Limits...
Neurobehavioral mechanisms of temporal processing deficits in Parkinson's disease.

Harrington DL, Castillo GN, Greenberg PA, Song DD, Lessig S, Lee RR, Rao SM - PLoS ONE (2011)

Bottom Line: First, we found that time-perception deficits were associated with striatal, cortical, and cerebellar dysfunction.Finally, DA therapy did not alleviate timing deficits.However, time perception impairments were not improved by DA treatment, likely due to inadequate restoration of neuronal activity and perhaps corticostriatal effective-connectivity.

View Article: PubMed Central - PubMed

Affiliation: Research, Neurology, and Radiology Services, Veterans Affairs San Diego Healthcare System, San Diego, California, United States of America. dharrington@ucsd.edu

ABSTRACT

Background: Parkinson's disease (PD) disrupts temporal processing, but the neuronal sources of deficits and their response to dopamine (DA) therapy are not understood. Though the striatum and DA transmission are thought to be essential for timekeeping, potential working memory (WM) and executive problems could also disrupt timing.

Methodology/findings: The present study addressed these issues by testing controls and PD volunteers 'on' and 'off' DA therapy as they underwent fMRI while performing a time-perception task. To distinguish systems associated with abnormalities in temporal and non-temporal processes, we separated brain activity during encoding and decision-making phases of a trial. Whereas both phases involved timekeeping, the encoding and decision phases emphasized WM and executive processes, respectively. The methods enabled exploration of both the amplitude and temporal dynamics of neural activity. First, we found that time-perception deficits were associated with striatal, cortical, and cerebellar dysfunction. Unlike studies of timed movement, our results could not be attributed to traditional roles of the striatum and cerebellum in movement. Second, for the first time we identified temporal and non-temporal sources of impaired time perception. Striatal dysfunction was found during both phases consistent with its role in timekeeping. Activation was also abnormal in a WM network (middle-frontal and parietal cortex, lateral cerebellum) during encoding and a network that modulates executive and memory functions (parahippocampus, posterior cingulate) during decision making. Third, hypoactivation typified neuronal dysfunction in PD, but was sometimes characterized by abnormal temporal dynamics (e.g., lagged, prolonged) that were not due to longer response times. Finally, DA therapy did not alleviate timing deficits.

Conclusions/significance: Our findings indicate that impaired timing in PD arises from nigrostriatal and mesocortical dysfunction in systems that mediate temporal and non-temporal control-processes. However, time perception impairments were not improved by DA treatment, likely due to inadequate restoration of neuronal activity and perhaps corticostriatal effective-connectivity.

Show MeSH

Related in: MedlinePlus

Spatial extent of activation in areas showing reduced volumes in the PD OFF condition.Activation volumes for the left and right hemispheres combined are displayed for the encoding and decision phases in the C (red bars), PD OFF (black bars) and PD ON (grey bars) groups. Areas are displayed that showed reduced volumes of more than 25 percent in the PD OFF condition relative to the control (C) group. See Figures S1 and S2 for activation volumes in the whole brain, and Tables S1 and S2 for details about activation foci.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3045463&req=5

pone-0017461-g002: Spatial extent of activation in areas showing reduced volumes in the PD OFF condition.Activation volumes for the left and right hemispheres combined are displayed for the encoding and decision phases in the C (red bars), PD OFF (black bars) and PD ON (grey bars) groups. Areas are displayed that showed reduced volumes of more than 25 percent in the PD OFF condition relative to the control (C) group. See Figures S1 and S2 for activation volumes in the whole brain, and Tables S1 and S2 for details about activation foci.

Mentions: Descriptive analyses of the spatial extent of activation indicated that total volume of activation was reduced in both phases by approximately 28% in the PD OFF group relative to the controls. Frontal, parietal, and temporal lobe volumes were reduced 15% to 20% in the OFF group, irrespective of phase. However, Figure 2 shows that for both phases volume reductions of more than 25% were seen OFF medication in the bilateral preSMA/SMA/cingulate (33% for both phases), thalamus (36% to 39%), striatum (27% to 30%), midbrain nuclei (27% to 30%), parahippocampus (83% to 85%), occipital lobe (39% to 49%), and cerebellum (65% for both phases). Whereas medication appeared to increase activation extent, Figure 2 shows that the spatial extent of activation typically remained lower relative to the control group (see Figures S1 and S2 for activation volumes in the whole brain, and Tables S1 and S2 for details about activation foci).


Neurobehavioral mechanisms of temporal processing deficits in Parkinson's disease.

Harrington DL, Castillo GN, Greenberg PA, Song DD, Lessig S, Lee RR, Rao SM - PLoS ONE (2011)

Spatial extent of activation in areas showing reduced volumes in the PD OFF condition.Activation volumes for the left and right hemispheres combined are displayed for the encoding and decision phases in the C (red bars), PD OFF (black bars) and PD ON (grey bars) groups. Areas are displayed that showed reduced volumes of more than 25 percent in the PD OFF condition relative to the control (C) group. See Figures S1 and S2 for activation volumes in the whole brain, and Tables S1 and S2 for details about activation foci.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045463&req=5

pone-0017461-g002: Spatial extent of activation in areas showing reduced volumes in the PD OFF condition.Activation volumes for the left and right hemispheres combined are displayed for the encoding and decision phases in the C (red bars), PD OFF (black bars) and PD ON (grey bars) groups. Areas are displayed that showed reduced volumes of more than 25 percent in the PD OFF condition relative to the control (C) group. See Figures S1 and S2 for activation volumes in the whole brain, and Tables S1 and S2 for details about activation foci.
Mentions: Descriptive analyses of the spatial extent of activation indicated that total volume of activation was reduced in both phases by approximately 28% in the PD OFF group relative to the controls. Frontal, parietal, and temporal lobe volumes were reduced 15% to 20% in the OFF group, irrespective of phase. However, Figure 2 shows that for both phases volume reductions of more than 25% were seen OFF medication in the bilateral preSMA/SMA/cingulate (33% for both phases), thalamus (36% to 39%), striatum (27% to 30%), midbrain nuclei (27% to 30%), parahippocampus (83% to 85%), occipital lobe (39% to 49%), and cerebellum (65% for both phases). Whereas medication appeared to increase activation extent, Figure 2 shows that the spatial extent of activation typically remained lower relative to the control group (see Figures S1 and S2 for activation volumes in the whole brain, and Tables S1 and S2 for details about activation foci).

Bottom Line: First, we found that time-perception deficits were associated with striatal, cortical, and cerebellar dysfunction.Finally, DA therapy did not alleviate timing deficits.However, time perception impairments were not improved by DA treatment, likely due to inadequate restoration of neuronal activity and perhaps corticostriatal effective-connectivity.

View Article: PubMed Central - PubMed

Affiliation: Research, Neurology, and Radiology Services, Veterans Affairs San Diego Healthcare System, San Diego, California, United States of America. dharrington@ucsd.edu

ABSTRACT

Background: Parkinson's disease (PD) disrupts temporal processing, but the neuronal sources of deficits and their response to dopamine (DA) therapy are not understood. Though the striatum and DA transmission are thought to be essential for timekeeping, potential working memory (WM) and executive problems could also disrupt timing.

Methodology/findings: The present study addressed these issues by testing controls and PD volunteers 'on' and 'off' DA therapy as they underwent fMRI while performing a time-perception task. To distinguish systems associated with abnormalities in temporal and non-temporal processes, we separated brain activity during encoding and decision-making phases of a trial. Whereas both phases involved timekeeping, the encoding and decision phases emphasized WM and executive processes, respectively. The methods enabled exploration of both the amplitude and temporal dynamics of neural activity. First, we found that time-perception deficits were associated with striatal, cortical, and cerebellar dysfunction. Unlike studies of timed movement, our results could not be attributed to traditional roles of the striatum and cerebellum in movement. Second, for the first time we identified temporal and non-temporal sources of impaired time perception. Striatal dysfunction was found during both phases consistent with its role in timekeeping. Activation was also abnormal in a WM network (middle-frontal and parietal cortex, lateral cerebellum) during encoding and a network that modulates executive and memory functions (parahippocampus, posterior cingulate) during decision making. Third, hypoactivation typified neuronal dysfunction in PD, but was sometimes characterized by abnormal temporal dynamics (e.g., lagged, prolonged) that were not due to longer response times. Finally, DA therapy did not alleviate timing deficits.

Conclusions/significance: Our findings indicate that impaired timing in PD arises from nigrostriatal and mesocortical dysfunction in systems that mediate temporal and non-temporal control-processes. However, time perception impairments were not improved by DA treatment, likely due to inadequate restoration of neuronal activity and perhaps corticostriatal effective-connectivity.

Show MeSH
Related in: MedlinePlus