The activity of frontal motor areas during hand-object interaction is coordinated by dense communication along specific white matter pathways. This architecture allows the continuous shaping of voluntary motor output and, despite extensively investigated in non-human primate studies, remains poorly understood in humans. Disclosure of this system is crucial for predicting and treatment of motor deficits after brain lesions. For this purpose, we investigated the effect of direct electrical stimulation on white matter pathways within the frontal lobe on hand-object manipulation. This was tested in thirty-four patients (15 left hemisphere, mean age 42 years, 17 male, 15 with tractography) undergoing awake neurosurgery for frontal lobe tumour removal with the aid of the brain mapping technique. The stimulation outcome was quantified based on hand-muscle activity required by task execution. The white matter pathways responsive to stimulation with an interference on muscles were identified by means of probabilistic density estimation of stimulated sites, tract-based lesion-symptom (disconnectome) analysis and diffusion tractography on the single patient level. Finally, we assessed the effect of permanent tracts disconnection on motor outcome in the immediate postoperative period using a multivariate lesion-symptom mapping approach. The analysis showed that stimulation disrupted hand-muscle activity during task execution in 66 sites within the white matter below dorsal and ventral premotor regions. Two different EMG interference patterns associated with different structural architectures emerged: 1) an arrest pattern, characterised by complete impairment of muscle activity associated with an abrupt task interruption, occurred when stimulating a white matter area below the dorsal premotor region. Local mid-U-shaped fibres, superior fronto-striatal, corticospinal and dorsal fronto-parietal fibres intersected with this region. 2) a clumsy pattern, characterised by partial disruption of muscle activity associated with movement slowdown and/or uncoordinated finger movements, occurred when stimulating a white matter area below the ventral premotor region. Ventral fronto-parietal and inferior fronto-striatal tracts intersected with this region. Finally, only resections partially including the dorsal white matter region surrounding the supplementary motor area were associated with transient upper-limb deficit (p = 0.05; 5000 permutations). Overall, the results identify two distinct frontal white matter regions possibly mediating different aspects of hand-object interaction via distinct sets of structural connectivity. We suggest the dorsal region, associated with arrest pattern and post-operative immediate motor deficits, to be functionally proximal to motor output implementation, while the ventral region may be involved in sensorimotor integration required for task execution.

中文翻译：

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额叶通路的刺激会在物体操纵过程中破坏手部肌肉控制

手-物体交互过程中额叶运动区域的活动是通过沿着特定白质通路的密集交流来协调的。这种架构允许连续塑造自愿运动输出，尽管在非人类灵长类动物研究中进行了广泛研究，但在人类中仍然知之甚少。该系统的披露对于预测和治疗脑损伤后的运动缺陷至关重要。为此，我们研究了直接电刺激对额叶内白质通路对手对象操作的影响。这是在 34 名患者（15 名左半球，平均年龄 42 岁，17 名男性，15 名有纤维束造影术）接受清醒神经外科手术以借助脑映射技术切除额叶肿瘤的患者中进行的测试。根据任务执行所需的手部肌肉活动对刺激结果进行量化。通过对受刺激部位的概率密度估计、基于束的病变症状（断开组）分析和单个患者水平的扩散束成像，确定了对刺激响应并干扰肌肉的白质通路。最后，我们使用多变量病变症状映射方法评估了永久性纤维束断开对术后即刻运动结果的影响。分析表明，在背侧和腹侧运动前区下方白质内的 66 个部位执行任务期间，刺激会破坏手部肌肉活动。出现了与不同结构架构相关的两种不同 EMG 干扰模式：1）逮捕模式，当刺激背侧前运动区下方的白质区域时，会发生与任务突然中断相关的肌肉活动完全受损。局部中 U 形纤维、上额纹状体、皮质脊髓和背侧额顶叶纤维与该区域相交。2）当刺激腹侧前运动区下方的白质区域时，出现了一种笨拙的模式，其特征是与运动减慢和/或手指运动不协调相关的肌肉活动的部分中断。腹侧额顶叶和下额纹状体束与该区域相交。最后，只有部分包括辅助运动区域周围的背侧白质区域的切除与短暂的上肢缺陷相关（p = 0.05；5000 排列）。全面的，结果确定了两个不同的额叶白质区域，可能通过不同的结构连接集调解手对象交互的不同方面。我们建议与停止模式和术后即刻运动缺陷相关的背侧区域在功能上接近运动输出实施，而腹侧区域可能参与任务执行所需的感觉运动整合。