Michael D. Crutcher

Bio: Michael D. Crutcher is an academic researcher from Johns Hopkins University School of Medicine. The author has contributed to research in topics: Direct pathway of movement & Indirect pathway of movement. The author has an hindex of 5, co-authored 5 publications receiving 7060 citations.

Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions.

Abstract: The central theme of the "segregated circuits" hypothesis is that structural convergence and functional integration occurs within, rather than between, each of the identified circuits Admittedly, the anatomical evidence upon which this scheme is based remains incomplete The hypothesis continues to be predicated largely on comparisons of anterograde and retrograde labeling studies carried out in different sets of animals Only in the case of the "motor" circuit has evidence for the continuity of the loop been demonstrated directly in individual subjects; for the other circuits, such continuity is inferred from comparisons of data on different components of each circuit obtained in separate experiments Because of the marked compression of pathways leading from cortex through basal ganglia to thalamus, comparisons of projection topography across experimental subjects may be hazardous Definitive tests of the hypothesis of maintained segregation await additional double- and multiple-label tract-tracing experiments wherein the continuity of one circuit, or the segregation of adjacent circuits, can be examined directly in individual subjects It is worthy of note, however, that the few studies to date that have employed this methodology have generated results consistent with the segregated circuits hypothesis Moreover, single cell recordings in behaving animals have shown striking preservation of functional specificity at the level of individual neurons throughout the "motor" and "oculomotor" circuits It is difficult to imagine how such functional specificity could be maintained in the absence of strict topographic specificity within the sequential projections that comprise these two circuits This is not to say, however, that we expect the internal structure of functional channels (eg, the "arm" channel within the "motor" circuit) to have cable-like, point-to-point topography When the grain of analysis is sufficiently fine, anatomical studies have shown repeatedly that the terminal fields of internuclear projections (eg, to striatum, pallidum, nigra, thalamus, etc) often appear patchy and highly divergent, suggesting that neighboring groups of projection cells tend to influence interdigitating clusters of postsynaptic neurons While more intricate and complex than simple point-to-point topography, however, this type arrangement should also be capable of maintaining functional specificity As discussed briefly above, it is not yet clear to what extent the inputs to the "motor" circuit from the different precentral motor fields (eg, MC, SMA, APA) are integrated in their passage through the circuit It now appears that at the level of the putamen such inputs remain segregated(ABSTRACT TRUNCATED AT 400 WORDS)

Movement-Related Neuronal Activity Selectively Coding Either Direction or Muscle Pattern in Three Motor Areas of the Monkey

Abstract: 1. Movement-related neuronal activity in the supplementary motor area (SMA), primary motor cortex (MC), and putamen was studied in monkeys performing a visuomotor tracking task designed to determine 1) the extent to which neuronal activity in each of these areas represented the direction of visually guided arm movements versus the pattern of muscle activity required to achieve those movements and 2) the relative timing of different types of movement-related activity in these three motor areas. 2. A total of 455 movement-related neurons in the three motor areas were tested with a behavioral paradigm, which dissociated the direction of visually guided elbow movements from the accompanying pattern of muscular activity by the application of opposing and assisting torque loads. The movement-related activity described in this report was collected in the same animals performing the same behavioral paradigm used to study preparatory activity described in the preceding paper. Of the total sample, 87 neurons were located within the arm region of the SMA, 150 within the arm region of the MC, and 218 within the arm region of the putamen. 3. Movement-related cells were classified as "directional" if they showed an increase in discharge rate predominantly or exclusively during movements in one direction and did not have significant static or dynamic load effects. A cell was classified as "muscle-like" if its directional movement-related activity was associated with static and/or dynamic load effects whose pattern was similar to that of flexors or extensors of the forearm. Both directional and muscle-like cells were found in all three motor areas. The largest proportion of directional cells was located in the putamen (52%), with significantly smaller proportions in the SMA (38%) and MC (41%). Conversely, a smaller proportion of muscle-like cells was seen in the putamen (24%) than in the SMA (41%) or MC (36%). 4. The time of onset of movement-related discharge relative to the onset of movement ("lead time") was computed for each cell. On average, SMA neurons discharged significantly earlier (SMA lead times 47 +/- 8 ms, mean +/- SE) than those in MC (23 +/- 6 ms), which in turn were earlier than those in putamen (-33 +/- 6 ms). However, the degree of overlap of the distributions of lead times for the three areas was extensive.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of basal ganglia in limb movements.

Abstract: Recent anatomic and physiologic studies have shed new light on the functional organization of the basal ganglia and their role in movement. The basal ganglia receive topographically organized input from the entire neocortex. Influences from sensorimotor and "association" cortices appear to remain segregated in the basal ganglia. The concept of segregated parallel subcortical loops subserving "motor" and "complex" functions is discussed. Recent neurophysiologic studies in behaving primates suggest that basal ganglia output plays a role in controlling the direction and amplitude of movement but is not primarily involved in the initiation of limb movement or selection of specific muscles. These studies are generally consistent with data from patients with Parkinson's disease, which likewise indicates a deficit in the programming of movement amplitude in step-tracking tasks, with little or no change in reaction-time or pattern of muscular activity.

Functional organization of the basal ganglia: contributions of single-cell recording studies.

Abstract: Studies of single-cell discharge in the basal ganglia of behaving primates have revealed: characteristic patterns of spontaneous discharge in the striatum, external (GPe) and internal (GPi) globus pallidus, pars reticulata and pars compacta of the substantia nigra, and the subthalamic nucleus (STN); phasic changes in neural discharge in relation to movements of specific body parts (e.g. leg, arm, neck, face); short-latency (sensory) neural responses to passive joint rotation; a somatotopic organization of movement-related neurons in GPe, GPi, and STN; a clustering of functionally similar neurons in the putamen and globus pallidus; greater representation of the proximal than of the distal portion of the limb; changes in neural activity in reaction-time tasks, suggesting a greater role of the basal ganglia in the execution than in the initiation of movement in this paradigm; a clear relation of neuronal activity to direction, amplitude (?velocity) of movement, and force; a preferential relation of neural activity to the direction of movement, rather than to the pattern of muscular activity. Some of these findings suggest that the basal ganglia may play a role in the control of movement parameters rather than (or independent of) the pattern of muscular activity. Loss of basal ganglia output related to amplitude may account for the bradykinesia in Parkinson's disease. The presence of somatotopic organization in the putamen and globus pallidus, together with known topographic striopallidal connections, suggests that segregated, parallel cortico-subcortical loops subserve 'motor' and 'complex' functions.

The organization of the human cerebral cortex estimated by intrinsic functional connectivity

Abstract: Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.

The neural basis of human error processing: Reinforcement learning, dopamine, and the error-related negativity.

Abstract: The authors present a unified account of 2 neural systems concerned with the development and expression of adaptive behaviors: a mesencephalic dopamine system for reinforcement learning and a “generic” error-processing system associated with the anterior cingulate cortex The existence of the error-processing system has been inferred from the error-related negativity (ERN), a component of the event-related brain potential elicited when human participants commit errors in reaction-time tasks The authors propose that the ERN is generated when a negative reinforcement learning signal is conveyed to the anterior cingulate cortex via the mesencephalic dopamine system and that this signal is used by the anterior cingulate cortex to modify performance on the task at hand They provide support for this proposal using both computational modeling and psychophysiological experimentation

Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions.

Abstract: The central theme of the "segregated circuits" hypothesis is that structural convergence and functional integration occurs within, rather than between, each of the identified circuits Admittedly, the anatomical evidence upon which this scheme is based remains incomplete The hypothesis continues to be predicated largely on comparisons of anterograde and retrograde labeling studies carried out in different sets of animals Only in the case of the "motor" circuit has evidence for the continuity of the loop been demonstrated directly in individual subjects; for the other circuits, such continuity is inferred from comparisons of data on different components of each circuit obtained in separate experiments Because of the marked compression of pathways leading from cortex through basal ganglia to thalamus, comparisons of projection topography across experimental subjects may be hazardous Definitive tests of the hypothesis of maintained segregation await additional double- and multiple-label tract-tracing experiments wherein the continuity of one circuit, or the segregation of adjacent circuits, can be examined directly in individual subjects It is worthy of note, however, that the few studies to date that have employed this methodology have generated results consistent with the segregated circuits hypothesis Moreover, single cell recordings in behaving animals have shown striking preservation of functional specificity at the level of individual neurons throughout the "motor" and "oculomotor" circuits It is difficult to imagine how such functional specificity could be maintained in the absence of strict topographic specificity within the sequential projections that comprise these two circuits This is not to say, however, that we expect the internal structure of functional channels (eg, the "arm" channel within the "motor" circuit) to have cable-like, point-to-point topography When the grain of analysis is sufficiently fine, anatomical studies have shown repeatedly that the terminal fields of internuclear projections (eg, to striatum, pallidum, nigra, thalamus, etc) often appear patchy and highly divergent, suggesting that neighboring groups of projection cells tend to influence interdigitating clusters of postsynaptic neurons While more intricate and complex than simple point-to-point topography, however, this type arrangement should also be capable of maintaining functional specificity As discussed briefly above, it is not yet clear to what extent the inputs to the "motor" circuit from the different precentral motor fields (eg, MC, SMA, APA) are integrated in their passage through the circuit It now appears that at the level of the putamen such inputs remain segregated(ABSTRACT TRUNCATED AT 400 WORDS)

Driving fast-spiking cells induces gamma rhythm and controls sensory responses

Abstract: Corticalgammaoscillations(20280Hz)predictincreasesinfocusedattention,andfailureingammaregulationisahallmark of neurological and psychiatric disease. Current theory predicts that gamma oscillations are generated by synchronous activity of fast-spiking inhibitory interneurons, with the resulting rhythmic inhibition producing neural ensemble synchrony by generating a narrow window for effective excitation. We causally tested these hypotheses in barrel cortex in vivo by targeting optogenetic manipulation selectively to fast-spiking interneurons. Here we show that light-driven activation of fast-spiking interneurons atvariedfrequencies (82200Hz) selectivelyamplifies gamma oscillations. Incontrast, pyramidal neuron activation amplifies only lower frequency oscillations, a cell-type-specific double dissociation. We found that the timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses. Our data directly support the fast-spiking-gamma hypothesis and provide the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation.