Motor imagery in normal subjects and in asymmetrical Parkinson's disease: a PET study

OBJECTIVE: To investigate, using PET and H2(15)O, brain activation abnormalities of patients with PD during motor imagery. To determine whether motor imagery activation patterns depend on the hand used to complete the task. BACKGROUND: Previous work in PD has shown that bradykinesia is associated with slowness of motor imagery. METHODS: The PET study was performed in eight patients with PD with predominantly right-sided akinesia, and in eight age-matched control subjects, all right-handed. Regional cerebral blood flow was measured by PET and H2(15)O while subjects imagined a predetermined unimanual externally cued sequential movement with a joystick with either the left or the right hand, and during a rest condition. RESULTS: In normal subjects, the prefrontal cortex, supplementary motor area (SMA), superior parietal lobe, inferior frontal gyrus, and cerebellum were activated during motor imagery with either the left or the right hand. Contralateral primary motor cortex activation was noted only when the task was imagined with the right (dominant) hand, whereas activation of the dorsolateral prefrontal cortex was observed only during imagery with the left hand. In patients with PD, motor imagery with the right ("akinetic") hand was characterized by lack of activation of the contralateral primary sensorimotor cortex and the cerebellum, persistent activation of the SMA, and bilateral activation of the superior parietal cortex. Motor imagery with the left ("non-akinetic") hand was also abnormal, with lack of activation of the SMA compared with controls. CONCLUSIONS: In patients with PD with predominantly right-sided akinesia, brain activation during motor imagery is abnormal and may appear even with the less affected hand. In normal subjects, brain activation during motor imagery depends on the hand used in the imagined movement.     

Motor imagery in Parkinson's disease: a PET study.

We used positron emission tomography (PET) with 15O-labelled water to record patterns of cerebral activation in six patients with Parkinson's disease (PD), studied when clinically "off" and after turning "on" as a result of dopaminergic stimulation. They were asked to imagine a finger opposition movement performed with their right hand, externally paced at a rate of 1 Hz. Trials alternating between motor imagery and rest were measured. A pilot study of three age-matched controls was also performed. We chose the task as a robust method of activating the supplementary motor area (SMA), defects of which have been reported in PD. The PD patients showed normal degrees of activation of the SMA (proper) when both "off" and "on." Significant activation with imagining movement also occurred in the ipsilateral inferior parietal cortex (both "off" and when "on") and ipsilateral premotor cortex (when "off" only). The patients showed significantly greater activation of the rostral anterior cingulate and significantly less activation of the left lingual gyrus and precuneus when performing the task "on" compared with their performance when "off." PD patients when imagining movement and "off" showed less activation of several sites including the right dorsolateral prefrontal cortex (DLPFC) when compared to the controls performing the same task. No significant differences from controls were present when the patients imagined when "on." Our results are consistent with other studies showing deficits of pre-SMA function in PD with preserved function of the SMA proper. In addition to the areas of reduced activation (anterior cingulate, DLPFC), there were also sites of activation (ipsilateral premotor and inferior parietal cortex) previously reported as locations of compensatory overactivity for PD patients performing similar tasks. Both failure of activation and compensatory changes are likely to contribute to the motor deficit in PD.     

Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: a functional MRI case study.

Behavioral disturbances have been reported with subthalamic (STN) deep brain stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative functional imaging (fMRI) of mood and motor responses induced by successive right and left DBS. A 36-year-old woman with medically refractory PD and a history of clinically remitted depression underwent uncomplicated implantation of bilateral STN DBS. High-frequency stimulation of the left electrode improved motor symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of acute depressive dysphoria. Structural and functional magnetic resonance imaging (fMRI) imaging was carried out with sequential individual electrode stimulation. The electrode on the left was within the inferior STN, whereas the right electrode was marginally superior and lateral to the intended STN target within the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P < 0.001). Left DBS primarily showed changes in motor regions: increases in premotor and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar but less extensive change in motor regions. More prominent were the unique increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA] 24), anterior thalamus, caudate, and brainstem, and marked widespread decreases in medial prefrontal cortex (BA 9/10). The mood disturbance resolved spontaneously in 4 weeks despite identical stimulation parameters. Transient depressive mood induced by subcortical DBS stimulation was correlated with changes in mesolimbic cortical structures. This case provides new evidence supporting cortical segregation of motor and nonmotor cortico-basal ganglionic systems that may converge in close proximity at the level of the STN and the adjacent white matter tracts (Fields of Forel/zona incerta).     

Somatosensory Discrimination of Shape: Tactile Exploration and Cerebral Activation

This study of somatosensory discrimination of rectangular parallelepipeda with the right hand had three purposes: (i) to describe the exploratory finger movements; (ii) to reveal the anatomical brain structures specifically engaged in the production of exploratory finger movements; and (iii) to reveal the anatomical structures specifically engaged in the discrimination of tactually sensed shape. The thumb was the most active finger, moving with a mean exploration frequency of 2.4 Hz, as evident from videotape records of the exploratory finger movements. The cerebral structures activated during somatosensory discrimination were mapped by measurements of regional cerebral blood flow (rCBF) in six healthy male volunteers with positron emission tomography (PET) and the use of the computerized brain atlas of Greitz et al. (1991, J. Comp. Ass. Tomogr., 15, 26 - 38). The rCBF changes caused by somatosensory discrimination were compared point-to-point to a PET-study on right-hand finger movements and a PET-study on vibration stimulation of the right hand. From these results the following conclusions were drawn. The rCBF increase in the left superior parietal lobule indicated the site engaged in the analysis of shape. The rCBF increases in the left supplementary sensory area, bilaterally in premotor areas, in the left putamen, the right dentate nucleus and bilaterally in the posterior cerebellum were related to the control of the tactile exploratory finger movements. The rCBF increases in the right homologue of Broca's area, bilaterally in the superior prefrontal cortex and in the right midfrontal cortex probably resulted from working memory, the direction of attention, and the discrimination process.     

Cerebral activity modulation by extradural motor cortex stimulation in Parkinson's disease: a perfusion SPECT study

Extradural motor cortex stimulation (EMCS) has been proposed as alternative to deep brain stimulation (DBS) in the treatment of Parkinson's disease (PD). Its mechanisms of action are still unclear. Neuroimaging evidenced motor cortical dysfunction in PD that can be reversed by therapy. We performed left hemisphere EMCS surgery in six advanced PD patients fulfilling CAPSIT criteria for DBS with the exception of age >70 years. After 6 months, we measured regional cerebral blood flow (rCBF) at rest with SPECT and Tc-99m cysteinate dimer bicisate off-medication with stimulator off and on. Clinical assessment included Unified Parkinson's Disease Rating Scale part II and III, Abnormal Involuntary Movement Scale and mean dopaminergic medication dosage. We used statistical parametric mapping for imaging data analysis. Clinically we observed no mean changes in motor scales, although blinded evaluation revealed some benefit in individual patients. We found significant rCBF decrements in the pre-central gyrus, pre-motor cortex and caudate nucleus bilaterally, left prefrontal areas and right thalamus. Perfusion increments were found in cerebellum bilaterally. EMCS determined significant modulation of neuronal activity within the cortico-basal ganglia-thalamo-cortical motor loop in our cohort of advanced PD patients. However, these effects were paralleled by mild and variable clinical efficacy.     

Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study.

Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.     

Motor imagery in normal subjects and Parkinson's disease patients: an H215O PET study

Motor imagery paradigms can be used to investigate motor preparation. We used positron emission tomography to compare regional cerebral blood flow (rCBF) in patients with Parkinson's disease and normal controls under three conditions: rest, motor imagery and motor execution. In controls, imagery activated bilateral dorsolateral and mesial frontal cortex, inferior parietal cortex and precuneus. Motor execution additionally activated primary motor cortex (p < 0.001). Between-group, for imagery there was relative reduction in dorsolateral and mesial frontal activation in the patient group (p<0.01). For execution, there was impaired activation of right dorsolateral frontal cortex and basal ganglia (p<0.01). Our results support the notion that underfunctioning of mesial frontal and dorsolateral prefrontal cortex may underlie motor preparation in Parkinson's disease but also suggest that akinesia may occur in the absence of impaired mesial frontal cortex activation.     

Changes in cerebral activity pattern due to subthalamic nucleus or internal pallidum stimulation in Parkinson's disease

High-frequency electrical stimulation of the internal pallidum (GPi) or the subthalamic nucleus (STN) improves clinical symptoms of Parkinson's disease. In 12 parkinsonian patients, 6 with STN and 6 with GPi stimulators, we used H₂ ¹⁵O positron emission tomography to evaluate whether changes in movement performance were accompanied by change in regional cerebral blood flow (rCBF). Patients were scanned both at rest and while performing a free-choice joystick movement, under conditions of effective and ineffective electrostimulation. During effective STN stimulation, movement-related increases in rCBF were significantly higher in supplementary motor area, cingulate cortex, and dorsolateral prefrontal cortex (DLPFC) than during ineffective stimulation. No significant change was observed in any of these areas during GPi stimulation. The difference between the effect of STN and GPi stimulation on movement-related activity was mainly localized to DLPFC. These results confirm the dominant role of nonprimary motor areas in the control of movement in parkinsonian patients and demonstraste the importance of STN input in the control of these areas.     

Overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients

Regional cerebral blood flow (rCBF) was measured using PET and H2(15)O in Parkinson's disease (PD) patients with predominantly right-sided akinetic-rigid symptoms and in control subjects during the execution of an externally cued motor task either with the left or the right hand. During the execution of the task with the left, non-akinetic, hand, cerebral activation in PD patients appeared similar to that of controls. Activated areas were the primary motor cortex, premotor cortex, parietal cortex and cerebellum. When the task was executed with the right, akinetic, hand cerebral activation in PD patients differed from that of controls subjects. The most important change was a bilateral activation of the primary motor cortex. We conclude that overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients.     

Brain activations during motor imagery of locomotor-related tasks: a PET study

Positron emission tomography (PET) was used to study the involvement of supraspinal structures in human locomotion. Six right-handed adults were scanned in four conditions while imagining locomotor-related tasks in the first person perspective: Standing (S), Initiating gait (IG), Walking (W) and Walking with obstacles (WO). When these conditions were compared to a rest (control) condition to identify the neural structures involved in the imagination of locomotor-related tasks, the results revealed a common pattern of activations, which included the dorsal premotor cortex and precuneus bilaterally, the left dorsolateral prefrontal cortex, the left inferior parietal lobule, and the right posterior cingulate cortex. Additional areas involving the pre-supplementary motor area (pre-SMA), the precentral gyrus, were activated during conditions that required the imagery of locomotor movements. Further subtractions between the different locomotor conditions were then carried out to determine the cerebral regions associated with the simulation of increasingly complex locomotor functions. These analyses revealed increases in rCBF activity in the left cuneus and left caudate when the W condition was compared to the IG condition, suggesting that the basal ganglia plays a role in locomotor movements that are automatic in nature. Finally, subtraction of the W from the WO condition yielded increases in activity in the precuneus bilaterally, the left SMA, the right parietal inferior cortex and the left parahippocampal gyrus. Altogether, the present findings suggest that higher brain centers become progressively engaged when demands of locomotor tasks require increasing cognitive and sensory information processing.     

Representations of Graphomotor Trajectories in the Human Parietal Cortex: Evidence for Controlled Processing and Automatic Performance

The aim of this study was to identify the cerebral areas activated during kinematic processing of movement trajectories. We measured regional cerebral blood flow (rCBF) during learning, performance and imagery of right-hand writing in eight right-handed volunteers. Compared with viewing the writing space, increases in rCBF were observed in the left motor, premotor and frontomesial cortex, and in the right anterior cerebellum in all movement conditions, and the increases were related to mean tangential writing velocity. No rCBF increases occurred in these areas during imagery. Early learning of new ideomotor trajectories and deliberately exact writing of letters both induced rCBF increases in the cortex lining the right intraparietal sulcus. In contrast, during fast writing of overlearned trajectories and in the later phase of learning new ideograms the rCBF increased bilaterally in the posterior parietal cortex. Imagery of ideograms that had not been practised previously activated the anterior and posterior parietal areas simultaneously. Our results provide evidence suggesting that the kinematic representations of graphomotor trajectories are multiply represented in the human parietal cortex. It is concluded that different parietal subsystems may subserve attentive sensory movement control and whole-field visuospatial processing during automatic performance.     

Neural correlates of STN DBS-induced cognitive variability in Parkinson disease

BACKGROUND: Although deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson disease (PD) improves motor function, it has variable effects on working memory (WM) and response inhibition (RI) performance. The purpose of this study was to determine the neural correlates of STN DBS-induced variability in cognitive performance. METHODS: We measured bilateral STN DBS-induced blood flow changes (PET and [(15)O]-water on one day) in the supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and right inferior frontal cortex (rIFC) as well as in exploratory ROIs defined by published meta-analyses. STN DBS-induced WM and RI changes (Spatial Delayed Response and Go-No-Go on the next day) were measured in 24 PD participants. On both days, participants withheld PD medications overnight and conditions (OFF vs. ON) were administered in a counterbalanced, double-blind manner. RESULTS: As predicted, STN DBS-induced DLPFC blood flow change correlated with change in WM, but not RI performance. Furthermore, ACC blood flow change correlated with change in RI but not WM performance. For both relationships, increased blood flow related to decreased cognitive performance in response to STN DBS. Of the exploratory regions, only blood flow changes in DLPFC and ACC were correlated with performance. CONCLUSIONS: These results demonstrate that variability in the effects of STN DBS on cognitive performance relates to STN DBS-induced cortical blood flow changes in DLPFC and ACC. This relationship highlights the need to further understand the factors that mediate the variability in neural and cognitive response to STN DBS.     

Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study

The aim of this study was to examine the hypothesis, if the activation of some cerebral structures due to physiological stimulation is accompanied by deactivations of other structures elsewhere in the brain. A vibratory stimulus was applied to the right hand palm of healthy volunteers and the regional cerebral blood flow (rCBF) and regional cerebral oxygen metabolism (rCMRO2) were measured with positron emission tomography (PET). Regional analysis and voxel-by-voxel plots indicated that the stimulation induced increases and decreases of the rCBF were coupled to increases and decreases of the rCMRO2. The increases were localized in the left primary somatosensory area (SI), the left secondary somatosensory area (SII), the left retroinsular field (RI), the left anterior parietal cortex, the left primary motor area (MI), and the left supplementary motor area (SMA). The decreases occurred bilaterally in the superior parietal cortex, in paralimbic association areas, and the left globus pallidus. The increases and decreases of the rCBF and rCMRO2 were balanced in such a way that the mean global CBF and CMRO2 did not change compared with rest. We conclude that the decreases of the cerebral oxidative metabolism indicated regional depressions of synaptic activity.     

The measurement of regional cerebral blood flow during the complex cognitive task of meditation: a preliminary SPECT study

This study measured changes in regional cerebral blood flow (rCBF) during the complex cognitive task of meditation using single photon emission computed tomography. Eight experienced Tibetan Buddhist meditators were injected at baseline with 7 mCi HMPAO and scanned 20 min later for 45 min. The subjects then meditated for 1 h at which time they were injected with 25 mCi HMPAO and scanned 20 min later for 30 min. Values were obtained for regions of interest in major brain structures and normalized to whole brain activity. The percentage change between meditation and baseline was compared. Correlations between structures were also determined. Significantly increased rCBF (P<0.05) was observed in the cingulate gyrus, inferior and orbital frontal cortex, dorsolateral prefrontal cortex (DLPFC), and thalamus. The change in rCBF in the left DLPFC correlated negatively (P<0.05) with that in the left superior parietal lobe. Increased frontal rCBF may reflect focused concentration and thalamic increases overall increased cortical activity during meditation. The correlation between the DLPFC and the superior parietal lobe may reflect an altered sense of space experienced during meditation. These results suggest a complex rCBF pattern during the task of meditation.     

Learning of Sequential Finger Movements in Man: A Combined Kinematic and Positron Emission Tomography (PET) Study

The cerebral structures participating in learning of a manual skill were mapped with regional cerebral blood flow (rCBF) measurements and positron emission tomography in nine healthy volunteers. The task was a complicated right-hand finger movement sequence. The subjects were examined at three stages: during initial practice of the finger movement sequence, in an advanced stage of learning, and after they had learnt the finger movement sequence. Quantitative evaluation of video tapes and electromyographic records of the right forearm and hand muscles demonstrated that the finger movements significantly accelerated and became more regular. Significant mean rCBF increases were induced in the left motor hand area, the left premotor cortex, the left supplementary motor area, the left sensory hand area, the left supplementary sensory area and the right anterior lobe of the cerebellum. During the learning process significant depressions of the mean rCBF occurred bilaterally in the superior parietal lobule, the anterior parietal cortex and the pars triangularis of the right inferior frontal cortex. The mean rCBF increases in these structures during the initial stage of learning were related to somatosensory feedback processing and internal language for the guidance of the finger movements. These activations disappeared when the subjects had learnt the finger movement sequence. Conversely, the mean rCBF significantly rose during the course of learning in the midsector of the putamen and globus pallidus on the left side. It is suggested that during the learning phase of this movement sequence, the basal ganglia were critically involved in the establishment of the final motor programme.     

双侧丘脑底核电刺激对帕金森病患者脑局部糖代谢的影响

目的 研究双侧丘脑底核(subthalamic nucleus,STN)慢性电刺激术(deep brain stimulation,DBS)对晚期帕金森病(Parkinson's disease,PD)患者静止期脑局部糖代谢的影响,并探讨其作用机制。方法 对5例进行双侧STN的DBS治疗的晚期帕金森病患者,分别在术前以及术后1个月电刺激条件下,进行静止期18F-脱氧葡萄糖(FDG)/PET检查和UPDRS运动评分,并通过SPM99统计学软件进行数据分析,比较STN的DBS治疗对脑内代谢的影响。结果 双侧STN的DBS治疗使PD患者临床症状明显改善,同时脑局部糖代谢也发生了明显变化:双侧豆状核、脑干(中脑、脑桥)、双侧顶枕部、运动前区(BA6)及扣带回的脑代谢增加,双侧前额叶底部海马的脑代谢明显减少(P<0.05)。结论 双侧STN的DBS治疗可能通过兴奋STN轴突的方式,使其投射区域的基底上行和下行通路以及相应的皮层高级中枢的代谢改善,从而使PD患者的临床症状改善。     

Relative Changes in Regional Cerebral Blood Flow During Spinal Cord Stimulation in Patients with Refractory Angina Pectoris

Spinal cord stimulation applied at thoracic level 1 (T1) has a neurally mediated anti-anginal effect based on anti-ischaemic action in the myocardium. Positron emission tomography was used to study which higher brain centres are influenced by spinal cord stimulation. Nine patients with a spinal cord stimulator for angina pectoris were studied using H₂¹⁵O as a flow tracer. Relative changes in regional cerebral blood flow related to stimulation compared with non-stimulation were assessed and analysed using the method of statistical parametric mapping. Increased regional cerebral blood flow was observed in the left ventrolateral periaqueductal grey, the medial prefrontal cortex [Brodmann area (BA) 9/10], the dorsomedial thalamus bilaterally, the left medial temporal gyrus (BA 21), the left pulvinar of the thalamus, bilaterally in the posterior caudate nucleus, and the posterior cingulate cortex (BA 30). Relative decreases in rCBF were noticed bilaterally in the insular cortex (BA 20/21 and BA 38), the right inferior temporal gyrus (BA 19/37), the right inferior frontal gyrus (BA 45), the left inferior parietal lobulus (BA 40), the medial temporal gyrus (BA 39) and the right anterior cingulate cortex (BA 24). It is concluded that spinal cord stimulation used as an additional treatment for angina applied at TI modulates regional cerebral blood flow in brain areas known to be associated with nociception and in areas associated with cardiovascular control.     

Functional networks in motor sequence learning: abnormal topographies in Parkinson's disease

We examined the neural circuitry underlying the explicit learning of motor sequences in normal subjects and patients with early stage Parkinson's disease (PD) using 15O-water (H2 15O) positron emission tomography (PET) and network analysis. All subjects were scanned while learning motor sequences in a task emphasizing explicit learning, and during a kinematically controlled motor execution reference task. Because different brain networks are thought to subserve target acquisition and retrieval during motor sequence learning, we used separate behavioral indices to quantify these aspects of learning during the PET experiments. In the normal cohort, network analysis of the PET data revealed a significant covariance pattern associated with acquisition performance. This topography was characterized by activations in the left dorsolateral prefrontal cortex (PFdl), rostral supplementary motor area (preSMA), anterior cingulate cortex, and in the left caudate/putamen. A second independent covariance pattern was associated with retrieval performance. This topography was characterized by bilateral activations in the premotor cortex (PMC), and in the right precuneus and posterior parietal cortex. The normal learning-related topographies failed to predict acquisition performance in PD patients and predicted retrieval performance less accurately in the controls. A separate network analysis was performed to identify discrete learning-related topographies in the PD cohort. In PD patients, acquisition performance was associated with a covariance pattern characterized by activations in the left PFdl, ventral prefrontal, and rostral premotor regions, but not in the striatum. Retrieval performance in PD patients was associated with a covariance pattern characterized by activations in the right PFdl, and bilaterally in the PMC, posterior parietal cortex, and precuneus. These results suggest that in early stage PD sequence learning networks are associated with additional cortical activation compensating for abnormalities in basal ganglia function.     

Regional cerebral blood flow changes after low-frequency transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in treatment-resistant depression

Several studies have proved that low-frequency transcranial magnetic stimulation (TMS) of the right dorsolateral prefrontal cortex (DLPFC) showed an antidepressant effect, although its mechanism is still not completely elucidated. The aim of the present study was to clarify the alteration in neuroanatomical function elicited by low-frequency TMS of the right DLPFC in treatment-resistant depression and to detect the difference between responders and nonresponders to TMS. Single-photon emission computed tomography with (99m)Tc-ethyl cysteinate dimer was performed in 14 right-handed male patients with treatment-resistant unipolar depression before and after low-frequency TMS of the right DLPFC. Five 60-second 1-Hz trains were applied and 12 treatment sessions were administered within a 3-week period (total pulses, 3,600). The Hamilton Rating Scale for Depression was administered and the regional cerebral blood flow (rCBF) was analyzed using statistical parametric mapping (SPM2). After TMS treatment in 14 patients, the score on the Hamilton Rating Scale for Depression decreased significantly, and considerable decreases in rCBF were seen in the bilateral prefrontal, orbitofrontal, anterior insula, right subgenual cingulate, and left parietal cortex, but no significant increase in rCBF occurred. Additionally, as compared with 8 nonresponders, 6 responders showed significant increases in rCBF at baseline in the left hemisphere including the prefrontal and limbic-paralimbic regions. These results suggest that the antidepressant effect of low-frequency TMS of the right DLPFC is associated with a decrease in rCBF in the limbic-paralimbic regions via the ipsilateral subgenual cingulate, and increased rCBF at baseline in the left hemisphere may be involved in the response to low-frequency TMS treatment.     

Neuroanatomical correlates of therapeutic efficacy of low-frequency right prefrontal transcranial magnetic stimulation in treatment-resistant depression

Aims: Low‐frequency transcranial magnetic stimulation (TMS) to the right prefrontal cortex has been shown to be effective in treatment‐resistant depression. The aim of the present study was to investigate changes in regional cerebral blood flow (rCBF) after low‐frequency right prefrontal stimulation (LFRS), and neuroanatomical correlates of therapeutic efficacy of LFRS in treatment‐resistant depression. Methods: Twenty‐six patients with treatment‐resistant depression received five 60‐s 1‐Hz trains over the right prefrontal cortex, and 12 treatment sessions were administered during 3 weeks. Brain scans were acquired before and after LFRS using single photon emission computed tomography with ^99mTc‐ethyl cysteinate dimer. Severity of depression was assessed on the Hamilton Depression Rating Scale (HDRS). Results: Significant decreases in rCBF after LFRS were seen in the prefrontal cortex, orbitofrontal cortex, subgenual cingulate cortex, globus pallidus, thalamus, anterior and posterior insula, and midbrain in the right hemisphere. Therapeutic efficacy of LFRS was correlated with decreases in rCBF in the right prefrontal cortex, bilateral orbitofrontal cortex, right subgenual cingulate cortex, right putamen, and right anterior insula. Conclusion: The antidepressant effects of LFRS in treatment‐resistant depression may be associated with decreases in rCBF in the orbitofrontal cortex and the subgenual cingulate cortex via the right prefrontal cortex.