively. In contrast, virtual lesions of primary motor cortex did not influence mirror motor facilitation. The reported double dissociation suggests that vPMc and S1 play an active, differential role in simulating efferent and afferent components of observed actions.     

Matrix Metalloproteinases in the Neocortex and Spinal Cord of Amyotrophic Lateral Sclerosis Patients

Abstract: Matrix metalloproteinases (MMPs) were analyzed by immunohistochemistry and zymography in amyotrophic lateral sclerosis (ALS) and control brain and spinal cord specimens. Three major bands of enzyme activity (70, 100, and 130 kDa) were consistently observed and were subsequently identified as MMP-2 (70 kDa; also known as EC 3.4.24.24 or gelatinase A) and MMP-9 (100 and 130 kDa; also known as EC 3.4.24.35 or gelatinase B). Immunohistochemical studies established the presence of MMP-2 in astrocytes and MMP-9 in pyramidal neurons in the motor cortex and motor neurons in the spinal cord of ALS patients. Although a significant decrease in MMP-2 activity was noticed in the ALS motor cortex, statistically significant increases in MMP-9 (100-kDa) activity were observed in ALS frontal and occipital cortices (BA10 and 17) and all three spinal cord regions when compared with control specimens. The highest MMP-9 (100-kDa) activities in ALS were found in the motor cortex and thoracic and lumbar cord specimens. The abnormally high amount of MMP-9 and its possible release at the synapse may destroy the structural integrity of the surrounding matrix, thereby contributing to the pathogenesis of ALS.     

Does Shape Discrimination by the Mouth Activate the Parietal and Occipital Lobes? – Near-Infrared Spectroscopy Study

A cross-modal association between somatosensory tactile sensation and parietal and occipital activities during Braille reading was initially discovered in tests with blind subjects, with sighted and blindfolded healthy subjects used as controls. However, the neural background of oral stereognosis remains unclear. In the present study, we investigated whether the parietal and occipital cortices are activated during shape discrimination by the mouth using functional near-infrared spectroscopy (fNIRS). Following presentation of the test piece shape, a sham discrimination trial without the test pieces induced posterior parietal lobe (BA7), extrastriate cortex (BA18, BA19), and striate cortex (BA17) activation as compared with the rest session, while shape discrimination of the test pieces markedly activated those areas as compared with the rest session. Furthermore, shape discrimination of the test pieces specifically activated the posterior parietal cortex (precuneus/BA7), extrastriate cortex (BA18, 19), and striate cortex (BA17), as compared with sham sessions without a test piece. We concluded that oral tactile sensation is recognized through tactile/visual cross-modal substrates in the parietal and occipital cortices during shape discrimination by the mouth.     

Subjective Somatosensory Experiences Disclosed by Focused Attention: Cortical-Hippocampal-Insular and Amygdala Contributions

In order to explore the neurobiological foundations of qualitative subjective experiences, the present study was designed to correlate objective third-person brain fMRI measures with subjective first-person identification and scaling of local, subtle, and specific somatosensory sensations, obtained directly after the imaging procedure. Thus, thirty-four volunteers were instructed to focus and sustain their attention to either provoked or spontaneous sensations of each thumb during the fMRI procedure. By means of a Likert scale applied immediately afterwards, the participants recalled and evaluated the intensity of their attention and identified specific somatosensory sensations (e.g. pulsation, vibration, heat). Using the subject''s subjective scores as covariates to model both attention intensity and general somatosensory experiences regressors, the whole-brain random effect analyses revealed activations in the frontopolar prefrontal cortex (BA10), primary somatosensory cortex (BA1), premotor cortex (BA 6), precuneus (BA 7), temporopolar cortex (BA 38), inferior parietal lobe (BA 39), hippocampus, insula and amygdala. Furthermore, BA10 showed differential activity, with ventral BA10 correlating exclusively with attention (r(32) = 0.54, p = 0.0013) and dorsal BA10 correlating exclusively with somatosensory sensation (r(32) = 0.46, p = 0.007). All other reported brain areas showed significant positive correlations solely with subjective somatosensory experiences reports. These results provide evidence that the frontopolar prefrontal cortex has dissociable functions depending on specific cognitive demands; i.e. the dorsal portion of the frontopolar prefrontal cortex in conjunction with primary somatosensory cortex, temporopolar cortex, inferior parietal lobe, hippocampus, insula and amygdala are involved in the processing of spontaneous general subjective somatosensory experiences disclosed by focused and sustained attention.     

Physiological and pathological oscillatory networks in the human motor system.

Human brain functions are heavily contingent on neural interactions both at the single neuron and the neural population or system level. Accumulating evidence from neurophysiological studies strongly suggests that coupling of oscillatory neural activity provides an important mechanism to establish neural interactions. With the availability of whole-head magnetoencephalography (MEG) macroscopic oscillatory activity can be measured non-invasively from the human brain with high temporal and spatial resolution. To localise, quantify and map oscillatory activity and interactions onto individual brain anatomy we have developed the 'dynamic imaging of coherent sources' (DICS) method which allows to identify and analyse cerebral oscillatory networks from MEG recordings. Using this approach we have characterized physiological and pathological oscillatory networks in the human sensorimotor system. Coherent 8 Hz oscillations emerge from a cerebello-thalamo-premotor-motor cortical network and exert an 8 Hz oscillatory drive on the spinal motor neurons which can be observed as a physiological tremulousness of the movement termed movement discontinuities. This network represents the neurophysiological substrate of a discrete mode of motor control. In parkinsonian resting tremor we have identified an extensive cerebral network consisting of primary motor and lateral premotor cortex, supplementary motor cortex, thalamus/basal ganglia, posterior parietal cortex and secondary somatosensory cortex, which are entrained in the tremor or twice the tremor rhythm. This low frequency entrapment of motor areas likely plays an important role in the pathophysiology of parkinsonian motor symptoms. Finally, studies on patients with postural tremor in hepatic encephalopathy revealed that this type of tremor results from a pathologically slow thalamocortical and cortico-muscular coupling during isometric hold tasks. In conclusion, the analysis of oscillatory cerebral networks provides new insights into physiological mechanisms of motor control and pathophysiological mechanisms of tremor disorders.     

Brain Structural Correlates of Reward Sensitivity and Impulsivity in Adolescents with Normal and Excess Weight

Introduction

Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups.

Methods

Fifty-two adolescents (16 with normal weight and 36 with excess weight) were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM) was used to assess possible between-group differences in regional gray matter (GM) and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI) and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices) and motivation/impulse control (hippocampus, prefrontal cortex).

Results

Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII) were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents.

Conclusion

Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation.     

Tactile stimulation-induced rapid elevation of the synaptophysin mRNA expression level in rat somatosensory cortex

Synaptophysin is an integral membrane protein abundant in the synaptic vesicle and is found in nerve terminals throughout the brain. It was recently suggested that synaptophysin is also involved in the modulation of activity-dependent synapse formation. In this study, we examined at the individual level whether tactile stimulation selectively influenced the synaptophysin mRNA expression level in the somatosensory cortex of rats. Anesthetized rats were caressed on the back by an experimenter's palms for 20 min and the mRNA expression levels in the somatosensory and the visual cortices 5 min afterwards were determined using quantitative PCR methodology. The synaptophysin mRNA expression level was selectively higher in the experimental group than in the control group in the somatosensory cortex but not in the visual cortex. This suggests that the mRNA expression level of synaptophysin induced by neuronal activity is related to the regulation of synapse formation or remodeling or both.     

Independent Mobility Achieved through a Wireless Brain-Machine Interface

Individuals with tetraplegia lack independent mobility, making them highly dependent on others to move from one place to another. Here, we describe how two macaques were able to use a wireless integrated system to control a robotic platform, over which they were sitting, to achieve independent mobility using the neuronal activity in their motor cortices. The activity of populations of single neurons was recorded using multiple electrode arrays implanted in the arm region of primary motor cortex, and decoded to achieve brain control of the platform. We found that free-running brain control of the platform (which was not equipped with any machine intelligence) was fast and accurate, resembling the performance achieved using joystick control. The decoding algorithms can be trained in the absence of joystick movements, as would be required for use by tetraplegic individuals, demonstrating that the non-human primate model is a good pre-clinical model for developing such a cortically-controlled movement prosthetic. Interestingly, we found that the response properties of some neurons differed greatly depending on the mode of control (joystick or brain control), suggesting different roles for these neurons in encoding movement intention and movement execution. These results demonstrate that independent mobility can be achieved without first training on prescribed motor movements, opening the door for the implementation of this technology in persons with tetraplegia.     

The modification of cortical reorganization and chronic pain by sensory feedback

Recent neuroscientific evidence has revealed that the adult brain is capable of substantial plastic change in areas such as the primary somatosensory cortex that were formerly thought to be modifiable only during early experience. We discuss research on phantom limb pain as well as chronic back pain that revealed functional reorganization in both the somatosensory and the motor system in these chronic pain states. In phantom limb pain patients, cortical reorganization is correlated with the amount of phantom limb pain; in low back pain patients the amount of reorganizational change increases with chronicity. We present a model of the development of chronic pain that assumes an important role of somatosensory pain memories. In phantom limb pain, we propose that those patients who experienced intense pain prior to the amputation will later likely develop enhanced cortical reorganization and phantom limb pain. We show that cortical plasticity related to chronic pain can be reduced by behavioral interventions that provide feedback to the brain areas that were altered by somatosensory pain memories.     

Somatosensory precision in speech production

Speech production is dependent on both auditory and somatosensory feedback. Although audition may appear to be the dominant sensory modality in speech production, somatosensory information plays a role that extends from brainstem responses to cortical control. Accordingly, the motor commands that underlie speech movements may have somatosensory as well as auditory goals. Here we provide evidence that, independent of the acoustics, somatosensory information is central to achieving the precision requirements of speech movements. We were able to dissociate auditory and somatosensory feedback by using a robotic device that altered the jaw's motion path, and hence proprioception, without affecting speech acoustics. The loads were designed to target either the consonant- or vowel-related portion of an utterance because these are the major sound categories in speech. We found that, even in the absence of any effect on the acoustics, with learning subjects corrected to an equal extent for both kinds of loads. This finding suggests that there are comparable somatosensory precision requirements for both kinds of speech sounds. We provide experimental evidence that the neural control of stiffness or impedance--the resistance to displacement--provides for somatosensory precision in speech production.     

Organization of the Connections between the Parietal Associative Zone and the Primary Sensory Zones in the Cat Neocortex

In acute experiments on cats, we studied the impulse activity of 262 neurons of the parietal associative zone (PAZ, field 5). Among them, 129 cells [100 silent units and 29 units generating background activity (BA)] were identified as output neurons, while 133 cells with the BA were interneurons of the intrinsic cortical neuronal circuits. Electrical stimulation of the primary visual, auditory, or somatosensory cortices evoked no impulse responses in silent output PAZ neurons, while output neurons with the BA and interneurons (more than 65 and 80% of the cell units, respectively) generated clear responses (more frequently, phasic). Stimulation of the auditory and visual cortices exerted mostly inhibitory effects, while stimulation of the somatosensory cortex provided mostly excitatory influences. The ratios of neurons generating primary excitatory and inhibitory responses to stimulation of the visual, auditory, and somatic cortices were 0.3:1, 0.6:1, and 3.2:1, respectively. More than 95% of the field-5 neurons were influenced from the primary sensory zones via di- and/or polysynaptic pathways. Monosynaptic excitatory inputs from the visual cortex were identified for 3.8% of interneurons and 6.9% of output PAZ neurons; for the auditory cortical inputs, the respective figures were 1.7 and 3.5%. Monosynaptic connections with the somatic cortex were found only for 4% of the interneurons under study. It has been concluded that interaction of heteromodal signals coming to the PAZ via the corticopetal and associative inputs occurs on neurons of all the cortical layers.     

Detecting Static and Dynamic Differences between Eyes-Closed and Eyes-Open Resting States Using ASL and BOLD fMRI

Resting-state fMRI studies have increasingly focused on multi-contrast techniques, such as BOLD and ASL imaging. However, these techniques may reveal different aspects of brain activity (e.g., static vs. dynamic), and little is known about the similarity or disparity of these techniques in detecting resting-state brain activity. It is therefore important to assess the static and dynamic characteristics of these fMRI techniques to guide future applications. Here we acquired fMRI data while subjects were in eyes-closed (EC) and eyes-open (EO) states, using both ASL and BOLD techniques, at two research centers (NIDA and HNU). Static brain activity was calculated as voxel-wise mean cerebral blood flow (CBF) using ASL, i.e., CBF-mean, while dynamic activity was measured by the amplitude of low frequency fluctuations (ALFF) of BOLD, i.e., BOLD-ALFF, at both NIDA and HNU, and CBF, i.e., CBF-ALFF, at NIDA. We showed that mean CBF was lower under EC than EO in the primary visual cortex, while BOLD-ALFF was higher under EC in the primary somatosensory cortices extending to the primary auditory cortices and lower in the lateral occipital area. Interestingly, mean CBF and BOLD-ALFF results overlapped at the visual cortex to a very small degree. Importantly, these findings were largely replicated by the HNU dataset. State differences found by CBF-ALFF were located in the primary auditory cortices, which were generally a subset of BOLD-ALFF and showed no spatial overlap with CBF-mean. In conclusion, static brain activity measured by mean CBF and dynamic brain activity measured by BOLD- and CBF-ALFF may reflect different aspects of resting-state brain activity and a combination of ASL and BOLD may provide complementary information on the biophysical and physiological processes of the brain.     

研究报告: 大鼠感觉运动系统静息态脑网络研究

为了理解啮齿类动物的脑功能连接,本文利用9.4T fMRI获得轻度麻醉状态下大鼠静息状态及刺激激活的数据,通过互相关分析构建节点之间的相关系数矩阵并计算相应的网络参数．结果发现：给予前爪电刺激时,刺激对侧初级感觉皮层(S1)、丘脑(Tha)有较强的正激活,双侧尾状壳核(CPu)有较强的负激活．静息状态时大鼠感觉/运动皮层内部、丘脑内部的连接性较强,而感觉/运动皮层与丘脑之间的连接较弱,双侧感觉运动系统之间存在较强的同步低频振荡,感觉运动系统在静息态时的脑网络具有小世界属性．结果提示,啮齿类动物在大脑信息处理中的功能分离和整合可能与人类存在某些相似性,支持哺乳动物中枢神经系统的基本功能存在遗传保守性的观点．     

Definitions of state variables and state space for brain–computer interface

The hypothesis is proposed that the central dynamics of the action–perception cycle has five steps: emergence from an existing macroscopic brain state of a pattern that predicts a future goal state; selection of a mesoscopic frame for action control; execution of a limb trajectory by microscopic spike activity; modification of microscopic cortical spike activity by sensory inputs; construction of mesoscopic perceptual patterns; and integration of a new macroscopic brain state. The basis is the circular causality between microscopic entities (neurons) and the mesoscopic and macroscopic entities (populations) self-organized by axosynaptic interactions. Self-organization of neural activity is bidirectional in all cortices. Upwardly the organization of mesoscopic percepts from microscopic spike input predominates in primary sensory areas. Downwardly the organization of spike outputs that direct specific limb movements is by mesoscopic fields constituting plans to achieve predicted goals. The mesoscopic fields in sensory and motor cortices emerge as frames within macroscopic activity. Part 1 describes the action–perception cycle and its derivative reflex arc qualitatively. Part 2 describes the perceptual limb of the arc from microscopic MSA to mesoscopic wave packets, and from these to macroscopic EEG and global ECoG fields that express experience-dependent knowledge in successive states. These macroscopic states are conceived to embed and control mesoscopic frames in premotor and motor cortices that are observed in local ECoG and LFP of frontoparietal areas. The fields sampled by ECoG and LFP are conceived as local patterns of neural activity in which trajectories of multiple spike activities (MSA) emerge that control limb movements. Mesoscopic frames are located by use of the analytic signal from the Hilbert transform after band pass filtering. The state variables in frames are measured to construct feature vectors by which to describe and classify frame patterns. Evidence is cited to justify use of linear analysis. The aim of the review is to enable researchers to conceive and identify goal-oriented states in brain activity for use as commands, in order to relegate the details of execution to adaptive control devices outside the brain. http://sulcus.berkeley.edu     

Neural Dynamics of Learning Sound—Action Associations

A motor component is pre-requisite to any communicative act as one must inherently move to communicate. To learn to make a communicative act, the brain must be able to dynamically associate arbitrary percepts to the neural substrate underlying the pre-requisite motor activity. We aimed to investigate whether brain regions involved in complex gestures (ventral pre-motor cortex, Brodmann Area 44) were involved in mediating association between novel abstract auditory stimuli and novel gestural movements. In a functional resonance imaging (fMRI) study we asked participants to learn associations between previously unrelated novel sounds and meaningless gestures inside the scanner. We use functional connectivity analysis to eliminate the often present confound of ‘strategic covert naming’ when dealing with BA44 and to rule out effects of non-specific reductions in signal. Brodmann Area 44, a region incorporating Broca''s region showed strong, bilateral, negative correlation of BOLD (blood oxygen level dependent) response with learning of sound-action associations during data acquisition. Left-inferior-parietal-lobule (l-IPL) and bilateral loci in and around visual area V5, right-orbital-frontal-gyrus, right-hippocampus, left-para-hippocampus, right-head-of-caudate, right-insula and left-lingual-gyrus also showed decreases in BOLD response with learning. Concurrent with these decreases in BOLD response, an increasing connectivity between areas of the imaged network as well as the right-middle-frontal-gyrus with rising learning performance was revealed by a psychophysiological interaction (PPI) analysis. The increasing connectivity therefore occurs within an increasingly energy efficient network as learning proceeds. Strongest learning related connectivity between regions was found when analysing BA44 and l-IPL seeds. The results clearly show that BA44 and l-IPL is dynamically involved in linking gesture and sound and therefore provides evidence that one of the mechanisms required for the evolution of human communication is found within these motor regions.