1. 刺激电路

使用电刺激的方式实现对神经元兴奋或抑制的调控，是脑疾病治疗中最常见且重要的功能之一[91]。这种功能被广泛应用于脑机接口设备中，用于治疗各种脑部疾病和恢复功能。例如，深部脑刺激（deep brain stimulation，DBS）就被应用在帕金森的治疗上[92]，而视皮层刺激被证明可以帮助盲人实现部分视觉恢复[93, 94]。

1. 常用刺激波形

根据刺激方式的不同，植入式电刺激器主要分为电压控制输出和电流控制输出两种方式。在电压控制的刺激器中，用于产生电刺激的两个电极之间存在刺激电压，刺激电路的输出受到组织和电极之间的阻抗影响。然而，电极与组织之间的阻抗模型是不稳定的，并且会随着刺激过程而变化。因此，在单个刺激周期内，注入到组织中的电荷无法均匀释放。当剩余电荷积累到阈值时，可能会对神经组织造成无法预测的损害。在电流控制刺激中，注入组织的电荷可以由电流模式数模转换器 (DAC) 控制。 通过设置刺激器的振幅和时间，可以精确的控制电荷的注入情况。电流控制输出不受组织负载变化的影响，可对输出到组织中的电荷量进行监控，较电压控制输出而言安全性更加在实际应用中。因此，电流控制输出更为常见。

图8-31 不同刺激方式示意图

如图8-31所示，根据刺激方式的不同，刺激方式可以分为单相（monophasic）和双相刺激（biphasic）。在单相刺激中，电荷的积累可能会导致组织损伤并对影响电极使用寿命。因此，更常用的是双相电流刺激，通过控制电流刺激方向，可以补偿大部分电荷，避免组织损伤和电极损坏的发生[95]。典型的双相刺激波形具备可调的电流强度、脉冲宽度以及刺激间隔。根据刺激脑位置和电极的不同，电流强度一般在10uA至1mA，刺激电压则在2V至10V之间。

在双相刺激中，可采用如图8-32所示的单极（monopolar）或双极（bipolar）电极配置方式。单极刺激使用单个工作电极，利用一对电流源和电流沉产生正相和负相两个阶段的刺激。在双极刺激中，正相和负相两个阶段的刺激由桥式电路控制电流源或电流沉电流在一对电极间的流动方向来产生。在高密度电极阵列中，常采用单极刺激方式，而双极刺激则具有更好的定向刺激效果。

图8-32 单极和双极电神经刺激器的简化示意图

2. 神经刺激电路

在脑机接口中，刺激器电路主要包括控制器、数模转换器（DAC）、电流驱动器和升压电路等部分。神经刺激器的输出电流通常由微控制器单元（MCU）或状态机等数字控制模块控制。数字模拟转换器（DAC）将数字信号转换为参考模拟信号，供后续的电流驱动器使用。DAC的输出位数决定了神经刺激器输出电流的精度，一般根据刺激电流的动态范围和跨度进行设计。电流驱动器用于将DAC输出的参考模拟信号转换为刺激器所需的电流输出。如图8-33中所示，神经刺激电路中可采用一对源-沉电流驱动对或者带有H桥的单一电流驱动器来完成单极或双极刺激。电流驱动器需要具有较高的输出阻抗以及高电压兼容性。高输出阻抗可确保刺激器能够有效地将电流传输到不同的负载阻抗。高电压兼容性（high voltage compliance）可保证刺激器在传递所需电流的同时，能够适应负载阻抗的变化，不会导致输出电压达到其限制，确保稳定的电流输出。由于深亚微米工艺的影响，植入式芯片的电压往往无法满足神经刺激的要求，因此需要升压电路来提供系统所需的高电压。

图8-33典型神经刺激器框图

神经刺激电流中常采用的是基于电流源的数模转换器。图8-34展示了一个6位的DAC电路，图中的B0-B5为数字控制码，利用晶体管的宽长比来获得不同大小的电流。通过上拉信号U、下拉信号D以及数字控制码的控制电流方向和大小，电极上可产生所需的刺激电流，Vbp和Vbn为数模转换器的偏置电压，用于产生基准电流[96]。

图8-34 6位数模转换器电路示意图

通过电流镜配合DAC输出是刺激器电路中常用的方法。图8-35中展示了利用单管MOS电流镜、共源共栅电流镜以及宽摆幅电流镜的神经刺激电路。单管电流镜的主要问题是输出阻抗较低，采用共源共栅或宽摆幅电流镜虽然较大程度的提高了输出阻抗，但是摆幅均存在不同程度的降低，影响高电压兼容性[97]。除此之外，还可以采用电压-电流转换的方式产生所需刺激电流。图8-36中，利用跨导放大器负反馈可以形成一个简单的电流驱动器，电压型DAC控制Vref或者控制处于线性区的可变电阻实现对刺激电流的控制[98]。采用图8-36的方式可显著提高输出阻抗，但是输出电流线性度易受到线性区工作晶体管的影响。

图8-35 电流模式数模转换器控制电流镜用于神经刺激

电流微刺激

图8-36 通过电压-电流转换实现神经电刺激

电荷泵电路被广泛应用于刺激器电路中，以产生高直流供电电压并向组织输送所需的足够电流[99]。图8-37所示是一个N级电荷泵电路的示意图，主要包括电容、电荷传输开关（charge transfer switch，CTS）。其中每个第i级由一个CTS和电容C组成，最后一对CTS和电容C_L构成了输出级[100]。电荷泵利用周期性信号CLK与CLK_B的控制来实现对电容的充电，间接地将电荷从一个电容器传递至另一个电容并在过程中不断积累电荷，从而使得输出电压升高。CTS的主要作用是将电荷不可逆的从输入传输至输出，CTS的设计是不同类型电荷泵的主要差异所在[101]。

图8-37 通过电压-电流转换实现神经电刺激

3. 电荷平衡

在现实应用中，确保双相刺激中正负两相的总电荷量相等，以实现刺激电荷的平衡非常重要。尽管可以通过时钟来控制两相刺激，但如果刺激过程没有进行校准，阳极和阴极电流之间仍然存在一定误差。如果刺激器在短时间内进行大量的高负荷刺激，这种误差将会被迅速放大，导致大量的电荷积累。为了避免这种情况，通常在刺激电极上串联一个隔离电容器，以限制总的刺激电荷量[102]。为了保证刺激器的输出电压范围，隔离电容值一般较大。在功能性电刺激中，隔离电容器的容量通常在几十纳法到几微法之间，物理尺寸较大，难以在芯片上集成[98]。

除了采用隔离电容方法外，还可以在刺激过程中对两相刺激电流进行匹配和校准。如果电流匹配不足以实现净零电荷要求，可使用额外的放电阶段来去除残余电荷。被动放电直接简单地将刺激电极接地或连接到公共或参考电极。被动放电的缺点是放电电流取决于负载和电极阻抗，无法很好地控制。如果阻抗太低，放电电流容易过高，有损坏组织的可能，因此需要额外的电流限制电路；如果阻抗太高，放电时间久，残余电荷可能无法在下次刺激之前完全清除。

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